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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. Relationship between columnar cell changes and low-grade carcinoma in situ of the breast--a cytogenetic study.

    PubMed

    Go, Edna May L; Tsang, Julia Y S; Ni, Yun-Bi; Yu, Alex M; Mendoza, Paulo; Chan, Siu-Ki; Lam, Christopher C; Lui, Philip C; Tan, Puay-Hoon; Tse, Gary M

    2012-11-01

    Columnar cell lesions of the breast include columnar cell changes without atypia and columnar cell changes with atypia. The latter frequently coexist and share molecular changes with low-grade carcinoma in situ and invasive carcinoma, suggesting that columnar cell changes may be precursors to progression of low-grade advanced lesions. In this study, we assessed chromosomal aberrations at 16q, hallmark for low-grade lesions, in columnar cell changes with or without atypia and their adjacent carcinoma in situ by fluorescent in situ hybridization using 3 region-specific probes spanning the entire chromosomal arm. The results were correlated with the histomorphological features of the corresponding lesions. Forty-four percent of low-grade carcinoma in situ and 31% of high-grade carcinoma in situ were associated with columnar cell changes with atypia, suggesting a link between columnar cell changes with atypia and low-grade carcinoma in situ. For the genetic aberrations, heterozygous deletion of 16q was present in 56% of low-grade carcinoma in situ but only in 19% of high-grade carcinoma in situ. Conversely, aneuploidy was found mostly in high-grade carcinoma in situ (88%). Twenty percent of columnar cell changes with atypia but none of the columnar cell changes without atypia showed heterozygous deletion of 16q. Interestingly, the same changes in 16q were observed in the columnar cell changes and their associated low-grade carcinoma in situ lesions. These findings demonstrated a genetic commonality between columnar cell changes with atypia and low-grade carcinoma in situ and substantiated the precursor role of columnar cell changes with atypia for low-grade carcinoma in situ but not high-grade carcinoma in situ of the breast.

  3. Transition between columnar absorptive cells and goblet cells in the rat jejunal epithelium.

    PubMed

    Kurosumi, K; Shibuichi, I; Tosaka, H

    1981-11-01

    Electron microscopic observation of the jejunal epithelium of rats demonstrated morphological evidence of a transition between columnar absorptive cells and growing goblet cells. The columnar cells in both the villi and crypts have features suggestive of absorptive functions. They are provided with apical invaginations continuous to the intermicrovillous space. Absorbed lipid is observed in small vesicles in the terminal web layer, and chylomicrons derived here from are contained in large vacuoles near the Golgi apparatus. Ferritin particles artificially infused into the gut lumen were absorbed into the vacuoles in the subapical zone of columnar cells of suckling rats. Growing goblet cells situated in the crypt epithelium contain surface invaginations and lysosomes which are the same in structure as those found in absorptive cells nearby. Fat droplets evidently absorbed by the growing goblet cell were observed among immature mucus droplets. Artificially infused ferritin particles were found in vacuoles and lysosomes near the Golgi apparatus of some goblet cells of suckling rats. Some goblet cells on the intestinal villi of suckling rats looked immature and their microvilli and cytoplasmic matrix were clear like those of columnar absorptive cells. The transition between these goblet cells with clear cytoplasm and the mature goblet cells with dark cytoplasm was observed. These morphological evidences indicate that some of columnar cells already differentiated to absorptive cells are capable of transforming into mucus-producing (goblet) cells. It is suggested that not only undifferentiated columnar cells in the crypt base but also considerably differentiated columnar cells with absorptive function can differentiate into goblet cells.

  4. 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.

  5. Ghost cell lesions

    PubMed Central

    Rajesh, E.; Jimson, Sudha; Masthan, K. M. K.; Balachander, N.

    2015-01-01

    Ghost cells have been a controversy for a long time. Ghost cell is a swollen/enlarged epithelial cell with eosnophilic cytoplasm, but without a nucleus. In routine H and E staining these cells give a shadowy appearance. Hence these cells are also called as shadow cells or translucent cells. The appearance of these cells varies from lesion to lesion involving odontogenic and nonodontogenic lesions. This article review about the origin, nature and significance of ghost cells in different neoplasms. PMID:26015694

  6. Transition between columnar absorptive cells and goblet cells in the rat jejunal epithelium.

    PubMed

    Kurosumi, K; Shibuichi, I; Tosaka, H

    1981-11-01

    Electron microscopic observation of the jejunal epithelium of rats demonstrated morphological evidence of a transition between columnar absorptive cells and growing goblet cells. The columnar cells in both the villi and crypts have features suggestive of absorptive functions. They are provided with apical invaginations continuous to the intermicrovillous space. Absorbed lipid is observed in small vesicles in the terminal web layer, and chylomicrons derived here from are contained in large vacuoles near the Golgi apparatus. Ferritin particles artificially infused into the gut lumen were absorbed into the vacuoles in the subapical zone of columnar cells of suckling rats. Growing goblet cells situated in the crypt epithelium contain surface invaginations and lysosomes which are the same in structure as those found in absorptive cells nearby. Fat droplets evidently absorbed by the growing goblet cell were observed among immature mucus droplets. Artificially infused ferritin particles were found in vacuoles and lysosomes near the Golgi apparatus of some goblet cells of suckling rats. Some goblet cells on the intestinal villi of suckling rats looked immature and their microvilli and cytoplasmic matrix were clear like those of columnar absorptive cells. The transition between these goblet cells with clear cytoplasm and the mature goblet cells with dark cytoplasm was observed. These morphological evidences indicate that some of columnar cells already differentiated to absorptive cells are capable of transforming into mucus-producing (goblet) cells. It is suggested that not only undifferentiated columnar cells in the crypt base but also considerably differentiated columnar cells with absorptive function can differentiate into goblet cells. PMID:7325782

  7. Mixed columnar cell and tall cell variant of papillary carcinoma of thyroid: a case report and review of the literature.

    PubMed

    Putti, T C; Bhuiya, T A

    2000-11-01

    Columnar cell and tall cell carcinomas are newly described variants of papillary thyroid carcinoma associated with aggressive clinical behaviour. Although several cases of tall cell and columnar cell variants have been reported, only a single detailed case report of a mixed tall cell and columnar cell variant has been described in the English-language literature. We report another such composite tumour with predominant columna cell features in an elderly female. The tumour showed extrathyroidal extension with intraluminal superior thyroid vein invasion and lymph node metastasis. DNA ploidy analysis showed a diploid DNA content with no increase of S-phase fraction. Immunohistochemistry showed focal positivity for p53 and Ki-67 at the infiltrating margins of the tumour and diffuse positivity for proliferating cell nuclear antigen. The adverse clinical course warrants aggressive treatment and careful follow-up.

  8. Columnar deformation of human red blood cell by highly localized fiber optic Bessel beam stretcher.

    PubMed

    Lee, Sungrae; Joo, Boram; Jeon, Pyo Jin; Im, Seongil; Oh, Kyunghwan

    2015-11-01

    A single human red blood cell was optically stretched along two counter-propagating fiber-optic Bessel-like beams in an integrated lab-on-a-chip structure. The beam enabled highly localized stretching of RBC, and it induced a nonlinear mechanical deformation to finally reach an irreversible columnar shape that has not been reported. We characterized and systematically quantified this optically induced mechanical deformation by the geometrical aspect ratio of stretched RBC and the irreversible stretching time. The proposed RBC mechanism can realize a versatile and compact opto-mechanical platform for optical diagnosis of biological substances in the single cell level.

  9. 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

  10. Self-assembly Columnar Structure in Active Layer of Bulk Heterojunction Solar Cell

    NASA Astrophysics Data System (ADS)

    Pan, Cheng; Segui, Jennifer; Yu, Yingjie; Li, Hongfei; Akgun, Bulent; Satijia, Sushil. K.; Gersappe, Dilip; Nam, Chang-Yong; Rafailovich, Miriam

    2012-02-01

    Bulk Heterojunction (BHJ) polymer solar cells are an area of intense interest due to their flexibility and relatively low cost. However, due to the disordered inner structure in active layer, the power conversion efficiency of BHJ solar cell is relatively low. Our research provides the method to produce ordered self-assembly columnar structure within active layer of bulk heterojunction (BHJ) solar cell by introducing polystyrene (PS) into the active layer. The blend thin film of polystyrene, poly (3-hexylthiophene-2,5-diyl) (P3HT) and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) at different ratio are spin coated on substrate and annealed in vacuum oven for certain time. Atomic force microscopy (AFM) images show uniform phase segregation on the surface of polymer blend thin film and highly ordered columnar structure is then proven by etching the film with ion sputtering. TEM cross-section technology is also used to investigate the column structure. Neutron reflectometry was taken to establish the confinement of PCBM at the interface of PS and P3HT. The different morphological structures formed via phase segregation will be correlated with the performance of the PEV cells to be fabricated at the BNL-CFN.

  11. Asymmetric distribution of Spalt in Drosophila wing squamous and columnar epithelia ensures correct cell morphogenesis

    PubMed Central

    Tang, Wenqian; Wang, Dan; Shen, Jie

    2016-01-01

    The Drosophila wing imaginal disc is a sac-like structure that is composed of two opposing cell layers: peripodial epithelium (PE, also known as squamous epithelia) and disc proper (DP, also known as pseudostratified columnar epithelia). The molecular mechanism of cell morphogenesis has been well studied in the DP but not in the PE. Although proper Dpp signalling activity is required for proper PE formation, the detailed regulation mechanism is poorly understood. Here, we found that the Dpp target gene sal is only expressed in DP cells, not in PE cells, although pMad is present in the PE. Increasing Dpp signalling activity cannot activate Sal in PE cells. The absence of Sal in the PE is essential for PE formation. The ectopic expression of sal in PE cells is sufficient to increase the PE cell height. Down-regulation of sal in the DP reduced DP cell height. We further demonstrated that the known PE cell height regulator Lines, which can convert PE into a DP cell fate, is mediated by sal mis-activation in PE because sal-RNAi and lines co-expression largely restores PE cell morphology. By revealing the microtubule distribution, we demonstrated that Lines- and Sal-heightened PE cells are morphologically similar to the intermediate cell with cuboidal morphology. PMID:27452716

  12. Significance of acid-mucin-positive nongoblet columnar cells in the distal esophagus and gastroesophageal junction.

    PubMed

    Chen, Y Y; Wang, H H; Antonioli, D A; Spechler, S J; Zeroogian, J M; Goyal, R; Shahsafaei, A; Odze, R D

    1999-12-01

    Acidic mucin-positive nongoblet columnar cells (NGCC) have recently been observed in the surface epithelium of the gastroesophageal junction (GEJ) and distal esophagus in resections from patients with traditional long segment (>3 cm) Barrett's esophagus (BE). However, the significance of finding acidic mucin-positive NGCC in the surface epithelium of biopsy specimens from the distal esophagus/GEJ region in the absence of goblet cells (GC) remains unknown. Therefore, to determine the significance of mucin histochemical changes in the distal esophagus/GEJ region, we analyzed and compared the types, prevalence, and distribution of neutral and acidic mucins in biopsy specimens obtained from 2 groups of patients: those with (32 patients) and those without (107 patients) GC identified in this area. Various mucin histochemical stains (PAS-Ab pH 2.5, HID-Ab pH 2.5, PB/KOH/PAS) were used to identify neutral mucins, acidic mucins (sialomucins and sulphomucins), and o-acetylated sialomucins. The results were compared between the 2 patient groups and correlated with the clinical, endoscopic, and pathologic features. Compared with patients without GC, patients with GC had a significantly higher male/female ratio and a higher proportion of patients with greater than 3 cm of columnar epithelium within the esophagus. Acidic mucin (sialomucin and sulphomucin)-positive NGCC in the surface, foveolar, and glandular epithelium did not show any correlation with any of the clinical, endoscopic, or pathologic features, such as esophagitis, carditis, antritis, Helicobacter pylori infection, or length of columnar epithelium in the distal esophagus. However, acidic mucin-positive NGCC correlated strongly with the presence of GC (P < .001). For example, sialomucin-positive NGCC were present in 28 of 32 (88%) patients with GC compared with 31 of 107 (29%) patients without GC (P < .001). Similarly, sulphomucin-positive NGCC were present in 20 of 32 (62%) patients with GC, compared with 11 of

  13. Composite Mucoepidermoid Carcinoma and Columnar Cell Variant of Papillary Carcinoma of the Thyroid: A Case Report and Review of the Literature.

    PubMed

    Taconet, Sarah; Bosq, Jacques; Hartl, Dana; Schlumberger, Martin; Leboulleux, Sophie; Scoazec, Jean-Yves; Al-Ghuzlan, Abir

    2016-06-01

    Primary mucoepidermoid carcinoma (MEC) of the thyroid and columnar cell variant of papillary carcinoma of the thyroid (PCT) are uncommon neoplasms. We report the first case of composite MEC and columnar cell variant of PCT. An 86-year-old man consulted for a 47-mm thyroid nodule, cytologically compatible with PCT. Total thyroidectomy was performed. Histological diagnosis, with support of histochemistry and immunohistochemistry, was mixed primary carcinoma of the thyroid, associating an MEC component with predominantly columnar cell variant of PCT. Sixteen months after surgery and external beam radiation therapy, the patient was free of recurrence or distant metastasis. This case report offers an opportunity to highlight the potential pitfalls concerning the interpretation of mucin histochemistry in thyroid tumors. PMID:26755714

  14. Spindle cell melanocytic lesions: part II--an approach to intradermal proliferations and horizontally oriented lesions.

    PubMed

    Sade, Shachar; Al Habeeb, Ayman; Ghazarian, Danny

    2010-05-01

    Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes show a dendritic cytomorphology and territorial isolation, lesional nevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies, and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may either be a characteristic feature or a divergent appearance. The presence of spindle cells may mask the melanocytic nature of a lesion, and is often disconcerting, either due to its infrequent appearance in a particular lesion or its interpretation as a dedifferentiated phenotype. Spindle cell melanocytic lesions follow the full spectrum of potential biological outcomes, and difficulty may be experienced judging the nature of a lesion due to a lack of consistently reliable features to predict biological behaviour. Over time, recognition of numerous histomorphological features that may portend a more aggressive lesion have been identified; however, the translation of these features into a diagnostic entity requires a gestalt approach. Although most spindle cell melanocytic lesions may reliably be resolved through this standard approach, problem areas do exist for the surgical pathologist or dermatopathologist. With this review (part II of II), we complete our discussion of spindle cell melanocytic lesions, in order to: (1) model a systematic approach to such lesions; and (2) provide familiarity with those melanocytic lesions which either typically or occasionally display a spindled cytomorphology.

  15. 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...

  16. Scaling in Columnar Joints

    NASA Astrophysics Data System (ADS)

    Morris, Stephen

    2007-03-01

    Columnar jointing is a fracture pattern common in igneous rocks in which cracks self-organize into a roughly hexagonal arrangement, leaving behind an ordered colonnade. We report observations of columnar jointing in a laboratory analog system, desiccated corn starch slurries. Using measurements of moisture density, evaporation rates, and fracture advance rates, we suggest an advective-diffusive system is responsible for the rough scaling behavior of columnar joints. This theory explains the order of magnitude difference in scales between jointing in lavas and in starches. We investigated the scaling of average columnar cross-sectional areas in experiments where the evaporation rate was fixed using feedback methods. Our results suggest that the column area at a particular depth is related to both the current conditions, and hysteretically to the geometry of the pattern at previous depths. We argue that there exists a range of stable column scales allowed for any particular evaporation rate.

  17. 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

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

    SciTech Connect

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

    1993-12-31

    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 mobilis 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.

  19. 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.

  20. Spindle cell melanocytic lesions--part I: an approach to compound naevoidal pattern lesions with spindle cell morphology and Spitzoid pattern lesions.

    PubMed

    Sade, Shachar; Al Habeeb, Ayman; Ghazarian, Danny

    2010-04-01

    Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes reveal a dendritic cytomorphology and territorial isolation, lesional naevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may be either a characteristic feature or a divergent appearance. The presence of spindle cells may mask the melanocytic nature of a lesion, and is often disconcerting, either because of its infrequent appearance in a particular lesion or its interpretation as a dedifferentiated phenotype. Spindle cell melanocytic lesions follow the full spectrum of potential biological outcomes, and difficulty may be experienced judging the nature of a lesion because of a lack of consistently reliable features to predict biological behaviour. Over time, recognition of numerous histomorphological features that may portend a more aggressive lesion have been identified. However, the translation of these features into a diagnostic entity requires a gestalt approach. Although most spindle cell melanocytic lesions can reliably be resolved with this standard approach, problem areas do exist and cause no end of grief to the surgical pathologist or dermatopathologist. In this review, the authors present their algorithmic approach to spindle cell melanocytic lesions and discuss each entity in turn, in order to (1) model a systematic approach to such lesions, and (2) provide familiarity with those melanocytic lesions that either typically or occasionally display a spindled cytomorphology.

  1. A Contemporary Approach to Classify Ghost Cells Comprising Oral Lesions

    PubMed Central

    Yadav, Sumit Kumar; Narwal, Anjali; Devi, Anju

    2015-01-01

    Ghost cells are swollen eosinophilic epithelial cells that have lost their nuclei but retain the cellular and nuclear outline. Pathologic ghost cell formation could be the process of aberrant keratinization or the result of coagulative necrosis. Ghost cells have been described in several odontogenic lesions, which include calcifying epithelial odontogenic cysts or tumours like odontomas, ameloblastic fibro-odontomas, and ameloblastomas. This article present a view on the formation of ghost cells with proposal/introduction of a classification for ghost cell lesions of the oral cavity in an attempt to organize these lesions for the better understanding and academic purpose. PMID:26501039

  2. A Contemporary Approach to Classify Ghost Cells Comprising Oral Lesions.

    PubMed

    Yadav, Achla Bharti; Yadav, Sumit Kumar; Narwal, Anjali; Devi, Anju

    2015-09-01

    Ghost cells are swollen eosinophilic epithelial cells that have lost their nuclei but retain the cellular and nuclear outline. Pathologic ghost cell formation could be the process of aberrant keratinization or the result of coagulative necrosis. Ghost cells have been described in several odontogenic lesions, which include calcifying epithelial odontogenic cysts or tumours like odontomas, ameloblastic fibro-odontomas, and ameloblastomas. This article present a view on the formation of ghost cells with proposal/introduction of a classification for ghost cell lesions of the oral cavity in an attempt to organize these lesions for the better understanding and academic purpose. PMID:26501039

  3. Columnar lined Barrett's oesophagus.

    PubMed

    Sharma, Neel; Ho, Khek Yu

    2015-12-01

    Over the past few years, the definition of Barrett's oesophagus has altered with no real agreement on histological understanding. This article highlights the increasing confusion regarding Barrett's oesophagus with a focus on the all-too-frequently ignored aspect of the columnar lined oesophagus.

  4. Uniaxial alignment of nanoconfined columnar mesophases.

    PubMed

    Mouthuy, Pierre-Olivier; Melinte, Sorin; Geerts, Yves H; Jonas, Alain M

    2007-09-01

    By confining discotic phthalocyanines in a network of crisscrossed nanogrooves, we obtain a uniaxial alignment of the columnar mesophase. The alignment process is based on the anisotropy of interface tension between the mesophase and the nanogrooves' walls. Preferential mesophase alignment results from this nonhomogeneity combined with the anisotropy of the network cell dimensions. A simple model is proposed to explain the experimental observations.

  5. 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

  6. Molecular Characterization of Clear Cell Lesions of Head and Neck.

    PubMed

    Jain, Anshi; Shetty, Devi Charan; Juneja, Saurabh; Narwal, Nidhi

    2016-05-01

    The salivary glands, oral mucosa and jaws constitute a group of lesions which are heterogeneous in nature and are odontogenic, salivary or metastatic in origin. This group of tumours is termed as Clear Cell Tumours. Fixation artifacts are one of the most important reasons for the cell to appear clear but clearing of cells may also result from cytoplasmic accumulation of water, presence of glycogen within the cell, intermediate filaments, immature zymogen granules, or a paucity of cellular organelles. Clear cell Odontogenic neoplasms predominantly include odontogenic carcinoma, ameloblastoma and calcifying epithelial odontogenic tumour. Clear cell tumours of salivary gland origin are almost invariably malignant in nature but they do include two benign lesions. Very frequently, surgical pathologist encounters clear cells in many malignant neoplasms, the nature and sources of which are undetermined on the basis of conventional histopathology. This review will selectively discuss the clinicopathological features of neoplasms which at times may pose a diagnostic challenge and dilemma due to clear cell changes.

  7. Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions.

    PubMed

    Rudzitis-Auth, Jeannette; Nenicu, Anca; Nickels, Ruth M; Menger, Michael D; Laschke, Matthias W

    2016-08-01

    The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein(+)/Tie2(+) EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry. In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls. In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis. PMID:27315780

  8. Insight into the pathogenesis and nature of Central giant cell lesions of the jaws

    PubMed Central

    2015-01-01

    Central giant cell lesions of the jaws are not uncommon. While the majority of these represent single, sporadic lesions, histologically identical lesions are seen in association with a number of other bone lesions, as well as in certain syndromes. This manuscript offers a brief update on recent developments in this area that provide new insight into the pathogenesis and nature of Central Giant Cell Lesions of the Jaws. Key words:Central giant cell lesion, RASopathy PMID:25681371

  9. Quantification and Localization of Mast Cells in Periapical Lesions

    PubMed Central

    Mahita, VN; Manjunatha, BS; Shah, R; Astekar, M; Purohit, S; Kovvuru, S

    2015-01-01

    Background: Periapical lesions occur in response to chronic irritation in periapical tissue, generally resulting from an infected root canal. Specific etiological agents of induction, participating cell population and growth factors associated with maintenance and resolution of periapical lesions are incompletely understood. Among the cells found in periapical lesions, mast cells have been implicated in the inflammatory mechanism. Aim: Quantifications and the possible role played by mast cells in the periapical granuloma and radicular cyst. Hence, this study is to emphasize the presence (localization) and quantification of mast cells in periapical granuloma and radicular cyst. Materials and Methods: A total of 30 cases and out of which 15 of periapical granuloma and 15 radicular cyst, each along with the case details from the previously diagnosed cases in the department of oral pathology were selected for the study. The gender distribution showed male 8 (53.3%) and females 7 (46.7%) in periapical granuloma cases and male 10 (66.7%) and females 5 (33.3%) in radicular cyst cases. The statistical analysis used was unpaired t-test. Results: Mean mast cell count in periapical granuloma subepithelial and deeper connective tissue, was 12.40 (0.99%) and 7.13 (0.83%), respectively. The mean mast cell counts in subepithelial and deeper connective tissue of radicular cyst were 17.64 (1.59%) and 12.06 (1.33%) respectively, which was statistically significant. No statistical significant difference was noted among males and females. Conclusion: Mast cells were more in number in radicular cyst. Based on the concept that mast cells play a critical role in the induction of inflammation, it is logical to use therapeutic agents to alter mast cell function and secretion, to thwart inflammation at its earliest phases. These findings may suggest the possible role of mast cells in the pathogenesis of periapical lesions. PMID:25861530

  10. Extensive DNA fragmentation in oxyphilic cell lesions of the thyroid.

    PubMed

    Volante, M; Papotti, M; Gugliotta, P; Migheli, A; Bussolati, G

    2001-08-01

    The in situ end-labeling (ISEL) method demonstrates DNA fragmentation, commonly regarded as a marker of apoptosis. We investigated by the ISEL procedure a series of 52 thyroid lesions, including 24 lesions of mitochondrion-rich oxyphilic cells, both benign and malignant, and 28 non-oxyphilic control tumors. A high percentage of nuclear ISEL staining (approximating to 100% in most cases) was observed in the vast majority of oxyphilic cells from both adenomas and carcinomas, in the absence of morphological apoptotic changes and with no immunocytochemical evidence of caspase activation. This pattern of DNA fragmentation was not observed in non-oxyphilic lesions and was confirmed in total extracted DNA. Moreover, a peculiar cytoplasmic staining was also observed in oxyphilic cells from both benign and malignant lesions, probably related to abnormal fragmentation of mitochondrial DNA. Similar staining patterns were detected in oxyphilic cell tumors of other organs (parathyroids, salivary glands, and kidneys). These findings are consistent with an extensive DNA fragmentation peculiar to oxyphilic cells, which is not directly related to apoptosis and whose origin and biological significance are presently unknown.

  11. Oxidative Stress and DNA Lesions: The Role of 8-Oxoguanine Lesions in Trypanosoma cruzi Cell Viability

    PubMed Central

    Aguiar, Pedro H. N.; Furtado, Carolina; Repolês, Bruno M.; Ribeiro, Grazielle A.; Mendes, Isabela C.; Peloso, Eduardo F.; Gadelha, Fernanda R.; Macedo, Andrea M.; Franco, Glória R.; Pena, Sérgio D. J.; Teixeira, Santuza M. R.; Vieira, Leda Q.; Guarneri, Alessandra A.; Andrade, Luciana O.; Machado, Carlos R.

    2013-01-01

    The main consequence of oxidative stress is the formation of DNA lesions, which can result in genomic instability and lead to cell death. Guanine is the base that is most susceptible to oxidation, due to its low redox potential, and 8-oxoguanine (8-oxoG) is the most common lesion. These characteristics make 8-oxoG a good cellular biomarker to indicate the extent of oxidative stress. If not repaired, 8-oxoG can pair with adenine and cause a G:C to T:A transversion. When 8-oxoG is inserted during DNA replication, it could generate double-strand breaks, which makes this lesion particularly deleterious. Trypanosoma cruzi needs to address various oxidative stress situations, such as the mammalian intracellular environment and the triatomine insect gut where it replicates. We focused on the MutT enzyme, which is responsible for removing 8-oxoG from the nucleotide pool. To investigate the importance of 8-oxoG during parasite infection of mammalian cells, we characterized the MutT gene in T. cruzi (TcMTH) and generated T. cruzi parasites heterologously expressing Escherichia coli MutT or overexpressing the TcMTH enzyme. In the epimastigote form, the recombinant and wild-type parasites displayed similar growth in normal conditions, but the MutT-expressing cells were more resistant to hydrogen peroxide treatment. The recombinant parasite also displayed significantly increased growth after 48 hours of infection in fibroblasts and macrophages when compared to wild-type cells, as well as increased parasitemia in Swiss mice. In addition, we demonstrated, using western blotting experiments, that MutT heterologous expression can influence the parasite antioxidant enzyme protein levels. These results indicate the importance of the 8-oxoG repair system for cell viability. PMID:23785540

  12. 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.

  13. Amelanotic Melanoma Masquerading as a Granular Cell Lesion

    PubMed Central

    Pandiar, Deepak; Basheer, Shaini; Shameena, P. M.; Sudha, S.; Dhana, Lakshmi J.

    2013-01-01

    Amelanotic melanoma (AM) presents a diagnostic challenge due to its wide clinical presentations, lack of pigmentation, and varied histological appearances. Immunohistochemistry plays a crucial role in the diagnosis of these lesions. Amelanotic melanoma of oral mucosa is an uncommon lesion. We report a case of a 50-year-old male patient with a growth on the anterior mandibular gingiva of seven-month duration. In the present case, histologically, the tumour resembled a granular cell lesion, which has not been reported previously in AM. Diagnosis was possible by a sequential panel of immunohistochemical markers, of which finally vimentin, S100, HMB45, and Melan-A were positive. The tumor was surgically excised, and postsurgical radiotherapy was given. PMID:23533832

  14. Gingival squamous cell carcinoma mimicking as a desquamative lesion

    PubMed Central

    Keshava, Abbayya; Gugwad, Sushma; Baad, Rajendra; Patel, Rufi

    2016-01-01

    Oral squamous cell carcinoma (SCC) is the most frequently encountered neoplasm in the oral cavity, which accounts for more than 90% of all cancers. Except for carcinoma of the lip vermilion, the most common sites of oral SCC are the tongue and floor of mouth, followed at a lower frequency by the soft palate, gingiva, and buccal mucosa. Clinically, it may be misdiagnosed because of its variable appearances. This case report presents a case of well-differentiated SCC of gingiva. A 48-year-old male patient reported to the Department of Periodontology, School of Dental Sciences, Karad, with a 1-year history of burning sensation and painful lesion on the gingiva from 35 to 37 (mandibular) regions. On clinical examination, desquamated gingival lesion was seen with no purulent exudation. Clinical characteristics and differential diagnosis indicated the lesion for an excisional biopsy. Histopathological examination confirmed the lesion to be a well-differentiated SCC. The patient was referred for the treatment consisting of surgical excision of the lesion. Since an early diagnosis and treatment was possible in this case, it resulted in a good prognosis. In these instances, dentist plays an important role in early detection of gingival SCC. PMID:27041843

  15. Molecular Characterization of Clear Cell Lesions of Head and Neck

    PubMed Central

    Shetty, Devi Charan; Juneja, Saurabh; Narwal, Nidhi

    2016-01-01

    The salivary glands, oral mucosa and jaws constitute a group of lesions which are heterogeneous in nature and are odontogenic, salivary or metastatic in origin. This group of tumours is termed as Clear Cell Tumours. Fixation artifacts are one of the most important reasons for the cell to appear clear but clearing of cells may also result from cytoplasmic accumulation of water, presence of glycogen within the cell, intermediate filaments, immature zymogen granules, or a paucity of cellular organelles. Clear cell Odontogenic neoplasms predominantly include odontogenic carcinoma, ameloblastoma and calcifying epithelial odontogenic tumour. Clear cell tumours of salivary gland origin are almost invariably malignant in nature but they do include two benign lesions. Very frequently, surgical pathologist encounters clear cells in many malignant neoplasms, the nature and sources of which are undetermined on the basis of conventional histopathology. This review will selectively discuss the clinicopathological features of neoplasms which at times may pose a diagnostic challenge and dilemma due to clear cell changes. PMID:27437379

  16. Molecular Characterization of Clear Cell Lesions of Head and Neck.

    PubMed

    Jain, Anshi; Shetty, Devi Charan; Juneja, Saurabh; Narwal, Nidhi

    2016-05-01

    The salivary glands, oral mucosa and jaws constitute a group of lesions which are heterogeneous in nature and are odontogenic, salivary or metastatic in origin. This group of tumours is termed as Clear Cell Tumours. Fixation artifacts are one of the most important reasons for the cell to appear clear but clearing of cells may also result from cytoplasmic accumulation of water, presence of glycogen within the cell, intermediate filaments, immature zymogen granules, or a paucity of cellular organelles. Clear cell Odontogenic neoplasms predominantly include odontogenic carcinoma, ameloblastoma and calcifying epithelial odontogenic tumour. Clear cell tumours of salivary gland origin are almost invariably malignant in nature but they do include two benign lesions. Very frequently, surgical pathologist encounters clear cells in many malignant neoplasms, the nature and sources of which are undetermined on the basis of conventional histopathology. This review will selectively discuss the clinicopathological features of neoplasms which at times may pose a diagnostic challenge and dilemma due to clear cell changes. PMID:27437379

  17. Development of methods for the genetic manipulation of Flavobacterium columnare

    PubMed Central

    Staroscik, Andrew M; Hunnicutt, David W; Archibald, Kate E; Nelson, David R

    2008-01-01

    Background Flavobacterium columnare is the causative agent of columnaris disease, a disease affecting many freshwater fish species. Methods for the genetic manipulation for some of the species within the Bacteroidetes, including members of the genus Flavobacterium, have been described, but these methods were not adapted to work with F. columnare. Results As a first step toward developing a robust set of genetic tools for F. columnare, a protocol was developed to introduce the E. coli – Flavobacterium shuttle vector pCP29 into F. columnare strain C#2 by conjugal mating at an efficiency of 1.5 × 10-3 antibiotic-resistant transconjugants per recipient cell. Eight of eleven F. columnare strains tested were able to receive pCP29 using the protocol. pCP29 contains the cfxA and ermF genes, conferring both cefoxitin and erythromycin resistance to recipient cells. Selection for pCP29 introduction into F. columnare was dependent on cfxA, as ermF was found not to provide strong resistance to erythromycin. This is in contrast to other Flavobacterium species where ermF-based erythromycin resistance is strong. The green fluorescent protein gene (gfp) was introduced into F. columnare strains under the control of two different native Flavobacterium promoters, demonstrating the potential of this reporter system for the study of gene expression. The transposon Tn4351 was successfully introduced into F. columnare, but the method was dependent on selecting for erythromycin resistance. To work, low concentrations of antibiotic (1 μg ml-1) were used, and high levels of background growth occurred. These results demonstrate that Tn4351 functions in F. columnare but that it is not an effective mutagenesis tool due to its dependence on erythromycin selection. Attempts to generate mutants via homologous recombination met with limited success, suggesting that RecA dependent homologous recombination is rare in F. columnare. Conclusion The conjugation protocol developed as part of this

  18. Affinity cytochemistry analysis of mast cells in skin lesions: a possible tool to assess the timing of lesions after death.

    PubMed

    Bonelli, A; Bacci, S; Norelli, G A

    2003-12-01

    The histamine content in vital wounds is known to increase, with a zenith after 3 h, and then decrease until 24 h after wounding. We addressed whether this biochemical alteration has a morphological counterpart. Since the main source of skin histamine are mast cells, the distribution and number of these cells was assessed upon labeling with fluorescent avidin and with antibodies to the mast cell specific enzymes, chymase and tryptase. Analyses were performed on skin from 15 healthy controls (from surgical biopsies), from 15 post-mortem lesions and 75 vital lesions, obtained at autopsy from subjects who had survived from a few seconds to 24 h. The number of mast cells per unit area of section surface increased progressively with survival time, up to a maximum in subjects who survived 1-3 h ( p<0.01), and decreased thereafter becoming less than in the controls if lesions had occurred earlier than 6 h before death ( p<0.01). Samples from post-mortem lesions had significantly fewer mast cells than those of any other groups of samples ( p<0.01). We suggest that in association to other histological and circumstantial evidence the analysis of mast cells by affinity cytochemistry can help to discriminate vital from post-mortem lesions and to estimate survival time after lesions.

  19. Polyclonal T-Cells Express CD1a in Langerhans Cell Histiocytosis (LCH) Lesions

    PubMed Central

    West, Jennifer A.; Olsen, Sharon L.; Mitchell, Jenée M.; Priddle, Ross E.; Luke, Jennifer M.; Åkefeldt, Selma Olsson; Henter, Jan-Inge; Turville, Christopher; Kannourakis, George

    2014-01-01

    Langerhans cell histiocytosis (LCH) is a complex and poorly understood disorder that has characteristics of both inflammatory and neoplastic disease. By using eight-colour flow cytometry, we have identified a previously unreported population of CD1a+/CD3+ T-cells in LCH lesions. The expression of CD1a is regarded as a hallmark of this disease; however, it has always been presumed that it was only expressed by pathogenic Langerhans cells (LCs). We have now detected CD1a expression by a range of T-cell subsets within all of the LCH lesions that were examined, establishing that CD1a expression in these lesions is no longer restricted to pathogenic LCs. The presence of CD1a+ T-cells in all of the LCH lesions that we have studied to date warrants further investigation into their biological function to determine whether these cells are important in the pathogenesis of LCH. PMID:25343480

  20. 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...

  1. Carcinoid tumor associated with adjacent dysplastic columnar epithelium in the renal pelvis: A case report and literature review.

    PubMed

    Kim, Sung Sun; Choi, Chan; Kang, Taek Won; Choi, Yoo Duk

    2016-01-01

    Carcinoid tumors are well documented in the pulmonary and gastrointestinal systems, but very rare in the urinary tract, especially in the renal pelvis. We report on a 60-year-old female patient who presented with left flank pain and fever. Abdominal computed tomography demonstrated a heterogeneously enhancing mass in the left renal pelvis and a stone at the left proximal ureter. Multiple parenchymal lesions were also observed, which were identified as uneven caliectasis displaying air-fluid levels and renal parenchymal atrophy. The patient underwent simple nephro-ureterectomy. Macroscopically, a polypoid mass was observed in the renal pelvis. Microscopically, the tumor revealed acinar, tubular, and solid pattern and was composed of small, monotonous and hyperchromatic cells. Lining epithelia in renal pelvis and ureter revealed columnar epithelia with dysplastic change. The tumor cells were positive for chromogranin A, synaptophysin, CD56, and focally positive for cytokeratin. Immunohistochemical staining of synaptophysin and chromogranin A highlighted the neuroendocrine cells in the columnar epithelium. Ki-67 (1:50; MIB-1) labeling index was less than 1% in the area with highest uptake. We report here a case of carcinoid tumor of the renal pelvis that was associated with adjacent dysplastic columnar epithelium. PMID:26644387

  2. 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

  3. Genetic lesions in diffuse large B-cell lymphomas

    PubMed Central

    Testoni, M.; Zucca, E.; Young, K. H.; Bertoni, F.

    2015-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults, accounting for 35%–40% of all cases. The combination of the anti-CD20 monoclonal antibody rituximab with anthracycline-based combination chemotherapy (R-CHOP, rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) lead to complete remission in most and can cure more than half of patients with DLBCL. The diversity in clinical presentation, as well as the pathologic and biologic heterogeneity, suggests that DLBCL comprises several disease entities that might ultimately benefit from different therapeutic approaches. In this review, we summarize the current literature focusing on the genetic lesions identified in DLBCL. PMID:25605746

  4. 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. PMID:25743474

  5. 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...

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

    PubMed

    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.

  8. Columnar architecture improves noise robustness in a model cortical network.

    PubMed

    Bush, Paul C; Mainen, Zachary F

    2015-01-01

    Cortical columnar architecture was discovered decades ago yet there is no agreed upon explanation for its function. Indeed, some have suggested that it has no function, it is simply an epiphenomenon of developmental processes. To investigate this problem we have constructed a computer model of one square millimeter of layer 2/3 of the primary visual cortex (V1) of the cat. Model cells are connected according to data from recent paired cell studies, in particular the connection probability between pyramidal cells is inversely proportional both to the distance separating the cells and to the distance between the preferred parameters (features) of the cells. We find that these constraints, together with a columnar architecture, produce more tightly clustered populations of cells when compared to the random architecture seen in, for example, rodents. This causes the columnar network to converge more quickly and accurately on the pattern representing a particular stimulus in the presence of noise, suggesting that columnar connectivity functions to improve pattern recognition in cortical circuits. The model also suggests that synaptic failure, a phenomenon exhibited by weak synapses, may conserve metabolic resources by reducing transmitter release at these connections that do not contribute to network function.

  9. 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.

  10. Anchoring transition in confined discotic columnar liquid crystal films

    NASA Astrophysics Data System (ADS)

    Brunet, Thomas; Thiebaut, Olivier; Charlet, Émilie; Bock, Harald; Kelber, Julien; Grelet, Éric

    2011-01-01

    We report the achievement of ultrathin films (down to 25 nm thick) of thermotropic columnar liquid crystals in homeotropic alignment (columns normal to the interface) confined between a glass slide and a thin metallic electrode (about 150 nm thick). The face-on orientation of the discotic compound is obtained by anchoring transition of a columnar liquid crystalline phase from a degenerate planar orientation to the homeotropic alignment without any phase transition to the isotropic liquid phase. The kinetic dependence on temperature of such anchoring transition is investigated revealing various diffusive growth regimes of the homeotropic domains. Finally, confining effects are also considered by varying the thickness of the columnar liquid crystal film to reach the typical value required in organic solar cells thus demonstrating the reliability of such alignment process in a photovoltaic context.

  11. Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion).

    PubMed

    Metwaly, Hamdy; Cheng, Jun; Ida-Yonemochi, Hiroko; Ohshiro, Kazufumi; Jen, Kai Yu; Liu, Ai Ru; Saku, Takashi

    2003-07-01

    Lymphoepithelial lesions (LELs, or epi-myoepithelial islands) in lymphoepithelial sialadenitis (LESA, or benign lymphoepithelial lesion) of the salivary gland are known to be mainly composed of duct epithelial cells. However, other constituent cells are poorly characterized. Formalin-fixed paraffin sections obtained from six surgical specimens of LESA were examined using immunohistochemistry for cytoskeletal proteins, inflammatory cells, vascular endothelial cells, and extracellular matrix (ECM) molecules as well as by in situ hybridization for ECM molecules. In addition to keratin-immunopositive (+) duct-like epithelial cells, there were CD31/CD34+ vascular endothelial cells-which were either scattered in a singular fashion, in formed sheets, or in tubular structures-, CD20+ B lymphocytes, CD45RO+ T lymphocytes, and CD68 macrophages in the LELs. ECM molecules, such as heparan sulfate proteoglycan and tenascin, were immunolocalized in hyaline materials in the LELs. Their mRNAs were demonstrated mainly in endothelial cells and, to a lesser extent, in lympho-monocytic cells around hyaline materials, but were not as evident in epithelial constituent cells of LELs. The results indicate that endothelial cells as well as inflammatory cells are important constituents of the LELs, and the hyaline ECM cores mainly result from the intra-LEL angiogenesis by endothelial cells with the assistance of inflammatory cells. This intra-LEL vasculature seems to support regeneration and proliferation of salivary epithelial remnant cells.

  12. Laminar and columnar auditory cortex in avian brain

    PubMed Central

    Wang, Yuan; Brzozowska-Prechtl, Agnieszka; Karten, Harvey J.

    2010-01-01

    The mammalian neocortex mediates complex cognitive behaviors, such as sensory perception, decision making, and language. The evolutionary history of the cortex, and the cells and circuitry underlying similar capabilities in nonmammals, are poorly understood, however. Two distinct features of the mammalian neocortex are lamination and radially arrayed columns that form functional modules, characterized by defined neuronal types and unique intrinsic connections. The seeming inability to identify these characteristic features in nonmammalian forebrains with earlier methods has often led to the assumption of uniqueness of neocortical cells and circuits in mammals. Using contemporary methods, we demonstrate the existence of comparable columnar functional modules in laminated auditory telencephalon of an avian species (Gallus gallus). A highly sensitive tracer was placed into individual layers of the telencephalon within the cortical region that is similar to mammalian auditory cortex. Distribution of anterograde and retrograde transportable markers revealed extensive interconnections across layers and between neurons within narrow radial columns perpendicular to the laminae. This columnar organization was further confirmed by visualization of radially oriented axonal collaterals of individual intracellularly filled neurons. Common cell types in birds and mammals that provide the cellular substrate of columnar functional modules were identified. These findings indicate that laminar and columnar properties of the neocortex are not unique to mammals and may have evolved from cells and circuits found in more ancient vertebrates. Specific functional pathways in the brain can be analyzed in regard to their common phylogenetic origins, which introduces a previously underutilized level of analysis to components involved in higher cognitive functions. PMID:20616034

  13. 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.

  14. 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.

  15. 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...

  16. Patterns of hippocampal cell loss based on subregional lesions of the hippocampus.

    PubMed

    Jerman, Taylor S; Kesner, Raymond P; Lee, Inah; Berman, Robert F

    2005-12-14

    It is widely accepted that the hippocampus plays an essential role in memory. Furthermore, studies have suggested that subregions within the hippocampus contribute differentially to specific behavioral components of memory. These studies typically rely on lesions produced by localized injections of neurotoxins (e.g., ibotenic acid or colchicine) into targeted subregions of the hippocampus. In the present study, the specificity of ibotenic acid lesions into areas CA1 and CA3 and colchicine lesions into the dorsal dentate gyrus (DG) was tested. Specifically, the effects of lesions within the dorsal hippocampus, the ventral hippocampus, and areas outside the hippocampus (e.g., lateral septum and entorhinal cortex) were evaluated using Fluoro-Jade, a histofluorescent stain for degenerating neurons. The results show that cell loss is relatively uniform after ibotenic acid injections into areas CA1 and CA3 and variable after colchicine injections into DG. CA1 and CA3 lesions appeared mostly localized to those relative subregions, and DG lesions appeared highly localized to the DG. Using these lesion procedures, little cell loss was apparent in the ventral hippocampus, and no cell loss was apparent in the entorhinal cortex. It is suggested that the lesion procedures described in this study produce relatively selective lesions of neurons within specific subregions of the hippocampus and should be useful for studies examining possible differential contributions of hippocampal subregions to memory processes. PMID:16307731

  17. [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how to treat?].

    PubMed

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

    Increasing exposure to UV radiation is considered the most important etiologic factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp and face, are the primary areas for developing non-melanoma skin cancers. Once a patient has presented with one tumor, additional lesions are common. The diagnosis is based on typical clinical picture and biopsy or excision for histopathological analysis. Various non-surgical treatment options have been established. Superficial basal cell carcinoma, superficial carcinoma in situ and all actinic keratoses are preferentially treated non-surgically. Most other basal cell and squamous cell carcinomas should be surgically removed. PMID:24724463

  18. Transcription bypass of DNA lesions enhances cell survival but attenuates transcription coupled DNA repair

    PubMed Central

    Li, Wentao; Selvam, Kathiresan; Ko, Tengyu; Li, Shisheng

    2014-01-01

    Transcription-coupled DNA repair (TCR) is a subpathway of nucleotide excision repair (NER) dedicated to rapid removal of DNA lesions in the transcribed strand of actively transcribed genes. The precise nature of the TCR signal and how the repair machinery gains access to lesions imbedded in stalled RNA polymerase II (RNAP II) complexes in eukaryotic cells are still enigmatic. RNAP II has an intrinsic capacity for transcription bypass of DNA lesions by incorporation or misincorporation of nucleotides across the lesions. It has been suggested that transcription bypass of lesions, which exposes the lesions, may be required for TCR. Here, we show that E1103G mutation of Rpb1, the largest subunit of RNAP II, which promotes transcription bypass of UV-induced cyclobutane pyrimidine dimers (CPDs), increases survival of UV irradiated yeast cells but attenuates TCR. The increased cell survival is independent of any NER subpathways. In contrast, G730D mutation of Rpb1, which impairs transcription bypass of CPDs, enhances TCR. Our results suggest that transcription bypass of lesions attenuates TCR but enhances cell tolerance to DNA lesions. Efficient stalling of RNAP II is essential for efficient TCR. PMID:25389266

  19. 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.

  20. 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.

  1. 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

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

    SciTech Connect

    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.

  3. Characteristics of Multipotent Mesenchymal Stromal Cells Isolated from Human Endometrium and Endometriosis Lesions.

    PubMed

    Savilova, A M; Yushina, M N; Rudimova, Yu V; Khabas, G N; Chuprynin, V D; Sukhikh, G T

    2016-08-01

    Cell cultures isolated from endometriosis lesions by enzymatic dissociation consisted of fibroblast-like cells expressing CD90, CD73, and CD105; cell viability in these cultures was >90%, but this parameter decreased by passage 3. Zero passage cultures contained 10-25% epithelial cells expressing cytokeratin-7, but by passage 2, the cultures became more homogeneous and epithelial cells disappeared. The proportion of proliferating cells and population doubling level increased from passage 1 to passage 3. The cultures from the endometrium were induced to adipogenic and osteogenic differentiation in vitro. The cultures derived from ectopic endometrium have properties of multipotent mesenchymal stromal cells that exhibited in vitro similarities and differences from cell cultures from eutopic endometrium, which allows using this cell model for the search and testing of new drugs and technologies aimed at suppression of the growth and spread of endometriosis lesions. PMID:27590769

  4. Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion

    PubMed Central

    Bas, Esperanza; Van De Water, Thomas R.; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M.

    2014-01-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  5. 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

  6. Fine-needle aspiration of spindle cell and mesenchymal lesions of the salivary glands.

    PubMed

    Chhieng, D C; Cohen, J M; Cangiarella, J F

    2000-10-01

    Fine-needle aspiration (FNA) biopsy can accurately diagnose epithelial lesions of the salivary gland. Its role in the evaluation of salivary gland lesions containing a significant spindle cell component is less clear. We describe the cytologic features of 25 spindle cell lesions of the salivary gland and discuss the differential diagnosis and potential diagnostic pitfalls. Twenty-five aspiration smears (3.0%) containing a significant spindle cell or mesenchymal component were identified out of 844 salivary gland FNAs performed over a 5-year period. These aspiration smears were from 25 patients. The smears were classified into three categories: 1) reactive or inflammatory conditions, including one granulation tissue and four granulomatous sialoadenitis; 2) benign neoplasms, including one schwannoma, one fibromatosis, four lipomas, and nine pleomorphic adenomas; 3) malignant neoplasms, including one recurrent malignant fibrous histiocytoma (MFH), two metastatic melanomas, and two metastatic osteosarcomas. There was one false-negative biopsy. The metastatic desmoplastic malignant melanoma was initially interpreted as a reactive lymph node with fibrosis. A specific diagnosis was rendered in 21 (84%) cases. The schwannoma was diagnosed cytologically as benign spindle cell lesion, not otherwise specified (NOS), fibromatosis as an atypical cellular proliferation, and MFH as poorly differentiated malignant neoplasm. Salivary gland lesions with a significant spindle cell component are rarely encountered on FNA and constitute a heterogeneous group. A specific diagnosis can be rendered in the majority of cases by correlating clinical and cytologic findings.

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

    PubMed

    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

  8. Increased Sensitivity of DNA Damage Response-Deficient Cells to Stimulated Microgravity-Induced DNA Lesions

    PubMed Central

    Li, Nan; An, Lili; Hang, Haiying

    2015-01-01

    Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG). In this study we used mouse embryonic stem (MES) and mouse embryonic fibroblast (MEF) cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs) in Rad9-/- MES and Mdc1-/- MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9-/- MES. As the exposure to SMG was prolonged, Rad9-/- MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9-/- MES were due to SMG-induced reactive oxygen species (ROS). Interestingly, Mdc1-/- MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1-/- MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR) defects. PMID:25915950

  9. Increased sensitivity of DNA damage response-deficient cells to stimulated microgravity-induced DNA lesions.

    PubMed

    Li, Nan; An, Lili; Hang, Haiying

    2015-01-01

    Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG). In this study we used mouse embryonic stem (MES) and mouse embryonic fibroblast (MEF) cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs) in Rad9-/- MES and Mdc1-/- MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9-/- MES. As the exposure to SMG was prolonged, Rad9-/- MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9-/- MES were due to SMG-induced reactive oxygen species (ROS). Interestingly, Mdc1-/- MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1-/- MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR) defects.

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

    PubMed

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

    2015-02-18

    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

  11. 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

  12. Identification of Mesenchymal Stem Cell Marker STRO-1 in Oral Reactive Lesions by Immunofluorescence Method

    PubMed Central

    Dehghani Nazhvani, Ali; Hosseini, Seyed-Mojtaba; Tahoori, Bita; Tavangar, Maryam-Sadat; Attar, Armin

    2015-01-01

    Statement of the Problem Stem cells are considered as new implement for tissue regeneration. Several niches in adult human body are colonized by multipotent stem cells but access to these potential reservoirs is often limited. Although human dental pulp stem cells isolated from healthy teeth have been extensively characterized, it is still unknown whether stem cells also exist in reactive lesions of oral cavity such as pyogenic granuloma and peripheral ossifying fibroma which are deliberated as inflammatory proliferation of different cell families. Purpose The aim of this study was to explore for clues to see whether pyogenic granuloma or peripheral ossifying fibroma contain dental mesenchymal stem cell (DMSC). Materials and Method Four pyogenic granuloma and four peripheral ossifying fibroma specimens were collected by excisional biopsy and preserved in PBS-EDTA at -86 °C. Then we cut them in 5µm diameter using Cryostat. Having been rinsed with PBS, the samples were stained with a primary mouse anti-human STRO-1 monoclonal IgM antibody. Afterward, a secondary goat anti-mouse IgM-FITC antibody was applied to detect STRO-1+ cells as probable stem cells by immunofluorescence technique. Results Immunofluorescence microscopy revealed presence of STRO-1+ cells in these lesions, particularly localized on perivascular zone. The negative control group was not glowing. Conclusion Based on these results, it was found that reactive lesions of pyogenic granuloma and peripheral ossifying fibroma have STRO-1 positive cells, which raises the possibility that these cells may be DMSCs. PMID:26535404

  13. Conversions of excision-repairable DNA lesions to micronuclei within one cell cycle in human lymphocytes

    SciTech Connect

    Fenech, M.; Neville, S. )

    1992-01-01

    The human lymphocyte micronucleus (MN) assay is relatively insensitive to genotoxic agents that predominantly induce excision-repairable lesions such as adducts and abasic sites. In this study the authors have explored the possibility of using cytosine arabinoside (ARA) to convert excision-repairable DNA lesions to micronuclei (MN) within one cell cycle. The system consisted of human lymphocytes as target cells, the cytokinesis-block (CB) method for identifying cells that had completed one nuclear division only, and X-rays, methylnitrosourea (MNU), and ultraviolet light (UV) as mutagens. With each mutagen they have observed significant increments induced MN in the cultures that had also been treated with ARA during G{sub 1}. These observations suggested that the combined ARA and cytokinesis-block micronucleus (CBMN) method may enhance the detection of exposure to genotoxic agents that predominantly induce excision-repairable lesions.

  14. Local immunological reactivity in oral squamous cell lesions of possible HPV (human papillomavirus) origin.

    PubMed

    Syrjänen, K J; Syrjänen, S M; Lamberg, M A; Happonen, R P

    1983-01-01

    The immunocompetent cells (B and T lymphocytes, mononuclear phagocytes, MPS cells) known to be responsible for the rejection of the HPV- (Human Papillomavirus) induced tumors in the skin (warts) were analyzed in the infiltrates of 63 oral squamous cell lesions of suspected HPV origin (Condyloma, CA; Focal Epithelial Hyperplasia, FEH; Squamous Cell Papilloma, SQP) as well as in tumors thought to be unrelated to HPV (Fibrous Hyperplasia, FH; Papillary Hyperplasia, PH; True Fibroma, TF; Keratoacanthoma, KA), using the ANAE (acid alpha-naphthyl acetate esterase) technique. All tumors were also stained by the indirect immunoperoxidase-PAP method for the demonstration of HPV antigens. Of the SQP's, 60% were HPV-positive, as were 80% of CA's and one third of FEH's. In addition, 1/18 FH's and 2/14 PH's stained HPV-positive. On electron microscopy, viral particles could be disclosed within the nuclei of HPV-lesions. The highest proportions of the T and MPS cells (the elements of cell-mediated immunity) were found in CA's and SQP's (15-17%), as compared with the values of less than 10% in all others. The infiltrates in FEH's also showed low values of MPS and T cells, interpreted to suggest an etiology of the HPV type (determining the type of immune reaction) different from that of CA and SQP. HPV-positivity in the lesions did not influence the distribution of the immunocompetent cells. The results indicate that immunological mechanisms are involved in HPV lesions of the oral cavity as they are at other sites. The role of HPV in the etiology of these (and possibly of the oral squamous cell carcinoma) was discussed. Further analyses of the lymphocyte subsets are needed to establish the role of host reactions in the development and eradication of HPV lesions in oral cavity.

  15. Radioautographic visualization of differences in the pattern of (/sup 3/H)uridine and (/sup 3/H)orotic acid incorporation into the RNA of migrating columnar cells in the rat small intestine

    SciTech Connect

    Uddin, M.; Altmann, G.G.; Leblond, C.P.

    1984-05-01

    The epithelium of rat small intestine was radioautographed to examine whether RNA is synthesized by the salvage pathway as shown after (/sup 3/H)uridine injection or by the de novo pathway as shown after (/sup 3/H)orotic acid injection. The two modes of RNA synthesis were thus investigated during the migration of columnar cells from crypt base to villus top, and the rate of synthesis was assessed by counting silver grains over the nucleolus and nucleoplasm at six levels along the duodenal epithelium - that is, in the base, mid, and top regions of the crypts and in the base, mid, and top regions of the villi. Concomitant biochemical analyses established that, after injection of either (5-/sup 3/H)uridine or (5-/sup 3/H)orotic acid: (a) buffered glutaraldehyde fixative was as effective as perchloric acid or trichloroacetic acid in insolubilizing the nucleic acids of rat small intestine; (b) a major fraction of the nucleic acid label was in RNA, that is, 91% after (/sup 3/H)uridine and 72% after (/sup 3/H)orotic acid, with the rest in DNA; and (c) a substantial fraction of the RNA label was in poly A/sup +/ RNA (presumed to be messenger RNA). In radioautographs of duodenum prepared after (/sup 3/H)uridine injection, the count of silver grains was high over nucleolus and nucleoplasm in crypt base cells and gradually decreased at the upper levels up to the villus base. In the rest of the villus, the grain count over the nucleolus was negligible, while over the nucleoplasm it was low but significant.

  16. Immunohistochemical demonstration of human papilloma virus (HPV) antigens in oral squamous cell lesions.

    PubMed

    Syrjänen, K J; Pyrhönen, S; Syrjänen, S M; Lamberg, M A

    1983-06-01

    Six oral squamous cell tumours classified as focal epithelial hyperplasia (FEH), Condyloma acuminatum (CA) and squamous cell papilloma (SQP) were subjected to indirect immunoperoxidase staining with anti-human papillomavirus (anti-HPV) antiserum to demonstrate the possible presence of HPV antigens in these lesions. The results are discussed in the light of the observations on HPV-lesions elsewhere in the body (in uterine cervix), and a suggestion is made to adopt the name condyloma for all those tumours where HPV aetiology can be established by ultrastructural or immunohistochemical means.

  17. 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. ...

  18. 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

  19. Quantitative analysis of disturbed cell maturation in dysplastic lesions of the respiratory tract epithelium

    SciTech Connect

    Klein-Szanto, A.J.P.; Nettesheim, P.; Topping, D.C.; Olson, A.C.

    1980-01-01

    Autoradiographic patterns of (/sup 3/H)thymidine incorporation, nuclear/cytoplasmic ratios (N/C), and the percentage of dark epithelial cells were analyzed in a group of epithelial lesions induced by 7,12-dimethylbenz(a)anthracene (DMBA) in rat tracheal transplants. It was found that similar lesions of different age exhibit the same labeling indices (LIs), therefore the lesions of different age were subsequently pooled in the following groups and studied by high resolution light microscopic autoradiography: squamous metaplasia without or with only mild atypia, squamous metaplasia with moderate atypia, squamous metaplasia with severe atypia, carcinoma in situ, and microinvasive carcinoma. Normal tracheal and esophageal epithelia were also analyzed. Gradients of increasing N/C (nucleus-cytoplasm ratios) values could be observed as the lesions increased in severity, especially in the middle and surface layers (e.g., in the surface layer regular metaplasia N/C = 0.08, squamous metaplasia with moderate atypia N/C = 0.26, and carcinoma in situ N/C = 0.50). Dark cells were absent in the normal esophageal epithelium, were present in moderate numbers in the basal layer of regular squamous metaplasia (18%), and increased markedly in the atypical epithelial lesions (approximately 50% in the atypical squamous metaplasias and 70% in carcinoma in situ). In the suprabasal layer dark cells increased from 3% in squamous metaplasia with moderate atypia to 28% in metaplasia with severe atypia and 56% in carcinoma in situ. The results confirm in a quantitative fashion that disturbances of cell maturation and cell proliferation are key features of dysplastic lesions induced by chemical carcinogens, and suggest the use of objective parameters for evaluation and classification of preneoplastic alterations.

  20. Mesenchymal Stem Cells Ameliorate Atherosclerotic Lesions via Restoring Endothelial Function

    PubMed Central

    Lin, Yu-Ling; Yet, Shaw-Fang; Hsu, Yuan-Tong

    2015-01-01

    Transplantation of mesenchymal stem cells (MSCs) is beneficial in myocardial infarction and hind limb ischemia, but its ability to ameliorate atherosclerosis remains unknown. Here, the effects of MSCs on inhibiting endothelial dysfunction and atherosclerosis were investigated in human/mouse endothelial cells treated with oxidized low-density lipoprotein (oxLDL) and in apolipoprotein E-deficient (apoE−/−) mice fed a high-fat diet. Treatment with oxLDL inactivated the Akt/endothelial nitric-oxide synthase (eNOS) pathway, induced eNOS degradation, and inhibited nitric oxide (NO) production in endothelial cells. Coculture with human MSCs reversed the effects of oxLDL on endothelial cells and restored Akt/eNOS activity, eNOS level, and NO production. Reduction of endothelium-dependent relaxation and subsequent plaque formation were developed in apoE−/− mice fed a high-fat diet. Systemic infusion with mouse MSCs ameliorated endothelial dysfunction and plaque formation in high-fat diet-fed apoE−/− mice. Interestingly, treatment with interleukin-8 (IL8)/macrophage inflammatory protein-2 (MIP-2) alone induced the similar effects of human/mouse MSCs on oxLDL-treated human/mouse endothelial cells. Neutralization antibodies (Abs) against IL8/MIP-2 also blocked the effects of human/mouse MSCs on oxLDL-treated human/mouse endothelial cells. Consistently, MIP-2 injection alone induced the similar effect of MSCs on the endothelial function in high-fat diet-fed apoE−/− mice. The improvement in endothelial dysfunction by mouse MSCs was also blocked when pretreating MSCs with anti-MIP-2 Abs. In conclusion, MSC transplantation improved endothelial function and plaque formation in high-fat diet-fed apoE−/− mice. Activation of the Akt/eNOS pathway in endothelium by IL8/MIP-2 is involved in the protective effect of MSCs. The study helps support the use and clarify the mechanism of MSCs for ameliorating atherosclerosis. PMID:25504897

  1. 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 ...

  2. Endothelial cell proliferation associated with lesions of murine systemic candidiasis.

    PubMed Central

    Ashman, R B; Papadimitriou, J M

    1994-01-01

    Neovascularization is associated with tumor growth and some inflammatory diseases but has not been reported to be induced by infectious agents. In a mouse model of systemic Candida albicans infection, extensive endothelial cell proliferation was seen in the periphery of brain abscesses and in the areas of fungal pyelonephritis in the kidney. This finding is important for an understanding of the pathogenesis of fungal infections and may contribute to an analysis of the mechanisms of angiogenesis. Images PMID:7523305

  3. Efficacy of florfenicol for control of mortality caused by Flavobacterium columnare infection in channel catfish.

    PubMed

    Gaunt, Patricia S; Gao, Dana; Sun, Fangshi; Endris, Richard

    2010-06-01

    The studied in channel catfish Ictalurus punctatus fingerlings held in 80-L aquaria. Nonabraded fish were challenged by immersion on day 0. Thirty 80-L tanks were randomly assigned in equal numbers to two treatment groups, one in which fish were fed a commercial diet without florfenicol (unmedicated feed) and one in which they were fed a diet containing 10 mg of florfenicol/kg of body weight (medicated feed) for ten consecutive days. Mortality was monitored during the treatment period and a 14-d posttreatment observation period. At the end of the posttreatment period, all fish were euthanized, examined for gross lesions, and cultured for F. columnare. Significantly fewer fish fed the medicated diet died (8.0%) than fish fed the unmedicated diet (54.2%). Flavobacterium columnare was cultured from 15.0% of the medicated fish, compared with 68.9% of the unmedicated fish. The gross lesions in the fish were consistent with columnaris disease, and F. columnare was cultured from 99.5% of the dead fish. No differences were observed in weight gain and appetence between the medicated and unmedicated groups. For the F. columnare strain used in this study, the minimal inhibitory concentration of florfenicol ranged from 0.5 to 1.0 mg/mL in the 30 bacterial cultures obtained from infected fish, and the mean disk diffusion zone of inhibition was 40 mm. There were no adverse effects among the medicated fish. Administration of florfenicol at a dosage of 10 mg/kg body weight for 10 d was efficacious and safe for the control of mortality from F. columnare infection in channel catfish.

  4. Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney.

    PubMed

    Martignoni, Guido; Bonetti, Franco; Chilosi, Marco; Brunelli, Matteo; Segala, Diego; Amin, Mahul B; Argani, Pedram; Eble, John N; Gobbo, Stefano; Pea, Maurizio

    2012-01-01

    The perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly α-smooth muscle actin), melanocytic markers, including microphthalmia-associated transcription factor (MITF), and estrogen and progesterone receptors. It is constantly present in a group of tumors called PEComas. Renal PEComas include the common angiomyolipoma as well as less common lesions such as microscopic angiomyolipoma, intraglomerular lesions, angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma, oncocytoma-like angiomyolipoma and lymphangioleiomyomatosis of the renal sinus. It has been demonstrated that most of these lesions are determined by mutations affecting genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway, and it has been observed that some PEComas regressed during sirolimus therapy, an MTOR inhibitor. Recently, overexpression of MITF has been related to the expression of the papain-like cysteine protease cathepsin K in osteoclasts where it has inhibited MTOR. The aim of this study is to evaluate cathepsin K immunohistochemically in the entire spectrum of PEComa lesions in the kidney. The study population consisted of 84 renal PEComa lesions, including 5 composed predominantly of fat (lipoma-like angiomyolipoma), 15 almost exclusively composed of spindle-shaped smooth muscle cells (leiomyoma-like angiomyolipoma) and 31 common angiomyolipomas composed of a mixture of fat, spindle and epithelioid smooth muscle cells, and abnormal thick-walled blood vessels, 15 microscopic angiomyolipomas, 5 intraglomerular lesions, 2 oncocytoma-like angiomyolipomas, 8 epithelioid angiomyolipomas, 2 angiomyolipomas with epithelial cysts and 1 example of lymphangioleiomyomatosis of the renal sinus. In all of the renal PEComas, cathepsin K was found to be constantly and strongly expressed and seems to be a more powerful marker than other commonly

  5. 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.

  6. 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.

  7. Cortisol directly impacts Flavobacterium columnare in vitro growth characteristics.

    PubMed

    Declercq, Annelies Maria; Aerts, Johan; Ampe, Bart; Haesebrouck, Freddy; De Saeger, Sarah; Decostere, Annemie

    2016-01-01

    Teleost fish faced with stressful stimuli launch an endocrine stress response through activation of the hypothalamic-pituitary-interrenal axis to release glucocorticoids, in particular cortisol, into the blood. For the majority of bacterial fish pathogens, stress is considered a key factor in disease outbreaks. Based upon studies in mammals, there is considerable evidence to suggest that, besides impairing the immune system, cortisol can have a direct effect on bacterial cells. Hitherto, this intriguing field of microbial endocrinology has remained largely unexplored in aquatic diseases. The present study investigated in vitro the impact of cortisol on phenotypic traits of the fresh water fish pathogen Flavobacterium columnare. Colonies obtained from the highly virulent (HV) isolates resulted in significantly larger and more spreading colonies compared to those from the low virulent (LV) isolates. High cortisol doses added displayed a direct effect on the bacterial cells and induced a significant decrease in colony size. An additional intriguing finding was the inverse relationship between cortisol concentrations added to the broth and the spreading character of colonies retrieved, with higher cortisol doses resulting in less rhizoid to rough and even smooth colony formation (the latter only in the LV trout isolate), suggesting a dose-response effect. The loss of the rhizoid appearance of the F. columnare colonies upon administration of cortisol, and hence the loss of motility, might indicate a phenotypic change to the biofilm state. These findings form the basis for further research on the impact of glucocorticoids on other virulence factors and biofilm formation of F. columnare. PMID:27530746

  8. Multisystem Langerhans Cell Histiocytosis in Adults Revealed by Skin Lesions.

    PubMed

    Atarguine, Hanane; Hocar, Ouafa; Oussmane, Samia; Mouafik, Sara Batoul; Hamdaoui, Abderrachid; Hafiane, Hanan; Belbaraka, Rhizlane; Akhdari, Nadia; Amal, Said

    2016-01-01

    A 37-year-old woman with no remarkable medical or family history presented with papules and vesicles on an erythematous background involving the neck, sacrum, and folds (postauricular, axillary, inguinal, and under the breasts) (Figure 1). During the previous year, she was treated with local and systemic antifungals without improvement. Her history included a secondary amenorrhea, polydipsia, and polyuria (6 L/d) that started 2 years prior. Physical examination revealed chronic bilateral purulent otorrhea with thick eardrums. Histologic examination of skin biopsy revealed a highly suggestive appearance of multisystem Langerhans cell histiocytosis (LCH) with immunohistochemistry (anti-PS100 and anti-CD1a), which were positive (Figure 2A and 2B). Pituitary magnetic resonance imaging showed a thickening of the pituitary stalk in relation to a location histiocytic (Figure 3). Bone gaps were objectified on two radiographic tibial diaphyseal. Results from computed tomography (CT) scan showed a magma coelio mesenteric, axillary, and inguinal lymph nodes. PMID:27319965

  9. 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

  10. Distribution and immunophenotype of the inflammatory cell population in the benign lymphoepithelial lesion (Mikulicz's disease).

    PubMed

    Andrade, R E; Hagen, K A; Manivel, J C

    1988-08-01

    Benign lymphoepithelial lesion (BLL) is an autoimmune process characterized by swelling and diffuse inflammation of the major salivary glands. Autoantibodies have been isolated from lymphocyte cultures obtained from affected salivary glands, but the pathogenesis is still unknown. Previous studies have shown that the predominant population of inflammatory cells is represented by helper T cells, with only brief mention of the B cell population. Twenty-five surgical specimens from patients with BLL were studied immunohistochemically. Antisera used included monoclonal antibodies LN-1 and LN-2 for B cells, LN-3 for cells expressing human leukocyte antigen-DR (HLA-DR) antigens, UCHL-1 for T cells, Leu-7 for natural killer (NK) cells, and T suppressor lymphocytes and the polyclonal antibody to S100 protein for dendritic cells. A peculiar distribution of the inflammatory infiltrate was observed in all cases, characterized by the presence of very irregular "germinal centers" with pseudopod-like extensions surrounding epimyoepithelial islands. Lymphoid cells in this location were reactive with LN-1 and LN-2 antibodies. These structures were surrounded by a "mantle" of mixed small B and T lymphocytes. A well-defined "interfollicular" zone was composed of cells strongly reactive with UCHL-1 and LN-3 antibodies, indicating the presence and activation of T cells. Dendritic cells defined by S100 and LN-2 reactivity were intermixed with epimyoepithelial cells, and were identified in 18 cases. Epithelial expression of HLA-DR antigens was restricted to inflamed areas. In contrast to previous reports denying the presence of Leu-7-positive cells in these lesions, cells reactive for this antibody were identified in 13 of 20 cases, predominantly within germinal centers. The presence of dendritic cells, complex organization of the inflammatory infiltrate into well-defined B cell proliferation centers and activated interfollicular T areas, and the abnormal expression of HLA-DR antigens in

  11. Impaired Head Direction Cell Representation in the Anterodorsal Thalamus after Lesions of the Retrosplenial Cortex

    PubMed Central

    Clark, Benjamin J.; Bassett, Joshua P.; Wang, Sarah S.; Taube, Jeffrey S.

    2010-01-01

    The retrosplenial cortex (RSP), a brain region frequently linked to processes of spatial navigation, contains neurons that discharge as a function of a rat’s head direction (HD). HD cells have been identified throughout the limbic system including the anterodorsal thalamus (ADN) and postsubiculum (PoS), both of which are reciprocally connected to the RSP. The functional relationship between HD cells in the RSP and those found in other limbic regions is presently unknown, but given the intimate connectivity between the RSP and regions such as the ADN and PoS, and the reported loss of spatial orientation in rodents and humans with RSP damage, it is likely that the RSP plays an important role in processing the limbic HD signal. To test this hypothesis, we produced neurotoxic or electrolytic lesions of the RSP and recorded HD cells in the ADN of female Long-Evans rats. HD cells remained present in the ADN after RSP lesions, but the stability of their preferred firing directions was significantly reduced even in the presence of a salient visual landmark. Subsequent tests revealed that lesions of the RSP moderately impaired landmark control over the cells’ preferred firing directions, but spared the cells directional stability when animals were required to update their orientation using self-movement cues. Taken together, these results suggest that the RSP plays a prominent role in processing landmark information for accurate HD cell orientation and may explain the poor directional sense in humans that follows damage to the RSP. PMID:20392951

  12. 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.

  13. 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.

  14. B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10.

    PubMed

    Strom, Asa C; Cross, Amanda J; Cole, Jennifer E; Blair, Paul A; Leib, Christoph; Goddard, Michael E; Rosser, Elizabeth C; Park, Inhye; Hultgårdh Nilsson, Anna; Nilsson, Jan; Mauri, Claudia; Monaco, Claudia

    2015-10-01

    Whilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (B(reg)) have been described. In experimental arthritis and lupus-like disease, B(reg) are contained within the CD21(hi)CD23(hi)CD24(hi) B cell pool. The existence and role of B(reg) in vascular disease is not known. We sought to investigate the existence, identity and location of B(reg) in vascular disease. The representation of B2-B cell subsets in the spleens and lymph nodes (LNs) of Apolipoprotein E(-/-) (ApoE(-/-)) mice compared to controls was characterised by flow cytometry. Additionally, we utilised a model of neointima formation based on the placement of a perivascular collar around the carotid artery in ApoE(-/-) mice to ascertain whether B cells and B cell subsets confer protection against lesion development. Adoptive transfer of B cells was performed from wild type or genetically modified mice. We showed that CD21(hi)CD23(hi)CD24(hi) B cells are unexpectedly increased in the draining LNs of ApoE(-/-) mice. Adoptive transfer of LN-derived B2-B cells or purified CD21(hi)CD23(hi)CD24(hi) B cells to syngeneic mice reduced lesion size and inflammation without changing serum cholesterol levels. Follicular B2-B cells did not confer protection. IL-10 blockade or transfer of IL10-deficient B cells prevented LN-derived B cell-mediated protection. This is the first identification of a specific LN-derived B2-B(reg) subset that confers IL-10 mediated protection from neointima formation. This may open the way for immune modulatory approaches in cardiovascular disease.

  15. Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines.

    PubMed

    van den Berg, Henk; Schreuder, Willem Hans; Jongmans, Marjolijn; van Bommel-Slee, Danielle; Witsenburg, Bart; de Lange, Jan

    2016-08-01

    A patient with Noonan syndrome with multiple lentigines (NSML) and multiple giant cell lesions (MGCL) in mandibles and maxillae is described. A mutation p.Thr468Met in the PTPN11-gene was found. This is the second reported NSML patient with MGCL. Our case adds to the assumption that, despite a different molecular pathogenesis and effect on the RAS/MEK pathway, NSML shares the development of MGCL, with other RASopathies. PMID:27238887

  16. Squamous Cell Carcinoma Arising from an Oral Lichenoid Lesion: A Case Report

    PubMed Central

    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. PMID:22991632

  17. 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

  18. Co-expression of metalloproteinases 11 and 12 in cervical scrapes cells from cervical precursor lesions

    PubMed Central

    Valdivia, Alejandra; Peralta, Raúl; Matute-González, Manuel; García Cebada, Juan Manuel; Casasola, Ivonne; Jiménez-Medrano, Cristina; Aguado-Pérez, Rogelio; Villegas, Vanessa; González-Bonilla, Cesar; Manuel-Apolinar, Leticia; Ibáñez, Miguel; Salcedo, Mauricio

    2011-01-01

    The metalloproteinases (MMP) 11 and 12 have been shown to be expressed in cervical cancer (CC). In order to extend our previous results, these MMPs were evaluated in cervical precursor lesions. One hundred seventeen cervical scrapes: thirty-six normal, thirty-six Low grade squamous lesions (LSIL), thirty-six High grade (HSIL), nine CC; and, also ninety-nine paraffin-embedded cervical lesions: fifteen normal cervices, thirty eight LSIL, sixteen HSIL, and five CC were collected. The samples were analyzed for relative expression by real time RT-PCR or immunohistochemistry assay. We were able to identify a relative increased expression of MMP11 in 75% and 78% from LSIL and HSIL samples, respectively. While MMP12 expression was 64% and 75% in LSIL and HSIL, respectively. Positive samples for MMP11 expression were also positive for MMP12 expression and also increased according to illness progression. In the tissues, MMP11 or MMP12 expression was observed in the cytoplasm of the neoplastic cells, while in the normal epithelium was absent. The reaction was always stronger for MMP12 than MMP11. MMP11 expression was present in 77% and 66% of LSIL and HSIL, while MMP12 expression was 73% and 68%. There was a relationship between MMP11 or MMP12 expression and HPV infection. Our data are showing a relationship between diagnostic of precursor lesions and the MMP11 and 12 expressions, suggesting that their expression could be an early event in the neoplastic lesions of the cervix and could have clinical significance. PMID:22076168

  19. Co-expression of metalloproteinases 11 and 12 in cervical scrapes cells from cervical precursor lesions.

    PubMed

    Valdivia, Alejandra; Peralta, Raúl; Matute-González, Manuel; García Cebada, Juan Manuel; Casasola, Ivonne; Jiménez-Medrano, Cristina; Aguado-Pérez, Rogelio; Villegas, Vanessa; González-Bonilla, Cesar; Manuel-Apolinar, Leticia; Ibáñez, Miguel; Salcedo, Mauricio

    2011-01-01

    The metalloproteinases (MMP) 11 and 12 have been shown to be expressed in cervical cancer (CC). In order to extend our previous results, these MMPs were evaluated in cervical precursor lesions. One hundred seventeen cervical scrapes: thirty-six normal, thirty-six low grade squamous lesions (LSIL), thirty-six high grade (HSIL), nine CC; and, also ninety-nine paraffin-embedded cervical lesions: fifteen normal cervices, thirty eight LSIL, sixteen HSIL, and five CC were collected. The samples were analyzed for relative expression by real time RT-PCR or immunohistochemistry assay. We were able to identify a relative increased expression of MMP11 in 75% and 78% from LSIL and HSIL samples, respectively. While MMP12 expression was 64% and 75% in LSIL and HSIL, respectively. Positive samples for MMP11 expression were also positive for MMP12 expression and also increased according to illness progression. In the tissues, MMP11 or MMP12 expression was observed in the cytoplasm of the neoplastic cells, while in the normal epithelium was absent. The reaction was always stronger for MMP12 than MMP11. MMP11 expression was present in 77% and 66% of LSIL and HSIL, while MMP12 expression was 73% and 68%. There was a relationship between MMP11 or MMP12 expression and HPV infection. Our data are showing a relationship between diagnostic of precursor lesions and the MMP11 and 12 expressions, suggesting that their expression could be an early event in the neoplastic lesions of the cervix and could have clinical significance.

  20. 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

  1. 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.

  2. 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.

  3. /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.

  4. Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis.

    PubMed

    Antonelli, Lis R V; Dutra, Walderez O; Almeida, Roque P; Bacellar, Olivia; Carvalho, Edgar M; Gollob, Kenneth J

    2005-11-15

    Leishmaniasis is an important parasitic disease affecting millions worldwide. In attempts to understand the clinical relevance of immunological measurements as determined using flow cytometry, several immunological phenotypes were determined for a group of well defined human leishmaniasis patients and correlated with clinical measurements of the disease (Montenegro skin test (MST) and lesion area). The analysis demonstrated a positive correlation between the MST size and the frequency of ex vivo recent activated CD4(+) T cells. In contrast, higher frequencies of recent activated CD8(+) T cells were correlated with a smaller MST size. Moreover, a positive correlation was observed between the lesion total area and the frequency of activated CD69(+) (ex vivo) and CD40L(+) (cultured with Leishmania soluble antigen (SLA)) T lymphocytes. Finally, larger lesions were also correlated with a higher frequency of SLA specific inflammatory cytokine (IFN-gamma or TNF-alpha) producing lymphocytes. These studies demonstrate that immunological markers are correlated with clinical indicators of human leishmaniasis and serve to better understand the evolution of this important parasitic disease.

  5. Human Embryonic Stem Cell Lines with Lesions in FOXP3 and NF1

    PubMed Central

    Zhu, Hui; Behr, Barry; Reddy, Vikrant V.; Hughes, Mark; Pan, Yuqiong; Baker, Julie

    2016-01-01

    Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of blastocyst staged embryos. Spare blastocyst staged embryos were obtained by in vitro fertilization (IVF) and donated for research purposes. hESCs carrying specific mutations can be used as a powerful cell system in modeling human genetic disorders. We obtained preimplantation genetic diagnosed (PGD) blastocyst staged embryos with genetic mutations that cause human disorders and derived hESCs from these embryos. We applied laser assisted micromanipulation to isolate the inner cell mass from the blastocysts and plated the ICM onto the mouse embryonic fibroblast cells. Two hESC lines with lesions in FOXP3 and NF1 were established. Both lines maintain a typical undifferentiated hESCs phenotype and present a normal karyotype. The two lines express a panel of pluripotency markers and have the potential to differentiate to the three germ layers in vitro and in vivo. The hESC lines with lesions in FOXP3 and NF1 are available for the scientific community and may serve as an important resource for research into these disease states. PMID:26990425

  6. Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions.

    PubMed Central

    van der Wal, A. C.; Das, P. K.; Tigges, A. J.; Becker, A. E.

    1992-01-01

    Atherosclerotic lesions show features of a cell-mediated immune inflammatory process. From this viewpoint, the potential role of arterial endothelium in the recruitment of mononuclear cells (T lymphocytes and macrophages) was studied. The endothelium of diffuse intimal thickening (DIT) and atheromatous plaques (AP) in human coronary arteries and abdominal aortas was characterized for the expression of adhesion molecules ELAM-1, ICAM-1, and the major histocompatibility complex (MHC) class II antigens HLA-DR/DP. A marked increase in expression of ICAM-1 and ELAM-1, and to a lesser extent HLA-DR/DP was observed on endothelial cells that were adjacent to subendothelial infiltrates of T lymphocytes (CD3+, CD11a+, HLA-DR/DP+) and macrophages (CD14+, CD11a+, CD11c+, HLA-DR/DP+). This contrasted with a lower or absent expression of these activation markers at sites without prominent inflammatory cell infiltrates. These findings could be demonstrated in DIT as well as in AP. The observations suggest that cytokines produced by the subintimal infiltrates may activate the endothelium in a similar way as is observed in the microvasculature at sites of immune inflammation. The expression of these activation markers in the microvasculature is associated with enhanced leukocyte adhesion, permeability for macromolecules, and procoagulant activity, features known to occur also in early experimental atherosclerosis. The findings therefore support the concept that arterial endothelium plays an active role in the recruitment of mononuclear cells in atherosclerotic lesions. Images Figure 1 PMID:1281621

  7. Histological lesions, cell cycle arrest, apoptosis and T cell subsets changes of spleen in chicken fed aflatoxin-contaminated corn.

    PubMed

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

    2014-08-20

    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.

  8. 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. PMID:24333829

  9. 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.

  10. Laser-induced autofluorescence properties of base-cell lesions: analysis and algorithms for diagnosis and differentiation

    NASA Astrophysics Data System (ADS)

    Borisova, E.; Troyanova, P.; Avramov, L.

    2006-09-01

    The goals of this work were investigation of base-cell skin lesions by the method of laser-induced autofluorescence spectroscopy. Fluorescence spectra were obtained from benign base-cell papilloma and malignant base-cell carcinoma, as well as from healthy skin areas near to the lesions that were used posteriori to reveal changes between healthy and lesion skin spectra. Preliminarily lesions were classified by dermatoscopic method (MoleMax II, DERMA Instruments). All suspicious lesions were excised and were investigated histologically. The experimental set-up consists of a nitrogen laser (337 nm, 14 μJ, 10 Hz), lenses, filters, optical fibers, and a microspectrometer (PC2000, "Ocean Optics"). A computer controls this system. Spectrum of healthy skin consists of one main maximum at 470-500 nm spectral region and secondary maxima at in the regions around 400 and 440 nm. In cases of papilloma and base-cell carcinoma an intensity decrease was observed, related to accumulation of pigments in these cutaneous lesions. An relative increase of the fluorescence peak at 440 nm were registered in the case of base-cell carcinoma, related to metabolism activity increase, and appearance of green fluorescence, related to increase of keratin content in benign papilloma lesions were detected. The results, obtained were used to develop multispectral diagnostic algorithm of these base-cell lesions. An sensitivity of 89,4% and 91,0% and specificity of 99,6% and 97,4% for differentiation between normal skin and papilloma and carcinoma respectively were obtained. The capability of the human skin fluorescence spectroscopy for early diagnosis and differentiation of cutaneous lesions is shown.

  11. Lesion-induced accumulation of platelets promotes survival of adult neural stem / progenitor cells.

    PubMed

    Kazanis, Ilias; Feichtner, Martina; Lange, Simona; Rotheneichner, Peter; Hainzl, Stefan; Öller, Michaela; Schallmoser, Katharina; Rohde, Eva; Reitsamer, Herbert A; Couillard-Despres, Sebastien; Bauer, Hans-Christian; Franklin, Robin J M; Aigner, Ludwig; Rivera, Francisco J

    2015-07-01

    The presence of neural stem/progenitor cells (NSPCs) in specific areas of the central nervous system (CNS) supports tissue maintenance as well as regeneration. The subependymal zone (SEZ), located at the lateral ventricle's wall, represents a niche for NSPCs and in response to stroke or demyelination becomes activated with progenitors migrating towards the lesion and differentiating into neurons and glia. The mechanisms that underlie this phenomenon remain largely unknown. The vascular niche and in particular blood-derived elements such as platelets, has been shown to contribute to CNS regeneration in different pathological conditions. Indeed, intracerebroventricularly administrated platelet lysate (PL) stimulates angiogenesis, neurogenesis and neuroprotection in the damaged CNS. Here, we explored the presence of platelets in the activated SEZ after a focal demyelinating lesion in the corpus callosum of mice and we studied the effects of PL on proliferating SEZ-derived NSPCs in vitro. We showed that the lesion-induced increase in the size of the SEZ and in the number of proliferating SEZ-resident NSPCs correlates with the accumulation of platelets specifically along the activated SEZ vasculature. Expanding on this finding, we demonstrated that exposure of NSPCs to PL in vitro led to increased numbers of cells by enhanced cell survival and reduced apoptosis without differences in proliferation and in the differentiation potential of NSPCs. Finally, we demonstrate that the accumulation of platelets within the SEZ is spatially correlated with reduced numbers of apoptotic cells when compared to other periventricular areas. In conclusion, our results show that platelet-derived compounds specifically promote SEZ-derived NSPC survival and suggest that platelets might contribute to the enlargement of the pool of SEZ NSPCs that are available for CNS repair in response to injury.

  12. Lesion-induced accumulation of platelets promotes survival of adult neural stem / progenitor cells.

    PubMed

    Kazanis, Ilias; Feichtner, Martina; Lange, Simona; Rotheneichner, Peter; Hainzl, Stefan; Öller, Michaela; Schallmoser, Katharina; Rohde, Eva; Reitsamer, Herbert A; Couillard-Despres, Sebastien; Bauer, Hans-Christian; Franklin, Robin J M; Aigner, Ludwig; Rivera, Francisco J

    2015-07-01

    The presence of neural stem/progenitor cells (NSPCs) in specific areas of the central nervous system (CNS) supports tissue maintenance as well as regeneration. The subependymal zone (SEZ), located at the lateral ventricle's wall, represents a niche for NSPCs and in response to stroke or demyelination becomes activated with progenitors migrating towards the lesion and differentiating into neurons and glia. The mechanisms that underlie this phenomenon remain largely unknown. The vascular niche and in particular blood-derived elements such as platelets, has been shown to contribute to CNS regeneration in different pathological conditions. Indeed, intracerebroventricularly administrated platelet lysate (PL) stimulates angiogenesis, neurogenesis and neuroprotection in the damaged CNS. Here, we explored the presence of platelets in the activated SEZ after a focal demyelinating lesion in the corpus callosum of mice and we studied the effects of PL on proliferating SEZ-derived NSPCs in vitro. We showed that the lesion-induced increase in the size of the SEZ and in the number of proliferating SEZ-resident NSPCs correlates with the accumulation of platelets specifically along the activated SEZ vasculature. Expanding on this finding, we demonstrated that exposure of NSPCs to PL in vitro led to increased numbers of cells by enhanced cell survival and reduced apoptosis without differences in proliferation and in the differentiation potential of NSPCs. Finally, we demonstrate that the accumulation of platelets within the SEZ is spatially correlated with reduced numbers of apoptotic cells when compared to other periventricular areas. In conclusion, our results show that platelet-derived compounds specifically promote SEZ-derived NSPC survival and suggest that platelets might contribute to the enlargement of the pool of SEZ NSPCs that are available for CNS repair in response to injury. PMID:25819103

  13. Olig2-expressing progenitor cells preferentially differentiate into oligodendrocytes in cuprizone-induced demyelinated lesions.

    PubMed

    Islam, Mohammad Shyful; Tatsumi, Kouko; Okuda, Hiroaki; Shiosaka, Sadao; Wanaka, Akio

    2009-01-01

    Many oligodendrocyte progenitor cells (OPCs) are found in acute or chronic demyelinated area, but not all of them differentiate efficiently into mature oligodendrocytes in the demyelinated central nervous system (CNS). Recent studies have shown that the basic helix-loop-helix transcription factor Olig2, which stimulates OPCs to differentiate into oligodendrocyte, is strongly up-regulated in many pathological conditions including acute or chronic demyelinating lesions in the adult CNS. Despite their potential role in the treatment of demyelinating diseases, the long-term fate of these up-regulated Olig2 cells has not been identified due to the lack of stable labeling methods. To trace their fate we have used double-transgenic mice, in which we were able to label Olig2-positive cells conditionally with green fluorescent protein (GFP). Demyelination was induced in these mice by feeding cuprizone, a copper chelator. After 6 weeks of cuprizone exposure, GFP-positive (GFP(+)) cells were processed for a second labeling with antibodies to major neural cell markers APC (mature oligodendrocyte marker), GFAP (astrocyte marker), NeuN (neuron marker), Iba1 (microglia marker) and NG2 proteoglycan (oligodendrocyte progenitor marker). More than half of the GFP(+) cells in the external capsule showed co-localization with NG2 proteoglycan. While the percentages of NG2-positive (NG2(+)) and APC-positive (APC(+)) oligodendrocyte lineage cells in cuprizone-treated mice were significantly higher than those in the normal diet group, no significant difference was observed for GFAP-positive (GFAP(+)) astrocytic lineage cells. Our data therefore provide direct evidence that proliferation and differentiation of local and/or recruited Olig2 progenitors contribute to remyelination in demyelinated lesions. PMID:19070638

  14. Behavioural consequences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord.

    PubMed

    Jeffery, N D; Crang, A J; O'leary, M T; Hodge, S J; Blakemore, W F

    1999-05-01

    Glial cell transplantation has the potential to be developed into a clinical treatment for human demyelinating diseases because of its demonstrated efficacy in remyelinating experimentally demyelinated axons. As a step towards clinical application it is necessary to demonstrate that the procedure is safe and efficacious in promoting behavioural recovery. In this study we transplanted glial cell progenitors into demyelinating lesions induced by intraspinal injection of ethidium bromide in the rat. Locomotor function after transplantation was assessed using a beam-walking test that has previously been shown able to detect deficits associated with demyelination in the dorsal funiculus of the rat spinal cord. Two groups of animals with transplants were examined. In one group, spontaneous remyelination was prevented by exposure of the lesion to 40 Gy of X-irradiation; in the other, male glial cells were transplanted into nonirradiated female recipients, permitting their identification by use of a probe specific to the rat Y chromosome. Following transplantation, there was severe axon loss in a large proportion of the irradiated animals and those affected did not recover normal behavioural function. In contrast, both the small proportion of the irradiated group that sustained only mild axon loss and the nonirradiated recipients of transplants recovered normal function on our behavioural test. We conclude that glial cell transplantation is able to reverse the functional deficits associated with demyelination, provided axonal loss is minimal. PMID:10215903

  15. 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.

  16. 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.

  17. 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. PMID:26064970

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

    PubMed Central

    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. PMID:26064970

  19. Squamous Cell Carcinoma Developing in a Cutaneous Lichen Planus Lesion: A Rare Case

    PubMed Central

    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. PMID:24839562

  20. Dietary excess vanadium induces lesions and changes of cell cycle of spleen in broilers.

    PubMed

    Cui, Wei; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Liu, Xiaodong; Wu, Bangyuan

    2011-11-01

    The purpose of this 42-day study was to investigate the effects of dietary excess vanadium on spleen growth and lesions by determining morphological changes and cell cycle of spleen. Four hundred twenty 1-day-old avian broilers were divided into six groups and fed on a corn-soybean basal diet as control diet or the same diet amended to contain 5, 15, 30, 45, 60 ppm of vanadium supplied as ammonium metavanadate. When compared with that of control group, the relative weight of spleen was significantly raised in 5- and 15-ppm groups, but depressed in 45- and 60-ppm groups. The gross lesions of spleen showed obvious atrophy with decreased volume and pale color in 45- and 60-ppm groups. Histopathologically, lymphocytes in splenic corpuscle and periarterial lymphatic sheath were variously decreased in number in 30-, 45-, and 60-ppm groups. The percentage of static phase (G0/G1) was significantly decreased, and the percentage of synthesis period (S) phase and the proliferating index (PI) were significantly increased in 5- and 15-ppm groups. The percentage of G0/G1 phase was significantly increased, and the percentage of mitotic phase (G2+M), S phase, and PI significantly decreased in 45- and 60-ppm groups. These results suggested that dietary excess vanadium (45 and 60 ppm) could inhibit growth of spleen and induce lesions in spleen in chicken.

  1. Involvement of mast cells and microvessels density in reactive lesions of oral cavity: A comparative immunohistochemical study.

    PubMed

    Ferreira, Stephany Vasco; Xavier, Flávia Caló Aquino; Freitas, Maria da Conceição Andrade de; Nunes, Fábio Daumas; Gurgel, Clarissa Araújo; Cangussu, Maria Cristina Teixeira; Martins, Manoela Domingues; Freitas, Valéria Souza; Dos Santos, Jean Nunes

    2016-09-01

    In view of the similarity of clinicopathological features between reactive lesions of the oral cavity, the objective of the present study was to investigate the density of MCs (mast cells) and microvessels in a series of these lesions. Thirty-seven cases of reactive lesions including fibrous hyperplasia (FH, n=10), inflammatory fibrous hyperplasia (IFH, n=10), peripheral giant cell lesion (PGCL, n=10) and lobular capillary hemangioma (LCH, n=7) were investigated using immunohistochemistry for mast cell tryptase and CD34. For comparative purposes, central giant cell lesions (CGCL, n=5) were included. A higher MC density was observed in LCH (37.01), while CGCL exhibited the lowest density (n=8.14). There was a significant difference in MC density when all reactive lesions were compared to CGCL (p=0.001). The largest mean density of microvessels was observed in LCH (n=21.69). The smallest number was observed in CGCL (n=6.24). There was a significant difference in microvessel density when the reactive lesions were compared to CGCL (p=0.003). There was a significant and direct correlation between the density of MCs and microvessels only for IFH (p=0.048) and CGCL (p=0.005). A significant and direct correlation between the mean density of MCs and microvessels was observed when the reactive lesions were analyzed as a whole (p=0.005). Our results suggest that mast cells contribute to the connective tissue framework and angiogenic function, as well as the development, of reactive lesions of the oral cavity, including FH, IFH, LCH and PGCL. PMID:27493102

  2. Involvement of mast cells and microvessels density in reactive lesions of oral cavity: A comparative immunohistochemical study.

    PubMed

    Ferreira, Stephany Vasco; Xavier, Flávia Caló Aquino; Freitas, Maria da Conceição Andrade de; Nunes, Fábio Daumas; Gurgel, Clarissa Araújo; Cangussu, Maria Cristina Teixeira; Martins, Manoela Domingues; Freitas, Valéria Souza; Dos Santos, Jean Nunes

    2016-09-01

    In view of the similarity of clinicopathological features between reactive lesions of the oral cavity, the objective of the present study was to investigate the density of MCs (mast cells) and microvessels in a series of these lesions. Thirty-seven cases of reactive lesions including fibrous hyperplasia (FH, n=10), inflammatory fibrous hyperplasia (IFH, n=10), peripheral giant cell lesion (PGCL, n=10) and lobular capillary hemangioma (LCH, n=7) were investigated using immunohistochemistry for mast cell tryptase and CD34. For comparative purposes, central giant cell lesions (CGCL, n=5) were included. A higher MC density was observed in LCH (37.01), while CGCL exhibited the lowest density (n=8.14). There was a significant difference in MC density when all reactive lesions were compared to CGCL (p=0.001). The largest mean density of microvessels was observed in LCH (n=21.69). The smallest number was observed in CGCL (n=6.24). There was a significant difference in microvessel density when the reactive lesions were compared to CGCL (p=0.003). There was a significant and direct correlation between the density of MCs and microvessels only for IFH (p=0.048) and CGCL (p=0.005). A significant and direct correlation between the mean density of MCs and microvessels was observed when the reactive lesions were analyzed as a whole (p=0.005). Our results suggest that mast cells contribute to the connective tissue framework and angiogenic function, as well as the development, of reactive lesions of the oral cavity, including FH, IFH, LCH and PGCL.

  3. 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.

  4. Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions

    PubMed Central

    Zhang, Hui; Wen, Jia; Xu, Pi-Li; Chen, Rui; Yang, Xi; Zhou, Lian-Er; Jiang, Ping; Wan, An-Xia; Liao, Qin-Ping

    2016-01-01

    Background: Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions. Methods: A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB. Results: The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%. Conclusions: CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions. PMID:27270542

  5. An approach to the diagnosis of spindle cell lesions of the breast.

    PubMed

    Rakha, Emad A; Aleskandarany, Mohammed A; Lee, Andrew H S; Ellis, Ian O

    2016-01-01

    Although most breast spindle cell lesions (BSCLs) are rare, they constitute a wide spectrum of diseases, ranging from reactive processes to aggressive malignant tumours. Despite their varied histogenesis and behaviour, some lesions show an overlap of morphological features, making accurate diagnosis a challenging task, particularly in needle core biopsies. Clinical history and immunohistochemistry can help in making a correct diagnosis in morphologically challenging cases. To make an accurate diagnosis, it is important to maintain a wide differential diagnosis and be familiar with the diverse morphological appearances of these different entities. BSCLs can generally be classified into bland-looking and malignant-looking categories. In the former, the commonest diagnosis is scarring. However, it is important to distinguish low-grade spindle cell metaplastic breast carcinoma from other benign entities, as the management is clearly different. In the malignant category, it is important to differentiate metaplastic carcinoma from other malignant primary and metastatic malignant spindle cell tumours of the breast, such as malignant phyllodes tumour, angiosarcoma, and melanoma. This review focuses on the classification and histological and molecular diagnosis of various BSCLs, with an emphasis on the diagnostic approach, including in core biopsies. PMID:26768028

  6. Interplay between columnar and smectic stability in suspensions of polydisperse colloidal platelets.

    PubMed

    Velasco, Enrique; Martínez-Ratón, Yuri

    2014-01-14

    The phase behavior of a model suspension of colloidal polydisperse platelets is studied using density-functional theory. Platelets are modelled as parallel rectangular prisms of square section l(2) and height h, with length and height distributions given by different polydispersities δ(l) and δ(h). The model is intended to qualitatively represent experimental colloidal platelet suspensions at high densities with a high degree of orientational ordering. We obtain the phase behavior of the model, including nematic, smectic and columnar phases and its dependence on the two polydispersities δ(l) and δ(h). When δ(l) > δ(h) we observe that the smectic phase stabilises first with respect to the columnar. If δ(h) > δ(l) we observe the opposite behavior. Other more complicated cases occur, e.g. the smectic stabilises from the nematic first but then exists a first-order transition to the columnar phase. Our model assumes plate-rod symmetry, but the regions of stability of smectic and columnar phases are non-symmetric in the δ(l) - δ(h) plane due to the different dimensionality of ordering in the two phases. Microsegregation effects, i.e. different spatial distribution for different sizes within the periodic cell, take place in both phases and, in each case, is more apparent in the variable associated with ordering.

  7. 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...

  8. 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...

  9. 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...

  10. 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

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

    PubMed

    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

  12. Differential Expression of Viral Bcl-2 Encoded by Kaposi's Sarcoma-Associated Herpesvirus and Human Bcl-2 in Primary Effusion Lymphoma Cells and Kaposi's Sarcoma Lesions

    PubMed Central

    Widmer, Isabelle; Wernli, Marion; Bachmann, Felix; Gudat, Fred; Cathomas, Gieri; Erb, Peter

    2002-01-01

    Expression of human herpesvirus 8 viral Bcl-2 protein was demonstrated in spindle cells of late-stage Kaposi's sarcoma lesions but not in primary effusion lymphoma cell lines. In contrast, strong expression of human Bcl-2 was found in stimulated primary effusion lymphoma cells, whereas in Kaposi's sarcoma lesions preferential mononuclear cells, and to a lesser extent spindle cells, stained positive. PMID:11836434

  13. Two rare entities in the same palate lesion: hyalinizing-type clear cell carcinoma and necrotizing sialometaplasia.

    PubMed

    Arpaci, Rabia Bozdoğan; Kara, Tuba; Porgali, Canan; Serinsoz, Ebru; Polat, Ayse; Vayisoglu, Yusuf; Ozcan, Cengiz

    2014-05-01

    Hyalinizing clear cell carcinoma is a low-grade malignant epithelial neoplasm of the salivary glands. The tumor has epithelial cells and lacks myoepithelial cells. Necrotizing sialometaplasia is a benign, self-limiting lesion of the salivary glands. The clinical and histologic features mimic those of mucoepidermoid carcinoma or squamous cell carcinoma. The importance of these entities are the rarity of both of them and their potential to be misdiagnosed as other lesions. Pathologists and clinicians should be aware of these entities to prevent misdiagnosis. This is the first clinical report of 2 rare and consecutive different entities of the same location on the hard palate to our knowledge.

  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. High-frequency micromechanical columnar resonators

    NASA Astrophysics Data System (ADS)

    Kehrbusch, Jenny; Ilin, Elena A.; Bozek, Peter; Radzio, Bernhard; Oesterschulze, Egbert

    2009-06-01

    High-frequency silicon columnar microresonators are fabricated using a simple but effective technological scheme. An optimized fabrication scheme was invented to obtain mechanically protected microcolumns with lateral dimensions controlled on a scale of at least 1 μm. In this paper, we investigate the influence of the environmental conditions on the mechanical resonator properties. At ambient conditions, we observed a frequency stability δf/f of less than 10-6 during 5 h of operation at almost constant temperature. However, varying the temperature shifts the frequency by approximately -173 Hz °C- 1. In accordance with a viscous damping model of the ambient gas, we perceived that the quality factor of the first flexural mode decreased with the inverse of the square root of pressure. However, in the low-pressure regime, a linear dependence was observed. We also investigated the influence of the type of the immersing gas on the resonant frequency.

  16. Langerhans cells increase in the dermal lesions of adult T cell leukaemia in Japan

    PubMed Central

    Shamoto, M

    1983-01-01

    In cases of adult T cell leukaemia neoplastic T cell infiltration in the skin was accompanied by an increase in Langerhans cells. This is in keeping with the view that Langerhans cells may induce antigen-specific and allogenic T cell activation. Images PMID:6600750

  17. 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.

  18. Columnar structures from asymmetrically tapered biphenylamide.

    PubMed

    Park, Soo-Jin; Hwang, Seok-Ho; Kim, Namil; Kuo, Shiao-Wei; Kim, Hak Yong; Park, Seul-Ki; Kim, Young-Jin; Nah, Changwoon; Lee, Joong Hee; Jeong, Kwang-Un

    2009-10-15

    An asymmetrically tapered N,N'-tris[[(2-dodecylaminocarbonyl)ethyl]methyl]-4-biphenylamide (asym-C(12)PhA, where n is the number of carbon atoms in the alkyl chains, n = 12) was newly designed and synthesized. In this asymmetrically tapered asym-C(12)PhA biphenylamide, H-bondable hydrophilic amide moieties are located at between a rigid hydrophobic biphenyl rod and three flexible hydrophobic alkyl chains. Computer energy minimization indicated that three-dimensional (3D) geometry of asym-C(12)PhA biphenylamide looks like a cone with dimensions of 3.01 nm in height and 1.44 nm in bottom radius. Phase transitions and supra-molecular structures were identified utilizing the combined techniques of differential scanning calorimetry, 1D wide-angle X-ray diffraction (1D WAXD), Fourier-transform infrared spectroscopy, and solid-state (13)C nuclear magnetic resonance analyses. The asym-C(12)PhA self-assembled into a highly ordered columnar mesophase just below the isotropization temperature and then transformed to 3D columnar crystalline phase (Phi(Cr)) on further cooling. Selected area electron diffractions in transmission electron microscopy (TEM) along with 1D WAXD and cross-polarized optical microscopy suggested that discotic building blocks were constructed by rotating 120 degrees of three asym-C(12)PhA with respect to neighboring ones and the tmb (top-middle-bottom) stacked discotic building blocks further self-organized into columns. These columns are laterally intercalated to form the Phi(Cr) phase. On the basis of the TEM image and polyethylene surface decoration technology, it was identified that the self-assembled asym-C(12)PhA fibers with approximately 1 mum in diameter and several millimeters in length were braids of tiny single crystals.

  19. 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. PMID:25626118

  20. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene.

    PubMed Central

    von der Leyen, H E; Gibbons, G H; Morishita, R; Lewis, N P; Zhang, L; Nakajima, M; Kaneda, Y; Cooke, J P; Dzau, V J

    1995-01-01

    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 beta-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 vessels. 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. Images Fig. 1 Fig. 2 Fig. 5 PMID:7532305

  1. 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.

  2. Step by step approach to rare breast lesions containing spindle cells.

    PubMed

    Ünal, Betül; Erdoğan, Gülgün; Karaveli, Fatma Şeyda

    2015-01-01

    Differential diagnosis of spindle cell lesions of breast is challenging for certain reasons. The most important reason is the presence of cytological atypia and mitosis in all three conditions: reactive, benign, and malignant. Patients diagnosed with benign and malignant tumor/tumor-like lesions that had spindle cell components following the histopathological examination were included in the study. The patients' medical records were accessed to obtain the clinical history, follow-up notes, and radiological findings. Following histopathological, immunohistochemical, and clinical evaluations, the patients were diagnosed as follows: pseudoangiomatous stromal hyperplasia (PASH), bilateral desmoid-type fibromatosis (FM), adenomyoepithelioma (AME), myofibroblastoma (MFB), malignant phyllodes tumor (MF), high-grade AS, post-chemotherapy osteosarcoma (OS) + Paget's disease, and metaplastic carcinoma (MC). An algorithmic approach should be used in the diagnosis; cellular structure, presence and grade of atypia, growth pattern, mitotic activity, immunohistochemical staining, and clinical and radiological features should be evaluated together. Detection of some molecular changes can be useful in differential diagnosis. PMID:26558181

  3. Incidence and predictive factors of benign renal lesions in Korean patients with preoperative imaging diagnoses of renal cell carcinoma.

    PubMed

    Park, Seo Yong; Jeon, Seong Soo; Lee, Seo Yeon; Jeong, Byong Chang; Seo, Seong Il; Lee, Hyun Moo; Choi, Han Yong

    2011-03-01

    The present study was performed to determine the incidence and predictive factors of benign renal lesions in Korean patients undergoing nephrectomy for presumed renal cell carcinoma on preoperative imaging. We analyzed the pathologic reports and medical records of 1,598 eligible patients with unilateral, nonmetastatic, and nonfamilial renal masses. Of the 1,598 renal masses, 114 (7.1%) were benign lesions, including angiomyolipoma in 47 (2.9%), oncocytoma in 23 (1.4%), and complicated cysts in 18 (1.1%) patients. On univariate analysis, the proportion of benign lesions was significantly higher in female patients, and in patients with smaller tumors, cystic renal masses, and without gross hematuria as a presenting symptom. When renal lesions were stratified by tumor size, the proportion of benign as opposed to malignant lesions decreased significantly as tumor size increased. On multivariate analysis, female gender, smaller tumor size, and cystic lesions were significantly associated with benign histological features. The findings in this large cohort of Korean patients show a lower incidence (7.1%) of benign renal lesions than those of previous Western reports. Female gender, cystic renal lesions, and smaller tumor size are independent predictors of benign histological features.

  4. 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.

  5. 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. PMID:26253667

  6. Immunohistochemical/histochemical double staining method in the study of the columnar metaplasia of the oesophagus.

    PubMed

    Cabibi, D; Giannone, A G; Mascarella, C; Guarnotta, C; Castiglia, M; Pantuso, G; Fiorentino, E

    2014-03-05

    Intestinal metaplasia in Barrett's oesophagus (BO) represents an important risk factor for oesophageal adenocarcinoma. Instead, few and controversial data are reported about the progression risk of columnar-lined oesophagus without intestinal metaplasia (CLO), posing an issue about its clinical management. The aim was to evaluate if some immunophenotypic changes were present in CLO independently of the presence of the goblet cells. We studied a series of oesophageal biopsies from patients with endoscopic finding of columnar metaplasia, by performing some immunohistochemical stainings (CK7, p53, AuroraA) combined with histochemistry (Alcian-blue and Alcian/PAS), with the aim of simultaneously assess the histochemical features in cells that shows an aberrant expression of such antigens. We evidenced a cytoplasmic expression of CK7 and a nuclear expression of Aurora A and p53,  both in goblet cells of BO and in non-goblet cells of CLO, some of which showing mild dysplasia. These findings suggest that some immunophenotypic changes are present in CLO and they can precede the appearance of the goblet cells or can be present independently of them, confirming the conception of BO as the condition characterized by any extention of columnar epithelium. This is the first study in which a combined immunohistochemical/histochemical method has been applied to Barrett pathology.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. Isolation and characterization of Flavobacterium columnare (Bernardet et al. 2002) from four tropical fish species in Brazil.

    PubMed

    Pilarski, F; Rossini, A J; Ceccarelli, P S

    2008-05-01

    Flavobacterium columnare is the causative agent of columnaris disease in freshwater fish, implicated in skin and gill disease, often causing high mortality. The aim of this study was the isolation and characterization of Flavobacterium columnare in tropical fish in Brazil. Piracanjuba (Brycon orbignyanus), pacu (Piaractus mesopotamicus), tambaqui (Colossoma macropomum) and cascudo (Hypostomus plecostomus) were examined for external lesions showing signs of colunmaris disease such as greyish white spots, especially on the head, dorsal part and caudal fin of the fish. The sampling comprised 50 samples representing four different fish species selected for study. Samples for culture were obtained by skin and kidney scrapes with a sterile cotton swabs of columnaris disease fish and streaked onto Carlson and Pacha (1968) artificial culture medium (broth and solid) which were used for isolation. The strains in the liquid medium were Gram negative, long, filamentous, exhibited flexing movements (gliding motility), contained a large number of long slender bacteria and gathered into columns'. Strains on the agar produced yellow-pale colonies, rather small, flat that had rhizoid edges. A total of four Flavobacterium columnare were isolated: 01 Brycon orbignyanus strain, 01 Piaractus mesopotamicus strain, 01 Colossoma macropomum strain, and 01 Hypostomus plecostomus strain. Biochemical characterization, with its absorption of Congo red dye, production of flexirubin-type pigments, H2S production and reduction of nitrates proved that the isolate could be classified as Flavobacterium columnare.

  12. Pineal mixed germ cell tumor with a synchronous sellar lesion in the sixth decade.

    PubMed

    Bohara, Manoj; Hirano, Hirofumi; Tokimura, Hiroshi; Hanaya, Ryosuke; Yonezawa, Hajime; Campos, Francia; Sugiyama, Kazuhiko; Sugata, Sei; Arita, Kazunori

    2011-04-01

    Intracranial germ cell tumors (GCTs) typically affect children and adolescents. We here report on a 59-year-old male patient presenting with diplopia, polydipsia and polyuria. On clinical examination, slight restriction of the upward gaze was seen on the left side. Computed tomography demonstrated calcifications in the pineal region and enhanced neurohypophysis. Magnetic resonance imaging displayed a heterogeneous pineal mass of 3-cm diameter, which was multicystic with an enhanced cyst wall, and also swelling of the pituitary stalk. The pineal lesion of the tumor, which included calcifications and keratinaceous components, was totally excised using an occipital transtentorial approach. Histopathological examination showed it to be a mixed GCT with germinoma and mature teratoma components. Postoperative chemoradiotherapy provided complete disappearance of the suprasellar lesion. To our knowledge, this is the first case of mixed bifocal GCT in an older adult reported in the literature, although a few cases of tumors with a single histological component have been reported. Hence, our case further underlines the possibility of the occurrence of GCTs in older adults and advocates the consideration of GCTs in the differential diagnosis of such cases for appropriate management. PMID:21287366

  13. 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

  14. Cystic trophoblastic tumor: a nonaggressive lesion in postchemotherapy resections of patients with testicular germ cell tumors.

    PubMed

    Ulbright, Thomas M; Henley, John D; Cummings, Oscar W; Foster, Richard S; Cheng, Liang

    2004-09-01

    Cystic trophoblastic tumor (CTT) is an uncommon lesion that is usually seen after chemotherapy in patients with testicular germ cell tumors. Its clinical significance has not been well studied. We identified 17 patients with CTT in retroperitoneal lymph node dissections (RPLNDs) after cisplatin-based chemotherapy for testicular germ cell tumors. None had other forms of persistent germ cell tumor except for teratoma, and no patient received additional chemotherapy after RPLND. At the time of RPLND, 7 patients were known to have had normal serum levels of beta-subunit of human chorionic gonadotropin (beta-hCG), whereas 5 had relatively mild elevations (1.6-165 mIU/mL, median, 8.0 mIU/mL). The CTTs consisted of circumscribed, small cysts, usually multifocal, lined by mostly mononucleated trophoblast cells with abundant eosinophilic cytoplasm, often with smudged nuclei and showing only infrequent mitotic figures. Although the epithelial lining was often stratified to several layers in thickness or formed intracystic papillary tufts, solid proliferations of trophoblast cells within the stroma were absent, as were clearly biphasic admixtures of mononucleated and multinucleated trophoblast cells. The cysts were either empty or contained fibrinoid material and were set in a hypocellular, fibrous stroma with adjacent teratoma. Stains for hCG highlighted rare cells. On follow-up of 15 patients, 11 were disease free (mean, 80 months). Three recurred with serum alpha-fetoprotein elevations at 25, 31, and 107 months, respectively, and one with beta-hCG elevation at 2 months. The latter patient, however, also had unresected mediastinal tumor postchemotherapy. We conclude that the finding of CTT in postchemotherapy resections does not warrant additional chemotherapy. Its clinical significance appears similar to that of residual teratoma.

  15. αβ T-cell receptors from multiple sclerosis brain lesions show MAIT cell–related features

    PubMed Central

    Held, Kathrin; Bhonsle-Deeng, Latika; Siewert, Katherina; Sato, Wakiro; Beltrán, Eduardo; Schmidt, Stephan; Rühl, Geraldine; Ng, Judy K.M.; Engerer, Peter; Moser, Markus; Klinkert, Wolfgang E.F.; Babbe, Holger; Misgeld, Thomas; Wekerle, Hartmut; Laplaud, David-Axel; Hohlfeld, Reinhard

    2015-01-01

    Objectives: To characterize phenotypes of T cells that accumulated in multiple sclerosis (MS) lesions, to compare the lesional T-cell receptor (TCR) repertoire of T-cell subsets to peripheral blood, and to identify paired α and β chains from single CD8+ T cells from an index patient who we followed for 18 years. Methods: We combined immunohistochemistry, laser microdissection, and single-cell multiplex PCR to characterize T-cell subtypes and identify paired TCRα and TCRβ chains from individual brain-infiltrating T cells in frozen brain sections. The lesional and peripheral TCR repertoires were analyzed by pyrosequencing. Results: We found that a TCR Vβ1+ T-cell population that was strikingly expanded in active brain lesions at clinical onset comprises several subclones expressing distinct yet closely related Vα7.2+ α chains, including a canonical Vα7.2-Jα33 chain of mucosal-associated invariant T (MAIT) cells. Three other α chains bear striking similarities in their antigen-recognizing, hypervariable complementarity determining region 3. Longitudinal repertoire studies revealed that the TCR chains that were massively expanded in brain at onset persisted for several years in blood or CSF but subsequently disappeared except for the canonical Vα7.2+ MAIT cell and a few other TCR sequences that were still detectable in blood after 18 years. Conclusions: Our observation that a massively expanded TCR Vβ1-Jβ2.3 chain paired with distinct yet closely related canonical or atypical MAIT cell–related α chains strongly points to an antigen-driven process in early active MS brain lesions. PMID:25977934

  16. Precambrian columnar stromatolite diversity: reflection of metazoan appearance.

    PubMed

    Awramik, S M

    1971-11-19

    Columnar stromatolites (organosedimentary structures built by bluegreen algae) show a marked decrease in diversity in the Late Precambrian; this decrease in diversity occurs at approximately the same time as the appearance of metazoans, 600 to 700 million years ago.

  17. Vaccination of fish against Flavobacterium columnare and F. psychrophilum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are two primary Flavobacterium spp. involved in disease of aquaculture raised fish worldwide including, F. columnare, and F. psychrophilum; the etiologic agents of columnaris disease and bacterial coldwater disease (CWD) or rainbow trout fry syndrome (RTFS), respectively. Traditional vaccines...

  18. 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...

  19. Benchmark experiments and numerical modelling of the columnar-equiaxed dendritic growth in the transparent alloy Neopentylglycol-(d)Camphor

    NASA Astrophysics Data System (ADS)

    Sturz, L.; Wu, M.; Zimmermann, G.; Ludwig, A.; Ahmadein, M.

    2015-06-01

    Solidification benchmark experiments on columnar and equiaxed dendritic growth, as well as the columnar-equiaxed transition have been carried out under diffusion-dominated conditions for heat and mass transfer in a low-gravity environment. The system under investigation is the transparent organic alloy system Neopentylglycol-37.5wt.-%(d)Camphor, processed aboard a TEXUS sounding rocket flight. Solidifications was observed by standard optical methods in addition to measurements of the thermal fields within the sheet like experimental cells of 1 mm thickness. The dendrite tip kinetic, primary dendrite arm spacing, temporal and spatial temperature evolution, columnar tip velocity and the critical parameters at the CET have been analysed. Here we focus on a detailed comparison of the experiment “TRACE” with a 5-phase volume averaging model to validate the numerical model and to give insight into the corresponding physical mechanisms and parameters leading to CET. The results are discussed in terms of sensitivity versus numerical parameters.

  20. 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.

  1. 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

  2. Regulatory T-cells and IL17A(+) cells infiltrate oral lichen planus lesions.

    PubMed

    Javvadi, L R; Parachuru, V P B; Milne, T J; Seymour, G J; Rich, A M

    2016-10-01

    Oral lichen planus (OLP) is a complex immunological disorder, mediated in part by the release of cytokines from activated T-cells. Of late, two closely related T-helper (Th) cell subsets; regulatory T-cells (Tregs; FoxP3(+)) and Th17 cells (IL17(+)) have been described in various chronic inflammatory diseases. The aim of this study was to determine the expression of FoxP3 and IL17 in OLP using immunohistochemistry (IHC) and quantitative real-time reverse transcriptase polymerase chain reaction (qPCR). For IHC, formalin fixed, paraffin embedded archival specimens, an OLP group (n=10) and a non-specific inflammatory (NSI) control group (n=9) were used. In addition, 12 fresh tissue samples were used to determine gene expression of FoxP3 and IL17. Significantly more FoxP3(+) cells were present in OLP than in NSI. IL17(+) cells were significantly more frequent in the control tissues than in OLP. The gene expression experiments revealed a significantly higher expression of FoxP3 in OLP when compared to the controls. IL17 gene expression was not different between the groups. Double labelling immunofluorescence indicated co-localisation of IL17 with tryptase(+) mast cells. These findings suggest FoxP3(+) Tregs have a more prominent role in the pathogenesis of OLP when compared to IL17(+)cells. PMID:27594511

  3. Bacteria-reactive immune response may induce RANKL-expressing T-cells in the mouse periapical bone loss lesion

    PubMed Central

    Silva, Marcelo J.B.; Kajiya, Mikihito; AlShwaimi, Emad; Sasaki, Hajime; Hong, Jennifer; Ok, Peter; Rezende, Taia M.B.; Pagonis, Tom C.; White, Robert R.; Paster, Bruce J; Stashenko, Philip; Kawai, Toshihisa

    2012-01-01

    Introduction The present study investigated if T-cells infiltrating the periapical lesion produce RANKL and whether bacteria infecting the root canal can activate T-cells to produce RANKL. Methods Using a mouse model of periapical lesion induced by artificial dental pulp exposure, the presence of RANKL-positive T-cells and osteoclasts in the periapical lesion was examined by an immuno-histochemical approach. The bacteria colonizing the exposed root canal were identified by 16S ribosomal RNA (rRNA) sequence analysis. The isolated endodontic bacteria were further immunized to normal mice, and sRANKL production by the T-cells isolated from the immunized mice was evaluated by ex vivo culture system. Results RANKL-positive T-cells, along with TARP+ osteoclasts, were identified in periapical bone resorption lesions. The Gram-negative bacterium Pasterurella pnumotropica (P. pnumotropica), which was most frequently detected from root canal of exposed pulp, showed remarkably elevated serum IgG antibody response in pulp-exposed mice compared to control non-treated mice. Immunization of mice with P. pneumotropica induced not only serum IgG antibody but also primed bacteria reactive T-cells that produced sRANKL in response to ex vivo exposure to P. pneumotropica. Conclusion T-cells infiltrating the periapical region express RANKL, and the endodontic bacteria colonizing the root canal appear to induce RANKL expression from bacteria-reactive T-cells, suggesting the possible pathogenic engagement of immune response to endodontic bacteria in the context of developing boneresorptive periapical lesions. PMID:22341072

  4. 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

  5. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma.

    PubMed

    Yang, J; He, J; Wang, J; Cao, Y; Ling, J; Qian, J; Lu, Y; Li, H; Zheng, Y; Lan, Y; Hong, S; Matthews, J; Starbuck, M W; Navone, N M; Orlowski, R Z; Lin, P; Kwak, L W; Yi, Q

    2012-09-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into severe combined immunodeficient (SCID) or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism-activation of p38 signaling in myeloma cells-by which myeloma cells induce osteolytic bone lesions, and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  6. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    PubMed Central

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  7. 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.

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

    PubMed

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

    2015-03-01

    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.

  9. Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord.

    PubMed

    Reginensi, Diego; Carulla, Patricia; Nocentini, Sara; Seira, Oscar; Serra-Picamal, Xavier; Torres-Espín, Abel; Matamoros-Angles, Andreu; Gavín, Rosalina; Moreno-Flores, María Teresa; Wandosell, Francisco; Samitier, Josep; Trepat, Xavier; Navarro, Xavier; del Río, José Antonio

    2015-07-01

    Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.

  10. Diagnosis of a multifocal B cell lymphoma with preceding demyelinating central nervous system lesions by single voxel proton MR spectroscopy

    PubMed Central

    Kuhlmann, T; Schroter, A; Dechent, P; Weber, F; Rustenbeck, H; Fuzesi, L; Bruck, W; Ehrenreich, H; Frahm, J

    2001-01-01

    Single voxel proton magnetic resonance spectroscopy (MRS) provides a rapid non-invasive fingerprint of tissue chemistry. A case history is presented in which a B cell lymphoma with antecedent demyelinating lesions of the CNS was suspected by MRS and confirmed by neuropathological examination and immunoglobulin gene rearrangement.

 PMID:11160483

  11. Fibroblast growth factor signaling in oligodendrocyte-lineage cells facilitates recovery of chronically demyelinated lesions but is redundant in acute lesions.

    PubMed

    Furusho, Miki; Roulois, Aude J; Franklin, Robin J M; Bansal, Rashmi

    2015-10-01

    Remyelination is a potent regenerative process in demyelinating diseases, such as multiple sclerosis, the effective therapeutic promotion of which will fill an unmet clinical need. The development of proregenerative therapies requires the identification of key regulatory targets that are likely to be involved in the integration of multiple signaling mechanisms. Fibroblast growth factor (FGF) signaling system, which comprises multiple ligands and receptors, potentially provides one such target. Since the FGF/FGF receptor (FGFR) interactions are complex and regulate multiple diverse functions of oligodendrocyte lineage cells, it is difficult to predict their overall therapeutic potential in the regeneration of oligodendrocytes and myelin. Therefore, to assess the integrated effects of FGFR signaling on this process, we simultaneously inactivated both FGFR1 and FGFR2 in oligodendrocytes and their precursors using two Cre-driver mouse lines. Acute and chronic cuprizone-induced or lysolecithin-induced demyelination was established in Fgfr1/Fgfr2 double knockout mice (dKO). We found that in the acute cuprizone model, there was normal differentiation of oligodendrocytes and recovery of myelin in the corpus callosum of both control and dKO mice. Similarly, in the spinal cord, lysolecithin-induced demyelinated lesions regenerated similarly in the dKO and control mice. In contrast, in the chronic cuprizone model, fewer differentiated oligodendrocytes and less efficient myelin recovery were observed in the dKO compared to control mice. These data suggest that while cell-autonomous FGF signaling is redundant during recovery of acute demyelinated lesions, it facilitates regenerative processes in chronic demyelination. Thus, FGF-based therapies have potential value in stimulating oligodendrocyte and myelin regeneration in late-stage disease.

  12. 2-Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal-cannabidiol-sensitive receptors on microglial cells.

    PubMed

    Kreutz, Susanne; Koch, Marco; Böttger, Charlotte; Ghadban, Chalid; Korf, Horst-Werner; Dehghani, Faramarz

    2009-02-01

    Endocannabinoids like 2-arachidonoylglycerol (2-AG) exert neuroprotective effects after brain injuries. According to current concepts, these neuroprotective effects are due to interactions between 2-AG and cannabinoid (CB)1 receptors on neurons. Moreover, 2-AG modulates migration and proliferation of microglial cells which are rapidly activated after brain lesion. This effect is mediated via CB2- and abnormal-cannabidiol (abn-CBD)-sensitive receptors. In the present study, we investigated whether the abn-CBD-sensitive receptor on microglial cells contributes to 2-AG-mediated neuroprotection in organotypic hippocampal slice cultures (OHSCs) after excitotoxic lesion induced by NMDA (50 microM) application for 4 h. This lesion caused neuronal damage and accumulation of microglial cells within the granule cell layer. To analyze the role of abn-CBD-sensitive receptors for neuroprotection and microglial cell accumulation, two agonists of the abn-CBD-sensitive receptor, abn-CBD or 2-AG, two antagonists, 1,3-dimethoxy-5-methyl-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen1-yl]-benzene (O-1918) or cannabidiol (CBD), and the CB1 receptor antagonist AM251, were applied to NMDA-lesioned OHSC. Propidium iodide (PI) labeling was used as a marker of degenerating neurons and isolectin B(4) (IB(4)) as a marker of microglial cells. Application of both, abn-CBD or 2-AG to lesioned OHSC significantly decreased the number of IB(4)(+) microglial cells and PI(+) neurons in the dentate gyrus. In contrast to AM251, application of O-1918 or CBD antagonized these effects. When microglial cells were depleted by preincubation of OHSC with the bisphosphonate clodronate (100 microg/mL) for 5 days before excitotoxic lesion, 2-AG and abn-CBD lost their neuroprotective effects. We therefore propose that the endocannabinoid 2-AG exerts its neuroprotective effects via activation of abn-CBD-sensitive receptors on microglial cells.

  13. Breast Cancer Cells Induce Osteolytic Bone Lesions In vivo through a Reduction in Osteoblast Activity in Mice

    PubMed Central

    Gregory, Laura S.; Choi, Wilson; Burke, Leslie; Clements, Judith A.

    2013-01-01

    Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer

  14. Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions.

    PubMed

    Iijima, Keiya; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Puentes, Sandra; Imai, Hideaki; Yoshimoto, Yuhei; Mikuni, Masahiko; Ishizaki, Yasuki

    2015-11-01

    We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases.

  15. Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions.

    PubMed

    Iijima, Keiya; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Puentes, Sandra; Imai, Hideaki; Yoshimoto, Yuhei; Mikuni, Masahiko; Ishizaki, Yasuki

    2015-11-01

    We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases. PMID:26212499

  16. A novel germline mutation in a patient with nevoid basal cell carcinoma syndrome showing cystic lesion in the lung.

    PubMed

    Miyata, Ryo; Kurosawa, Manabu; Sato, Masaaki; Kono, Tomoya; Takubo, Yasutaka; Okai, Shinsaku; Yamada, Keisuke; Shinkura, Reiko; Date, Hiroshi; Matsuda, Fumihiko

    2015-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS) manifests multiple defects involving the skin, endocrine and nervous systems, eyes and bones. Mutations in the patched homologue 1 (PTCH1) gene are the underlying causes of NBCCS, leading to aberrant cell proliferation through constitutive activation of the hedgehog signaling pathway. We identified a novel frameshift mutation (c.1207dupT) of PTCH1 in a NBCCS patient, which might explain multiple cystic lesions and neoplastic growth in the patient. PMID:27081528

  17. 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.

  18. Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions

    PubMed Central

    Vazquez-Martin, Alejandro; López-Bonetc, Eugeni; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Del Barco, Sonia; Martin-Castillo, Begoña; Menendez, Javier A.

    2013-01-01

    Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin (“old drugs”) to their recently recognized CSC targets (“new uses”) within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the “old drugs–new uses” repurposing strategy to open a new CSC-targeted chemoprevention era. PMID:21600837

  19. Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions.

    PubMed

    Vazquez-Martin, Alejandro; López-Bonetc, Eugeni; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Del Barco, Sonia; Martin-Castillo, Begoña; Menendez, Javier A

    2011-01-01

    Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin ("old drugs") to their recently recognized CSC targets ("new uses") within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the "old drugs-new uses" repurposing strategy to open a new CSC-targeted chemoprevention era. PMID:21600837

  20. 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

  1. Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions

    PubMed Central

    Anlauf, M; Perren, A; Henopp, T; Rudolph, T; Garbrecht, N; Schmitt, A; Raffel, A; Gimm, O; Weihe, E; Knoefel, W T; Dralle, H; Heitz, Ph U; Komminoth, P; Klöppel, G

    2007-01-01

    Background Patients with a multiple endocrine neoplasia type 1 (MEN1)‐associated Zollinger–Ellison syndrome (ZES) show multifocal duodenal gastrinomas and precursor lesions. Aims To test these lesions for loss of heterozygosity (LOH) of the MEN1 gene locus on chromosome 11q13, and to investigate whether the MEN1‐related endocrine cell changes also involved somatostatin cells. Material and methods Tissue specimens from six patients with MEN1 and ZES were analysed by immunohistochemistry and immunofluorescence. LOH analysis was performed by fluorescence in situ hybridisation (FISH), using probes containing the MEN1 gene locus and the centromere 11 (C11) region. For simultaneous analysis of hormones and allelic deletions, a combined FISH/immunofluorescence protocol was established. Results 28 of a total of 33 duodenal neuroendocrine tumours (NETs) were gastrin‐producing tumours; 13/28 (46.4%) revealed LOH on 11q13 and/or C11. Five of the NETs were somatostatin‐expressing tumours, two revealing LOH. Allelic loss was detected in tumours as small as 300 μm (gastrin) and 400 μm (somatostatin) in diameter. The gastrin‐producing tumours showed different deletion/retention patterns. Hyperplastic somatostatin cell lesions, similar to those of the gastrin cells, were present in all patients. The hyperplastic lesions of both cell lines consistently retained both 11q13 alleles. Conclusions Allelic deletion of the MEN1 gene may reflect a pivotal event in the development of multifocal gastrin and somatostatin cell neoplasms in the duodenum of patients with MEN1. The observation of distinct deletion patterns in small synchronous tumours supports the concept that each gastrin‐producing tumour in an individual MEN1 patient arises from an independent cell clone. PMID:17135306

  2. Experimental investigation of the scaling of columnar joints.

    PubMed

    Goehring, Lucas; Morris, Stephen W; Lin, Zhenquan

    2006-09-01

    Columnar jointing is a fracture pattern common in igneous rocks in which cracks self-organize into a roughly hexagonal arrangement, leaving behind an ordered colonnade. We report observations of columnar jointing in a laboratory analog system, desiccated corn starch slurries. Using measurements of moisture density, evaporation rates, and fracture advance rates as evidence, we suggest that an advective-diffusive system is responsible for the rough scaling behavior of columnar joints. This theory explains the order of magnitude difference in scales between jointing in lavas and in starches. We investigated the scaling of average columnar cross-sectional areas due to the evaporation rate, the analog of the cooling rate of igneous columnar joints. We measured column areas in experiments where the evaporation rate depended on lamp height and time, in experiments where the evaporation rate was fixed using feedback methods, and in experiments where gelatin was added to vary the rheology of the starch. Our results suggest that the column area at a particular depth is related to both the current conditions, and hysteretically to the geometry of the pattern at previous depths. We argue that there exists a range of stable column scales allowed for any particular evaporation rate.

  3. Experimental investigation of the scaling of columnar joints.

    PubMed

    Goehring, Lucas; Morris, Stephen W; Lin, Zhenquan

    2006-09-01

    Columnar jointing is a fracture pattern common in igneous rocks in which cracks self-organize into a roughly hexagonal arrangement, leaving behind an ordered colonnade. We report observations of columnar jointing in a laboratory analog system, desiccated corn starch slurries. Using measurements of moisture density, evaporation rates, and fracture advance rates as evidence, we suggest that an advective-diffusive system is responsible for the rough scaling behavior of columnar joints. This theory explains the order of magnitude difference in scales between jointing in lavas and in starches. We investigated the scaling of average columnar cross-sectional areas due to the evaporation rate, the analog of the cooling rate of igneous columnar joints. We measured column areas in experiments where the evaporation rate depended on lamp height and time, in experiments where the evaporation rate was fixed using feedback methods, and in experiments where gelatin was added to vary the rheology of the starch. Our results suggest that the column area at a particular depth is related to both the current conditions, and hysteretically to the geometry of the pattern at previous depths. We argue that there exists a range of stable column scales allowed for any particular evaporation rate. PMID:17025716

  4. Experimental investigation of the scaling of columnar joints

    NASA Astrophysics Data System (ADS)

    Goehring, Lucas; Morris, Stephen W.; Lin, Zhenquan

    2006-09-01

    Columnar jointing is a fracture pattern common in igneous rocks in which cracks self-organize into a roughly hexagonal arrangement, leaving behind an ordered colonnade. We report observations of columnar jointing in a laboratory analog system, desiccated corn starch slurries. Using measurements of moisture density, evaporation rates, and fracture advance rates as evidence, we suggest that an advective-diffusive system is responsible for the rough scaling behavior of columnar joints. This theory explains the order of magnitude difference in scales between jointing in lavas and in starches. We investigated the scaling of average columnar cross-sectional areas due to the evaporation rate, the analog of the cooling rate of igneous columnar joints. We measured column areas in experiments where the evaporation rate depended on lamp height and time, in experiments where the evaporation rate was fixed using feedback methods, and in experiments where gelatin was added to vary the rheology of the starch. Our results suggest that the column area at a particular depth is related to both the current conditions, and hysteretically to the geometry of the pattern at previous depths. We argue that there exists a range of stable column scales allowed for any particular evaporation rate.

  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. 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.

  7. A novel method for monitoring functional lesion-specific recruitment of repair proteins in live cells

    PubMed Central

    Woodrick, Jordan; Gupta, Suhani; Khatkar, Pooja; Dave, Kalpana; Levashova, Darya; Choudhury, Sujata; Elias, Hadi; Saha, Tapas; Mueller, Susette; Roy, Rabindra

    2015-01-01

    DNA-protein relationships have been studied by numerous methods, but a particular gap in methodology lies in the study of DNA adduct-specific interactions with proteins in vivo, which particularly affects the field of DNA repair. Using the repair of a well-characterized and ubiquitous adduct, the abasic (AP) site, as a model, we have developed a comprehensive method of monitoring DNA lesion-specific recruitment of proteins in vivo over time. We utilized a surrogate system in which a Cy3-labeled plasmid containing a single AP-site was transfected into cells, and the interaction of the labeled DNA with BER enzymes, including APE1, Polβ, LIG1, and FEN1, was monitored by immunofluorescent staining of the enzymes by Alexafluor-488-conjugated secondary antibody. The recruitment of enzymes was characterized by quantification of Cy3-Alexafluor-488 co-localization. To validate the microscopy-based method, repair of the transfected AP-site DNA was also quantified at various time points post-transfection using a real time PCR-based method. Notably, the recruitment time kinetics for each enzyme were consistent with AP-site repair time kinetics. This microscopy-based methodology is reliable in detecting the recruitment of proteins to specific DNA substrates and can be extended to study other in vivo DNA-protein relationships in any DNA sequence and in the context of any DNA structure in transfectable proliferating or quiescent cells. The method may be applied to a variety of disciplines of nucleic acid transaction pathways, including repair, replication, transcription, and recombination. PMID:25879709

  8. A novel method for monitoring functional lesion-specific recruitment of repair proteins in live cells.

    PubMed

    Woodrick, Jordan; Gupta, Suhani; Khatkar, Pooja; Dave, Kalpana; Levashova, Darya; Choudhury, Sujata; Elias, Hadi; Saha, Tapas; Mueller, Susette; Roy, Rabindra

    2015-05-01

    DNA-protein relationships have been studied by numerous methods, but a particular gap in methodology lies in the study of DNA adduct-specific interactions with proteins in vivo, which particularly affects the field of DNA repair. Using the repair of a well-characterized and ubiquitous adduct, the abasic (AP) site, as a model, we have developed a comprehensive method of monitoring DNA lesion-specific recruitment of proteins in vivo over time. We utilized a surrogate system in which a Cy3-labeled plasmid containing a single AP-site was transfected into cells, and the interaction of the labeled DNA with BER enzymes, including APE1, Polβ, LIG1, and FEN1, was monitored by immunofluorescent staining of the enzymes by Alexafluor-488-conjugated secondary antibody. The recruitment of enzymes was characterized by quantification of Cy3-Alexafluor-488 co-localization. To validate the microscopy-based method, repair of the transfected AP-site DNA was also quantified at various time points post-transfection using a real time PCR-based method. Notably, the recruitment time kinetics for each enzyme were consistent with AP-site repair time kinetics. This microscopy-based methodology is reliable in detecting the recruitment of proteins to specific DNA substrates and can be extended to study other in vivo DNA-protein relationships in any DNA sequence and in the context of any DNA structure in transfectable proliferating or quiescent cells. The method may be applied to a variety of disciplines of nucleic acid transaction pathways, including repair, replication, transcription, and recombination. PMID:25879709

  9. Effect of arsenic and cadmium on the persistence of mutagen-induced DNA lesions in human cells

    SciTech Connect

    Hartmann, A.; Speit, G.

    1996-12-31

    The alkaline single cell gel electrophoresis (SCG test or comet assay) was used to characterize the influence of sodium arsenite (NaAsO{sub 2}) and cadmium sulphate (CdSO{sub 4}) on the persistence of mutagen-induced DNA lesions. Human blood and SV40-transformed fibroblasts (MRC5CV1) were treated for 2 hr with methyl methanesulphonate (MMS) or benzo(a)pyrene (BaP). MMS induced concentration-related DNA damage in white blood cells (WBC) and fibroblasts in similar concentrations. For the induction of DNA damage by BaP, higher concentrations had to be applied to WBC than to the fibroblast cell line. To study the influence of metal ions on the persistence of DNA lesions, treated cells were further incubated for 2 hr in the absence (post-incubation) or presence (posttreatment) of NaAsO{sub 2} or CdSO{sub 4}, BaP- and MMS-induced DNA lesions persisted in both cell types, indicating an inhibition of DNA repair by these metals. The results suggest a strong interaction of arsenic and cadmium with BaP- and MMS-induced DNA repair processes. 34 refs., 5 figs., 2 tabs.

  10. COLUMNAR ORGANIZATION OF SPATIAL PHASE IN VISUAL CORTEX

    PubMed Central

    Wang, Yushi; Jin, Jianzhong; Kremkow, Jens; Lashgari, Reza; Komban, Stanley J.; Alonso, Jose M.

    2014-01-01

    Images are processed in the primary visual cortex by neurons that encode different stimulus orientations and spatial phases. In primates and carnivores, neighboring cortical neurons share similar orientation preferences but spatial phases were thought to be randomly distributed. Here we reveal a columnar organization for spatial phase in cats that shares resemblances with the columnar organization for orientation. For both orientation and phase, the mean difference across vertically aligned neurons was less than 1/4 of a cycle. Cortical neurons showed three times more diversity in phase than orientation preference, however, the average phase of local neuronal populations was similar through the depth of layer 4. We conclude that columnar organization for visual space is not only defined by the spatial location of the stimulus but also by absolute phase. Taken together with previous studies, our results suggest that this phase-visuotopy is responsible for the emergence of orientation maps. PMID:25420070

  11. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability.

    PubMed Central

    Björkerud, S.; Björkerud, B.

    1996-01-01

    Death of intimal tissue may lead to plaque rupture with thrombosis, which is the basis of the most severe clinical consequences of atherosclerosis. Little is known about the mechanisms that promote intimal cell death or its nature. This work was undertaken to elucidate the extent to which, the cell types in which, and where programmed cell death, apoptosis, might occur in atherosclerotic lesions. The material was fibrous or fibro-fatty non-ulcerated lesions from the human thoracic aorta and coronary arteries. Apoptosis was indicated by the in situ labeling of internucleosomally degraded DNA with the TUNEL technique, which has a preference for apoptosis as compared with cell necrosis and was combined with the immunohistochemical typing of cells. Apoptosis was corroborated by morphological criteria on the light and electron microscope levels and by the presence of an apoptosis-specific protein. It was common in the lesions and virtually absent in non-atherosclerotic regions. It occurred in smooth muscle cells subendothelially, in places of the fibrous cap, and in the underlying media, which may destabilize the plaque and promote rupture. Inflammatory cells, ie, macrophages and T cells, appeared abundantly subendothelially, in the fibrous cap, and in the shoulder regions, and apoptosis was common, maybe reflecting a means for quenching of the inflammatory reaction. Many macrophages contained abundant apoptotic material indicative of phagocytosis of apoptotic cells, but the occurrence of apoptosis, even in some of these cells, and of apoptotic material extracellularly and the very high numbers of apoptotic cells that were encountered may indicate insufficient mechanisms for the removal of apoptotic cells in the atherosclerotic lesion. It is not possible to decide as yet whether this is due to overloading with cellular material by inflammation and cell multiplication, to an increased frequency of apoptosis, to a reduction of the removal/degradation of apoptotic material

  12. Sensitivity of the Giant LOop Binary LEsion (GLOBLE) cell survival model on parameters characterising dose rate effects.

    PubMed

    Herr, L; Friedrich, T; Durante, M; Scholz, M

    2015-09-01

    The sensitivity of the Giant LOop Binary LEsion model for cell survival probabilities after arbitrary photon irradiation schedules on its parameters is presented. Since these parameters are closely linked to observable features of cell repair, the modelled influence of the parameters on cell survival gives indications about the relation between cell line-specific repair characteristics and the radiation response. To visualise the general findings about the impact of parameter changes on cell survival probabilities, survival curves for an exemplary cell line are shown. Furthermore, the relative change in the effect of radiation after a change in parameter values is investigated over the range of doses and dose rates usually applied in cell survival experiments.

  13. 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.

  14. Ventromedial hypothalamic lesions change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets

    PubMed Central

    Kiba, Takayoshi; Ishigaki, Yasuhito

    2014-01-01

    Studies in normal rats and ob/ob mice indicated that islet neogenesis does not occur in the intact rodent pancreas. We previously reported that ventromedial hypothalamic (VMH) lesions stimulated cell proliferation of rat pancreatic islet B and acinar cells primarily through a cholinergic receptor mechanism and examined how gene families involved in cell proliferation in total pancreatic tissue are regulated after VMH lesions formation. This study examined how gene families involved in cell proliferation in pancreatic islets alone are regulated after VMH lesions formation. Pancreatic islet RNA was extracted, and differences in gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH-lesioned rats were investigated using DNA microarray and real-time polymerase chain reaction. VMH lesions regulated genes that were involved in functions related to cell cycle and differentiation, growth, binding, apoptosis and morphology in pancreas islets. Real-time polymerase chain reaction also confirmed that gene expression of polo-like kinase 1 (Plk1) and topoisomerase (DNA) II α 170 kDa (Top2a), and stanniocalcin 1 (Stc1) were upregulated at day 3 after the VMH lesions. Ventromedial hypothalamic lesions may change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets. PMID:25658146

  15. 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.

  16. On the scaling and ordering of columnar joints

    NASA Astrophysics Data System (ADS)

    Goehring, Lucas Allan Ziola

    Columnar jointing is a fracture pattern, best known from locations such as the Giant's Causeway, or Fingal's Cave, in which cracks self-organize into a nearly hexagonal arrangement, leaving behind an ordered colonnade. In this thesis observations of columnar jointing are reported from both a controlled laboratory setting, and in cooled lava flows. Experiments were performed in slurries of corn starch and water, which form columnar joints when dried. This drying process is examined in detail, and it is shown how desiccation leads to the propagation of a sharp shrinkage front. In general, but with some significant exceptions, the size of columnar joints is inversely dependent on the speed of this shrinkage front during their formation. The exceptions, which include sudden jumps in column scale, show that hysteresis is also important in choosing the column scale. Novel observations of the 3D structure of joints in starch show that columnar joints do not settle down to a perfect hexagonal pattern, but rather mature into a continuously evolving dynamic pattern. This pattern is scale invariant, and the same statistical distribution of column shapes applies equally to joints in both starch and lava. Field work was performed to study columnar jointing in the basalts of the Columbia River Basalt Group and the island of Staffa, and the more heterogeneous lava flows of Southwestern British Columbia. The widths of columns and the heights of striae (chisel-like markings that record details of cooling) were examined in detail, and these length scales are shown to be inversely proportional to each other. An additional length scale, that of wavy columns, is also first reported here. Based on these measurements, empirical advective-diffusive models are developed to describe the transport of water in a drying starch-cake, and the transport of heat in a cooling lava flow. These models have only a single scaling parameter, the Peclet number, which relates the fracture front velocity

  17. Toward noninvasive microspectrofluorometry of skin lesions for diagnostic and prognostic evaluation of cell metabolism and organelle interactions

    NASA Astrophysics Data System (ADS)

    Hirschberg, Joseph G.; Schachtschabel, Astrid; Kohen, Elli; Kohen, Cahide; Schachtschabel, Dietrich O.

    1995-02-01

    The basic principle of this approach relies on microspectrofluorometric observations of upheavals in the cell's energy metabolism and cell-to-cell metabolic communication in human and mouse melanoma cells. A striking feature is the definition of a highly active nuclear energy metabolism in M8255 human melanoma cells which is characterized by an intense fluorescence response associated with NAD(P) reduction by substrates of glycolysis or the hexose monophosphate shunt. Changes are also expected in the steady state levels of reduced/oxidized NAD(P) in the nuclear, cytoplasmic and mitochondrial compartments, which are probably dependent on ATP levels and distribution (as determined by cell metabolism and eventually the presence of ATP traps). A topographic scanning of skin lesions, either under metabolic steady state conditions or in the presence of permeating substrates, can lead to the recognition of characteristic patterns associated with pigmented and nonpigmented, malignant and nonmalignant skin lesions. The method is, in a way, an extension of microscopic transillumination techniques which have led to the identification of specific patterns associated with such lesions. However, here, a new dimension is added by introduction of fluorescence evaluations. This can represent the first step in a multiparameter approach to the non-invasive in situ fluorescence scan of dermatological lesions by inclusion of: (1) fluorescence excitation and emission spectra; (2) new fluorescence probes of cytoplasmic organelles and nuclear components. Primary emphasis should be placed on the highly active nuclear energy metabolism, which can be triggered to maximum levels when the role of mitochondria as the `cells's policeman' with regard to metabolic control is suppressed by use of topically cytotoxic agents such as the `antipsoriatic' anthralin and dicarboxylic acids used in the local treatment of melanoma. Fluorescence excitation spectroscopy may be of particular advantage in

  18. Genetic and epigenetic changes in vulvar squamous cell carcinoma and its precursor lesions: a review of the current literature.

    PubMed

    Trietsch, Marjolijn D; Nooij, Linda S; Gaarenstroom, Katja N; van Poelgeest, Mariette I E

    2015-01-01

    Vulvar cancer is a relatively rare gynecologic malignancy with an annual incidence in developed countries of approximately 2 per 100,000 women. Vulvar squamous cell carcinoma (VSCC) has two etiological pathways: a high risk human papillomavirus (HPV)-dependent route, which has usual vulvar intraepithelial neoplasia (uVIN) as a precursor lesion, and an HPV-independent route, which is associated with differentiated VIN (dVIN), lichen sclerosus, and genetic alterations, such as TP53 mutations. Research on the molecular etiology of vulvar cancer has increased in the past years, not only regarding genetic alterations, but also epigenetic changes. In genetic alterations, a mutation irreversibly changes the nucleotide sequence of the DNA, or the number of copies of chromosomes per cell is altered. In epigenetics, the nucleotide sequence remains the same but genes can be 'switched' on or off by, for example, DNA methylation or histone modification. We searched the current literature on genetic and epigenetic alterations in VSCC and its precursor lesions. Many studies have reported a higher incidence of somatic mutations in HPV-negative tumors compared to HPV-positive tumors, with TP53 mutations being the most frequent. Allelic imbalances or loss of heterozygosity are more frequently found in higher stages of dysplasia and in invasive carcinomas, but it is not exclusive to HPV-negative tumors. A limited number of studies are available on epigenetic changes in vulvar lesions, with hypermethylation of CDKN2A being the most frequently investigated change. For most genes, hypermethylation occurs more frequently in vulvar squamous cell carcinomas than in precursor lesions. As most studies have focused on HPV infection and TP53 mutations, we suggest that more research should be performed using whole genome or next generation sequencing to determine the true landscape of genetic and epigenetic alterations in vulvar squamous cell carcinoma.

  19. Lesion-induced and activity-dependent structural plasticity of Purkinje cell dendritic spines in cerebellar vermis and hemisphere.

    PubMed

    Gelfo, Francesca; Florenzano, Fulvio; Foti, Francesca; Burello, Lorena; Petrosini, Laura; De Bartolo, Paola

    2016-09-01

    Neuroplasticity allows the brain to encode experience and learn behaviors, and also to re-acquire lost functions after damage. The cerebellum is a suitable structure to address this topic because of its strong involvement in learning processes and compensation of lesion-induced deficits. This study was aimed to characterize the effects of a hemicerebellectomy (HCb) combined or not with the exposition to environmental enrichment (EE) on dendritic spine density and size in Purkinje cell proximal and distal compartments of cerebellar vermian and hemispherical regions. Male Wistar rats were housed in enriched or standard environments from the 21st post-natal day (pnd) onwards. At the 75th pnd, rats were submitted to HCb or sham lesion. Neurological symptoms and spatial performance in the Morris water maze were evaluated. At the end of testing, morphological analyses assessed dendritic spine density, area, length, and head diameter on vermian and hemispherical Purkinje cells. All hemicerebellectomized (HCbed) rats showed motor compensation, but standard-reared HCbed animals exhibited cognitive impairment that was almost completely compensated in enriched HCbed rats. The standard-reared HCbed rats showed decreased density with augmented size of Purkinje cell spines in the vermis, and augmented both density and size in the hemisphere. Enriched HCbed rats almost completely maintained the spine density and size induced by EE. Both lesion-induced and activity-dependent cerebellar plastic changes may be interpreted as "beneficial" brain reactions, aimed to support behavioral performance rescuing. PMID:26420278

  20. SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions

    PubMed Central

    Beneteau, Claire; Cavé, Hélène; Moncla, Anne; Dorison, Nathalie; Munnich, Arnold; Verloes, Alain; Leheup, Bruno

    2009-01-01

    We report five cases of multiple giant cell lesions in patients with typical Noonan syndrome. Such association has frequently been referred to as Noonan-like/multiple giant cell (NL/MGCL) syndrome before the molecular definition of Noonan syndrome. Two patients show mutations in PTPN11 (p.Tyr62Asp and p.Asn308Asp) and three in SOS1 (p.Arg552Ser and p.Arg552Thr). The latter are the first SOS1 mutations reported outside PTPN11 in NL/MGCL syndrome. MGCL lesions were observed in jaws (‘cherubism') and joints (‘pigmented villonodular synovitis'). We show through those patients that both types of MGCL are not PTPN11-specific, but rather represent a low penetrant (or perhaps overlooked) complication of the dysregulated RAS/MAPK signaling pathway. We recommend discarding NL/MGCL syndrome from the nosology, as this presentation is neither gene-nor allele-specific of Noonan syndrome; these patients should be described as Noonan syndrome with MGCL (of the mandible, the long bone…). The term cherubism should be used only when multiple giant cell lesions occur without any other clinical and molecular evidence of Noonan syndrome, with or without mutations of the SH3BP2 gene. PMID:19352411

  1. Nematic-columnar phase transition in oriented hard rectangles

    NASA Astrophysics Data System (ADS)

    Nath, Trisha; Dhar, Deepak; Rajesh, R.

    We consider an assembly of monodispersed hard rectangles of size 2 × d on a square lattice with only hard core interactions amongst them. The long axes of the rectangles can be oriented along the horizontal or vertical directions. For large enough aspect ratio, it is known that this system undergoes three phase transitions as the density (ρ) of rectangles is increased: first an isotropic-nematic transition (at ρ1*), second a nematic-columnar transition (at ρ2*), and third a columnar-sublattice transition (at ρ3*). In the nematic phase, only the orientational symmetry is broken. The columnar and sublattice phases correspond to additional broken translational symmetries along one (perpendicular to the nematic orientation) and both directions respectively. Interestingly, the critical value ρ2* remains finite, approximately 0 . 73 , even as d --> ∞ . We develop a systematic high density expansion for the surface tension between two differently-ordered columnar phases. Keeping only the first order perturbative correction term and setting this surface tension to zero, we get an estimate of ρ2* in excellent agreement with estimates from Monte Carlo simulations, for all d >= 2 .

  2. 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)).

  3. Investigations of electromagnetic scattering by columnar ice crystals

    NASA Technical Reports Server (NTRS)

    Weil, H.; Senior, T. B. A.

    1976-01-01

    An integral equation approach was developed to determine the scattering and absorption of electromagnetic radiation by thin walled cylinders of arbitrary cross-section and refractive index. Based on this method, extensive numerical data was presented at infrared wavelengths for hollow hexagonal cross section cylinders which simulate columnar sheath ice crystals.

  4. Flavobacterium Columnare studies in rainbow trout (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare (Fc) is the causative agent for columnaris disesase and is a problem for several fish species. Recently, columnaris has been recognized as an emerging problem in farmed trout cultured within the Hagerman valley of Idaho. The aim of this study was two-fold. First determine...

  5. 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. ...

  6. 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 ...

  7. Antibodies to Endothelial Cell Growth Factor and Obliterative Microvascular Lesions in Synovia of Patients with Antibiotic-Refractory Lyme Arthritis

    PubMed Central

    Londoño, Diana; Cadavid, Diego; Drouin, Elise E.; Strle, Klemen; McHugh, Gail; Aversa, John; Steere, Allen C.

    2014-01-01

    Objective Endothelial cell growth factor (ECGF) was recently identified as the first autoantigen known to be a target of T and B cell responses in about 20% of patients with antibiotic-refractory Lyme arthritis. The goal of the current study was to look for a pathologic correlate between ECGF autoantibody responses and histologic findings in synovial tissue. Methods Synovial tissue was examined from 14 patients with antibiotic-refractory Lyme arthritis and 6 patients with other forms of chronic inflammatory arthritis, primarily rheumatoid arthritis. The tissue sections were subjected to chemical and immunostaining, and IgG antibody responses to ECGF were determined by ELISA. Each finding was ranked for statistical analysis. Results In each disease, synovial tissue showed synovial hypertrophy, vascular proliferation, immune cell infiltrates, and fibrosis. However, among the 14 patients with antibiotic-refractory arthritis, 8 (57%) had obliterative microvascular lesions in the tissue compared with none of 6 patients with other forms of chronic inflammatory arthritis (P=0.04). Among the patients with Lyme arthritis, 5 (36%) had autoantibody responses to ECGF, and all 5 had obliterative lesions compared with only 3 of 9 patients who lacked ECGF antibody responses (P=0.009). Moreover, the magnitude of ECGF antibody responses correlated directly with the extent of obliterative lesions (P=0.02) and with greater vascularity in the tissue (P=0.05). Conclusions The correlations of ECGF autoantibody reactivity with obliterative microvascular lesions imply that these autoantibodies may be involved in the obliterative process, suggesting that anti-ECGF antibodies have specific pathologic consequences in synovial tissue in patients with antibiotic-refractory Lyme arthritis. PMID:24623727

  8. Peroxisome-proliferator activator receptor-gamma activation decreases attachment of endometrial cells to peritoneal mesothelial cells in an in vitro model of the early endometriotic lesion.

    PubMed

    Kavoussi, S K; Witz, C A; Binkley, P A; Nair, A S; Lebovic, D I

    2009-10-01

    The aim of this study was to investigate whether peroxisome proliferator-activated receptor (PPAR)-gamma activation has an effect on the attachment of endometrial cells to peritoneal mesothelial cells in a well-established in vitro model of the early endometriotic lesion. The endometrial epithelial cell line EM42 and mesothelial cell line LP9 were used for this study. EM42 cells, LP9 cells or both were treated with the PPAR-gamma agonist ciglitazone (CTZ) at varying concentrations (10, 20 and 40 microM) x 48 h with subsequent co-culture of EM42 and LP9 cells. The rate of EM42 attachment and invasion through LP9 cells was then assessed and compared with control (EM42 and LP9 cells co-cultured without prior treatment with CTZ). Next, attachment of CTZ-treated and untreated EM42 cells to hyaluronic acid (HA), a cell adhesion molecule (CAM) on peritoneal mesothelial cells, were assessed. Although there was no difference in EM42 attachment when LP9 cells alone were treated with CTZ, treatment of EM42 cells with 40 microM CTZ decreased EM42 attachment to LP9 cells by 27% (P < 0.01). Treatment of both EM42 and LP9 cells with 40 microM CTZ decreased EM42 attachment to LP9 by 37% (P < 0.01). Treatment of EM42 cells with 40 microM CTZ decreased attachment to HA by 66% (P = 0.056). CTZ did not decrease invasion of EM42 cells through the LP9 monolayer. CTZ may inhibit EM42 cell proliferation. In conclusion, CTZ significantly decreased EM42 attachment to LP9 cells and HA in an in vitro model of the early endometriotic lesion. PMID:19643817

  9. 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

  10. Impact of the accuracy of automatic segmentation of cell nuclei clusters on classification of thyroid follicular lesions.

    PubMed

    Jung, Chanho; Kim, Changick

    2014-08-01

    Automatic segmentation of cell nuclei clusters is a key building block in systems for quantitative analysis of microscopy cell images. For that reason, it has received a great attention over the last decade, and diverse automatic approaches to segment clustered nuclei with varying levels of performance under different test conditions have been proposed in literature. To the best of our knowledge, however, so far there is no comparative study on the methods. This study is a first attempt to fill this research gap. More precisely, the purpose of this study is to present an objective performance comparison of existing state-of-the-art segmentation methods. Particularly, the impact of their accuracy on classification of thyroid follicular lesions is also investigated "quantitatively" under the same experimental condition, to evaluate the applicability of the methods. Thirteen different segmentation approaches are compared in terms of not only errors in nuclei segmentation and delineation, but also their impact on the performance of system to classify thyroid follicular lesions using different metrics (e.g., diagnostic accuracy, sensitivity, specificity, etc.). Extensive experiments have been conducted on a total of 204 digitized thyroid biopsy specimens. Our study demonstrates that significant diagnostic errors can be avoided using more advanced segmentation approaches. We believe that this comprehensive comparative study serves as a reference point and guide for developers and practitioners in choosing an appropriate automatic segmentation technique adopted for building automated systems for specifically classifying follicular thyroid lesions.

  11. Leukemic manifestation of blastic plasmacytoid dendritic cell neoplasm lacking skin lesion : a borderline case between acute monocytic leukemia.

    PubMed

    Takiuchi, Yoko; Maruoka, Hayato; Aoki, Kazunari; Kato, Aiko; Ono, Yuichiro; Nagano, Seiji; Arima, Hiroshi; Inoue, Daichi; Mori, Minako; Tabata, Sumie; Yanagita, Soshi; Matsushita, Akiko; Nishio, Mari; Imai, Yukihiro; Imai, Yukihiro; Ito, Kiminari; Fujita, Haruyuki; Kadowaki, Norimitsu; Ishikawa, Takayuki; Takahashi, Takayuki

    2012-01-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with a poor prognosis. We encountered a unique case of BPDCN that was leukemic at presentation without skin lesion and expressed CD33 antigen. A 74-year-old man was admitted because of dyspnea. Physically, hepatosplenomegaly, but not skin lesions and superficial lymph node swelling, was noted. The white blood count was 33.6 × 10(9)/L with 19% giant abnormal cells. These cells were positive for CD4, CD86, CD123 (bright), BDCA-2, and HLA-DR, but negative for CD1a, CD3, CD11b, CD11c, CD13, CD14, CD19, CD64, and CD68. From these findings, a diagnosis of BPDCN was made. In terms of unusual expression, these tumor cells were positive for CD33 but negative for CD56. The karyotype was 47, XY, t(6;8) (p21;q24), + r. We performed combination chemotherapy (Ara-C + VP-16 + MIT), which resulted in a marked reduction of tumor cells and improvement of the dyspnea. On day 16, however, he died of sepsis due to Bacillus cereus. The clinical picture of this patient is unusual and may provide new information on the clinicopathology of BPDCN. PMID:23037626

  12. Quantitative, real-time analysis of base excision repair activity in cell lysates utilizing lesion-specific molecular beacons.

    PubMed

    Svilar, David; Vens, Conchita; Sobol, Robert W

    2012-01-01

    We describe a method for the quantitative, real-time measurement of DNA glycosylase and AP endonuclease activities in cell nuclear lysates using base excision repair (BER) molecular beacons. The substrate (beacon) is comprised of a deoxyoligonucleotide containing a single base lesion with a 6-Carboxyfluorescein (6-FAM) moiety conjugated to the 5'end and a Dabcyl moiety conjugated to the 3' end of the oligonucleotide. The BER molecular beacon is 43 bases in length and the sequence is designed to promote the formation of a stem-loop structure with 13 nucleotides in the loop and 15 base pairs in the stem. When folded in this configuration the 6-FAM moiety is quenched by Dabcyl in a non-fluorescent manner via Förster Resonance Energy Transfer (FRET). The lesion is positioned such that following base lesion removal and strand scission the remaining 5 base oligonucleotide containing the 6-FAM moiety is released from the stem. Release and detachment from the quencher (Dabcyl) results in an increase of fluorescence that is proportionate to the level of DNA repair. By collecting multiple reads of the fluorescence values, real-time assessment of BER activity is possible. The use of standard quantitative real-time PCR instruments allows the simultaneous analysis of numerous samples. The design of these BER molecular beacons, with a single base lesion, is amenable to kinetic analyses, BER quantification and inhibitor validation and is adaptable for quantification of DNA Repair activity in tissue and tumor cell lysates or with purified proteins. The analysis of BER activity in tumor lysates or tissue aspirates using these molecular beacons may be applicable to functional biomarker measurements. Further, the analysis of BER activity with purified proteins using this quantitative assay provides a rapid, high-throughput method for the discovery and validation of BER inhibitors.

  13. CD4+ T cells defined by their Vβ T cell receptor expression are associated with immunoregulatory profiles and lesion size in human leishmaniasis

    PubMed Central

    Keesen, T S L; Antonelli, L R V; Faria, D R; Guimarães, L H; Bacellar, O; Carvalho, E M; Dutra, W O; Gollob, K J

    2011-01-01

    Leishmaniasis is caused by infection with the protozoan parasite, Leishmania, that parasitizes human cells, and the cellular immune response is essential for controlling infection. In order to measure the host T cell response to Leishmania infection, we have measured the expansion, activation state and functional potential of specific T cells as identified by their T cell receptor Vβ region expression. In a group of cutaneous leishmaniasis (CL) patients, we evaluated these characteristics in nine different T cell subpopulations as identified by their Vβ region expression, before and after specific Leishmania antigen stimulation. Our results show: (1) an increase in CD4+ T cells expressing Vβ 5·2 and Vβ 24 in CL compared to controls; (2) a Leishmania antigen-induced increase in CD4+ T cells expressing Vβ 5·2, 11, 12 and 17; (3) a profile of previous activation of CD4+ Vβ 5·2-, 11- and 24-positive T cells, with higher expression of CD45RO, HLA-DR, interferon-γ, tumour necrosis factor-α and interleukin-10 compared to other Vβ-expressing subpopulations; (4) a positive correlation between higher frequencies of CD4+Vβ5·2+ T cells and larger lesions; and (5) biased homing of CD4+ T cells expressing Vβ 5·2 to the lesion site. Given that CL disease involves a level of pathology (ulcerated lesions) and is often followed by long-lived protection and cure, the identification of specific subpopulations active in this form of disease could allow for the discovery of immunodominant Leishmania antigens important for triggering efficient host responses against the parasite, or identify cell populations most involved in pathology. PMID:21726211

  14. Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats.

    PubMed

    Cai, Jingli; Yang, Ming; Poremsky, Elizabeth; Kidd, Sarah; Schneider, Jay S; Iacovitti, Lorraine

    2010-07-01

    Cell replacement therapy could be an important treatment strategy for Parkinson's disease (PD), which is caused by the degeneration of dopamine neurons in the midbrain (mDA). The success of this approach greatly relies on the discovery of an abundant source of cells capable of mDAergic function in the brain. With the paucity of available human fetal tissue, efforts have increasingly focused on renewable stem cells. Human induced pluripotent stem (hiPS) cells offer great promise in this regard. If hiPS cells can be differentiated into authentic mDA neuron, hiPS could provide a potential autologous source of transplant tissue when generated from PD patients, a clear advantage over human embryonic stem (hES) cells. Here, we report that mDA neurons can be derived from a commercially available hiPS cell line, IMR90 clone 4, using a modified hES differentiation protocol established in our lab. These cells express all the markers (Lmx1a, Aldh1a1, TH, TrkB), follow the same mDA lineage pathway as H9 hES cells, and have similar expression levels of DA and DOPAC. Moreover, when hiPS mDA progenitor cells are transplanted into 6-OHDA-lesioned PD rats, they survive long term and many develop into bona fide mDA neurons. Despite their differentiation and integration into the brain, many Nestin+ tumor-like cells remain at the site of the graft. Our data suggest that as with hES cells, selecting the appropriate population of mDA lineage cells and eliminating actively dividing hiPS cells before transplantation will be critical for the future success of hiPS cell replacement therapy in PD patients.

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

    SciTech Connect

    Morales-Ramirez, P.; Vallarino-Kelly, T.; Rodriguez-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.

  16. The natural history of benign lymphoepithelial lesion of the salivary gland in which there is a monoclonal population of B cells. A report of two cases.

    PubMed

    Falzon, M; Isaacson, P G

    1991-01-01

    In two patients, a diagnosis of benign lymphoepithelial lesion of the salivary gland was followed by the development of extrasalivary gland lymphoma after 10- and 9-year intervals, respectively. On review, immunohistochemistry revealed immunoglobulin light-chain restriction in the initial biopsy in each case and there was both morphological and immunohistochemical evidence linking the extrasalivary gland lymphoma with the initial lesion. It is argued that in the presence of a monoclonal B-cell population, a diagnosis of benign lymphoepithelial lesion is inappropriate. These patients fulfill the criteria for a diagnosis of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue and should be treated accordingly.

  17. [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.

  18. 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.

  19. 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. PMID:27574323

  20. Response Gene to Complement 32 Promotes Vascular Lesion Formation through Stimulation of Smooth Muscle Cell Proliferation and Migration

    PubMed Central

    Wang, Jia-Ning; Shi, Ning; Xie, Wei-bing; Guo, Xia; Chen, Shi-You

    2011-01-01

    Objective The objectives of this study are to determine the role of response gene to complement 32 (RGC-32) in vascular lesion formation after experimental angioplasty and to explore the underlying mechanisms. Methods and Results Using a rat carotid artery balloon-injury model, we documented for the first time that neointima formation was closely associated with a significantly increased expression of RGC-32 protein. shRNA Knockdown of RGC-32 via adenovirus (Ad)-mediated gene delivery dramatically inhibited the lesion formation by 62% as compared to control groups 14 days after injury. Conversely, RGC-32 overexpression significantly promoted the neointima formation by 33%. Gain and loss of function studies in primary culture of rat aortic smooth muscle cells (RASMCs) indicated that RGC-32 is essential for both the proliferation and migration of RASMCs. RGC-32 induced RASMC proliferation by enhancing p34CDC2 activity. RGC-32 stimulated the migration of RASMC via inducing focal adhesion contact and stress fiber formation. These effects were caused by the enhanced ROKα activity due to RGC-32-induced downregulation of Rad GTPase. Conclusions RGC-32 plays an important role in vascular lesion formation following vascular injury. Increased RGC-32 expression in vascular injury appears to be a novel mechanism underlying the migration and proliferation of vascular SMCs. Therefore, targeting RGC-32 is a potential therapeutic strategy for the prevention of vascular remodeling in proliferative vascular diseases. PMID:21636805

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

    PubMed Central

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

    2016-01-01

    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. DOI: http://dx.doi.org/10.7554/eLife.12034.001 PMID:26809587

  2. 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.

  3. 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

  4. Numerical Investigation of Buoyancy-Induced Columnar Vortices

    NASA Astrophysics Data System (ADS)

    Malaya, Nicholas; Stogner, Roy; Moser, Robert

    2014-11-01

    Buoyancy driven columnar vortices arise naturally in the atmosphere. A new energy harvesting approach makes use of this phenomenon by creating and anchoring the vortices artificially and extracting energy from them. In this talk, we explore the characteristics of these ``solar vortices'' through numerical simulation. Computational models of the turning vane system used to generate the solar vortex and the turbine used to extract energy have been developed. The formulation of these models and their validation against available experimental measurements will be discussed, as will the details of the columnar vortex structure and its interaction with the turbine. In addition, the computational models are being used to optimize the turning vane configuration and the turbine characteristics to maximize the power extraction, and to characterize the effects of environmental conditions such as cross winds and topography. Preliminary results from these studies will also be presented. This work supported by the Department of Energy [ARPA-E] under Award Number [DE-FOA-0000670].

  5. Detection of Intranasally Delivered Bone Marrow-Derived Mesenchymal Stromal Cells in the Lesioned Mouse Brain: A Cautionary Report

    PubMed Central

    Chartoff, Elena H.; Damez-Werno, Diane; Sonntag, Kai C.; Hassinger, Linda; Kaufmann, Daniel E.; Peterson, Jesse; McPhie, Donna; Cataldo, Anne M.; Cohen, Bruce M.

    2011-01-01

    Bone marrow-derived mesenchymal stromal cells (MSCs) hold promise for autologous treatment of neuropathologies. Intranasal delivery is relatively noninvasive and has recently been reported to result in transport of MSCs to the brain. However, the ability of MSCs to migrate from nasal passages to sites of neuropathology and ultimately survive has not been fully examined. In this paper, we harvested MSCs from transgenic mice expressing enhanced green fluorescent protein (cells hereafter referred to as MSC-EGFP) and delivered them intranasally to wild-type mice sustaining mechanical lesions in the striatum. Using fluorescent, colorimetric, and ultrastructural detection methods, GFP-expressing cells were undetectable in the brain from 3 hours to 2 months after MSC delivery. However, bright autofluorescence that strongly resembled emission from GFP was observed in the olfactory bulb and striatum of lesioned control and MSC-EGFP-treated mice. In a control experiment, we directly implanted MSC-EGFPs into the mouse striatum and detected robust GFP expression 1 and 7 days after implantation. These findings suggest that—under our conditions—intranasally delivered MSC-EGFPs do not survive or migrate in the brain. Furthermore, our observations highlight the necessity of including appropriate controls when working with GFP as a cellular marker. PMID:22190964

  6. Quantum depinning of flux lines from columnar defects

    SciTech Connect

    Chudnovsky, E.M. ); Ferrera, A.; Vilenkin, A. )

    1995-01-01

    The depinning of a flux line from a columnar defect is studied within the path-integral approach. Instantons of the quantum field theory in 1+1 dimensions are computed for the flux line whose dynamics is dominated by the Magnus force. The universal temperature dependence of the decay rate in the proximity of the critical current is obtained. This problem provides an example of macroscopic quantum tunneling, which is accessible to the direct comparison between theory and experiment.

  7. 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.

  8. Extragastric Dieulafoy's lesion

    PubMed Central

    Gauci, James; Galea, Samuel; Galea, Joseph; Schembri, Mark

    2014-01-01

    A 74-year-old man on warfarin for aortic valve replacement presented with recurrent episodes of melaena. An initial oesophagogastroduodenoscopy (OGD) was normal, as were red cell scanning and colonoscopy. It was a third OGD that revealed the cause of the melaena—a vascular lesion in the duodenum, at the junction between D1 and D2. An extragastric Dieulafoy's lesion was diagnosed, and the lesion was injected with epinephrine and tattooed. Over the following months, episodes of bleeding recurred despite further attempts at injection. Percutaneous radiologically assisted embolisation of the gastroduodenal artery, and eventually duodenotomy and oversuturing of the lesion were performed to no avail. The patient has undergone over 10 endoscopies, and has received over 70 units of packed red cells to date, since his initial presentation 6 years ago. Attempts to stop the bleeding permanently have been difficult, highlighting the complexity of managing such a lesion. PMID:25216921

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

    PubMed

    Evenhuis, Jason P; LaFrentz, Benjamin R

    2016-08-01

    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. PMID:27503917

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

    PubMed

    Evenhuis, Jason P; LaFrentz, Benjamin R

    2016-08-01

    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.

  11. Experimental xenoimplantation of antlerogenic cells into mandibular bone lesions in rabbits: two-year follow-up.

    PubMed

    Cegielski, Marek; Dziewiszek, Wojciech; Zabel, Maciej; Dziegiel, Piotr; Kuryszko, Jan; Izykowska, Ilona; Zatoński, Maciej; Bochnia, Marek

    2010-01-01

    Different types of cells require activation, and take part in annual, dynamic growth of deer antlers. Stem cells play the most important role in this process. This report shows the results of a two-year long observation of xenogenic implant of antlerogenic stem cells (cell line MIC-1). The cells were derived from growing antler of a deer (Cervus elaphus), seeded onto Spongostan and placed in postoperative lesions of mandibular bones of 15 experimental rabbits. The healing process observed in the implantation sites in all rabbits was normal, and no local inflammatory response was ever observed. Histological and immunohistochemical evaluations were performed after 1, 2, 6, 12 and 24 months, and confirmed the participation of xenogenic cells in the regeneration processes, as well as a lack of rejection of the implants. The deficiencies in the bones were replaced by newly formed, thick fibrous bone tissue that underwent mineralization and was later remodelled into lamellar bone. The results of the experiment with rabbits allow us to believe that antlerogenic cells could be used in reconstruction of bone tissues in other species as well.

  12. 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

  13. 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.

  14. Imaging characteristic analysis of metastatic spine lesions from breast, prostate, lung, and renal cell carcinomas for surgical planning: Osteolytic versus osteoblastic

    PubMed Central

    Reddington, Justin A.; Mendez, Gustavo A.; Ching, Alex; Kubicky, Charlotte Dai; Klimo, Paul; Ragel, Brian T.

    2016-01-01

    Background: Surgeons treating metastatic spine disease can use computed tomography (CT) imaging to determine whether lesions are osteolytic, osteoblastic, or mixed. This enables treatment that considers the structural integrity of the vertebral body (VB), which is impaired with lytic lesions but not blastic lesions. The authors analyzed CT imaging characteristics of spine metastasis from breast, lung, prostate, and renal cell carcinomas (RCCs) to determine the metastasis patterns of each of these common tumors. Methods: The authors identified patients with metastatic spine disease treated during a 3-year period. Variables studied included age, sex, and cancer type. Lesions from breast, lung, prostate, and RCC primary lesions were selected for imaging analysis. Results: Sixty-six patients were identified: 17 had breast metastasis, 14 prostate, 18 lung, and 17 RCC. Breast cancer metastasis involved 33% of VBs with 56%, 20%, and 24% osteolytic, osteoblastic, and mixed, respectively. Prostate cancer metastasis involved 35% of VBs with 14%, 62%, and 24% osteolytic, osteoblastic, and mixed, respectively. Lung cancer metastasis involved 13% of VBs with 64%, 33%, and 3% osteolytic, osteoblastic, and mixed, respectively. RCC metastasis involved 11% of VBs with 91%, 7%, and 2% osteolytic, osteoblastic, and mixed lesions, respectively. Conclusions: To improve surgical planning, we advocate the use of CT prior to surgery to evaluate whether spine metastases are osteolytic or osteoblastic. In cases of osteolytic lesions, the concern is of segmental instability requiring reconstruction and the risk for screw pull out should instrumentation be considered. In cases of osteoblastic lesions, surgeons should consider debulking dense bone. PMID:27274410

  15. Columnar Processing in Primate pFC: Evidence for Executive Control Microcircuits

    PubMed Central

    Opris, Ioan; Hampson, Robert E.; Gerhardt, Greg A.; Berger, Theodore W.; Deadwyler, Sam A.

    2013-01-01

    A common denominator for many cognitive disorders of human brain is the disruption of neural activity within pFC, whose structural basis is primarily interlaminar (columnar) microcircuits or “mini-columns.” The importance of this brain region for executive decision-making has been well documented; however, because of technological constraints, the minicolumnar basis is not well understood. Here, via implementation of a unique conformal multielectrode recording array, the role of interlaminar pFC minicolumns in the executive control of task-related target selection is demonstrated in nonhuman primates performing a visuomotor DMS task. The results reveal target-specific, interlaminar correlated firing during the decision phase of the trial between multielectrode recording array-isolated minicolumnar pairs of neurons located in parallel in layers 2/3 and layer 5 of pFC. The functional significance of individual pFC minicolumns (separated by 40 μm) was shown by reduced correlated firing between cell pairs within single minicolumns on error trials with inappropriate target selection. To further demonstrate dependence on performance, a task-disrupting drug (cocaine) was administered in the middle of the session, which also reduced interlaminar firing in minicolumns that fired appropriately in the early (nondrug) portion of the session. The results provide a direct demonstration of task-specific, real-time columnar processing in pFC indicating the role of this type of microcircuit in executive control of decision-making in primate brain. PMID:23016850

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

    PubMed

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

    2016-05-01

    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. PMID:27120162

  17. Columnar processing in primate pFC: evidence for executive control microcircuits.

    PubMed

    Opris, Ioan; Hampson, Robert E; Gerhardt, Greg A; Berger, Theodore W; Deadwyler, Sam A

    2012-12-01

    A common denominator for many cognitive disorders of human brain is the disruption of neural activity within pFC, whose structural basis is primarily interlaminar (columnar) microcircuits or "minicolumns." The importance of this brain region for executive decision-making has been well documented; however, because of technological constraints, the minicolumnar basis is not well understood. Here, via implementation of a unique conformal multielectrode recording array, the role of interlaminar pFC minicolumns in the executive control of task-related target selection is demonstrated in nonhuman primates performing a visuomotor DMS task. The results reveal target-specific, interlaminar correlated firing during the decision phase of the trial between multielectrode recording array-isolated minicolumnar pairs of neurons located in parallel in layers 2/3 and layer 5 of pFC. The functional significance of individual pFC minicolumns (separated by 40 μm) was shown by reduced correlated firing between cell pairs within single minicolumns on error trials with inappropriate target selection. To further demonstrate dependence on performance, a task-disrupting drug (cocaine) was administered in the middle of the session, which also reduced interlaminar firing in minicolumns that fired appropriately in the early (nondrug) portion of the session. The results provide a direct demonstration of task-specific, real-time columnar processing in pFC indicating the role of this type of microcircuit in executive control of decision-making in primate brain. PMID:23016850

  18. 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

  19. 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

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

    PubMed

    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

  1. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers. PMID:27390104

  2. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers.

  3. 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

  4. 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 Central

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

    2015-01-01

    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. PMID:25800594

  5. 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

    2015-02-01

    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.

  6. 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.

  7. 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.

  8. Tenosynovial giant cell tumor presenting as a parotid gland mass: Expanding the differential diagnosis of giant cell-rich lesions in salivary glands.

    PubMed

    Guo, Ling; Qasem, Shadi; Bergman, Simon; Salih, Ziyan T

    2014-01-01

    Tenosynovial giant cell tumors (TGCT) are rare benign soft tissue tumors affecting mostly young adults. The most common affected sites include the knee, ankle, elbow, shoulder, and fingers. The temporomandibular joint is occasionally affected. Herein, we report a case of a 31-year-old Caucasian male who presented clinically with a parotid gland mass. The initial clinical and radiological work-up failed to reveal any involvement of the adjacent temporomandibular joint. Fine-needle aspiration revealed a cellular tumor composed of mononuclear and multinucleated giant cells with fibrosis and hemosiderin deposition. This was subsequently found to be a TGCT arising from the temporomandibular joint. Giant cell-rich lesions are uncommon in salivary glands. Herein, we describe the cytomorphology and clinico-radiographic features of this tumor with emphasis on the differential diagnosis of giant cell-rich lesions presenting in salivary glands. Despite its rare occurrence, this entity should be considered when giant cells are prominent in specimens acquired from this location.

  9. Apparent mesonephric duct (rete anlage) origin for cysts and proliferative epithelial lesions in the mouse ovary.

    PubMed

    Long, Gerald G

    2002-01-01

    Ovaries and adjacent parovarian (mesovarial) tissues of CD-1 mice of various ages were examined to characterize cystic and proliferative epithelial lesions of the ovary and parovarian tissues. Ovaries and adjacent tissues from 6 mice each at approximately 3 and 8 months of age were processed for light microscopy and step-sections (50-micron intervals) of the entire tissue were examined. Tissues were collected from 40 mice each at 16 through 24 months of age and 3 step sections per mouse were examined. Mesonephric duct remnants were found in all mice at 3 and 8 months. Ducts were usually in the mesovarial adipose tissue and near or within the ovarian hilus and were often loosely associated with smooth muscle of the mesovarial ligament. The epithelium of the ducts varied from low cuboidal to columnar, occasional individual cells were ciliated, and small papillary configurations of epithelium were occasionally present. Ducts were dilated (> 1 mm) more often in mice at 8 months compared to 3 months, and some were continuous with cystic spaces within the ovaries. As mice aged (16-24 months), dilation and cystic change in ducts and associated compression of ovarian tissue away from the ovarian hilus became common. The epithelium of dilated ducts was generally flattened, but foci of cuboidal to columnar epithelium and/or occasional ciliated cells were present. Many ducts contained foci of hyperplastic and/or hypertrophic epithelium, and papillary projections of epithelium were occasionally found. Some of the latter lesions were consistent with a diagnosis of papillary cystadenoma. Hyperplasia of associated fibromuscular stroma was limited to a few apparently extraovarian ducts. The results of this study indicate that remnant mesonephric ductular structures are common in and adjacent to the ovaries of CD-1 mice. As mice age, these ducts become dilated and, in some, the epithelium becomes hyperplastic and/or hyperptrophic. These mesonephric duct remnants appear to be a

  10. Excision repair of bulky lesions in the DNA of mammalian cells

    SciTech Connect

    Setlow, R B; Grist, E

    1980-01-01

    The report examines the process of excision repair of pyrimidine dimers from uv-irradiated and chemically challenged human cells. It is shown by means of a sensitive endonuclease assay that the amount of excision observed depends upon the isotope used to label cells, and that XP heterozygotes are between normals and XPs. (ACR)

  11. Unravelling columnar joints temperatures: a thermo-mechanical experimental approach

    NASA Astrophysics Data System (ADS)

    Lavallée, Yan; Lamur, Anthony; Iddon, Fiona E.; Kendrick, Jackie E.; Hornby, Adrian J.; Eggertson, Gudjon H.; Von Aulock, Felix W.; Wadsworth, Fabian B.

    2016-04-01

    Columnar joints are a widespread, spectacular volcanic phenomenon representing a complex cracking pattern induced by contraction of the lava upon cooling. The hexagonal geometry results from the complex interaction between heat dissipation, contraction and tensile fracturing of the material. While the formation mechanism is nowadays fairly well constrained, very little is known on the temperature at which these features form. Here, we present the results of a novel type of thermo-mechanical experiment, in which the ends of 16 mm rods of basalt were locked into position during cooling at different rates. We monitored the stress build-up and temperature within the samples in order to constrain the temperature of columnar jointing. Our experiments were applied to basaltic rocks sampled on a lava flow at the base of Eyjafjallajoküll volcano in Iceland. Results demonstrate that thermal contraction upon cooling triggers microscopic fracturing (at ~820 °C) that quickly evolves into localised macroscopic fracturing at 750-780 °C. Striaes observed along fracture planes can hence be interpreted as the reflection of this two-stage fracture propagation dynamics. We emphasize that columnar jointing occurs well within the solid state of volcanic rocks, not in a molten regime. These results are supported by complementary analysis of the expansion coefficient of these lavas as well as strain-to-failure acquired during Brazilian tensile tests. The nonlinearity of the coefficient of expansion has important implications for the development of a permeable network. At higher temperatures, micro-fracturing is caused by a quasi-linear coefficient of expansion, leading to a small increase in permeability. As cooling occurs, the coefficient of expansion drops increasingly rapidly, leading to an increasingly faster developing permeable network, which is controlled in-part by the scale of the columns that influences crack aperture opening. Our findings hence have implications in volcanic

  12. A discotic disguised as a smectic: A hybrid columnar bragg glass

    PubMed

    Saunders; Radzihovsky; Toner

    2000-11-13

    We show that discotics, lying deep in the columnar phase, can exhibit an x-ray scattering pattern which mimics that of a somewhat unusual smectic liquid crystal. This exotic, new glassy phase of columnar liquid crystals, which we call a "hybrid columnar Bragg glass," can be achieved by confining a columnar liquid crystal in an anisotropic random environment of, e.g., strained aerogel. Long-ranged orientational order in this phase makes single-domain x-ray scattering possible, from which a wealth of information could be extracted. We give detailed quantitative predictions for the scattering pattern in addition to exponents characterizing anomalous elasticity of the system. PMID:11060625

  13. A case of blastic plasmacytoid dendritic cell neoplasm with ecchymotic lesions on the whole body

    PubMed Central

    Cui, Xiao-Bin; Jin, Jing; Pang, Xue-Lian; Li, Su; Liu, Chun-Xia; Li, Ting-Ting; Peng, Hao; Zhang, Shu-Mao; Li, Li; Liang, Wei-Hua; Chen, Yun-Zhao; Li, Feng

    2014-01-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from plasmacytoid dendritic cell precursors is a very rare, and characterized by cutaneous and bone marrow involvement and leukemic spread. The neoplasm presents with an aggressive behavior, and the clinical findings include cytopenia, particularly thrombocytopenia. The tumor cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and CD123, which are markers of plasmacytoid dendritic cells, and negative for Epstein-Barr virus (EBV). From this point of view, a 71-year-old man who was initially found to have a cutaneous mass on his face and thorax was reported here, and initially was diagnosed as “eczema”. The skin rashes then became aggravated on a trial of low dose topical corticosteroid for 2 months. According to skin biopsy, the tumor cells reveal an immature blastic appearance and positive for CD4 and CD56, negative for CD3, CD20, indicating a diagnosis of BPDCN. Here, we report the dismal course of a patient with BPDCN without accepting further therapy, and only survived 3 months. PMID:25120824

  14. Ultraviolet spectrophotometer for measuring columnar atmospheric ozone from aircraft.

    PubMed

    Hanser, F A; Sellers, B; Briehl, D C

    1978-05-15

    An ultraviolet spectrophotometer (UVS) to measure downward solar fluxes from an aircraft or other high altitude platform is described. The UVS uses an ultraviolet diffuser to obtain large angular response with no aiming requirement, a twelve-position filter wheel with narrow (2-nm) and broad (20-nm) bandpass filters, and an ultraviolet photodiode. The columnar atmospheric ozone above the UVS (aircraft) is calculated from the ratios of the measured ultraviolet fluxes. Comparison with some Dobson station measurements gives agreement to 2%. Some UVS measured ozone profiles over the Pacific Ocean for November 1976 are shown to illustrate the instrument's performance.

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

    NASA Astrophysics Data System (ADS)

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

    2007-06-01

    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.

  16. Architecture of columnar nacre, and implications for its formation mechanism.

    PubMed

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

    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.

  17. Periodically patterned columnar thin films as blazed diffraction gratings

    SciTech Connect

    Dutta, Jhuma; Anantha Ramakrishna, S.; Lakhtakia, Akhlesh

    2013-04-22

    Periodically patterned columnar thin films (PP-CTFs) were made by evaporating CaF{sub 2} and directing the vapor flux obliquely towards lithographically fabricated micrometer/sub-micrometer gratings. The growth of the PP-CTFs was controlled by the deposition rate to form prismatic air cavities within them. These PP-CTFs function like blazed diffraction gratings with asymmetric diffraction patterns and diffraction efficiencies up to 80% in transmission at ultraviolet-visible wavelengths. Diffraction theory adequately establishes that the blazing action arises due to the prismatic cavities and explains the measured diffraction efficiencies.

  18. 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.

  19. Rapid eye movement (REM) sleep deprivation in 6-OHDA nigro-striatal lesioned rats with and without transplants of dissociated chromaffin cells.

    PubMed

    Drucker-Colín, R; Durán-Vázquez, A; Salín-Pascual, R J; Verdugo-Díaz, L; Mendoza-Ramírez, J L; Jiménez-Anguiano, A

    1996-08-12

    Since both REM sleep deprivation and unilateral 6-OHDA lesions induce supersensitivity of DA receptors, the purpose of this study was to determine whether the response of rats with such lesions would be modified by REM sleep deprivation. In addition, the effect of grafts of dissociated chromaffin cells was also tested. Rats with 6-OHDA lesions were subjected to 24 or 72 h of REM sleep deprivation and tested with various doses of apomorphine to determine turning behavior frequencies. At end of those experiments, the animals were transplanted with dissociated chromaffin cells and turning behavior was tested again. The results showed that REM sleep deprivation nearly doubled the turning behavior frequency, that chromaffin cell grafts decreased it, but that REM deprivation in grafted animals still seemed to produce an increase of post-synaptic supersensitivity independent of denervation. The results were discussed in terms of the possible relationship of sleep with Parkinson's disease through the DA system.

  20. [A model of using magnetic resonance imaging in osteoarticular tumor lesion in case of giant cell tumors].

    PubMed

    Sherman, L A

    2004-01-01

    Fifty-eight patients with giant cell tumors (GCT) underwent a comprehensive radiation diagnosis involving X-ray study and magnetic resonance imaging (MRI). The obtained MR images indicated the high efficiency of this combination of radiation diagnostic techniques in solving the problems in the visualization of osteoarticular tumor lesions. GCT is characterized by well-known primary X-ray semiotics; MR images are also rather pathognomonic of these tumors and they illustrate the process of morphogenesis of these masses. MRI made it possible to solve the specific problems facing a physician (a radiation diagnostician), to determine the site, shape, sizes, volume, and local extent of a tumor, which permitted the planning of surgical treatment policy; to assess its results, to reveal possible inflammatory complications; and to visualize a local recurrence and on-going growth of a tumor, including the signs of GCT malignancy.

  1. Langerhans cells (CD1a and CD207), dermal dendrocytes (FXIIIa) and plasmacytoid dendritic cells (CD123) in skin lesions of leprosy patients.

    PubMed

    Hirai, Kelly Emi; Aarão, Tinara Leila de Sousa; Silva, Luciana Mota; de Sousa, Jorge Rodrigues; de Souza, Juarez; Dias, Leonidas Braga; Carneiro, Francisca Regina Oliveira; Fuzii, Hellen Thais; Quaresma, Juarez Antonio Simões

    2016-02-01

    The clinical course of infection with Mycobacterium leprae varies widely and depends on the pattern of the host immune response. Dendritic cells play an important role in the activation of the innate and adaptive immune system and seem to be essential for the development of the disease. To analyze the presence of epidermal dendritic cells (CD1a and CD207), plasmacytoid dendritic cells (CD123) and dermal dendrocytes (factor XIIIa) in lesion fragments of leprosy patients, skin samples from 30 patients were studied. These samples were submitted to immunohistochemistry against CD1a, CD207, FXIIIa, and CD123. The results showed a larger number of Langerhans cells, detected with the CD1a or CD207 marker, dermal dendrocytes and plasmacytoid dendritic cells in patients with the tuberculoid form. A positive correlation was observed between the Langerhans cell markers CD1a and CD207 in both the tuberculoid and lepromatous forms, and between Langerhans cells and dermal dendrocytes in samples with the tuberculoid form. The present results indicate the existence of a larger number of dendritic cells in patients at the resistant pole of the disease (tuberculoid) and suggest that the different dendritic cells studied play a role, favoring an efficient immune response against infection with M. leprae.

  2. Walking pattern analysis after unilateral 6-OHDA lesion and transplantation of foetal dopaminergic progenitor cells in rats.

    PubMed

    Klein, Alexander; Wessolleck, Johanna; Papazoglou, Anna; Metz, Gerlinde A; Nikkhah, Guido

    2009-05-16

    Functional sensorimotor recovery after transplantation of mesencephalic dopaminergic (DAergic) neurons has been well documented in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. However, the functional restoration of more specific gait-related patterns such as skilled walking, balance, and individual limb movements have been insufficiently studied. The purpose of this study was to investigate the behavioural effects of intrastriatal DA grafts on different aspects of normal and skilled walking in rats following unilateral 6-OHDA lesions of the medial forebrain bundle. Rats were subjected to drug-induced rotation, detailed footprint analysis, and assessment of skilled walking in the ladder rung walking test prior and after the transplantation of E14 ventral mesencephalon-derived progenitor cells. Good DAergic graft survival, as revealed by immunohistochemistry, was accompanied by a compensation of drug-induced rotational asymmetries. Interestingly, the analysis of walking patterns displayed a heterogeneous graft-induced response in skilled and non-skilled limb use. Grafted animals made fewer errors with their contralateral limbs in skilled walking than the sham-transplanted rats, and they improved their ipsi- and contralateral limb rotation. However, the parameter distance between feet showed a delayed recovery, and the stride length was not affected by the DA grafts at all. These findings indicate that ectopic intrastriatal transplantation of E14 ventral mesencephalon-derived cells promotes recovery of gait balance and stability, but does not ameliorate the shuffling gait pattern associated with 6-OHDA lesions. A full restoration of locomotor gait pattern might require a more complete and organotypic reconstruction of the mesotelencephalic DAergic pathway. PMID:19124044

  3. Differences among lesions with exon 19, exon 21 EGFR mutations and wild types in surgically resected non-small cell lung cancer

    PubMed Central

    Jin, Ying; Chen, Ming; Yu, Xinmin

    2016-01-01

    The clinical behavior of patients with advanced non-small cell lung cancer (NSCLC) differ between epidermal growth factor receptor (EGFR) exon 19 deletion (Ex19) and EGFR exon 21 L858R mutation (Ex21). This study aimed to evaluate whether these differences exist in surgically resected NSCLC. A total of 198 patients with surgically resected NSCLC harbouring Ex19 (n = 53), Ex21 (n = 51), and EGFR wild-type (Wt) (n = 94) were analyzed. The clinicopathological features, laboratory parameters, recurrent sites and disease-free survival (DFS) were compared according to mutational EGFR status. Ex21 occurred more frequently in female (p < 0.001), never-smokers (p < 0.001), adenocarcinoma (p < 0.001), low grade (p = 0.013) than Wt lesions. Ex19 occurred more frequently in female (p = 0.016), never-smokers (p = 0.008), adenocarcinoma (p < 0.001), low grade (p = 0.025) than Wt lesions. Ex 21 lesions (p = 0.026) had larger lepidic components than Wt lesions. Wt lesions had larger mucinous variant components than Ex21 lesions (p = 0.045) and Ex19 lesions (p = 0.015). Ex21 lesions were associated with lower pretreatment neutrophil: lymphocyte ratio (NLR) than Wt lesions (p = 0.017). The recurrent sites and DFS were similar among patients with Wt, Ex19 and Ex21. PMID:27527915

  4. Histologic changes in type A chronic atrophic gastritis indicating increased risk of neuroendocrine tumor development: the predictive role of dysplastic and severely hyperplastic enterochromaffin-like cell lesions.

    PubMed

    Vanoli, Alessandro; La Rosa, Stefano; Luinetti, Ombretta; Klersy, Catherine; Manca, Rachele; Alvisi, Costanza; Rossi, Sandro; Trespi, Erminio; Zangrandi, Adriano; Sessa, Fausto; Capella, Carlo; Solcia, Enrico

    2013-09-01

    The role of putative preneoplastic enterochromaffin-like cell lesions, either hyperplastic or dysplastic, in the genesis of type 1 enterochromaffin-like cell neuroendocrine tumors associated with type A chronic atrophic gastritis, their actual neoplastic risk, and their precise histogenetic mechanism deserve further clarification by specific histopathologic studies coupled with patient follow-up. A total of 100 patients with severe type A chronic atrophic gastritis, enterochromaffin-like cell hyperplasia, and antral G-cell hyperplasia were endoscopically and histologically followed up for a median of 90.1 months (total of 9118 person-months). Preneoplastic enterochromaffin-like cell lesions and newly developed neuroendocrine tumors were investigated histologically and histochemically, in parallel with enterochromaffin-like cell lesions found in nontumor mucosa of another 32 well-characterized and previously reported type 1 neuroendocrine tumors. Both neuroendocrine and nonneuroendocrine mucosa changes were analyzed and statistically evaluated. During follow-up, 7 of 100 patients developed neuroendocrine tumors: 5 were in a group of 20 cases with previous enterochromaffin-like cell dysplasia and 2 were among 80 cases showing only enterochromaffin-like cell hyperplasia throughout the study (hazard ratio, 20.7; P < .001). The severity of enterochromaffin-like cell hyperplasia at first biopsy, with special reference to linear hyperplasia with 6 chains or more per linear millimeter, also increased the risk of neuroendocrine tumor development during follow-up (hazard ratio, 13.0; P < .001). Enterochromaffin-like cell microinvasive dysplastic lesions arising at the epithelial renewal zone level, in connection with immature proliferating mucous-neck cells, were found to be linked to early intramucosal neuroendocrine tumor histogenesis. Both enterochromaffin-like cell dysplasia and severe hyperplasia indicate increased risk of neuroendocrine tumor development in type A

  5. Landmark Control and Updating of Self-Movement Cues Are Largely Maintained in Head Direction Cells After Lesions of the Posterior Parietal Cortex

    PubMed Central

    Calton, Jeffrey L.; Turner, Carol S.; Cyrenne, De-Laine M.; Lee, Brian R.; Taube, Jeffrey S.

    2009-01-01

    Head direction (HD) cells discharge as a function of the rat’s directional orientation with respect to its environment. Because animals with posterior parietal cortex (PPC) lesions exhibit spatial and navigational deficits, and the PPC is indirectly connected to areas containing HD cells, we determined the effects of bilateral PPC lesions on HD cells recorded in the anterodorsal thalamus. HD cells from lesioned animals had similar firing properties compared to controls and their preferred firing directions shifted a corresponding amount following rotation of the major visual landmark. Because animals were not exposed to the visual landmark until after surgical recovery, these results provide evidence that the PPC is not necessary for visual landmark control or the establishment of landmark stability. Further, cells from lesioned animals maintained a stable preferred firing direction when they foraged in the dark and were only slightly less stable than controls when they self-locomoted into a novel enclosure. These findings suggest that PPC does not play a major role in the use of landmark and self-movement cues in updating the HD cell signal, or in its generation. PMID:18729636

  6. Validation of simulated point response of columnar phosphor screens

    NASA Astrophysics Data System (ADS)

    Badano, Aldo; Kyprianou, Iacovos S.; Tang, Katherine H.; Saha, Anindita

    2007-03-01

    Typical methods to measure the resolution properties of x-ray detectors use slit or edge devices. However, complete models of imaging systems for system optimization require knowledge of the point-response function of the detector. In this paper, we report on the experimental methods developed for the validation of the point-response function of an indirect columnar CsI:Tl detector predicted by Monte Carlo using mantis. We describe simulation results that replicate experimental resolution measurements using edge and pinhole devices. The experimental setup consists of a high-resolution CCD camera with a 1-to-1fiber optic faceplate that allows measurements for different scintillation screens. The results of these experiments and simulations constitute a resource for the development and validation of the columnar models of phosphor screens proposed as part of previous work with mantis. We compare experimental high-resolution pinhole responses of two different CsI(Tl) screens to predictions from mantis. The simulated response matches reasonably well the measurements at normal and off-normal x-ray incidence angle when a realistic pinhole is used in the simulation geometry. Our results will be combined with results on Swank factors determined from Monte Carlo pulse-height spectra to provide a comprehensive validation of the phosphor models, therefore allowing their use for in silico system optimization.

  7. Loss of Reelin protects against atherosclerosis by reducing leukocyte-endothelial cell adhesion and lesion macrophage accumulation.

    PubMed

    Ding, Yinyuan; Huang, Linzhang; Xian, Xunde; Yuhanna, Ivan S; Wasser, Catherine R; Frotscher, Michael; Mineo, Chieko; Shaul, Philip W; Herz, Joachim

    2016-03-15

    The multimodular glycoprotein Reelin controls neuronal migration and synaptic transmission by binding to apolipoprotein E receptor 2 (Apoer2) and very low density lipoprotein receptor (Vldlr) on neurons. In the periphery, Reelin is produced by the liver, circulates in blood, and promotes thrombosis and hemostasis. To investigate if Reelin influences atherogenesis, we studied atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice in which we inducibly deleted Reelin either ubiquitously or only in the liver, thus preventing the production of circulating Reelin. In both types of Reelin-deficient mice, atherosclerosis progression was markedly attenuated, and macrophage content and endothelial cell staining for vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were reduced at the sites of atherosclerotic lesions. Intravital microscopy revealed decreased leukocyte-endothelial adhesion in the Reelin-deficient mice. In cultured human endothelial cells, Reelin enhanced monocyte adhesion and increased ICAM1, VCAM1, and E-selectin expression by suppressing endothelial nitric oxide synthase (eNOS) activity and increasing nuclear factor κB (NF-κB) activity in an Apoer2-dependent manner. These findings suggest that circulating Reelin promotes atherosclerosis by increasing vascular inflammation, and that reducing or inhibiting circulating Reelin may present a novel approach for the prevention of cardiovascular disease.

  8. FoxP3+ Regulatory T Cells Suppress Early Stages of Granuloma Formation but Have Little Impact on Sarcoidosis Lesions

    PubMed Central

    Taflin, Cécile; Miyara, Makoto; Nochy, Dominique; Valeyre, Dominique; Naccache, Jean-Marc; Altare, Frédéric; Salek-Peyron, Pascale; Badoual, Cécile; Bruneval, Patrick; Haroche, Julien; Mathian, Alexis; Amoura, Zahir; Hill, Gary; Gorochov, Guy

    2009-01-01

    Sarcoidosis is characterized by a disproportionate Th1 granulomatous immune response in involved organs. It is also associated with both peripheral and intratissular regulatory T cell (Treg) expansion. These cells exhibit powerful antiproliferative activity, yet do not completely inhibit the production of either tumor necrosis factor-α or interferon-γ. The origin of the observed Treg amplification and, more importantly, its impact on the evolution of sarcoidosis remain unresolved issues. Here, we show that CD4+CD45RA−FoxP3bright Tregs proliferate and accumulate within granulomas. However, circulating and tissue Treg numbers are neither correlated with the dissemination of the disease nor correlated locally with the extent of granulomatous inflammation. Rather, we found a positive correlation between the presence of Tregs in renal granulomas and the degree of interstitial fibrosis (r = 0.46, P = 0.03, n = 20). Furthermore, Treg depletion accelerates in vitro granuloma growth in mononuclear cell cultures of healthy controls, but not in those from patients with active sarcoidosis. The results of this study show that although healthy Tregs suppress the initial steps of granuloma formation, they have no positive influence on sarcoidosis lesions. Our findings argue for a more preventive than curative effect of Tregs on inflammatory processes. PMID:19147826

  9. 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.

  10. Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors.

    PubMed

    Galli, Uwe M; Sauter, Marlies; Lecher, Bernd; Maurer, Simone; Herbst, Hermann; Roemer, Klaus; Mueller-Lantzsch, Nikolaus

    2005-04-28

    Germ cell tumors (GCTs) are among the most common malignancies in young men. We have previously documented that patients with GCT frequently produce serum antibodies directed against proteins encoded by human endogenous retrovirus (HERV) type K sequences. Transcripts originating from the env gene of HERV-K, including the rec-relative of human immunodeficiency virus rev, are highly expressed in GCTs. We report here that mice that inducibly express HERV-K rec show a disturbed germ cell development and may exhibit, by 19 months of age, changes reminiscent of carcinoma in situ, the predecessor lesion of classic seminoma in humans. This provides the first direct evidence that the expression of a human endogenous retroviral gene previously established as a marker in human germ cell tumors may contribute to organ-specific tumorigenesis in a transgenic mouse model.

  11. Expansion of natural killer cells in peripheral blood in a Japanese elderly with human T-cell lymphotropic virus type 1-related skin lesions.

    PubMed

    Imashuku, Shinsaku; Kudo, Naoko; Kubo, Kagekatsu; Ohshima, Kouichi

    2014-01-01

    Natural killer (NK) cells were proposed to play an important role in the pathogenesis of human T-cell lymphotropic virus type 1- (HTLV-1-) associated neurologic disease. Our patient was a 77-year-old Japanese man, who had been treated for infective dermatitis associated with HTLV-1 for nearly 10 years. When referred to us, he had facial eczema/edema as well as extensive dermatitis at the neck/upper chest and nuchal area/upper back regions. Dermal lesions had CD3+CD4+ cells, but no NK cells. Flow cytometry of his peripheral blood showed a phenotype of CD2+ (97%), CD3+ (17%), CD4+ (12%), CD7+ (94%), CD8+ (6%), CD11c+ (70%), CD16+ (82%), CD19+ (0%), CD20+ (0%), CD56+ (67%), HLA-DR+ (68%), and NKp46+ (36%). Absolute numbers of CD56+NK cells in the peripheral blood were in a range of 986/μL-1,270/μL. The expanded NK cells in the peripheral blood are considered to be reactive, to maintain the confinement of the HTLV-1-positive CD4+ cells in the skin, and to prevent the progression of the disease.

  12. Complete Genome Sequence of the Fish Pathogen Flavobacterium columnare Strain C#2.

    PubMed

    Bartelme, Ryan P; Newton, Ryan J; Zhu, Yongtao; Li, Nan; LaFrentz, Benjamin R; McBride, Mark J

    2016-01-01

    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 predicted coding genes. PMID:27340080

  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. Complete Genome Sequence of the Fish Pathogen Flavobacterium columnare Pf1

    PubMed Central

    Zhang, Yulei

    2016-01-01

    Flavobacterium columnare is the etiologic agent of columnaris disease, a devastating fish disease prevailing in worldwide aquaculture industry. Here, we describe the complete genome of F. columnare strain Pf1, a highly virulent strain isolated from yellow catfish (Pelteobagrus fulvidraco) in China. PMID:27587818

  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. 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...

  18. 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...

  19. Complete Genome Sequence of the Fish Pathogen Flavobacterium columnare Pf1.

    PubMed

    Zhang, Yulei; Nie, Pin; Lin, Li

    2016-01-01

    Flavobacterium columnare is the etiologic agent of columnaris disease, a devastating fish disease prevailing in worldwide aquaculture industry. Here, we describe the complete genome of F. columnare strain Pf1, a highly virulent strain isolated from yellow catfish (Pelteobagrus fulvidraco) in China. PMID:27587818

  20. CD19+ B cell subsets in the peripheral blood and skin lesions of psoriasis patients and their correlations with disease severity

    PubMed Central

    Lu, J.; Ding, Y.; Yi, X.; Zheng, J.

    2016-01-01

    T lymphocytes are important in the pathogenesis of psoriasis, and increasing evidence indicates that B cells also play an important role. The mechanisms of action, however, remain unclear. We evaluated the ratios of CD19+ B cells in peripheral blood mononuclear cells (PBMCs) from 157 patients with psoriasis (65 patients with psoriasis vulgaris, 32 patients with erythrodermic psoriasis, 30 patients with arthropathic psoriasis, and 30 patients with pustular psoriasis) and 35 healthy controls (HCs). Ratios of CD19+ B cells in skin lesions were compared with non-lesions in 7 erythrodermic psoriasis patients. The Psoriasis Area Severity Index (PASI) was used to measure disease severity. CD19+ B cell ratios in PBMCs from psoriasis vulgaris (at both the active and stationary stage) and arthropathic psoriasis patients were higher compared with HCs (P<0.01), but ratios were lower in erythrodermic and pustular psoriasis patients (P<0.01). CD19+ B cell ratios in erythrodermic psoriasis skin lesions were higher than in non-lesion areas (P<0.001). Different subsets of CD19+CD40+, CD19+CD44+, CD19+CD80+, CD19+CD86+, CD19+CD11b+, and CD19+HLA-DR+ B cells in PBMCs were observed in different psoriasis clinical subtypes. PASI scores were positively correlated with CD19+ B cell ratios in psoriasis vulgaris and arthropathic psoriasis cases (r=0.871 and r=0.692, respectively, P<0.01), but were negatively correlated in pustular psoriasis (r=-0.569, P<0.01). The results indicated that similar to T cells, B cells activation may also play important roles in different pathological stages of psoriasis. PMID:27532281

  1. Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

    PubMed

    Chen, Yao-Tseng; Panarelli, Nicole C; Piotti, Kathryn C; Yantiss, Rhonda K

    2014-05-01

    Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions.

  2. 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

  3. Star Photometry for the Characterization of Columnar Aerosol Properties

    NASA Astrophysics Data System (ADS)

    Perez-Ramirez, D.; Lyamani, H.; Olmo Reyes, F. J.; Alados-Arboledas, L.; Whiteman, D. N.; Aceituno, J.

    2015-12-01

    Knowledge of columnar aerosol particles at nighttime is essential to completely understand aerosol dynamics and so will largely improve aerosol models. However, the current knowledge columnar nighttime aerosol is poor due to the lack of continuous measurements partly associated with previous technological limitations. Here we present the development, set up, calibration and data quality algorithms for the star photometer at the station of Granada (37.16 N, 3.60 W, 680 m a.s.l.) in Spain. The main advantage of this instrument is that make uses of a CCD camera as detector allowing direct star flux measurements. Filters center at 380, 440, 500, 670, 880 and 1020 nm allows spectral aerosol optical depth (AOD) measurements. Among all the stars, only those that are isolated and possess constant extratarrestial flux are considered. Two methods for the calibration of the system at high mountain places are presented. The first one consists of doing a Langley calibration of a selected star together with measurements of other stars. From the Langley calibration, we transferred AOD and get the calibration constants for other stars. The second method is the Astronomical Langley Method that consists of dividing the measurements by the optical air mass and so more stable calibration constant are obtained. On the other hand, the atmospheric turbulence is important for very short exposure times (< 1 s) and so uncertainties in AOD are of ±0.02 for λ < 800nm and ±0.01 for λ > 800nm. The instrument operated continuously for more than four consecutive years and so a large database was created. Cloud screening and data quality algorithms following AERONET inheritance were developed. Basically, moving averages are applied with different temporal-windows combined with a procedure to detect outliers. On the other hand, with quality data guaranteed the analysis of day-to-night columnar aerosol properties is presented. Mean AOD(440 nm) (0.18 ± 0.10 and 0.19 ± 0.11 for daytime and

  4. Vascular Lesions.

    PubMed

    Jahnke, Marla N

    2016-08-01

    Vascular lesions in childhood are comprised of vascular tumors and vascular malformations. Vascular tumors encompass neoplasms of the vascular system, of which infantile hemangiomas (IHs) are the most common. Vascular malformations, on the other hand, consist of lesions due to anomalous development of the vascular system, including the capillary, venous, arterial, and lymphatic systems. Capillary malformations represent the most frequent type of vascular malformation. IHs and vascular malformations tend to follow relatively predictable growth patterns in that IHs grow then involute during early childhood, whereas vascular malformations tend to exhibit little change. Both vascular tumors and vascular malformations can demonstrate a wide range of severity and potential associated complications necessitating specialist intervention when appropriate. Evaluation and treatment of the most common types of vascular lesions are discussed in this article. [Pediatr Ann. 2016;45(8):e299-e305.]. PMID:27517358

  5. Analysis of a photosensitive lesion induced by sunlamp UV greater than 315 nm exposure of 254-nm-irradiated human cells.

    PubMed

    Rosenstein, B S

    1988-11-01

    Normal human skin fibroblasts were exposed to 0-10 J m-2 of 254 nm UV, incubated 0-16 h and then treated with 0-150 kJ m-2 of sunlamp UV greater than 315 nm. For each treatment, the cells were subjected to alkaline elution in order to measure the yield of single strand breaks (ssb) produced. It was found that treatment of 254-nm-irradiated cells with sunlamp UV greater than 315 nm resulted in the production of a higher level of ssb than that produced by separate exposures. Hence, lesions are produced by the 254 nm irradiation that are photolyzed through exposure to sunlamp UV greater than 315 nm. Approximately 50% of these lesions are removed following a 2-4 h incubation of the 254-nm-irradiated cells and nearly complete removal is achieved by 16 h. In addition, the profiles for elutions performed at pH 12.8 with cells exposed to the combined treatment were indicative of the presence of alkali labile sites. The repair kinetics of this lesion and alkaline lability of the photolysis product suggest that this photosensitive lesion may represent pyrimidine(6-4)pyrimidone photoproducts. Hence, this approach may represent a relatively simple and sensitive assay for the measurement of this DNA damage.

  6. Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

    PubMed Central

    2009-01-01

    Background Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection. Methods NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays. Results We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients. Conclusion Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression. PMID:19531227

  7. 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

  8. Eruptive dermal clear cell desmo-plastic mesenchymal tumors with perivascular myoid differentiation in a young boy. A clinical, histopathologic, immunohistochemical and electron microscopy study of 17 lesions.

    PubMed

    Tomasini, Carlo; Metze, Dieter; Osella-Abate, Simona; Novelli, Mauro; Kutzner, Heinz

    2014-02-01

    Clear cell tumors of the skin are observed in a wide variety of benign and malignant conditions with different histogenesis, sharing the presence of cells with abundant clear cytoplasm. Herein, we report the clinicopathologic features of a healthy young patient affected by asymptomatic, eruptive and disseminated, benign clear cell dermal tumors since early infancy. Neither family history nor genetic testing and counseling provided further useful information. The lesions were mostly confined to the face and lower left extremity with pink teleangiectatic papules and small nodules. Over a 4-year period, a total of 16 different cutaneous lesions were biopsied and histopathologic and immunohistochemical studies carried out; an additional lesion was also removed for electron microscopy examination. Histopathology evidenced multiple perivascular growths of spindle to oval and round cells intermingled with clear/granular cells throughout the dermis, with prominent desmoplasia and numerous capillary-like vessels with focal hemangiopericytoma-like features. Immunohistochemical neoplastic cells were uniformly positive for h-caldesmon and focally smooth muscle α-actin and CD13 indicating myoid differentiation whereas the consistent diffuse cytoplasmic staining for lysosome antigen, such as CD68PG-M1 and NKI/C3 along with the ultrastructural findings supported the view of a lysosome-mediated apoptotic process. The differential diagnosis with other clear cell cutaneous neoplasms is discussed.

  9. Gold nanoparticles in columnar matrix of discotic liquid crystal

    NASA Astrophysics Data System (ADS)

    Supreet, Kumar, Rishi; Pratibha, R.; Kumar, Sandeep; Raina, K. K.

    2013-06-01

    Hexanethiolate-stabilized gold nanoparticles (GNP) were synthesized by the method adopted by Song et al.[2]. Average size of GNPs was determined by scanning transmission electron microscopy (STEM). This method yielded nanoparticles with average particle size of 1.5 nm. In the present work, we have incorporated GNPs in columnar matrix of discotic liquid crystal. The thermo-physical properties of these mixtures were investigated using polarizing optical micrography (POM), differential scanning calorimetry (DSC) and dielectric spectroscopy. Results show GNPs does not affect the hexagonal arrangement of columns of DLC. However, there is decrease in mesophase to crystallization temperature as confirmed by DSC. This approach of crossing of the field of nanotechnology with DLC may lead to novel materials with interesting properties that are useful for many device applications.

  10. 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.

  11. 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.

  12. Structural studies in columnar basalts from crystallographic and magnetic fabrics

    NASA Astrophysics Data System (ADS)

    Tiphaine, Boiron; Jérôme, Bascou; Pierre, Camps; Eric, Ferre; Claire, Maurice; Bernard, Guy; Marie-Christine, Gerbe

    2010-05-01

    The purpose of this study is to better characterize the columnar and the associated microstructure development in basalt flows. The thermal contraction (O'Reilly, 1879) is the main hypothesis to explain the columnar formation. However, neither the structures which appear in basalt flow constituted of three levels (Tomkeieff, 1940) nor circular and radial structures within the prisms (for which weathering nor fracturing can account for) can be explained by the thermal contraction theory alone. An early structuring process during solidification (Guy and Le Coze, 1990) could play for a part that must be discussed (Guy, 2010). We studied two recent basalt flows (75 000 years) from the French Massif Central, in which the three flow levels are clearly observed. In the first basalt flow (La Palisse, Ardèche), the emission centre and the flow direction are known. In the second one (Saint Arcons d'Allier, Haute Loire), the prismatic columns are particularly well developed. In order to characterize the flow structure at different scales, from the flow to the grain scale, anisotropy of magnetic susceptibility (AMS) measurements were performed. The AMS data were coupled with crystallographic preferred orientation measurements of magnetite, plagioclase and clinopyroxene using Electron Backscattered Diffraction (EBSD) and image analyses from perpendicular thin sections. Magnetic mineralogy studies of the La Palisse basalts, in particular the thermomagnetic curves, indicate that the main carrier of AMS is high-Ti titanomagnetite (Tc≈130°C). AMS measurements of about a hundred samples show a higher degree of AMS (P parameter) in the middle level in comparison to the base. Inversely, the bulk magnetic susceptibility (Km) is higher at the flow base. Distinctive parameters for the different levels of the basaltic flows could be then provided by AMS measurements.. Moreover, the comparison between AMS and EBSD data indicate that the magnetic susceptibility carried by the magnetic

  13. Electric field controlled columnar and planar patterning of cholesteric colloids.

    PubMed

    D'Adamo, G; Marenduzzo, D; Micheletti, C; Orlandini, E

    2015-05-01

    We study how dispersions of colloidal particles in a cholesteric liquid crystal behave under a time-dependent electric field. By controlling the amplitude and shape of the applied field wave, we show that the system can be reproducibly driven out of equilibrium through different kinetic pathways and navigated through a glassylike free energy landscape encompassing many competing metastable equilibria. Such states range from simple Saturn rings to complex structures featuring amorphous defect networks, or stacks of disclination loops. A nonequilibrium electric field can also trigger the alignment of particles into columnar arrays, through defect-mediated force impulses, or their repositioning within a plane. Our results are promising in terms of providing new avenues towards controlled patterning and self-assembly of soft colloid-liquid crystal composite materials. PMID:25978263

  14. Electric field controlled columnar and planar patterning of cholesteric colloids.

    PubMed

    D'Adamo, G; Marenduzzo, D; Micheletti, C; Orlandini, E

    2015-05-01

    We study how dispersions of colloidal particles in a cholesteric liquid crystal behave under a time-dependent electric field. By controlling the amplitude and shape of the applied field wave, we show that the system can be reproducibly driven out of equilibrium through different kinetic pathways and navigated through a glassylike free energy landscape encompassing many competing metastable equilibria. Such states range from simple Saturn rings to complex structures featuring amorphous defect networks, or stacks of disclination loops. A nonequilibrium electric field can also trigger the alignment of particles into columnar arrays, through defect-mediated force impulses, or their repositioning within a plane. Our results are promising in terms of providing new avenues towards controlled patterning and self-assembly of soft colloid-liquid crystal composite materials.

  15. Experimental study of columnar recombination in fission chambers

    NASA Astrophysics Data System (ADS)

    Filliatre, P.; Lamirand, V.; Geslot, B.; Jammes, C.

    2016-05-01

    In this paper, we present experimental saturation curves of a small gap miniature fission chamber obtained in the MINERVE reactor. The chamber is filled with argon at various pressures, and the fissile material can be coated on the anode, cathode, or both. For analyzing the recombination regime, we consider a model of columnar recombination and discuss its applicability to our chamber. By applying this model to the data, it is possible to estimate the ratio between the recombination coefficient k and an effective column radius b, appearing in the model, to be k / b =(2.5 ± 0.9) ×10-6m2 / s for argon. From these results, a routine measurement of the recombination regime is proposed in order to detect gas leakage. This online diagnosis would be beneficial in terms of lifetime and reliability of the neutron instrumentation of nuclear reactors.

  16. Azimuthal Frustration and Bundling in Columnar DNA Aggregates

    PubMed Central

    Harreis, H. M.; Likos, C. N.; Löwen, H.

    2003-01-01

    The interaction between two stiff parallel DNA molecules is discussed using linear Debye-Hückel screening theory with and without inclusion of the dielectric discontinuity at the DNA surface, taking into account the helical symmetry of DNA. The pair potential furthermore includes the amount and distribution of counterions adsorbed on the DNA surface. The interaction does not only depend on the interaxial separation of two DNA molecules, but also on their azimuthal orientation. The optimal mutual azimuthal angle is a function of the DNA-DNA interaxial separation, which leads to azimuthal frustrations in an aggregate. On the basis of the pair potential, the positional and orientational order in columnar B-DNA assemblies in solution is investigated. Phase diagrams are calculated using lattice sums supplemented with the entropic contributions of the counterions in solution. A variety of positionally and azimuthally ordered phases and bundling transitions is predicted, which strongly depend on the counterion adsorption patterns. PMID:12770870

  17. 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

  18. NF-kappaB dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma.

    PubMed

    Rhodus, Nelson L; Ho, Vu; Miller, Craig S; Myers, Sandra; Ondrey, Frank

    2005-01-01

    Previous investigations in our laboratory and others (Chen et al., 1998) have shown that the levels of certain inflammatory, proangiogenic cytokines in saliva and tissue specimens of patients with oral premalignant lesions (OPML) are elevated. We have also shown that these cytokines are elevated in tissue culture of oral squamous cell carcinoma (OSCC) cell lines. The purpose of this pilot study was to determine the level of several inflammatory, NF-kappaB-dependent cytokines in whole unstimulated saliva (WUS), in subjects with OPML as compared to those with diagnosed OSCC. Subjects (n=13) with OMPL, OSCC (n=13), and age-sex matched controls without oral lesions (C) (n=13) were enrolled. The mean age was 58.7 years. WUS was collected by standard techniques for 5 min (Navazesh, 1993). WUS samples were centrifuged and the cytokine analysis was performed on the supernatants by ELISA as previously described by Ondrey et al. (1991). The cytokines analyzed were: TNF-alpha, interleukin-1, interleukin-6, and interleukin-8 (TNF-alpha, IL-1, IL-6, and IL-8). The results as analyzed by Pairwise t-tests revealed significant differences in the salivary levels of: (1) TNF-alpha: (mean+/-S.E.M.: TNF-alpha-OSSC=28.9+/-14.6* pcg/ml versus OPML=10.5+/-7.4* pcg/ml versus controls=3.0+/-1.0 pcg/ml; *p<0.01); (2) IL-1: (IL-1-OSSC=454.4+/-215.8* pcg/ml versus OPML=255.1+/-124.8* pcg/ml versus controls=173.2+/-66.9 pcg/ml; *p<0.01); (3) IL-6: (mean+/-S.E.M.: IL-6-OSSC=88.2+/-43.2* pcg/ml versus OPML=70.8+/-24.3* pcg/ml versus controls=1.4+/-1.0 pcg/ml; *p<0.001) and (4) IL-8 in saliva: (mean+/-S.E.M.: IL-8-OSSC=3154.1+/-1023.2* pcg/ml versus OPML=1918.2+/-899.1* pcg/ml versus controls=1580.7+/-789.0 pcg/ml; *p<0.001). There was a significant increase in the levels of all cytokines in the saliva of the OPML as compared to controls, and a significant difference in the cytokines of OSSC saliva compared to the OPML and controls. These results suggest that these proangiogenic, proinflammatory

  19. Pharmacokinetic analysis of the uptake of liposomes by macrophages and foam cells in vitro and their distribution to atherosclerotic lesions in mice.

    PubMed

    Chono, Sumio; Tauchi, Yoshihiko; Morimoto, Kazuhiro

    2006-02-01

    In order to evaluate the efficacy of liposomes as a drug carrier for atherosclerotic therapy, a pharmacokinetic analysis of the uptake of liposomes by macrophages and foam cells in vitro and their distribution to atherosclerotic lesions in mice was carried out. In brief, liposomes of three particle sizes (500, 200 and 70 nm) were prepared, and the uptake of liposomes by these cells in vitro and the aortic distribution following intravenous administration to atherogenic mice were examined. The internalization rate constant calculated by measuring uptake and binding was size-dependent in both types of cells in vitro. The aortic clearance (CL(a)) was size-independent in atherogenic mice and the CL(a) of 200 nm particles was the highest. Surprisingly, the aortic distribution in vivo did not correspond with the internalization to macrophages and foam cells in vitro. These results suggest that there is an optimal size for the distribution of liposomes to atherosclerotic lesions.

  20. Grain texture evolution during the columnar growth of dendritic alloys

    NASA Astrophysics Data System (ADS)

    Gandin, Ch. A.; Rappaz, M.; West, D.; Adams, B. L.

    1995-06-01

    The grain selection that operates in the columnar zone of a directionally solidified (DS) INCONEL X750 superalloy has been investigated using standard metallography and an automatic indexing technique of electron backscattered diffraction patterns (EBSPs). From the crystallographic orientations measured at 90,000 points in a longitudinal section, the grain structure was reconstructed. The grain density as measured by the inverse of the mean linear intercept was found to be a decreasing function of the distance from the chill. The evolution of the <100> pole figures along the columnar zone of the casting and the distribution of the angle θ characterizing the <100> direction of the grains that is closest to the temperature gradient were then deduced from the EBSPs measurement. It was found that, near the surface of the chill, the θ distribution was close to the theoretical curve calculated for randomly oriented grains. As the distance from the chill increased, the measured θ distribution became narrower and was displaced toward smaller θ values. At 2 mm from the chill, the most probable orientation of the grains was found to be about 0.21 rad (12 deg). The information obtained with the EBSPs was then compared with the results of a three-dimensional stochastic model (3D SM) describing the formation of grain structure during solidification. This model accounts for the random location and orientation of the nuclei, for the growth kinetics and preferential <100> growth directions of the dendrites. Although this model assumes a uniform temperature within the specimen, the simulation results were found to be in good agreement with the EBSPs measurement.

  1. Interobserver reproducibility in pathologist interpretation of columnar-lined esophagus.

    PubMed

    Mastracci, Luca; Piol, Nataniele; Molinaro, Luca; Pitto, Francesca; Tinelli, Carmine; De Silvestri, Annalisa; Fiocca, Roberto; Grillo, Federica

    2016-02-01

    Confirmation of endoscopically suspected esophageal metaplasia (ESEM) requires histology, but confusion in the histological definition of columnar-lined esophagus (CLE) is a longstanding problem. The aim of this study is to evaluate interpathologist variability in the interpretation of CLE. Thirty pathologists were invited to review three ten-case sets of CLE biopsies. In the first set, the cases were provided with descriptive endoscopy only; in the second and the third sets, ESEM extent using Prague criteria was provided. Moreover, participants were required to refer to a diagnostic chart for evaluation of the third set. Agreement was statistically assessed using Randolph's free-marginal multirater kappa. While substantial agreement in recognizing columnar epithelium (K = 0.76) was recorded, the overall concordance in clinico-pathological diagnosis was low (K = 0.38). The overall concordance rate improved from the first (K = 0.27) to the second (K = 0.40) and third step (K = 0.46). Agreement was substantial when diagnosing Barrett's esophagus (BE) with intestinal metaplasia or inlet patch (K = 0.65 and K = 0.89), respectively, in the third step, while major problems in interpretation of CLE were observed when only cardia/cardia-oxyntic atrophic-type epithelium was present (K = 0.05-0.29). In conclusion, precise endoscopic description and the use of a diagnostic chart increased consistency in CLE interpretation of esophageal biopsies. Agreement was substantial for some diagnostic categories (BE with intestinal metaplasia and inlet patch) with a well-defined clinical profile. Interpretation of cases with cardia/cardia-oxyntic atrophic-type epithelium, with or without ESEM, was least consistent, which reflects lack of clarity of definition and results in variable management of this entity.

  2. Frequent alterations of cell cycle regulators in early-stage breast lesions as detected by immunohistochemistry.

    PubMed Central

    Marsh, K. L.; Varley, J. M.

    1998-01-01

    Progression through G1 phase of the eukaryotic cell cycle is tightly controlled by cyclin-dependent kinases (CDK). These proteins form part of a regulatory pathway including the cyclin-dependent kinase inhibitor (CKI) p16, D-type cyclins and the product of the retinoblastoma gene pRb. Aberration of any one of these components may lead to uncontrolled proliferation contributing to neoplasia. Three of these proteins, cyclin D1, pRb and p16, were analysed by immunohistochemistry on archival paraffin sections to determine whether expression patterns were different in preinvasive ductal carcinoma in situ (DCIS) and invasive breast tumours relative to normal. Genetic analysis of the gene encoding cyclin D1 (CCND1) was also carried out, using an intragenic restriction fragment-length polymorphism (RFLP) to assess possible allelic imbalance. A majority of the tumours studied (approximately 90%) showed abnormalities in expression of at least one of these proteins. Overexpression of cyclin D1 was found in approximately 49% cases, reduced expression of p16 in approximately 46% and reduced expression of pRb in approximately 37%. Allelic imbalance of cyclin D1 was found in approximately 57% cases. Images Figure 2 PMID:9652762

  3. 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

    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; Trombone, Ana Paula F; Belone, Andrea de F F

    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

  4. 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

  5. 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

    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; Trombone, Ana Paula F; Belone, Andrea de F F

    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.

  6. 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

  7. 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.

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

    PubMed

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

    1983-09-01

    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.

  9. 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

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

    PubMed

    Peng, Ya; Wang, Jun; Zhang, Miao; 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

  11. 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

  12. Microseismic monitoring of columnar jointed basalt fracture activity: a trial at the Baihetan Hydropower Station, China

    NASA Astrophysics Data System (ADS)

    Chen, Bing-Rui; Li, Qing-Peng; Feng, Xia-Ting; Xiao, Ya-Xun; Feng, Guang-Liang; Hu, Lian-Xing

    2014-10-01

    Severe stress release has occurred to the surrounding rocks of the typically columnar jointed basalt after excavation at the Baihetan Hydropower Station, Jinsha River, China, where cracking, collapse, and other types of failure may take place occasionally due to relaxation fracture. In order to understand the relaxation fracture characteristics of the columnar jointed basalt in the entire excavation process at the diversion tunnel of the Baihetan Hydropower Station, real-time microseismic monitoring tests were performed. First, the applicability of a geophone and accelerometer was analyzed in the columnar jointed basalt tunnel, and the results show that the accelerometer was more applicable to the cracking monitoring of the columnar jointed basalt. Next, the waveform characteristics of the microseismic signals were analyzed, and the microseismic signals were identified as follows: rock fracture signal, drilling signal, electrical signal, heavy vehicle passing signal, and blast signal. Then, the attenuation characteristics of the microseismic signals in the columnar jointed basalt tunnel were studied, as well as the types and characteristics of the columnar jointed basalt fracture. Finally, location analysis was conducted on the strong rock fracture events, in which four or more sensors were triggered, to obtain the temporal and spatial evolution characteristics and laws of the columnar jointed basalt relaxation fracture after excavation. The test results are not only of important reference value to the excavation and support of diversion tunnel at the Baihetan Hydropower Station, but also of great referential significance and value to the conduction of similar tests.

  13. Proliferative lesions of ovarian granulosa cells and reversible hormonal changes induced in rats by a selective estrogen receptor modulator.

    PubMed

    Long, G G; Cohen, I R; Gries, C L; Young, J K; Francis, P C; Capen, C C

    2001-01-01

    . Intrafollicular granulosa cell hyperplasia was not seen in rats in the reversibility phase. Areas of prior focal cystic granulosa cell hyperplasia were represented by focal sclerosis that included hemorrhage and/or hemosiderin. The foci of sclerosis were associated with cystic spaces after 1 month and were solid after 3 months. A granulosa cell tumor, approximately 12-13 mm diameter, was present in a high-dose rat in the 3-month reversibility group. This tumor effaced 1 ovary and was characterized by proliferative granulosa cells, usually in papillary formations and cords within cystic spaces. This rat had atrophy of the uninvolved ovary, excessive plasma levels of E2 and prolactin, and high P4 levels considering the absence of CL. The results of this study indicate that ovarian granulosa cells in rats are susceptible to proliferative changes when stimulated chronically with excessive trophic hormones. Most of these proliferative changes were reversible upon cessation of the hormonal stimulation. However, the proliferative lesion in one treated rat progressed to apparent autonomous (neoplastic) growth.

  14. Proliferative lesions of ovarian granulosa cells and reversible hormonal changes induced in rats by a selective estrogen receptor modulator.

    PubMed

    Long, G G; Cohen, I R; Gries, C L; Young, J K; Francis, P C; Capen, C C

    2001-01-01

    . Intrafollicular granulosa cell hyperplasia was not seen in rats in the reversibility phase. Areas of prior focal cystic granulosa cell hyperplasia were represented by focal sclerosis that included hemorrhage and/or hemosiderin. The foci of sclerosis were associated with cystic spaces after 1 month and were solid after 3 months. A granulosa cell tumor, approximately 12-13 mm diameter, was present in a high-dose rat in the 3-month reversibility group. This tumor effaced 1 ovary and was characterized by proliferative granulosa cells, usually in papillary formations and cords within cystic spaces. This rat had atrophy of the uninvolved ovary, excessive plasma levels of E2 and prolactin, and high P4 levels considering the absence of CL. The results of this study indicate that ovarian granulosa cells in rats are susceptible to proliferative changes when stimulated chronically with excessive trophic hormones. Most of these proliferative changes were reversible upon cessation of the hormonal stimulation. However, the proliferative lesion in one treated rat progressed to apparent autonomous (neoplastic) growth.

  15. Intraventricular administration of endoneuraminidase-N facilitates ectopic migration of subventricular zone-derived neural progenitor cells into 6-OHDA lesioned striatum of mice.

    PubMed

    Li, Chen; Zhang, Yong-Xin; Yang, Chun; Hao, Fei; Chen, Sha-Sha; Hao, Qiang; Lu, Tao; Qu, Ting-Yu; Zhao, Li-Ru; Duan, Wei-Ming

    2016-03-01

    Polysialic acid (PSA), a carbohydrate polymer associated with the neural cell adhesion molecule (NCAM), plays an important role in the migration, differentiation and maturation of neuroblasts. Endoneuraminidase-N (Endo-N) can specifically cleave PSA from NCAM. The objective of the present study was to examine: the effect of Endo-N on characteristics of subventricular zone (SVZ)-derived neural progenitor cells (NPCs) in vitro; whether intraventricular administration of Endo-N could increase ectopic migration of SVZ-derived NPCs into 6-hydroxydopamine (6-OHDA)-lesioned striatum, and whether migrated NPCs could differentiate into neuronal and glial cells. In in vitro study, Endo-N was found to inhibit the migration of NPCs, and to enhance the differentiation of NPCs. In in vivo study, mice sequentially received injections of 6-OHDA into the right striatum, Endo-N into the right lateral ventricle, and bromodeoxyuridine (BrdU) intraperitoneally. The data showed that intraventricular injections of Endo-N disorganized the normal structure of the rostral migratory stream (RMS), and drastically increased the number of BrdU-immunoreactive (IR) cells in 6-OHDA-lesioned striatum. In addition, a number of BrdU-IR cells were double labeled for doublecortin (DCX), NeuN or glial fibrillary acidic protein (GFAP). The results suggest that interruption of neuroblast chain pathway with Endo-N facilitates ectopic migration of SVZ-derived NPCs into the lesioned striatum, and migrated NPCs can differentiate into neurons and astrocytes. PMID:26724216

  16. Human MMH (OGG1) type 1a protein is a major enzyme for repair of 8-hydroxyguanine lesions in human cells.

    PubMed

    Monden, Y; Arai, T; Asano, M; Ohtsuka, E; Aburatani, H; Nishimura, S

    1999-05-19

    8-Hydroxyguanine (8-OH-G) is the site of a frequent mutagenic lesion of DNA, produced by oxidative damage. MutM of E. coli and OGG1 of Saccharomyces cervisiae are known to possess 8-OH-G glycosylase activity and apurinic (AP) site lyase activity to repair 8-OH-G lesions. Recently, cDNA clones of human OGG1 homologues (hMMH) of four isoforms (type 1a, type 1b, type 1c, and type 2) were isolated. However, it is unknown whether expression of endogenous hMMH proteins actually occurs in mammalian cells. Here using hMMH type 1a-specific antibody and cells overexpressing tag-fused hMMH type 1a, we show the expression of hMMH type 1a protein in many types of human cells and show that endogenous hMMH type 1a protein has 8-OH-G glycosylase/AP lyase activity. Furthermore, we show that upon depletion of hMMH type 1a protein in a whole cell extract by its antibody, most of the AP lyase activity is lost, indicating that hMMH type 1a protein is a major enzyme for repair of 8-OH-G lesions in human cells. PMID:10329432

  17. Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell rolling in early atherosclerotic lesions of apolipoprotein E-deficient mice.

    PubMed

    Ramos, C L; Huo, Y; Jung, U; Ghosh, S; Manka, D R; Sarembock, I J; Ley, K

    1999-06-11

    Apolipoprotein E-deficient (ApoE-/-) mice develop atherosclerotic lesions throughout the arterial tree, including the carotid bifurcation. Although the expression of adhesion molecules such as ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and P-selectin on endothelium that overlie atherosclerotic plaques has been implicated in monocyte recruitment to developing lesions, monocyte adhesion in atherosclerotic vessels has not been observed directly. To investigate which adhesion molecules may be important in monocyte adhesion to atherosclerotic lesions, an isolated mouse carotid artery preparation was developed and perfused with mononuclear cells. We show rolling and attachment of the human monocytic cell line U937 and the mouse monocyte-macrophage cell line P388D1 in carotid arteries from 10- to 12-week-old ApoE-/- and C57BL/6 wild-type mice fed a Western-type diet (21% fat wt/wt) for 4 to 5 weeks. No rolling was observed in carotid arteries from C57BL/6 or BALB/c wild-type mice fed a chow diet and little was observed in BALB/c mice fed a Western-type diet. This model represents early lesion development as shown by minimal macrophage infiltration in the intima of carotid arteries from ApoE-/- mice fed a Western-type diet. Rolling was observed at shear stresses that were characteristic of the low-shear recirculation zone near the carotid bifurcation. Mononuclear cell attachment and rolling were significantly inhibited by monoclonal antibody blockade of P-selectin or its leukocyte ligand P-selectin glycoprotein ligand-1. Rolling velocities increased after monoclonal antibody blockade of mononuclear cell alpha4-integrin or VCAM-1, which indicates that alpha4-integrin interacting with VCAM-1 stabilizes rolling interactions and prolongs monocyte transit times.

  18. N-Cadherin Promotes Recruitment and Migration of Neural Progenitor Cells from the SVZ Neural Stem Cell Niche into Demyelinated Lesions

    PubMed Central

    Klingener, Michael; Chavali, Manideep; Singh, Jagdeep; McMillan, Nadia; Coomes, Alexandra; Dempsey, Peter J.; Chen, Emily I.

    2014-01-01

    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. PMID:25031401

  19. 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

  20. 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. PMID:22719209

  1. Expression of E-, P- and N-Cadherin and Its Clinical Significance in Cervical Squamous Cell Carcinoma and Precancerous Lesions

    PubMed Central

    Li, Baohua; Shi, Haiyan; Wang, Fenfen; Hong, Die; Lv, Weiguo; Xie, Xing; Cheng, Xiaodong

    2016-01-01

    Aberrant expression of classical cadherins has been observed in tumor invasion and metastasis, but its involvement in cervical carcinogenesis and cancer progression is not clear. We investigated E-, P- and N-cadherin expression and its significance in cervical squamous cell carcinoma (SCC) and cervical intraepithelial neoplasia (CIN). This retrospective study enrolled 508 patients admitted to Women's Hospital, School of Medicine, Zhejiang University with cervical lesions between January 2006 and December 2010. Immunochemical staining was performed in 98 samples of normal cervical epithelium (NC), 283 of CIN, and 127 of early-stage SCC. The association of cadherin staining with clinical characteristics and survival of the patients was evaluated by univariate and multivariate analysis. We found gradients of decreasing E-cadherin expression and increasing P-cadherin expression from NC through CIN to SCC. Aberrant E-cadherin and P-cadherin expression were significantly associated with clinical parameters indicating poor prognosis and shorter patient survival. Interestingly, we found very low levels of positive N-cadherin expression in CIN and SCC tissues that were not related to CIN or cancer. Pearson chi-square tests showed that E-cadherin expression in SCC was inversely correlated with P-cadherin expression (E-P switch), and was not correlated with N-cadherin expression. More important, patients with tissues exhibiting an E-P switch in expression had highly aggressive phenotypes and poorer prognosis than those without E-P switch expression. Our findings suggest that E-cadherin and P-cadherin, but not N-cadherin staining, might be useful in diagnosing CIN and for predicting prognosis in patients with early-stage SCC. PMID:27223886

  2. 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.

  3. 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. PMID:26502322

  4. 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.

  5. Scale selection in columnar jointing: Insights from experiments on cooling stearic acid and numerical simulations

    NASA Astrophysics Data System (ADS)

    Christensen, Amalie; Raufaste, Christophe; Misztal, Marek; Celestini, Franck; Guidi, Maria; Ellegaard, Clive; Mathiesen, Joachim

    2016-03-01

    Many natural fracture systems are characterized by a single length scale, which is the distance between neighboring fractures. Examples are mud cracks and columnar jointing. In columnar jointing the origin of this scale has been a long-standing issue. Here we present a comprehensive study of columnar jointing based on experiments on cooling stearic acids, numerical simulations using both discrete and finite element methods and basic analytical calculations. We show that the diameter of columnar joints is a nontrivial function of the material properties and the cooling conditions of the system. We determine the shape of this function analytically and show that it is in agreement with the experiments and the numerical simulations.

  6. A New Phase of Liquid Crystal with Quenched Disorder: The Columnar Elastic Glass

    NASA Astrophysics Data System (ADS)

    Toner, John; Saunders, Karl; Ettouhami, A. M.; Radzihovsky, Leo

    2002-03-01

    The properties of the columnar liquid crystal phase confined in random porous media, e.g. aerogel, are studied. It is found that the quenched disorder leads to a complete destruction of the long-ranged columnar translational order. Nevertheless, dislocations remain bound in the resulting phase, which therefore retains columnar topological and orientational order, and is referred to as a columnar elastic glass (CEG). The elasticity of the CEG is found to be anomalous, i.e. wavevector dependent, and is characterized by universal anomalous exponents, which are calculated using an ɛ = 7/2 - d expansion. The CEG also exhibits a negative universal Poisson ratio which is calculated. Furthemore, the recently predicted spontaneous vortex lattice in dirty ferromagnetic superconductors falls into the CEG universality class [1]. [1] Leo Radzihovsky, A. M. Ettouhami, Karl Saunders, John Toner, Phys. Rev. Lett.87, 27001 (2001).

  7. 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.

  8. 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...

  9. Host cell reactivation of plasmids containing oxidative DNA lesions is defective in Cockayne syndrome but normal in UV-sensitive syndrome fibroblasts.

    PubMed

    Spivak, Graciela; Hanawalt, Philip C

    2006-01-01

    UV-sensitive syndrome (UV(S)S) is a human DNA repair-deficient disease with mild clinical manifestations. No neurological or developmental abnormalities or predisposition to cancer have been reported. In contrast, Cockayne syndrome (CS) patients exhibit severe developmental and neurological defects, in addition to photosensitivity. The cellular and biochemical responses of UV(S)S and CS cells to UV are indistinguishable, and result from defective transcription-coupled repair (TCR) of photoproducts in expressed genes. We propose that UV(S)S patients develop normally because they are proficient in repair of oxidative base damage. Consistent with our model, we show that Cockayne syndrome cells from complementation groups A and B (CS-A, CS-B) are more sensitive to treatment with hydrogen peroxide than wild type or UV(S)S cells. Using a host cell reactivation assay with plasmids containing UV-induced photoproducts, we find that expression of the plasmid-encoded lacZ gene is reduced in the TCR-deficient CS-B and UV(S)S cells. When the plasmids contain the oxidative base lesion thymine glycol, CS-B cells are defective in recovery of expression, whereas UV(S)S cells show levels of expression similar to those in wild type cells. 8-oxoguanine in the plasmids result in similarly defective host cell reactivation in CS-A and CS-B cells; abasic sites or single strand breaks in the plasmids cause similar decreases in expression in all the cell lines examined. Repair of thymine glycols in the lacZ gene was measured in plasmids extracted from transfected cells; removal of the lesions is efficient and without strand bias in all the cell lines tested. PMID:16129663

  10. Characterization of different tissue changes in normal, betel chewers, potentially malignant lesions, conditions and oral squamous cell carcinoma using reflectance confocal microscopy: correlation with routine histopathology.

    PubMed

    Anuthama, Krishnamurthy; Sherlin, Herald J; Anuja, N; Ramani, Pratibha; Premkumar, Priya; Chandrasekar, T

    2010-04-01

    The goal of this study was to characterize the features of normal mucosa, mucosa in betel chewers and smokers, potentially malignant lesions and squamous cell carcinoma of oral mucosa using reflectance confocal microscopy. Oral cavity biopsies were acquired from 25 patients from College of Dental Surgery, Saveetha University who underwent screening for suspected lesions of Oral precancer and Oral cancer along with normal patients who underwent impaction. Biopsies were acquired from the clinically suspicious area and immediately placed in Dulbecco modified eagles growth medium (DMEM). Reflectance confocal images were obtained at multiple image plane depths from biopsies within 6h of excision. After imaging, biopsies were fixed in 10% formalin and submitted for routine histopathological examination by an experienced oral and maxillofacial pathologist. Reflectance confocal images were compared with histological images from the same sample to determine the tissue features which contribute to early cellular changes, image contrast and early diagnosis. The confocal images were obtained to a depth of up to 150 microns on intact biopsy specimens and subsequent 3-dimensional images, keratin thickness measurements, cell measurements, cell density analysis and graphical representations were performed using Leica image analysis software. In normal mucosa keratin deposition were seen as alternating dark and bright stacks and in different cell layers the nuclei were seen as disks of varying intensities. In pre-cancerous lesions the keratin thickness and cell nuclear density were found to be increased when compared to normal controls. In OSMF cases confocal images of fibrosis show scattering from individual fibres as hyperdense areas. Oral squamous cell carcinoma cases demonstrated extensive variations in cell size, nuclear size and nuclear morphology. At cellular level, dysplastic features like increased nuclear density, increased nuclear cytoplasmic ratio, nuclear and cellular

  11. Anisotropic Bruggeman effective medium approaches for slanted columnar thin films

    NASA Astrophysics Data System (ADS)

    Schmidt, Daniel; Schubert, Mathias

    2013-08-01

    Two different formalisms for the homogenization of composite materials containing ellipsoidal inclusions based on Bruggeman's original formula for spherical inclusions can be found in the literature. Both approximations determine the effective macroscopic permittivity of such an idealized composite assuming randomly distributed dielectric particles of equal shape and differ only in the definition of the depolarization factors. The two approaches are applied to analyze ellipsometric Mueller matrix spectra acquired in the visible and near-infrared spectral region from metal and semiconductor slanted columnar thin films. Furthermore, the effective dielectric function tensor generated by the two Bruggeman formalisms is compared to effective major axes dielectric functions individually determined with a homogeneous biaxial layer approach. Best-match model parameters of all three model approaches are discussed and compared to estimates from scanning electron microscope images. The structural parameters obtained from all three optical modeling approaches agree well with the electron microscopy technique. A comparative discussion is given for the validity and applicability of the three model approaches for analysis of future devices structures that may require optical readout using generalized ellipsometry methods.

  12. 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].

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

    PubMed

    Goehring, Lucas

    2013-01-01

    When cracks form in a thin contracting layer, they sequentially break the layer into smaller and smaller pieces. A rectilinear crack pattern encodes information about the order of crack formation, as later cracks tend to intersect with earlier cracks at right angles. In a hexagonal pattern, in contrast, the angles between all cracks at a vertex are near 120°. Hexagonal crack patterns are typically seen when a crack network opens and heals repeatedly, in a thin layer, or advances by many intermittent steps into a thick layer. Here, it is shown how both types of pattern can arise from identical forces, and how a rectilinear crack pattern can evolve towards a hexagonal one. Such an evolution is expected when cracks undergo many opening cycles, where the cracks in any cycle are guided by the positions of cracks in the previous cycle but when they can slightly vary their position and order of opening. The general features of this evolution are outlined and compared with a review of the specific patterns of contraction cracks in dried mud, polygonal terrain, columnar joints and eroding gypsum-sand cements.

  14. 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

  15. Responses of cultured smooth muscle cells from human nonatherosclerotic arteries and primary stenosing lesions after photoradiation: Implications for photodynamic therapy of vascular stenoses

    SciTech Connect

    Dartsch, P.C.; Ischinger, T.; Betz, E. )

    1990-06-01

    Cultured smooth muscle cells from human nonatherosclerotic arteries and from primary stenosing lesions were labeled with dihematoporphyrinester and ether, a photosensitizing probe used mainly for the detection and photodynamic therapy of tumors. After labeling for 24 h, cells were irradiated with ultraviolet light (wavelength 365 nm, energy densities ranging from 30 to 1,200 mJ/cm{sup 2}). Twenty-four hours after photoradiation, 80% of smooth muscle cells from nonatherosclerotic arteries and only 20% of smooth muscle cells from atherosclerotic plaques were viable and still adherent. Moreover, dynamic cell and cytoskeletal alterations in response to irradiation are described. The differential sensitivity of smooth muscle cells from nonatherosclerotic arteries and from atherosclerotic plaques provides evidence that a photodynamic treatment might be a valuable therapeutic approach to vascular stenosis.

  16. 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

  17. Statistic study on developing condition of horizontal columnar joints in Jeongja and Eupchon beach areas, SE Korea

    NASA Astrophysics Data System (ADS)

    Jin, K.; Kim, Y.; Geologic Structure; Geohazard Research Group

    2010-12-01

    Unusual patterns of columnar joints are developed in Tertiary volcanic rocks along the Jeongja and Eupchon beach areas, SE Korea. The columnar joints represent various features in shape and orientation, including horizontal and inclined column distribution. The shape and orientation of columnar joints were statistically analyzed to understand the causes of the unusual column patterns. For this purpose, the shape of the column face perpendicular to the column direction and the trend and plunge of the column are analyzed. Most columnar joints in the study areas have five or six column faces, and the column diameter perpendicular to the column direction is in a range of between 30 to 50 cm. Columnar joints generally develop vertically due to cooling from both top and bottom surfaces. However, unusual horizontal and inclined columnar joints are observed in the study areas. Therefore, the horizontal and inclined columnar joints developed in the study areas may suggest abnormal cooling condition. The volcanic rocks in the study areas intruded or extruded in late Miocene (22-16 Ma), which coincides with a period of high sea level in the Miocene. The sea level is almost the same as the present sea level. This may suggest that the unusual columnar joint patterns that have developed in the study areas may have been affected by sea water. Therefore, if the characteristics of these columnar joints are more intensively studied on a morphological, petrological, geochemical, and chronological level, we can better understand the developing mechanism of horizontal columnar joints.

  18. Cognitive performances and locomotor activity following dentate granule cell damage in rats: role of lesion extent and type of memory tested.

    PubMed

    Jeltsch, H; Bertrand, F; Lazarus, C; Cassel, J C

    2001-07-01

    Intradentate injection of colchicine is one of the techniques used to destroy granule cells. This study compared the behavioral effects of various amounts of colchicine (1.0, 3.0, and 6.0 microg; Col 1, Col 3, and Col 6, respectively) injected into the dentate gyrus of adult Long-Evans male rats. Starting 10 days after lesion surgery, behavioral testing assessed home-cage and open-field locomotion, alternation in a T-maze, water-maze, and radial-maze learning according to protocols placing emphasis on reference, and working memory. All of these tasks are sensitive to hippocampal disruption. Histological verifications showed that the extent of the lesions depends on the dose of colchicine (index of dentate gyrus shrinkage: -33% in Col 1, -54% in Col 3, and -67% in Col 6 rats). Colchicine dose-dependently increased nocturnal home cage activity (an effect found 10 days but not 5 months after surgery), but had no significant effect on open-field locomotion or T-maze alternation. A dose-dependent reference memory impairment was found during the acquisition of spatial navigation in the water maze; Col 3 and Col 6 rats were more impaired than Col 1 rats. During the probe trial (platform removed), control rats spent a longer distance swimming over the platform area than all rats with colchicine lesions. In the working memory version of the test, all rats with colchicine lesions showed significant deficits. The deficits were larger in Col 3 and Col 6 rats compared to Col 1 rats. The lesions had no effect on swimming speed. In the radial-maze test, there was also a dose-dependent working memory impairment. However, reference memory was disrupted in a manner that did not differ among the three groups of lesioned rats. Our data are in line with the view that the dentate gyrus plays an important role in the acquisition of new information and is an integral neural substrate for spatial reference and spatial working memory. They also suggest that damage to granule cells might

  19. 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.

  20. Novel variants of muscle calpain 3 identified in human melanoma cells: cisplatin-induced changes in vitro and differential expression in melanocytic lesions.

    PubMed

    Moretti, D; Del Bello, B; Cosci, E; Biagioli, M; Miracco, C; Maellaro, E

    2009-06-01

    Calpains are cysteine proteases comprising members ubiquitously expressed in human tissues and other tissue-specific isoforms. Alterations of calpain 3 (p94), the muscle-specific isoform that contains three peculiar sequences (NS, IS1 and IS2), are strictly associated to the limb-girdle muscular dystrophy type 2A, in which a myonuclear apoptosis has been documented. Our recent demonstration of a proapoptotic role of ubiquitous calpains in drug-induced apoptosis of melanoma cells prompted us to investigate the expression of calpain 3 in human melanoma cell lines undergoing apoptosis and in melanocytic lesions. In melanoma cell lines, we have identified two novel splicing variants of calpain 3 (hMp78 and hMp84): they have an atypical initiation exon and a putative nuclear localization signal, the shorter one lacks IS1 inset and both proteins are extremely unstable. Virtually, both isoforms (prevalently as cleavage forms) are localized in cytoplasm and in nucleoli. In cisplatin-treated preapoptotic cells, an increase of both transcription and autoproteolytic cleavage of the novel variants is observed; the latter event is prevented by the inhibitor of ubiquitous calpains, calpeptin, which is also able to protect from apoptosis. Interestingly, among melanocytic lesions, the expression of these novel variants is significantly downregulated, compared with benign nevi, in the most aggressive ones, i.e. in vertical growth phase melanoma and, even more, in metastatic melanoma cells, characterized by invasiveness properties and usually highly resistant to apoptosis. On the whole, our observations suggest that calpain 3 variants can play a proapoptotic role in melanoma cells and its downregulation, as observed in highly aggressive lesions, could contribute to melanoma progression. PMID:19386580

  1. Prefrontal cortical recordings with biomorphic MEAs reveal complex columnar-laminar microcircuits for BCI/BMI implementation

    PubMed Central

    Opris, Ioan; Fuqua, Joshua L; Gerhardt, Greg A.; Hampson, Robert E.; Deadwyler, Sam A.

    2015-01-01

    The mammalian prefrontal cortex known as the seat of high brain functions uses a six layer distribution of minicolumnar neurons to coordinate the integration of sensory information and the selection of relevant signals for goal driven behavior. To reveal the complex functionality of these columnar microcircuits we employed simultaneous recordings with several configurations of biomorphic microelectrode arrays (MEAs) within cortical layers in adjacent minicolumns, in four nohuman primates (NHPs) performing a delayed match-to-sample (DMS) visual discrimination task. We examined: 1) the functionality of inter-laminar, and inter-columnar interactions between pairs of cells in the same or different minicolumns by use of normalized cross-correlation histograms (CCH), 2) the modulation of Glutamate concentration in layer 2/3, and 3) the potential interactions within these microcircuits. The results demonstrate that neurons in both infra-granular and supra-granular layers interact through inter-laminar loops, as well as through intra-laminar to produce behavioral response signals. These results provide new insights into the manner in which prefrontal cortical microcircuitry integrates sensory stimuli used to provide behaviorally relevant signals that may be implemented in brain computer/machine interfaces (BCI/BMIs) during performance of the task. PMID:24954713

  2. Identification and expression profile of multiple genes in channel catfish fry 10 min after modified live Flavobacterium columnare vaccination.

    PubMed

    Pridgeon, Julia W; Klesius, Phillip H

    2010-11-15

    Using PCR-select subtractive cDNA hybridization technique, 32 expressed sequence tags (ESTs) were isolated from 96 clones of a channel catfish (Ictalurus punctatus) fry subtractive library 10min post-vaccination with a modified live Flavobacterium columnare vaccine. The transcription levels of the 32 ESTs in response to F. columnare vaccination were then evaluated by quantitative PCR (QPCR). Of the 32 ESTs, 28 were upregulated in at least one vaccinated fish. Of the 28 upregulated ESTs, 12 were consistently induced at least 2-fold higher in vaccinated fish compared to unvaccinated control fish. Of the 12 upregulated genes, three (triglyceride lipase, PIKK family atypical protein kinase, and CCR4-NOT transcription complex subunit 1) were consistently upregulated greater than 3-fold. The 12 consistently upregulated genes also included CD59, polymerase (RNA) I polypeptide C, pyrophosphatase (inorganic) 1, mannose-P-dolichol utilization defect 1, nascent polypeptide-associated complex subunit alpha, hemoglobin-beta, fetuin-B, glyoxalase domain containing 4, and putative histone H3. The 28 upregulated ESTs represent genes with putative functions in the following five major categories: (1) immune response (46%); (2) signal transduction (21%); (3) transcriptional regulation (11%); (4) cell maintenance (11%); and (5) unknown (11%).

  3. 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.

  4. Lesion mimic mutants

    PubMed Central

    Moeder, Wolfgang

    2008-01-01

    Over the last decade a substantial number of lesion mimic mutants (LMM) have been isolated and a growing number of the genes have been cloned. It is now becoming clear that these mutants are valuable tools to dissect various aspects of programmed cell death (PCD) and pathogen resistance pathways in plants. Together with other forward genetics approaches LMMs shed light on the PCD machinery in plant cells and revealed important roles for sphingolipids, Ca2+ and chloroplast-derived porphyrin-metabolites during cell death development. PMID:19513227

  5. 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.

  6. Evaluation for High-risk HPV in Squamous Cell Carcinomas and Precursor Lesions Arising in the Conjunctiva and Lacrimal Sac.

    PubMed

    Afrogheh, Amir H; Jakobiec, Frederick A; Hammon, Rebecca; Grossniklaus, Hans E; Rocco, James; Lindeman, Neal I; Sadow, Peter M; Faquin, William C

    2016-04-01

    High-risk human papilloma virus (HR-HPV) is a well-established causative agent of oropharyngeal squamous cell carcinoma (SCC). In addition, HR-HPV has occasionally been reported to be present in dysplastic and malignant lesions of the conjunctiva and lacrimal sac, although its overall incidence and etiological role in periocular SCC are controversial. Sequential surgical samples of 52 combined cases of invasive SCC (I-SCC) and SCC in situ (SCCIS) from 2 periocular sites (conjunctiva and lacrimal sac) diagnosed over a 14-year period (2000 to 2014) were selected for evaluation, and relevant patient characteristics were documented. p16 immunohistochemistry was performed as a screening test. All p16-positive cases were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by polymerase chain reaction (PCR). Of 43 ocular surface squamous neoplasias (OSSNs), 30% (n=13; 8 SCCIS and 5 I-SCC cases) were positive for HR-HPV. HPV-positive OSSNs occurred in 8 men and 5 women with a mean age of 60 years (range, 39 to 94 y). HPV type-16 was detected in all conjunctival cases evaluated by PCR. All 5 conjunctival I-SCCs were nonkeratinizing (n=4) or partially keratinizing (n=1) and managed by simple excision. In contrast, HPV-negative conjunctival I-SCCs were predominantly keratinizing (11 keratinizing and 2 nonkeratinizing). Of 9 lacrimal sac I-SCCs (LSSCCs), 66.7% (n=6) were positive for HR-HPV by p16 and DNA ISH; HPV subtypes were HPV-16 (n=5) and HPV-58 (n=1). In addition, 2 p16-positive cases with negative DNA ISH results were HR-HPV positive (HPV-16 and HPV-33) when evaluated by PCR, suggesting that the rate of HR-HPV positivity among the LSSCCs may be as high as 89% (n=8). The combined group of HR-HPV-positive LSSCCs was seen in 4 men and 4 women with a mean age of 60 years (range, 34 to 71 y). Seven of the 8 HPV-positive LSSCCs (87.5%) had a nonkeratinizing or partially keratinizing histomorphology, whereas 1 case (12

  7. Evaluation for High-risk HPV in Squamous Cell Carcinomas and Precursor Lesions Arising in the Conjunctiva and Lacrimal Sac.

    PubMed

    Afrogheh, Amir H; Jakobiec, Frederick A; Hammon, Rebecca; Grossniklaus, Hans E; Rocco, James; Lindeman, Neal I; Sadow, Peter M; Faquin, William C

    2016-04-01

    High-risk human papilloma virus (HR-HPV) is a well-established causative agent of oropharyngeal squamous cell carcinoma (SCC). In addition, HR-HPV has occasionally been reported to be present in dysplastic and malignant lesions of the conjunctiva and lacrimal sac, although its overall incidence and etiological role in periocular SCC are controversial. Sequential surgical samples of 52 combined cases of invasive SCC (I-SCC) and SCC in situ (SCCIS) from 2 periocular sites (conjunctiva and lacrimal sac) diagnosed over a 14-year period (2000 to 2014) were selected for evaluation, and relevant patient characteristics were documented. p16 immunohistochemistry was performed as a screening test. All p16-positive cases were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by polymerase chain reaction (PCR). Of 43 ocular surface squamous neoplasias (OSSNs), 30% (n=13; 8 SCCIS and 5 I-SCC cases) were positive for HR-HPV. HPV-positive OSSNs occurred in 8 men and 5 women with a mean age of 60 years (range, 39 to 94 y). HPV type-16 was detected in all conjunctival cases evaluated by PCR. All 5 conjunctival I-SCCs were nonkeratinizing (n=4) or partially keratinizing (n=1) and managed by simple excision. In contrast, HPV-negative conjunctival I-SCCs were predominantly keratinizing (11 keratinizing and 2 nonkeratinizing). Of 9 lacrimal sac I-SCCs (LSSCCs), 66.7% (n=6) were positive for HR-HPV by p16 and DNA ISH; HPV subtypes were HPV-16 (n=5) and HPV-58 (n=1). In addition, 2 p16-positive cases with negative DNA ISH results were HR-HPV positive (HPV-16 and HPV-33) when evaluated by PCR, suggesting that the rate of HR-HPV positivity among the LSSCCs may be as high as 89% (n=8). The combined group of HR-HPV-positive LSSCCs was seen in 4 men and 4 women with a mean age of 60 years (range, 34 to 71 y). Seven of the 8 HPV-positive LSSCCs (87.5%) had a nonkeratinizing or partially keratinizing histomorphology, whereas 1 case (12

  8. 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

  9. Modeling of current distribution on smooth and columnar platinum structures.

    PubMed

    Zinola, Carlos F

    2011-01-17

    Studying the growth and stability of anisotropic or isotropic disordered surfaces in electrodeposition is of importance in catalytic electrochemistry. In some cases, the metallic nature of the electrode defines the topography and roughness, which are also controlled by the experimental time and applied external potential. Because of the experimental restrictions in conventional electrochemical techniques and ex situ electron microscopies, a theoretical model of the surface geometry could aid in understanding the electrodeposition process and current distributions. In spite of applying a complex theory such as dynamic scaling method or perturbation theories, the resolution of mixed mass-/charge-transfer equations (tertiary distribution) for the electrodeposition process would give reliable information. One of the main problems with this type of distribution is the mathematics when solving the spatial n-dimensional differential equations. Use of a primary current distribution is proposed here to simplify the differential equations; however it limits wide application of the first assumption. Distributions of concentration profile, current density, and electrode potential are presented here as a function of the distance normal to the surface for the cases of smooth and rough platinum growth. In the particular case of columnar surfaces, cycloid curves are used to model the electrode, from which the concentration profile is presented in a parameterized form after solving a first-type curvilinear integral. The concentration contour results in a combination of a trigonometric inverse function and a linear distribution leading to a negative concavity curve. The calculation of the current density and electrode potential contours also show trigonometric shapes exhibiting forbidden imaginary values only at the minimal values of the trochoid curve.

  10. 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.

  11. 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

  12. Molecular pathobiology of human cervical high-grade lesions: paracrine STAT3 activation in tumor-instructed myeloid cells drives local MMP-9 expression.

    PubMed

    Schröer, Nadine; Pahne, Jennifer; Walch, Barbara; Wickenhauser, Claudia; Smola, Sigrun

    2011-01-01

    In many tumors, the switch from precancerous lesions to malignancy critically relies on expression of the matrix-metalloprotease MMP-9, which is predominantly provided by infiltrating inflammatory cells. Our study defines a novel molecular cascade, how human neoplastic cells instruct tumor-associated myeloid cells to produce MMP-9. In biopsies of human papillomavirus-associated precancerous cervical intraepithelial neoplasia (CIN III lesions), we show broad activation of the transcription factor STAT3 and coexpression of MMP-9 in perivascular inflammatory cells. For the first time, we establish a causative link between tumor-mediated paracrine STAT3 activation and MMP-9 production by human tumor-instructed monocytes, whereas NF-κB activation is dispensable for this response. Our data provide evidence that STAT3 does not directly induce MMP-9 but first leads to a strong production of the monocyte chemoattractant protein-1 (CCL2) in the nanogram range. In a second phase, autocrine stimulation of the CCR2 receptor in the tumor-instructed monocytes amplifies MMP-9 expression via intracellular Ca(2+) signaling. These findings elucidate a critical mechanism in the molecular pathobiology of cervical carcinogenesis at the switch to malignancy. Particularly in tumors, which are associated with infectious agents, STAT3-driven inflammation may be pivotal to promote carcinogenesis, while at the same time limit NF-κB-dependent immune responses and thus rejection of the infected preneoplastic cells. The molecular cascade defined in this study provides the basis for a rational design of future adjuvant therapies of cervical precancerous lesions.

  13. Correlation of E6 and E7 levels in high-risk HPV16 type cervical lesions with CCL20 and Langerhans cells.

    PubMed

    Jiang, B; Xue, M

    2015-09-08

    The human papillomavirus (HPV)16 E6 and E7 correlation with chemokine ligand (CCL)20 expression and Langerhans cells (LCs) in cervical lesions was investigated. We enrolled 43 patients with surgically treated cervical lesions from the Department of Gynecology in our hospital, and 20 controls without cervical lesions. Subjects were divided by pathology: HPV16(-) and HPV16(+) normal cervical groups (N = 10 each), and HPV16(+) cervical intraepithelial neoplasia (CIN), cervical invasive carcinoma (N = 15 each), and in situ carcinoma (N = 13) groups. E6, E7, the LC surface marker CD1a, and CCL20 were analyzed by immunohistochemistry. E6 and E7 in HPV16-type lesions were correlated with CCL20 and LCs. The average high power field cell numbers of CD1a+ LCs in the HPV(-) and HPV(+) normal cervix groups, and the CINI-II, CINIII in situ and cervical carcinoma groups were 22.89 ± 4.84, 13.7 ± 2.26, 9.2 ± 1.68, 5.9 ± 1.59, and 5.5 ± 1.58, respectively. Significant between-group differences existed except between cervical carcinoma and CINIII groups (P < 0.05). CCL20+ rates in each group were 70, 60, 60, 15.38, and 13.33%, respectively. E6/E7-positive expression rates in each group were 20/20, 66.7/66.7, 76.9/69.2, and 86.67/73.3%, respectively. CCL20 was positively correlated with CD1a (r = 0.649), and negatively correlated with E7 (r = -0.946) and E6 (r = -0.949). CD1a was negatively correlated with E6 (r = -0.632) and E7 (r = -0.632). Downregulation of CCL20 leading to LC decline is a key factor in cervical lesions. High-risk HPV-type lesions might inhibit the chemokine CCL20 through E6 and E7 to escape the immune response.

  14. 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.

  15. 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

  16. Brain lesions comprised of aluminum-rich cells that lack microtubules may be associated with the cognitive deficit of Alzheimer's disease.

    PubMed

    Walton, J R

    2009-11-01

    A recent longitudinal study described an inducible rodent model for age-related cognitive deterioration. This model was produced by chronically feeding rats aluminum, from age 12 months onwards, in measured amounts equivalent to total aluminum levels ingested by Americans from their food, beverages and aluminum additives. The rats performed a hippocampal-dependent spatial memory discrimination task weekly throughout middle age and old age. One-third of the rats attained significantly lower mean performance scores in old age than middle age, in an aluminum dose-dependent manner, and exhibited behavioral signs observed in dementia. The present study used histological and immunohistochemical techniques to identify neuropathological difference between brains of rats that showed cognitive deterioration and the cognitively intact controls. Most aged rat brains had large numbers of aluminum-loaded pyramidal cells in their entorhinal cortex and temporal association cortex but the cognitively deteriorated rats had threefold more such cells than controls (p<0.01). A distinguishing feature was that all brains of the cognitively deteriorated rats, and none of controls, had at least one substantial hippocampal lesion that consisted of aluminum-rich microtubule-depleted pyramidal cells with shriveled processes, and loss of synapse density. Corticolimbic sections from brains of humans with Alzheimer's disease also showed neuropathology consistent with this type of damage. The evidence suggests bioavailable aluminum gradually accumulates in cortical and limbic regions of susceptible subjects' brains, eventually producing hippocampal lesions consisting of dysfunctional aluminum-rich microtubule-depleted pyramidal cells with damaged neurites and synapse loss. These lesions expand over time, disrupting afferent and efferent hippocampal circuitry with the development of clinically overt dementia.

  17. 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.

  18. An enteric nervous system progenitor cell implant promotes a behavioral and neurochemical improvement in rats with a 6-OHDA-induced lesion.

    PubMed

    Parra-Cid, Carmen; García-López, Julieta; García, Esperanza; Ibarra, Clemente

    2014-01-01

    The enteric nervous system (ENS) of mammals is derived from neural crest (NC) cells during embryogenesis and at the beginning of postnatal life. However, neural progenitor cells from the ENS (or ENSPC) are also found in the adult intestine and can be used for neuronal regeneration in diseases that lead to a loss of cell population, such as Parkinson's disease (PD), in which there is a decrease of dopaminergic neurons. The objective of this study was to evaluate the capacity of ENSPC to restore damaged nervous tissue and to show that they are functional for a behavioral and neurochemical recovery. We found that animals with ENSPC implants exhibited a motor recovery of 35% vs. the lesion group. In addition, DA levels were partially restored in 34%, while Homovanillic acid (HVA) levels remained at 21% vs. the group with a 6-Hydroxydopamine (6-OHDA)-induced lesion, suggesting that ENSPC represent a possible alternative in the study of cell transplants and the preservation of functional dopaminergic neurons in PD.

  19. 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

  20. 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.

  1. 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

  2. Co-transplantation of carotid body and ventral mesencephalic cells as an alternative approach towards functional restoration in 6-hydroxydopamine-lesioned rats: implications for Parkinson's disease.

    PubMed

    Shukla, S; Agrawal, A K; Chaturvedi, R K; Seth, K; Srivastava, N; Sinha, C; Shukla, Y; Khanna, V K; Seth, P K

    2004-10-01

    Exogenous administration of various neurotrophic factors has been shown to protect neurons in animal model of Parkinson's disease (PD). Several attempts are being made to search a tissue source simultaneously expressing many of these neurotrophic factors. Carotid body (CB) contains oxygen-sensitive glomus cells rich in dopamine (DA) and expresses glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor and neurotrophin-3. We have attempted to study the functional restoration following co-transplantation of CB cells and ventral mesencephalic cells (VMC) in a 6-hydroxydopamine-lesioned rat model of PD. A significant recovery (p < 0.001) in d-amphetamine-induced circling behavior (80%) and spontaneous locomotor activity (85%) was evident in co-transplanted animals at 12 weeks post-transplantation as compared to lesioned animals. Similarly, a significant (p < 0.001) restoration was observed in DA-D(2) receptor binding (77%), striatal DA (87%) and 3,4-dihydroxyphenylacetic acid (DOPAC) (85%) levels and nigral DA (75%) and DOPAC (74%) levels. Functional recovery was accompanied by tyrosine hydroxylase (TH) expression and quantification of TH-positive cells by image analysis revealed a significant restoration in TH-immunoreactive (IR) fiber density in striatum, as well as TH-IR neurons in substantia nigra pars compacta in co-transplanted animals over VMC-transplanted animals. The result suggests that co-transplantation of CB cells along with VMC provides better and long-term functional restoration in the rat model of PD, possibly by supporting the survival of newly grafted cells as well as remaining host DA neurons. PMID:15447661

  3. A Large Repetitive RTX-Like Protein Mediates Water-Soaked Lesion Development, Leakage of Plant Cell Content and Host Colonization in the Pantoea stewartii subsp. stewartii Pathosystem.

    PubMed

    Roper, M Caroline; Burbank, Lindsey P; Williams, Kayla; Viravathana, Polrit; Tien, Hsin-Yu; von Bodman, Susanne

    2015-12-01

    Pantoea stewartii subsp. stewartii is the etiological agent of Stewart's wilt and is a serious bacterial pathogen affecting sweet corn. During the leaf blight phase, P. stewartii colonizes the leaf apoplast and causes a characteristic water-soaked lesion. The Hrp type III secretion system has been implicated in the water-soaking phenotype, and the goal of this study was to investigate other potential factors that contribute to the plant cellular disruption associated with these lesions. The P. stewartii genome contains a gene encoding a large repetitive RTX toxin, designated rtx2. RTX toxins comprise a large family of pore-forming proteins, which are widely distributed among gram-negative bacteria. These cytotoxins usually lyse their target host cells and cause significant tissue damage as a consequence. We hypothesized that this RTX-like toxin plays a role in the water-soaking phase of infection due to its predicted cytolytic properties. Based on the data reported here, we conclude that RTX2 contributes significantly to the development of water-soaked lesions and leakage of plant cellular contents and is an important pathogenicity factor for P. stewartii.

  4. Accuracy of autofluorescence in diagnosing oral squamous cell carcinoma and oral potentially malignant disorders: a comparative study with aero-digestive lesions

    PubMed Central

    Luo, Xiaobo; Xu, Hao; He, Mingjing; Han, Qi; Wang, Hui; Sun, Chongkui; Li, Jing; Jiang, Lu; Zhou, Yu; Dan, Hongxia; Feng, Xiaodong; Zeng, Xin; Chen, Qianming

    2016-01-01

    Presently, various studies had investigated the accuracy of autofluorescence in diagnosing oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) with diverse conclusions. This study aimed to assess its accuracy for OSCC and OPMD and to investigate its applicability in general dental practice. After a comprehensive literature search, a meta-analysis was conducted to calculate the pooled diagnostic indexes of autofluorescence for premalignant lesions (PML) and malignant lesions (ML) of the oral cavity, lung, esophagus, stomach and colorectum and to compute indexes regarding the detection of OSCC aided by algorithms. Besides, a u test was performed. Twenty-four studies detecting OSCC and OPMD in 2761 lesions were included. This demonstrated that the overall accuracy of autofluorescence for OSCC and OPMD was superior to PML and ML of the lung, esophagus and stomach, slightly inferior to the colorectum. Additionally, the sensitivity and specificity for OSCC and OPMD were 0.89 and 0.8, respectively. Furthermore, the specificity could be remarkably improved by additional algorithms. With relatively high accuracy, autofluorescence could be potentially applied as an adjunct for early diagnosis of OSCC and OPMD. Moreover, approaches such as algorithms could enhance its specificity to ensure its efficacy in primary care. PMID:27416981

  5. Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells.

    PubMed

    Steinsbø, Øyvind; Henry Dunand, Carole J; Huang, Min; Mesin, Luka; Salgado-Ferrer, Marlene; Lundin, Knut E A; Jahnsen, Jørgen; Wilson, Patrick C; Sollid, Ludvig M

    2014-06-09

    Coeliac disease (CD), an enteropathy caused by cereal gluten ingestion, is characterized by CD4(+) T cells recognizing deamidated gluten and by antibodies reactive to gluten or the self-antigen transglutaminase 2 (TG2). TG2-specific immunoglobulin A (IgA) of plasma cells (PCs) from CD lesions have limited somatic hypermutation (SHM). Here we report that gluten-specific IgA of lesion-resident PCs share this feature. Monoclonal antibodies were expression cloned from single PCs of patients either isolated from cultures with reactivity to complex deamidated gluten antigen or by sorting with gluten peptide tetramers. Typically, the antibodies bind gluten peptides related to T-cell epitopes and many have higher reactivity to deamidated peptides. There is restricted VH and VL combination and usage among the antibodies. Limited SHM suggests that a common factor governs the mutation level in PCs producing TG2- and gluten-specific IgA. The antibodies have potential use for diagnosis of CD and for detection of gluten.

  6. 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.

  7. A 3-phase model for mixed columnar-equiaxed solidification in DC casting of bronze

    NASA Astrophysics Data System (ADS)

    Hao, J.; Grasser, M.; Wu, M.; Ludwig, A.; Riedle, J.; Eberle, R.

    2012-01-01

    A three-phase Eulerian approach is used to model the columnar-to-equiaxed transition (CET) during solidification in DC casting of technical bronze. The three phases are the melt, the solidifying columnar dendrites and the equiaxed grains. They are considered as spatially interpenetrating and interacting continua by solving the conservation equations of mass, momentum, species and enthalpy for all three phases. The so defined solidification model is applied to a binary CuSn6 DC casting process as a benchmark to demonstrate the model potentials. Two cases are studied: one considering only feeding flow and one including both feeding flow and equiaxed sedimentation. The simulated results of mixed columnar and equiaxed solidification are presented and discussed including the occurrence of CET, phase distribution, feeding flow, equiaxed sedimentation and their influence on macrosegregation.

  8. 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. PMID:24110073

  9. 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.

  10. Examination of tissue distribution of Helicobacter pylori within columnar-lined esophagus.

    PubMed

    Sharma, V K; Demian, S E; Taillon, D; Vasudeva, R; Howden, C W

    1999-06-01

    H. pylori may colonize columnar-lined esophagus, although an etiologic role in esophageal adenocarcinoma is unproven. H. pylori can adhere to intestinal metaplasia in the stomach. This study was designed to examine if H. pylori adheres to specialized intestinal metaplasia in columnar-lined esophagus. Esophageal biopsies from patients with columnar-lined esophagus were reviewed. Patients with only gastric metaplasia were excluded. Sections with specialized intestinal metaplasia in at least one third of at least one gland were recut, stained using the Giemsa stain, and reexamined by two independent pathologists using strict criteria for adherence by H. pylori. The 209 esophageal biopsies with adequate specialized intestinal metaplasia from 58 patients were examined: H. pylori was only seen on gastric metaplasia in three patients-and never on specialized intestinal metaplasia. Within the esophagus, H. pylori adheres only to gastric metaplasia, which is not considered premalignant for esophageal adenocarcinoma. PMID:10389690

  11. A theoretical study of CsI:Tl columnar scintillator image quality parameters by analytical modeling

    NASA Astrophysics Data System (ADS)

    Kalyvas, N.; Valais, I.; Michail, C.; Fountos, G.; Kandarakis, I.; Cavouras, D.

    2015-04-01

    Medical X-ray digital imaging systems such as mammography, radiography and computed tomography (CT), are composed from efficient radiation detectors, which can transform the X-rays to electron signal. Scintillators are materials that emit light when excited by X-rays and incorporated in X-ray medical imaging detectors. Columnar scintillator, like CsI:T1 is very often used for X-ray detection due to its higher performance. The columnar form limits the lateral spread of the optical photons to the scintillator output, thus it demonstrates superior spatial resolution compared to granular scintillators. The aim of this work is to provide an analytical model for calculating the MTF, the DQE and the emission efficiency of a columnar scintillator. The model parameters were validated against published Monte Carlo data. The model was able to predict the overall performance of CsI:Tl scintillators and suggested an optimum thickness of 300 μm for radiography applications.

  12. A rare co-existence of focal xanthogranulomatous pyelonepheritis, angiomyolipoma and renal cysts simulating renal cell carcinoma.

    PubMed

    Nabi, G; Greene, D; Marsh, R; Viljoen, A

    A 70-year-old male presented with left flank pain and history of gross, total painless haematuria of 6 months duration. Investigations revealed a large solid and cystic mass suggestive of renal cell carcinoma in left kidney with possible infiltration of left psoas muscle. Histology of radical nephrectomy showed angiomyolipoma with multiple cysts lined by columnar epithelium suggestive of tuberous sclerosis and focal area of xanthogranulomatous pyelonepheritis. The rare combination of such lesions leading to diagnostic dilemma has not been reported in medical literature to the best of our knowledge.

  13. Peripheral facial nerve lesions induce changes in the firing properties of primary motor cortex layer 5 pyramidal cells.

    PubMed

    Múnera, A; Cuestas, D M; Troncoso, J

    2012-10-25

    Facial nerve lesions elicit long-lasting changes in vibrissal primary motor cortex (M1) muscular representation in rodents. Reorganization of cortical representation has been attributed to potentiation of preexisting horizontal connections coming from neighboring muscle representation. However, changes in layer 5 pyramidal neuron activity induced by facial nerve lesion have not yet been explored. To do so, the effect of irreversible facial nerve injury on electrophysiological properties of layer 5 pyramidal neurons was characterized. Twenty-four adult male Wistar rats were randomly subjected to two experimental treatments: either surgical transection of mandibular and buccal branches of the facial nerve (n=18) or sham surgery (n=6). Unitary and population activity of vibrissal M1 layer 5 pyramidal neurons recorded in vivo under general anesthesia was compared between sham-operated and facial nerve-injured animals. Injured animals were allowed either one (n=6), three (n=6), or five (n=6) weeks recovery before recording in order to characterize the evolution of changes in electrophysiological activity. As compared to control, facial nerve-injured animals displayed the following sustained and significant changes in spontaneous activity: increased basal firing frequency, decreased spike-associated local field oscillation amplitude, and decreased spontaneous theta burst firing frequency. Significant changes in evoked-activity with whisker pad stimulation included: increased short latency population spike amplitude, decreased long latency population oscillations amplitude and frequency, and decreased peak frequency during evoked single-unit burst firing. Taken together, such changes demonstrate that peripheral facial nerve lesions induce robust and sustained changes of layer 5 pyramidal neurons in vibrissal motor cortex. PMID:22877641

  14. 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.

  15. A Combined Study of Mesomorphism, Optical and Electronic Properties of Novel Columnar Liquid Crystals

    NASA Astrophysics Data System (ADS)

    Chen, Shuai

    Columnar mesophases of discotic liquid crystals (DLCs) are a separate class of organic semiconductors. Anisotropic charge transport, high charge carrier mobility, and self-organizing properties have been regarded as superior properties of DLCs but their performance in devices, such as organic light-emitting diodes, has been inferior to the best performing conventional organic semiconductors. Our group recently demonstrated that a DLC of donor-acceptor structure can bias electron over hole conduction if the occupied and unoccupied frontier orbitals are localized on different parts of the molecule and only the unoccupied frontier orbitals electronically interact in columnar stacks. This thesis describes the first systematic approach to different types of donor-acceptor DLCs and the investigation of their mesomorphism and optoelectronic properties. In spite of their large aspect ratios, four board-shaped donor-acceptor-donor quinoxalinophenanthrophenazine (QPP) dyes (Chapters 2 and 3) induce complex columnar mesomorphism over wide temperature ranges. These QPP derivatives also show strong fluorescence in solution and as thin films. This strong fluorescence in columnar mesophases is explained with a nonparallel orientation of the elongated donor-acceptor cores in the columnar stacks that minimizes interactions between transition dipole moments of co-facially stacked molecules. Opto-electronic properties suggest that the QPP derivatives are organic semiconductors. Inspired by the donor-acceptor concept, we generated novel ionic DLCs based on imidazole and imidazolium structures (Chapter 5). Unexpectedly, only the ionic triphenylenoimidazolium derivatives display columnar mesomorphism. Strong ionic interactions between the cores are apparently required for the formation of columnar mesophases. Overall, these compounds are rather unusual because few ionic DLCs have the charge localized on the aromatic core. Most often the charged group is attached via spacer chains. A

  16. 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

  17. [Elevated gastric lesions].

    PubMed

    de Careaga, B; Villagómez, G; Pabón, J; Calderón, O; Elío, D; Pérez, J; Martínez, M; Patiño, F; Ponce, R; Lora, J

    1986-01-01

    Elevated gastric lesions, represent an important group among gastric pathology. To establish its incidence in our experience, we studied the endoscopic reports of two important hospitals in La Paz city: Instituto de Gastroenterología Boliviano Japonés and Hospital Obrero No. 1. In order to make a good endoscopic diagnosis among different elevated lesions we use some parameters like: location, shape, size, diameter, surface of the lesion and surrounding mucosa and characteristics of the falls. 10.472 endoscopic reports were reviewed, 497 elevated gastric lesions were found, 475 corresponded to mucosal lesions (352 benign lesions and 123 malignant lesions), 11 to submucosal and 11 extragastric lesions.

  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. 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.

  20. 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...

  1. Evaluation of potassium permanganate against an experimental subacute infection of Flavobacterium columnare in channel catfish, Icatlurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficacy of potassium permanganate (KMnO4) as a prophylactic and therapeutic treatment for subacute infection of Flavobacterium columnare was demonstrated in experimentally infected channel catfish, Ictalurus punctatus. Catfish experimentally infected with F. columnare to mimic a subacute infec...

  2. Improved Pulsed-Field Gel Electrophoresis Procedure for the Analysis of F. columnare Isolates Previously Affected by DNA Degradation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium columnare is a fresh water bacterium that causes columnaris diseases in over 36 fish species. Intra-species typing of F. columnare can be performed by pulsed-field gel electrophoresis (PFGE). However, this method is hampered by the degradation of chromosomal DNA in about 10% of strain...

  3. 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...

  4. Decreased T-cell proliferative response to common environmental antigens could be an indicator of early human immunodeficiency virus-mediated lymphocyte lesions.

    PubMed Central

    Tassinari, P; Deibis, L; Blanca, I; Bianco, N E; Echeverría de Pérez, G

    1995-01-01

    To evaluate CD4+/CD29+ cells and their responses to different antigens in polar stages of human immunodeficiency virus (HIV) infection, we studied 26 HIV-seropositive carriers (SPCs) and 15 patients with AIDS simultaneously with 20 healthy volunteers (HVs) and 10 seronegative homosexual and bisexual men (SNH). CD3, CD4, CD29, and CD45RA phenotypes were analyzed by two-color flow cytometry. Significant depletion of CD4+ T cells and both memory (CD4+/CD29+) and naive (CD4+/CD45RA+) T-cell subsets was found among SPCs and AIDS patients compared with the numbers of such cells in the HV and SNH groups. Responses to optimal doses of Candida albicans, streptokinase, and tetanus toxoid were explored in peripheral blood mononuclear cells and CD4(+)- and CD4+/CD29(+)-enriched cell populations. In SPCs, the response to C. albicans in peripheral blood mononuclear cells showed a statistically significant diminution compared with the response of HVs (15,308 versus 35,951 cpm). In addition, a significantly reduced response to streptokinase was evident only when cell preparations were CD4+/CD29+ enriched (3,048 versus 10,367 cpm). Furthermore, the SPC group comprised seven responders to at least one antigen and seven nonresponders to any of the selected specific antigens. Absence of a response in these latter patients was independent of the absolute counts of memory and naive T-cell populations. The response to tetanus toxoid, although diminished in SPCs, was not significantly different from that in controls. Our results suggest that defective responses to common environmental antigens, unrelated to the absolute number of CD4+/CD29+ cells, is probably an early indicator of an HIV-induced lymphocyte lesion. PMID:7583914

  5. 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.

  6. Effect of SDF-1/CXCR4 axis on the migration of transplanted bone mesenchymal stem cells mobilized by erythropoietin toward lesion sites following spinal cord injury

    PubMed Central

    LI, JUN; GUO, WEICHUN; XIONG, MIN; HAN, HENG; CHEN, JIE; MAO, DAN; TANG, BING; YU, HUALONG; ZENG, YUN

    2015-01-01

    Accumulating evidence has indicated that the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis plays a crucial role in the recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) into lesion sites in animal models. The aim of this study was to investigate the effects of the SDF-1/CXCR4 axis on the migration of transplanted BMSCs mobilized by erythropoietin (EPO) toward the lesion site following spinal cord injury (SCI). A model of SCI was established in rats using the modified Allen's test. In the EPO group, EPO was administered at a distance of 2 mm cranially and then 2 mm caudally from the site of injury. In the BMSC group, 10 μl of BMSC suspension was administered in the same manner. In the BMSC + EPO group, both BMSCs and EPO were administered as described above. In the BMSC + EPO + AMD3100 group, in addition to the injection of BMSCs and EPO, AMD3100 (a chemokine receptor antagonist) was administered. The Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale and a grid walk test were used to estimate the neurological recovery following SCI. Enzyme-linked immunosorbent assay (ELISA) was performed to assess the tumor necrosis factor-α (TNF-α) and SDF-1 expression levels. An immunofluorescence assay was performed to identify the distribution of the BMSCs in the injured spinal cord. A Transwell migration assay was performed to examine BMSC migration. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to detect the apoptotic index (AI). Western blot analysis was performed to measure the expression levels of erythropoietin receptor (EPOR) and CXCR4. Significant improvements in locomotor function were detected in the BMSC + EPO group compared with the BMSC group (P<0.05). GFP-labeled BMSCs were observed and were located at the lesion sites. Additionally, EPO significantly decreased the TNF-α levels and increased the SDF-1 levels in the injured spinal cord (P<0.05). The AI in the

  7. 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.

  8. Characterization of Fetal Antigen 1/Delta-Like 1 Homologue Expressing Cells in the Rat Nigrostriatal System: Effects of a Unilateral 6-Hydroxydopamine Lesion

    PubMed Central

    Liechti, Rémy; Ducray, Angélique D.; Jensen, Pia; Di Santo, Stefano; Seiler, Stefanie; Jensen, Charlotte H.; Meyer, Morten; Widmer, Hans Rudolf

    2015-01-01

    Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been suggested as a potential supplementary marker of dopaminergic neurons. The present study aimed at investigating the distribution of FA1/dlk1-immunoreactive (-ir) cells in the early postnatal and adult midbrain as well as in the nigrostriatal system of 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc dopaminergic neurons and/or due to the stab wound. Our findings hint to a significant role of FA1/dlk1 in the SNc during early postnatal development. The differential expression of FA1/dlk1 in the SNc and the striatum of dopamine-depleted rats could indicate a potential involvement of FA1/dlk1 in the cellular response to the degenerative processes. PMID:25723595

  9. A liquid-crystalline hexagonal columnar phase in highly-dilute suspensions of imogolite nanotubes.

    PubMed

    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.

  10. 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...

  11. 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...

  12. A bundled-stack discotic columnar liquid crystalline phase with inter-stack electronic coupling

    DOE PAGES

    Wang, Bin; Sun, Runkun; Günbaş, Duygu D.; Zhang, Hao; Grozema, Ferdinand C.; Xiao, Kai; Jin, Shi

    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).

  13. 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.

  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. 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.

  16. 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.

  17. Anisotropic light absorption, refractive indices, and orientational order parameter of unidirectionally aligned columnar liquid crystal films.

    PubMed

    Charlet, Emilie; Grelet, Eric

    2008-10-01

    The anisotropic optical properties of thermotropic columnar liquid crystals absorbing in the visible range are investigated for different discotic compounds unidirectionally oriented in open supported thin films. Two methods to monitor the alignment of columnar mesophases in thin films are reported, making possible to achieve either homeotropic anchoring (columns normal to the substrate) by a specific thermal annealing, or unidirectional planar orientation (columns parallel to the substrate) by using a rubbed Teflon coating. The columnar liquid crystal anchoring is found to depend on the nature of the compound, either parallel or perpendicular to the Teflon orientation. Based on this control of the mesophase alignment, the dichroic ratio and the orientational order parameter of oriented samples are measured, and a high order parameter of 0.9 is found in the case of parallel alignment. From the polarized absorption data of the columnar liquid crystal films, the light wavelength dependence of the birefringence and of the real and imaginary parts (refractive index and extinction coefficient, respectively) of the anisotropic optical indices are determined over the whole visible range. PMID:18999445

  18. 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

  19. Complex columnar hexagonal polymorphism in supramolecular assemblies of a semifluorinated electron-accepting naphthalene bisimide.

    PubMed

    Wu, Yu-Chun; Leowanawat, Pawaret; Sun, Hao-Jan; Partridge, Benjamin E; Peterca, Mihai; Graf, Robert; Spiess, Hans W; Zeng, Xiangbing; Ungar, Goran; Hsu, Chain-Shu; Heiney, Paul A; Percec, Virgil

    2015-01-21

    Simple synthetic methods for a strongly electron-accepting naphthalene bisimide (NBI) derivative functionalized with a new environmentally friendly chiral racemic semifluorinated alkyl group and with AB3 minidendrons containing the same semifluorinated group are reported. The semifluorinated dendron was attached to the imide groups of the NBI via one, two, and three (m = 1, 2, 3) methylenic units. The NBI-containing semifluorinated groups and the dendronized NBI with m = 1 and 2 self-organize into lamellar crystals. The dendronized NBI with m = 3 self-assembles into an unprecedentedly complex and ordered column that self-organizes in a columnar hexagonal periodic array. This array undergoes a continuous transition to a columnar hexagonal superlattice that does not display a first-order phase transition during analysis by differential scanning calorimetry at heating and cooling rates of 10 and 1 °C/min. These complex columnar hexagonal periodic arrays with intramolecular order could be elucidated only by a combination of powder and fiber X-ray diffraction studies and solid-state NMR experiments. The lamellar crystals self-organized from m = 1 and the two highly ordered columnar hexagonal periodic arrays of m = 3 are assembled via thermodynamically controlled processes. Since strongly electron-accepting derivatives are of great interest to replace fullerene acceptors in organic photovoltaics and for other supramolecular electronic materials, the multitechnique structural analysis methodology elaborated here must be taken into consideration in all related studies.

  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. 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. PMID:25904015

  3. 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.

  4. 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

  5. Cannabinoids and neuronal damage: differential effects of THC, AEA and 2-AG on activated microglial cells and degenerating neurons in excitotoxically lesioned rat organotypic hippocampal slice cultures.

    PubMed

    Kreutz, Susanne; Koch, Marco; Ghadban, Chalid; Korf, Horst-Werner; Dehghani, Faramarz

    2007-01-01

    Cannabinoids (CBs) are attributed neuroprotective effects in vivo. Here, we determined the neuroprotective potential of CBs during neuronal damage in excitotoxically lesioned organotypic hippocampal slice cultures (OHSCs). OHSCs are the best characterized in vitro model to investigate the function of microglial cells in neuronal damage since blood-borne monocytes and T-lymphocytes are absent and microglial cells represent the only immunocompetent cell type. Excitotoxic neuronal damage was induced by NMDA (50 microM) application for 4 h. Neuroprotective properties of 9-carboxy-11-nor-delta-9-tetrahydrocannabinol (THC), N-arachidonoylethanolamide (AEA) or 2-arachidonoylglycerol (2-AG) in different concentrations were determined after co-application with NMDA by counting degenerating neurons identified by propidium iodide labeling (PI(+)) and microglial cells labeled by isolectin B(4) (IB(4)(+)). All three CBs used significantly decreased the number of IB(4)(+) microglial cells in the dentate gyrus but the number of PI(+) neurons was reduced only after 2-AG treatment. Application of AM630, antagonizing CB2 receptors highly expressed by activated microglial cells, did not counteract neuroprotective effects of 2-AG, but affected THC-mediated reduction of IB(4)(+) microglial cells. Our results indicate that (1) only 2-AG exerts neuroprotective effects in OHSCs; (2) reduction of IB(4)(+) microglial cells is not a neuroprotective event per se and involves other CB receptors than the CB2 receptor; (3) the discrepancy in the neuroprotective effects of CBs observed in vivo and in our in vitro model system may underline the functional relevance of invading monocytes and T-lymphocytes that are absent in OHSCs. PMID:17010339

  6. High risk human papillomavirus type 16 and 18 infection in the cervical lesions of women with epithelial cell abnormality in Pap smear: A cytohistomorphologic association in Bangladeshi women

    PubMed Central

    Banik, Urmila; Ahamad, M. Shahab Uddin; Bhattacharjee, Pradip; Adhikary, Arun Kumar; Rahman, Zillur

    2013-01-01

    Background: The aim of this study was to find out the extent of high-risk human papillomavirus (hrHPV) type 16/18 infection in the cervical tissue of women with epithelial cell abnormality in Pap smear and to establish an association between hrHPV type 16/18 infection and cytohistomorphology. Materials and Methods: A cross-sectional descriptive study was carried out in 1699 patients who went through Pap smear examination. Prevalence of epithelial cell abnormality was calculated. Forty eight of these women underwent routine histopathology and 47 were evaluated for human papillomavirus (HPV) type 16/18 by polymerase chain reaction assay. Results: Total 139 women revealed epithelial cell abnormality. Histopathology showed simple inflammation to malignancy. HPV type 16/18 infection was detected in 40.42% (19/47) of the patients. Individually type 16 and 18 were positive in 7 (14.9%) cases each and dual infection with type 16 and 18 were seen in 5 (10.6%) cases. While cervical intraepithelial neoplasia grade 1 (CIN 1) and < CIN 1 lesions showed 18.75% (3 out of 16) and 35% (7 out of 20) positivity respectively, ≥CIN 2 lesions revealed positivity of 81.82% (9 out of 11). Eighty percent HPV 16/18 positivity was seen in women of < 30 years of age. Conclusion: The findings of this study will contribute to HPV 16/18 knowledge in Bangladesh that will be useful in assessing the success of current vaccines with limited type spectra and augmenting cervical cancer screening strategies. PMID:23976895

  7. 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.

  8. 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.

  9. [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.

  10. 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

  11. Surgical injury-induced early neocortical microvascular changes and characteristics of the cells populating the peri-lesion zone.

    PubMed

    Sulejczak, Dorota; Chrapusta, Stanisław J; Kozłowski, Wojciech; Frontczak-Baniewicz, Małgorzata

    2016-01-01

    Adult mammalian brain contains a number of specialized neurovascular structures termed "niches" that act as sources of neuronal cells throughout the individual's life. Some of the niches generate neurons to satisfy the need for 'replacement' neurons within the same or closely located brain structures, whereas the other can provide such cells for more distant destinations in the brain. A common characteristic of known neurovascular niches is the presence of a complex 3-dimensional network of basal lamina processes, called fractones. It apparently plays a major role in communication between the various niche-populating cell types as well as in niche activity and output. We hypothesized that similar niches may form ad hoc after a mechanical brain trauma, and tested this possibility in a rat model of surgical brain injury. Four days after removing a small fragment of sensorimotor cortex, the peri-wound region showed numerous symptoms of active repair and remodeling of brain parenchyma, including the presence of multiple cell types of immature phenotypes. The latter, as shown by a variety of light and electron microscopy techniques, included endothelial cell precursors as well as nestin-positive immature neural cells of astrocytic or non-glial characteristics. However, there was no evidence of in situ neurogenesis or a considerable migration of cells from SVZ. The centers of the said repair processes were capillary blood vessels connected with basal lamina-formed fractones. These results indicate that surgical brain trauma causes the formation of a vascular niche with no apparent neurogenic potential. PMID:27373950

  12. The Comparative Protective Effects of Ganoderma Spores Lipid and Fish Oil on N-Methyl-N-Nitrosourea-Induced Photoreceptor Cell Lesion in Rats

    PubMed Central

    Gao, Yang; Deng, Xin-Guo; Li, Na; Luo, Guang-Wei; Chung, Peter C. K.

    2011-01-01

    Purpose. To compare Ganoderma spores lipid (GSL) and fish oil (FO) in inhibiting retinal photoreceptor cell lesions induced by N-methyl-N-nitrosourea (MNU) in rats. Methods. 120 rats were untreated (normal control, NC group) or treated with a single intraperitoneal injection of 40 mg/kg MNU (MNU group) then treated with GSL (GSL group) or FO (FO group). Eyes were obtained at 1, 3, 5, 7, and 10 days. Results. Light microscopy assay demonstrated that GSL and FO alleviated rat retinal photoreceptor cell damage (GSL and FO versus MNU group P < .001) similarly (GSL versus FO group P = .980). Electron microscopy confirmed that GSL and FO reversed damage to photoreceptor segments and photoreceptor cell nuclei. GSL-treated rats showed significantly elevated a-wave and b-wave amplitudes over MNU group (P < .05) but less than NC group (P < .05) and not significantly different from FO group (P > .05). Conclusion. GSL, like FO, alleviates rat retinal photoreceptor cell damage induced by MNU. PMID:21660315

  13. Salt and stress synergize H. pylori-induced gastric lesions, cell proliferation, and p21 expression in Mongolian gerbils.

    PubMed

    Gamboa-Dominguez, Armando; Ubbelohde, Tom; Saqui-Salces, Milena; Romano-Mazzoti, Luis; Cervantes, Minerva; Domínguez-Fonseca, Claudia; de la Luz Estreber, Maria; Ruíz-Palacios, Guillermo M

    2007-06-01

    Our aim was to determine if salt and stress enhance Helicobacter pylori (Hp) lesions in Meriones unguiculatus. Two hundred seventy-eight pathogen-free gerbils were allocated to seven groups: Hp-Sydney strain (45), 8% higher-salt diet (38), stress (60% space reduction/water immersion; 36), Hp + salt (33), Hp + stress (34), N-methyl-N-nitro-N-nitrosoguanidine (34), and sham (58). Gerbils were sacrificed at 1 week (67), 12 weeks (73), 52 weeks (65), and 68 weeks (73). Sydney, Padova, and Lauren classifications were blindly used. Proliferation, p53, p21, and apoptosis were assessed. Follicular active gastritis (grade 2/3) was observed in 10% of Hp gerbils, 38% of Hp + salt gerbils, and 29% of Hp + stress gerbils at 52 weeks and 67%, 83%, and 43% at 68 weeks (P < 0.05). Heterotopic proliferative glands were identified in synergy groups from 52 weeks, with increases in their number and size by 68 weeks. Higher proliferative rates were observed in Hp+salt gerbils (P < 0.0001), and p21 overexpression in Hp+salt and Hp+stress gerbils (both P's < 0.0001), by 68 weeks, without p53 increases. We conclude that salt and stress synergize Hp damage and increase pseudo-invasive gland foci. PMID:17404882

  14. [The surgical opportunity in metastatic lesions of renal-cell carcinoma after a response to adjuvant immunotherapy].

    PubMed

    Olivier, C; Carballido, J; Lao, A H; Bellido, D; Ramón y Cajal, S; Manzano, L; Ondina, L; Alvarez-Mon, M

    1995-03-01

    Surgical resection of primary lesions and single metastasis can be curative, but surgery, used as the only therapeutic option, is not unanimously accepted in patients with multiple metastasis and, apart from other considerations, there are no established clinical criteria to allow us to predict which patients will benefit from a metastectomy. This study evaluates four patients with advanced RCC. Three had multiple pulmonary metastasis at the time of diagnosis and one presented retroperitoneal mass at 36 months of follow-up. All patients were nephrectomized and received adjuvant immunotherapy with an association of IL-2 and 2b alpha-IFN subcutaneously, obtaining partial response of the disease after two treatment courses. Later, the patients underwent debulking surgery. Two patients are still alive and have no evidence of disease progression at 28 months and 8 months of follow-up. This data and that contrasted with other authors, suggests that surgical management would be a reasonable option in patients who have partially responded to immunotherapy, even though the selection of both candidates and surgical strategy should be considered on an individual basis.

  15. Aldehydic DNA lesions in calf thymus DNA and HeLa S3 cells produced by bacterial quinone metabolites of fluoranthene and pyrene.

    PubMed

    Zielinska-Park, Joanna; Nakamura, Jun; Swenberg, James A; Aitken, Michael D

    2004-09-01

    There is increasing concern that compounds formed during the chemical or biological transformation of pollutants in the environment may be more detrimental to human and environmental health than the original pollutant. In this study, two bacterial transformation products of polycyclic aromatic hydrocarbons (PAHs), pyrene-4,5-quinone (P45Q) and fluoranthene-2,3-quinone (F23Q), were evaluated for mutagenicity by measuring aldehydic DNA lesions (ADL) in calf thymus DNA and HeLa S3 cells. Both quinones caused oxidative DNA damage in vitro through a copper-mediated redox cycle and subsequent production of reactive oxygen species (ROS). Hydrogen peroxide and copper were essential for causing oxidative DNA damage and glutathione (GSH) prevented DNA damage from F23Q better than from P45Q. In experiments using HeLa cells, F23Q decreased cell viability, but did not produce measurable levels of ADL or base oxidation. To test the hypothesis that DNA damage was being prevented by conjugation of F23Q with GSH, GSH-depleted cells were treated with both quinones. GSH depletion did not increase the toxicity of F23Q or cause it to oxidize DNA. Treatment of HeLa cells with metal chelators did not decrease F23Q toxicity. It is therefore possible that F23Q affected cell viability through a ROS-independent mechanism, either by conjugation with essential cellular proteins or through cellular or mitochondrial membrane damage, which precluded oxidation of DNA. In contrast, P45Q caused both ADL and base oxidation in cells. Neocuproine reduced the amount of ADL caused by P45Q, indicating that copper was still important for the intracellular generation of damaging oxidants. P45Q is a novel metabolite and its effects on DNA have not been investigated previously. This study exemplifies the importance of considering not only primary environmental pollutants, but also their biologically or chemically generated transformation products.

  16. Prime-Boost Vaccination with rBCG/rAd35 Enhances CD8+ Cytolytic T-Cell Responses in Lesions from Mycobacterium Tuberculosis –Infected Primates

    PubMed Central

    Rahman, Sayma; Magalhaes, Isabelle; Rahman, Jubayer; Ahmed, Raija K; Sizemore, Donata R; Scanga, Charles A; Weichold, Frank; Verreck, Frank; Kondova, Ivanela; Sadoff, Jerry; Thorstensson, Rigmor; Spångberg, Mats; Svensson, Mattias; Andersson, Jan; Maeurer, Markus; Brighenti, Susanna

    2012-01-01

    To prevent the global spread of tuberculosis (TB) infection, a novel vaccine that triggers potent and long-lived immunity is urgently required. A plasmid-based vaccine has been developed to enhance activation of major histocompatibility complex (MHC) class I–restricted CD8+ cytolytic T cells using a recombinant Bacille Calmette-Guérin (rBCG) expressing a pore-forming toxin and the Mycobacterium tuberculosis (Mtb) antigens Ag85A, 85B and TB10.4 followed by a booster with a nonreplicating adenovirus 35 (rAd35) vaccine vector encoding the same Mtb antigens. Here, the capacity of the rBCG/rAd35 vaccine to induce protective and biologically relevant CD8+ T-cell responses in a nonhuman primate model of TB was investigated. After prime/boost immunizations and challenge with virulent Mtb in rhesus macaques, quantification of immune responses at the single-cell level in cryopreserved tissue specimen from infected organs was performed using in situ computerized image analysis as a technological platform. Significantly elevated levels of CD3+ and CD8+ T cells as well as cells expressing interleukin (IL)-7, perforin and granulysin were found in TB lung lesions and spleen from rBCG/rAd35-vaccinated animals compared with BCG/rAd35-vaccinated or unvaccinated animals. The local increase in CD8+ cytolytic T cells correlated with reduced expression of the Mtb antigen MPT64 and also with prolonged survival after the challenge. Our observations suggest that a protective immune response in rBCG/rAd35-vaccinated nonhuman primates was associated with enhanced MHC class I antigen presentation and activation of CD8+ effector T-cell responses at the local site of infection in Mtb-challenged animals. PMID:22396020

  17. 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.

  18. Diminished regulatory T cells in cutaneous lesions of thymoma-associated multi-organ autoimmunity: a newly described paraneoplastic autoimmune disorder with fatal clinical course.

    PubMed

    Hanafusa, T; Azukizawa, H; Kitaba, S; Murota, H; Umegaki, N; Terao, M; Sano, S; Nakagiri, T; Okumura, M; Katayama, I

    2011-11-01

    Thymoma-associated multi-organ autoimmunity is a rare, autoimmune disease that causes colitis, liver dysfunction and cutaneous graft-versus-host (GVH)-like skin damage. This paraneoplastic autoimmune disorder may be due to inadequate T cell selection in the tumour environment of the thymus. Although sporadic case reports have revealed its clinical features, little is known about its pathological mechanism. By comparing the skin-infiltrating T cell subsets with those of GVH disease (GVHD) and other inflammatory skin diseases, we sought to elucidate the pathological mechanism of thymoma-associated multi-organ autoimmunity. Histopathological and immunohistochemical analysis of skin biopsies was performed for three patients with thymoma-associated multi-organ autoimmunity. Histopathological findings of thymoma-associated multi-organ autoimmunity were indistinguishable from those of patients with acute GVHD, although the aetiologies of these diseases are completely different. The frequency of regulatory T cells (T(regs)) is reduced in cutaneous lesions and CD8+ cytotoxic T lymphocytes that massively infiltrate into the epidermis of patients with thymoma-associated multi-organ autoimmunity. Additionally, the ratio of T helper type 17 (Th17) cells to CD4+ cells in patients with thymoma-associated multi-organ autoimmunity and acute GVHD was higher than that in healthy controls, but similar to that in psoriasis vulgaris patients. Similarity of the skin-infiltrating T cell subsets with those of acute GVHD suggested that skin damage in patients with thymoma-associated multi-organ autoimmunity might be induced by self-reactive cytotoxic T lymphocytes under the diminished suppressive capacity of T(regs).

  19. 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

  20. The feasibility of molecular testing on cell blocks created from brush tip washings in the assessment of peripheral lung lesions

    PubMed Central

    Christie, Michael; Beaty, Anne; Lunke, Sebastian; Taylor, Graham; Irving, Louis; Steinfort, Daniel

    2016-01-01

    Background With the rapid development of genotype-guided therapies, molecular testing is becoming important in the management of lung cancer. Bronchoscopy is one of the most common investigations performed to diagnose and investigate lung cancer. Given the limited samples often produced by bronchoscopy, this study aims to evaluate the feasibility of performing molecular testing on cell blocks created from bronchoscope cytology brush tip washings (BTW). Methods Patients with positive brush cytology for tumour cells had cell blocks created from the BTW. Mutations were detected using amplicon-based massively parallel sequencing of targeted regions of EGFR, KRAS, and BRAF genes. Results A total of 45 patients were included in this study. Of those, 91% had adequate specimens for molecular analysis and 66% of patients with adenocarcinoma had mutations detected. Bronchial brush tip wash cell blocks were the sole specimen available for molecular testing in 27 (60%) patients. Conclusions The findings of this study demonstrate that molecular testing can be performed on cell blocks created from BTW and this technique may allow for an increase in bronchoscope specimens amenable to molecular testing without further increasing morbidity and mortality. PMID:27747008

  1. 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.

  2. Fine-needle sample of salivary gland lesions. V: Cytology of 22 cases of acinic cell carcinoma with histologic correlation.

    PubMed

    Klijanienko, J; Vielh, P

    1997-11-01

    Fine-needle sampling (FNS) of 22 acinic cell carcinomas, including 17 primary tumors, 4 local recurrences, and 1 lymph node metastasis was performed preoperatively in 17 patients. Cytologic diagnoses were concordant with histology in 3 (13.7%) cases, whereas 15 (68.2%) cases were cytologically classified as malignant, 2 (9.1%) as suspicious, and 1 (4.5%) as benign (pleomorphic adenoma). The material was unsatisfactory for cytologic evaluation in 1 (4.5%) case. Preoperative FNS technique is, therefore, useful in acinic cell carcinoma with a concordant malignant/suspicious rate of 91%.

  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. Lesion simulating disease 1 and enhanced disease susceptibility 1 differentially regulate UV-C-induced photooxidative stress signalling and programmed cell death in Arabidopsis thaliana.

    PubMed

    Wituszyńska, Weronika; Szechyńska-Hebda, Magdalena; Sobczak, Mirosław; Rusaczonek, Anna; Kozłowska-Makulska, Anna; Witoń, Damian; Karpiński, Stanisław

    2015-02-01

    As obligate photoautotrophs, plants are inevitably exposed to ultraviolet (UV) radiation. Because of stratospheric ozone depletion, UV has become more and more dangerous to the biosphere. Therefore, it is important to understand UV perception and signal transduction in plants. In the present study, we show that lesion simulating disease 1 (LSD1) and enhanced disease susceptibility 1 (EDS1) are antagonistic regulators of UV-C-induced programmed cell death (PCD) in Arabidopsis thaliana. This regulatory dependence is manifested by a complex deregulation of photosynthesis, reactive oxygen species homeostasis, antioxidative enzyme activity and UV-responsive genes expression. We also prove that a UV-C radiation episode triggers apoptotic-like morphological changes within the mesophyll cells. Interestingly, chloroplasts are the first organelles that show features of UV-C-induced damage, which may indicate their primary role in PCD development. Moreover, we show that Arabidopsis Bax inhibitor 1 (AtBI1), which has been described as a negative regulator of plant PCD, is involved in LSD1-dependent cell death in response to UV-C. Our results imply that LSD1 and EDS1 regulate processes extinguishing excessive energy, reactive oxygen species formation and subsequent PCD in response to different stresses related to impaired electron transport.

  5. Lesion simulating disease 1 and enhanced disease susceptibility 1 differentially regulate UV-C-induced photooxidative stress signalling and programmed cell death in Arabidopsis thaliana.

    PubMed

    Wituszyńska, Weronika; Szechyńska-Hebda, Magdalena; Sobczak, Mirosław; Rusaczonek, Anna; Kozłowska-Makulska, Anna; Witoń, Damian; Karpiński, Stanisław

    2015-02-01

    As obligate photoautotrophs, plants are inevitably exposed to ultraviolet (UV) radiation. Because of stratospheric ozone depletion, UV has become more and more dangerous to the biosphere. Therefore, it is important to understand UV perception and signal transduction in plants. In the present study, we show that lesion simulating disease 1 (LSD1) and enhanced disease susceptibility 1 (EDS1) are antagonistic regulators of UV-C-induced programmed cell death (PCD) in Arabidopsis thaliana. This regulatory dependence is manifested by a complex deregulation of photosynthesis, reactive oxygen species homeostasis, antioxidative enzyme activity and UV-responsive genes expression. We also prove that a UV-C radiation episode triggers apoptotic-like morphological changes within the mesophyll cells. Interestingly, chloroplasts are the first organelles that show features of UV-C-induced damage, which may indicate their primary role in PCD development. Moreover, we show that Arabidopsis Bax inhibitor 1 (AtBI1), which has been described as a negative regulator of plant PCD, is involved in LSD1-dependent cell death in response to UV-C. Our results imply that LSD1 and EDS1 regulate processes extinguishing excessive energy, reactive oxygen species formation and subsequent PCD in response to different stresses related to impaired electron transport. PMID:24471507

  6. 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

  7. The guggulsterone derivative GG-52 inhibits NF-κB signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice.

    PubMed

    Kim, Jung Mogg; Kim, Su Hyun; Ko, Su Hyuk; Jung, Jireh; Chun, Jaeyoung; Kim, Nayoung; Jung, Hyun Chae; Kim, Joo Sung

    2013-01-15

    Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.

  8. Imaging of Retrosternal Space Lesions - A Pictorial Review.

    PubMed

    Chandrashekhara, S H; Rahul, Kumar; Handa, Nayha; Panda, Ananya

    2016-01-01

    The retrosternal region (RSS) can be involved by diverse lesions. The RSS is the region behind the sternum and anterior to the ascending aorta. It normally is less than 3 cm deep. Chest X-ray is usually the first imaging modality to raise a suspicion of RSS pathology; however computed tomography is the mainstay to delineate and characterize lesions in this location. Lesions in this location include thyroid, thymic and lymph node lesions; germ cell tumors and vascular lesions. Lesions arising from the sternum, lungs as well as the pleura can also involve this space. The pictorial review depicts the diverse spectrum of lesions in this location. PMID:27504144

  9. Imaging of Retrosternal Space Lesions – A Pictorial Review

    PubMed Central

    Chandrashekhara, S.H.; Rahul, Kumar; Handa, Nayha; Panda, Ananya

    2016-01-01

    Summary The retrosternal region (RSS) can be involved by diverse lesions. The RSS is the region behind the sternum and anterior to the ascending aorta. It normally is less than 3 cm deep. Chest X-ray is usually the first imaging modality to raise a suspicion of RSS pathology; however computed tomography is the mainstay to delineate and characterize lesions in this location. Lesions in this location include thyroid, thymic and lymph node lesions; germ cell tumors and vascular lesions. Lesions arising from the sternum, lungs as well as the pleura can also involve this space. The pictorial review depicts the diverse spectrum of lesions in this location. PMID:27504144

  10. Pediatric Knee Osteochondritis Dissecans Lesions.

    PubMed

    Cruz, Aristides I; Shea, Kevin G; Ganley, Theodore J

    2016-10-01

    Osteochondritis dissecans (OCD) can cause knee pain and dysfunction in children. The etiology of OCD remains unclear; theories on causes include inflammation, ischemia, ossification abnormalities, genetic factors, and repetitive microtrauma. Most OCD lesions in skeletally immature patients will heal with nonoperative treatment. The success of nonoperative treatment decreases once patients reach skeletal maturity. The goals of surgical treatment include maintenance of articular cartilage congruity, rigid fixation of unstable fragments, and repair of osteochondral defects with cells or tissues that can adequately replace lost or deficient cartilage. Unsalvageable OCD lesions can be treated with various surgical techniques. PMID:27637663

  11. Benign breast lesions: Ultrasound

    PubMed Central

    Masciadri, N.; Ferranti, C.

    2011-01-01

    Benign breast diseases constitute a heterogeneous group of lesions arising in the mammary epithelium or in other mammary tissues, and they may also be linked to vascular, inflammatory or traumatic pathologies. Most lesions found in women consulting a physician are benign. Ultrasound (US) diagnostic criteria indicating a benign lesion are described as well as US findings in the most frequent benign breast lesions. PMID:23396888

  12. Topological Control of Columnar Stacking Made of Liquid-Crystalline Thiophene-Fused Metallonaphthalocyanines.

    PubMed

    Suzuki, Hiroyuki; Kawano, Koki; Ohta, Kazuchika; Shimizu, Yo; Kobayashi, Nagao; Kimura, Mutsumi

    2016-04-01

    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

  13. 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.

  14. Columnar order and Ashkin-Teller criticality in mixtures of hard squares and dimers.

    PubMed

    Ramola, Kabir; Damle, Kedar; Dhar, Deepak

    2015-05-15

    We show that critical exponents of the transition to columnar order in a mixture of 2×1 dimers and 2×2 hard squares on the square lattice depends on the composition of the mixture in exactly the manner predicted by the theory of Ashkin-Teller criticality, including in the hard-square limit. This result settles the question regarding the nature of the transition in the hard-square lattice gas. It also provides the first example of a polydisperse system whose critical properties depend on composition. Our ideas also lead to some interesting predictions for a class of frustrated quantum magnets that exhibit columnar ordering of the bond energies at low temperature. PMID:26024157

  15. Self-assembly of luminescent N-annulated perylene tetraesters into fluid columnar phases.

    PubMed

    Gupta, Ravindra Kumar; Pathak, Suraj Kumar; Pradhan, Balaram; Shankar Rao, D S; Krishna Prasad, S; Achalkumar, Ammathnadu S

    2015-05-14

    A new class of N-annulated perylene tetraesters and their N-alkylated derivatives has been synthesized. N-Annulated perylene tetraesters stabilize a hexagonal columnar phase over a broad temperature range. The hexagonal columnar phase exhibited by these compounds shows good homeotropic alignment with few defects. Annulation in the bay region of the perylene tetraesters enhanced the width of the mesophase compared with the parent tetraesters. N-Alkylation of these compounds perturbed the self-assembly behaviour and the resulting compounds were non-mesomorphic. A bright green luminescence was visible under long wavelength UV light. These properties suggest that these materials may have promising applications in organic electronics. PMID:25812168

  16. The effect of vapor incidence angle upon thin film columnar growth

    SciTech Connect

    Mazor, A.; Bukiet, B.G.; Srolovitz, D.J.

    1988-01-01

    We present a generalized theory for the growth of columnar microstructure in vapor deposited thin films under the joint influence of a constant uniform deposition flux coming down with arbitrarily chosen incidence angle, and surface diffusion. The dependences of the Zone I to Zone II transition temperature, and the characteristic length scales associated with the unstable modes on the deposition angle are predicted. The surface morphology is obtained as a function of vapor incidence angle. For a specific deposition angle, there is a one-parameter family of steady-state surface profiles which corresponds to a range of possible columnar orientation angles, among which only one angle is associated with the tangent rule. These results agree with experimental observations. 10 refs., 6 figs.

  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. 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.

  19. 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.

  20. Example Based Lesion Segmentation

    PubMed Central

    Roy, Snehashis; He, Qing; Carass, Aaron; Jog, Amod; Cuzzocreo, Jennifer L.; Reich, Daniel S.; Prince, Jerry; Pham, Dzung

    2016-01-01

    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.

  1. Survival of vaccinated, feed-trained largemouth bass fry (Micropterus salmoides floridanus) during natural exposure to Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccinated, feed-trained largemouth bass fry (Micropterus salmoides floridanus) were cohabited with sham-vaccinated fish. Fish were exposed, under natural conditions, to Flavobacterium columnare, a ubiquitous bacterium associated with columnaris disease. During every time interval, the probability...

  2. 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...

  3. A cyclopalladated complex of corannulene with a pyridine pendant and its columnar self-assembly.

    PubMed

    Yamada, Mihoko; Tashiro, Shohei; Miyake, Ryosuke; Shionoya, Mitsuhiko

    2013-03-14

    Bowl-shaped corannulene provides various metal binding modes with its curved π-surfaces and rim. Herein, we report the syntheses of 2-pyridylcorannulene and its cyclopalladated complex. Its expanded π-system and columnar self-assembly in the crystal state were revealed by NMR and UV-vis spectroscopies, ESI-TOF mass spectrometry and single-crystal X-ray analysis. PMID:23338944

  4. 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. PMID:24929118

  5. 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.

  6. Benign lymphoepithelial lesion and malignancy.

    PubMed

    Hordijk, G J; Meyer, C J

    1981-01-01

    Whereas most patients with benign lymphoepithelial lesion suffer from the involvement of a major salivary gland a number evolve into a clinical form of Sjögren's syndrome or Mikulicz's disease. In a small number development of malignant lymphomas, especially non-Hodgkin's lymphomas, have been described. Therefore, regular follow-up and appropriate histological evaluation of suspected areas in all patients with a benign lymphoepithelial lesion is indicated. Histologically, diagnosis of a non-Hodgkin's lymphoma may be difficult. Demonstration of a cell pattern, monoclonal for cytoplasmic Ig by means of the immunoperoxidase technique may facilitate the diagnosis. In this report we present the history of two cases out of our series with benign lymphoepithelial lesion who developed a non-Hodgkin's lymphoma.

  7. [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.

  8. White bass Morone chrysops is less susceptible than its hybrid to experimental infection with Flavobacterium columnare.

    PubMed

    Fuller, S Adam; Farmer, Bradley D; Beck, Benjamin H

    2014-04-23

    Hybrid striped bass (HSB) and white bass (WB) were evaluated for their susceptibility to Flavobacterium columnare, the causative agent of columnaris disease, in 3 fundamental studies. In the first experiment, we determined whether columnaris disease could be developed by experimental challenge in HSB. This challenge consisted of 3 levels of F. columnare (10, 30, and 60 ml volumes) determined to be 2.25 × 10(7), 6.75 × 10(7), and 1.35 × 10(8) CFU ml(-1), respectively. Each treatment group exhibited significantly different survival rates: 0, 3.3, and 13.3% in the 60, 30, and 10 ml groups, respectively. In Expt 2, using the 30 ml dose, both HSB and WB had a 0% survival rate, with WB taking significantly longer to reach 100% mortality. In Expt 3, using the 10 ml dose, no HSB survived, whereas 33% of WB survived (p < 0.0001). Compared to controls, HSB treated with 10 ml showed extensive gill damage at 24 h, which could have contributed to the higher mortality observed in HSB; in contrast, WB gills showed noticeably less damage. From these series of experiments, it is clear that HSB are more sensitive to F. columnare, having lower survival and more extensive histological damage compared to WB following challenge. PMID:24781793

  9. 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.

  10. White bass Morone chrysops is less susceptible than its hybrid to experimental infection with Flavobacterium columnare.

    PubMed

    Fuller, S Adam; Farmer, Bradley D; Beck, Benjamin H

    2014-04-23

    Hybrid striped bass (HSB) and white bass (WB) were evaluated for their susceptibility to Flavobacterium columnare, the causative agent of columnaris disease, in 3 fundamental studies. In the first experiment, we determined whether columnaris disease could be developed by experimental challenge in HSB. This challenge consisted of 3 levels of F. columnare (10, 30, and 60 ml volumes) determined to be 2.25 × 10(7), 6.75 × 10(7), and 1.35 × 10(8) CFU ml(-1), respectively. Each treatment group exhibited significantly different survival rates: 0, 3.3, and 13.3% in the 60, 30, and 10 ml groups, respectively. In Expt 2, using the 30 ml dose, both HSB and WB had a 0% survival rate, with WB taking significantly longer to reach 100% mortality. In Expt 3, using the 10 ml dose, no HSB survived, whereas 33% of WB survived (p < 0.0001). Compared to controls, HSB treated with 10 ml showed extensive gill damage at 24 h, which could have contributed to the higher mortality observed in HSB; in contrast, WB gills showed noticeably less damage. From these series of experiments, it is clear that HSB are more sensitive to F. columnare, having lower survival and more extensive histological damage compared to WB following challenge.

  11. Retinal Ganglion Cell Atrophy in Homonymous Hemianopia due to Acquired Occipital Lesions Observed Using Cirrus High-Definition-OCT

    PubMed Central

    Yamashita, Tsutomu; Miki, Atsushi; Goto, Katsutoshi; Araki, Syunsuke; Takizawa, Go; Ieki, Yoshiaki; Kiryu, Junichi; Tabuchi, Akio; Iguchi, Yasuyuki; Kimura, Kazumi; Yagita, Yoshiki

    2016-01-01

    Purpose. To report a reduction in macular ganglion cell layer and inner plexiform layer (GCL+IPL) thickness and circumpapillary retinal nerve fiber layer (cpRNFL) thickness using spectral-domain optical coherence tomography in patients with homonymous hemianopia due to posterior cerebral artery (PCA) stroke. Methods. Seven patients with PCA stroke were examined using Cirrus high-definition-OCT. The GCL+IPL thicknesses were divided into the hemianopic and unaffected sides. The relationship between the time after stroke and the GCL+IPL thicknesses in the hemianopic side was evaluated. Results. The average thicknesses of the GCL+IPL were 64.6 and 82.0 μm on the hemianopic and unaffected sides, respectively, and the measurement was significantly thinner on the former side (p = 0.018). A regression analysis revealed a negative linear relationship (R2 = 0.574, p = 0.049) between the time after stoke and the GCL+IPL thicknesses on the hemianopic side. The supratemporal and inferotemporal cpRNFL thicknesses in the eyes ipsilateral to the stroke showed a significant reduction. Conclusion. Our findings confirmed our previous observations that the degeneration of retinal ganglion cells can occur after PCA stroke. GCL+IPL thinning was demonstrated in the hemiretinae corresponding to the affected hemifields. Also, it is suggested that the retinal changes observed are progressive. PMID:27274865

  12. Retinal Ganglion Cell Atrophy in Homonymous Hemianopia due to Acquired Occipital Lesions Observed Using Cirrus High-Definition-OCT.

    PubMed

    Yamashita, Tsutomu; Miki, Atsushi; Goto, Katsutoshi; Araki, Syunsuke; Takizawa, Go; Ieki, Yoshiaki; Kiryu, Junichi; Tabuchi, Akio; Iguchi, Yasuyuki; Kimura, Kazumi; Yagita, Yoshiki

    2016-01-01

    Purpose. To report a reduction in macular ganglion cell layer and inner plexiform layer (GCL+IPL) thickness and circumpapillary retinal nerve fiber layer (cpRNFL) thickness using spectral-domain optical coherence tomography in patients with homonymous hemianopia due to posterior cerebral artery (PCA) stroke. Methods. Seven patients with PCA stroke were examined using Cirrus high-definition-OCT. The GCL+IPL thicknesses were divided into the hemianopic and unaffected sides. The relationship between the time after stroke and the GCL+IPL thicknesses in the hemianopic side was evaluated. Results. The average thicknesses of the GCL+IPL were 64.6 and 82.0 μm on the hemianopic and unaffected sides, respectively, and the measurement was significantly thinner on the former side (p = 0.018). A regression analysis revealed a negative linear relationship (R (2) = 0.574, p = 0.049) between the time after stoke and the GCL+IPL thicknesses on the hemianopic side. The supratemporal and inferotemporal cpRNFL thicknesses in the eyes ipsilateral to the stroke showed a significant reduction. Conclusion. Our findings confirmed our previous observations that the degeneration of retinal ganglion cells can occur after PCA stroke. GCL+IPL thinning was demonstrated in the hemiretinae corresponding to the affected hemifields. Also, it is suggested that the retinal changes observed are progressive. PMID:27274865

  13. 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.

  14. 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

  15. 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. PMID:24909885

  16. A new platelet storage lesion index based on paired samples, without and with EDTA and cell counting: comparison of three types of leukoreduced preparations.

    PubMed

    Seghatchian, Jerard

    2006-12-01

    Platelets derived from whole blood and diverse apheresis procedures come in contact with various artificial surfaces and undergo contact activation, sheer stress-induced shape changes, aggregation and microvesiculation during collection, processing and storage. These dynamic changes are qualitatively reflected in the log-normal platelet size distribution patterns seen, when using modern automated cell counters and can be measured quantitatively by counting the paired samples, without and with added EDTA, and calculating the differences (d) in platelet cellular indices (dPLT/dMPV/dPDW). Reporting the differences instead of the absolute values of cellular indices makes the measurements independent of basic principles used for cell counting (i.e. aperture-impedance or flow-optic). The measurements can be performed either in blood centres, hospital blood banks or nearby patient clinics equipped with a validated cell counter. At least three useful quality indices could be derived simultaneously from this procedure (accurate estimation of platelet yields using the value of the EDTA-containing sample); quantitative assessment of the % of reversible platelet aggregates, an age/pH/temperature-dependent degree of microvesiculation/apoptosis/PS exposure, based on the response to EDTA. This new set of indices correlate significantly with other conventional tests for platelet quality; hence, provide additional supportive evidence for confirming the low pH values and the subjective poor swirling data occasionally seen with stored PC. In the following study, the Sysmex SE 9000 was successfully employed for estimation of platelet cellular indices comparing the platelet storage lesion index of three types of leukoreduced platelet concentrates in current practice. The relationship between this in vitro response to clinical outcome remains to be established. PMID:17113347

  17. Periplogenin induces necroptotic cell death through oxidative stress in HaCaT cells and ameliorates skin lesions in the TPA- and IMQ-induced psoriasis-like mouse models.

    PubMed

    Zhang, Wen-Jing; Song, Zhen-Bo; Bao, Yong-Li; Li, Wen-Liang; Yang, Xiao-Guang; Wang, Qi; Yu, Chun-Lei; Sun, Lu-Guo; Huang, Yan-Xin; Li, Yu-Xin

    2016-04-01

    Psoriasis is a multifactorial skin disease that inconveniences many patients. Considering the side effects and drug resistance of the current therapy, it is urgent to discover more effective and safer anti-psoriatic drugs. In the present study, we screened over 250 traditional Chinese medicine compounds for their ability to inhibit the cell viability of cultured human HaCaT keratinocytes, a psoriasis-relevant in vitro model, and found that periplogenin was highly effective. Mechanistic studies revealed that apoptosis and autophagy were not induced by periplogenin in HaCaT cells. However, periplogenin caused PI to permeate into cells, increased lactate LDH release and rapidly increased the number of necrotic cells. Additionally, the typical characteristics of necrosis were observed in the periplogenin-treated HaCaT cells. Notably, the necroptosis inhibitor Nec-1 and NSA were able to rescue the cells from necrotic cell death, supporting that necroptosis was involved in periplogenin-induced cell death. Furthermore, the ROS levels were elevated in the periplogenin-treated cells, NAC (an antioxidant) and Nec-1 could inhibit the ROS levels, and NAC could attenuate necroptotic cell death, indicating that the periplogenin-induced necroptotic cell death was mediated by oxidative stress. More importantly, in the murine models of TPA-induced epidermal hyperplasia and IMQ-induced skin inflammation, topical administration of periplogenin ameliorated skin lesions and inflammation. In sum, our results indicate, for the first time, that periplogenin is a naturally occurring compound with potent anti-psoriatic effects in vitro and in vivo, making it a promising candidate for future drug research. PMID:26850986

  18. Periplogenin induces necroptotic cell death through oxidative stress in HaCaT cells and ameliorates skin lesions in the TPA- and IMQ-induced psoriasis-like mouse models.

    PubMed

    Zhang, Wen-Jing; Song, Zhen-Bo; Bao, Yong-Li; Li, Wen-Liang; Yang, Xiao-Guang; Wang, Qi; Yu, Chun-Lei; Sun, Lu-Guo; Huang, Yan-Xin; Li, Yu-Xin

    2016-04-01

    Psoriasis is a multifactorial skin disease that inconveniences many patients. Considering the side effects and drug resistance of the current therapy, it is urgent to discover more effective and safer anti-psoriatic drugs. In the present study, we screened over 250 traditional Chinese medicine compounds for their ability to inhibit the cell viability of cultured human HaCaT keratinocytes, a psoriasis-relevant in vitro model, and found that periplogenin was highly effective. Mechanistic studies revealed that apoptosis and autophagy were not induced by periplogenin in HaCaT cells. However, periplogenin caused PI to permeate into cells, increased lactate LDH release and rapidly increased the number of necrotic cells. Additionally, the typical characteristics of necrosis were observed in the periplogenin-treated HaCaT cells. Notably, the necroptosis inhibitor Nec-1 and NSA were able to rescue the cells from necrotic cell death, supporting that necroptosis was involved in periplogenin-induced cell death. Furthermore, the ROS levels were elevated in the periplogenin-treated cells, NAC (an antioxidant) and Nec-1 could inhibit the ROS levels, and NAC could attenuate necroptotic cell death, indicating that the periplogenin-induced necroptotic cell death was mediated by oxidative stress. More importantly, in the murine models of TPA-induced epidermal hyperplasia and IMQ-induced skin inflammation, topical administration of periplogenin ameliorated skin lesions and inflammation. In sum, our results indicate, for the first time, that periplogenin is a naturally occurring compound with potent anti-psoriatic effects in vitro and in vivo, making it a promising candidate for future drug research.

  19. Composition of innate lymphoid cell subsets in the human skin: enrichment of NCR(+) ILC3 in lesional skin and blood of psoriasis patients.

    PubMed

    Teunissen, Marcel B M; Munneke, J Marius; Bernink, Jochem H; Spuls, Phyllis I; Res, Pieter C M; Te Velde, Anje; Cheuk, Stanley; Brouwer, Marijke W D; Menting, Stef P; Eidsmo, Liv; Spits, Hergen; Hazenberg, Mette D; Mjösberg, Jenny

    2014-09-01

    Innate lymphoid cells (ILCs) are increasingly appreciated as important regulators of tissue homeostasis and inflammation. However, their role in human skin remains obscure. We found that healthy peripheral blood CD117(+) ILC3, lacking the natural cytotoxicity receptor (NCR) NKp44 (NCR(-) ILC3), CD117(-)NCR(-)CRTH2(-)CD161(+) ILC1, and CRTH2(+) ILC2, express the skin-homing receptor cutaneous lymphocyte antigen (CLA). NCR(+) ILC3 were scarce in peripheral blood. Consistently, we identified in normal skin ILC2 and NCR(-) ILC3, a small proportion of CD161(+) ILC1, and hardly any NCR(+) ILC3, whereas NCR(+) ILC3 were present in cultured dermal explants. The skin ILC2 and NCR(+) ILC3 subsets produced IL-13 and IL-22, respectively, upon cytokine stimulation. Remarkably, dermal NCR(-) ILC3 converted to NCR(+) ILC3 upon culture in IL-1β plus IL-23, cytokines known to be involved in psoriatic inflammation. In line with this observation, significantly increased proportions of NCR(+) ILC3 were present in lesional skin and peripheral blood of psoriasis patients as compared with skin and blood of healthy individuals, respectively, whereas the proportions of ILC2 and CD161(+) ILC1 remained unchanged. NCR(+) ILC3 from skin and blood of psoriasis patients produced IL-22, which is regarded as a key driver of epidermal thickening, suggesting that NCR(+) ILC3 may participate in psoriasis pathology.

  20. Analysis of the transcriptomic profilings of Mandarin fish (Siniperca chuatsi) infected with Flavobacterium columnare with an emphasis on immune responses.

    PubMed

    Zhou, Weidong; Zhang, Yulei; Wen, Yi; Ji, Wei; Zhou, Yang; Ji, Yachan; Liu, Xiaoling; Wang, Weimin; Asim, Muhammad; Liang, Xufang; Ai, Taoshan; Lin, Li

    2015-03-01

    Flavobacterium columnare (FC) is the causative pathogen of columnaris which has caused great economic loss in fish culture worldwide, including in Mandarin fish (Siniperca chuatsi) culture. In the present study, the transcriptomic profiles of the head kidneys from FC-infected and non-infected Mandarin fish were obtained using HiSeq™ 2000 (Illumina). Totally 31,168 unigenes with high quality were obtained. Genes involved in protein folding, metabolism and energy, immune responses, oxidoreductase activity, cell growth and death were identified as enriched classes. 1019 differently expressed genes between the two groups were identified, including 603 up-regulated and 416 down-regulated genes. 27 differently expressed immune related genes were scrutinized, including 17 up-regulated and 10 down-regulated genes. Six of the differently expressed genes were further validated by qRT-PCR. The roles of the immune related genes were discussed. Identification of the host genes in response to FC infection will shed a new light on the prevention of columnaris.

  1. Proliferation and Glia-Directed Differentiation of Neural Stem Cells in the Subventricular Zone of the Lateral Ventricle and the Migratory Pathway to the Lesions after Cortical Devascularization of Adult Rats

    PubMed Central

    Wan, Feng; Bai, Hua-Jing; Liu, Jun-Qi; Tian, Mo; Wang, Yong-Xue; Niu, Xin; Si, Yin-Chu

    2016-01-01

    We investigated the effects of cortical devascularization on the proliferation, differentiation, and migration of neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricle of adult rats. 60 adult male Wistar rats were randomly divided into control group and devascularized group. At 15 and 30 days after cerebral cortices were devascularized, rats were euthanized and immunohistochemical analysis was performed. The number of PCNA-, Vimentin-, and GFAP-positive cells in the bilateral SVZ of the lateral wall and the superior wall of the lateral ventricles of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). The area density of PCNA-, Vimentin-, and GFAP-positive cells in cortical lesions of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). PCNA-, GFAP-, and Vimentin-positive cells in the SVZ migrated through the rostral migratory stream (RMS), and PCNA-, GFAP-, and Vimentin-positive cells from both the ipsilateral and contralateral dorsolateral SVZ (dl-SVZ) migrated into the corpus callosum (CC) and accumulated, forming a migratory pathway within the CC to the lesioned site. Our study suggested that cortical devascularization induced proliferation, glia-directed differentiation, and migration of NSCs from the SVZ through the RMS or directly to the corpus callosum and finally migrating radially to cortical lesions. This may play a significant role in neural repair. PMID:27294116

  2. Mandibular destructive radiolucent lesion: The first sign of multiple myeloma

    PubMed Central

    Fregnani, Eduardo-Rodrigues; Leite, Amanda-Almeida; Parahyba, Claudia-Joffily; Nesrallah, Ana-Cristina-Alo; Ramos-Perez, Flávia-Maria-de Moraes

    2016-01-01

    The occurrence of a mandibular lesion as the first sign of multiple myeloma (MM) is uncommon. This report describes a case of MM diagnosed because of a mandibular lesion. A 62-year-old woman presented a destructive radiolucent lesion in the right mandibular ramus. The lesion caused rupture of the anterior cortical bone and extended from the retromolar area to the coronoid process. An incisional biopsy was performed. Histopathological examination revealed numerous pleomorphic plasma cells, some with binucleated nuclei. The tumor cells showed kappa light-chain restriction. Bone marrow biopsy showed findings of massive infiltration of neoplastic plasma cells, besides lesions in the vertebrae. The diagnosis of MM was established. The patient underwent autologous hematopoietic stem-cell transplantation. Currently, the patient is under regular follow up after 40 months of initial treatment. In conclusion, MM should be considered in the differential diagnosis of destructive mandibular lesions. Key words:Mandible, multiple myeloma, radiolucent lesion. PMID:27703618

  3. Cystic Lesions in Autoimmune Pancreatitis.

    PubMed

    Gompertz, Macarena; Morales, Claudia; Aldana, Hernán; Castillo, Jaime; Berger, Zoltán

    2015-01-01

    Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases.

  4. Cystic lesions of the pancreas

    PubMed Central

    Karoumpalis, Ioannis; Christodoulou, Dimitrios K.

    2016-01-01

    Different types of benign or malignant cystic lesions can be observed in the pancreas. Pancreatic cystic lesions are classified under pathology terms into simple retention cysts, pseudocysts and cystic neoplasms. Mucinous cystic neoplasm is a frequent type of cystic neoplasm and has a malignant potential. Serous cystadenoma follows in frequency and is usually benign. Intraductal papillary mucinous neoplasms are the most commonly resected cystic pancreatic neoplasms characterized by dilated segments of the main pancreatic duct and/or side branches, the wall of which is covered by mucus secreting cells. These neoplasms can occupy the pancreatic head or any part of the organ. Solid pseudopapillary tumor is rare, has a low tendency for malignancy, and is usually located in the pancreatic body or tail. Endoscopic ultrasound with the use of fine-needle aspiration and cytology permits discrimination of those lesions. In this review, the main characteristics of those lesions are presented, as well as recommendations regarding their follow up and management according to recent guidelines. PMID:27065727

  5. Retrieval of absorptive gas columnar amounts using atmospheric hyper-spectral irradiance measurements within visible spectrum

    NASA Astrophysics Data System (ADS)

    Xu, Hua; Li, Zhengqiang; Li, Donghui; Xie, Yisong; Li, Kaitao; Qie, Lili; Zhang, Ying; Chen, Xingfeng; Zheng, Xiaobin; Li, Xin; Zhang, Yanna

    2015-10-01

    A hyper spectral ground-based instrument named Atmosphere-Surface Radiation Automatic Instrument (ASRAI) has been developed for the purpose of in-situ calibration of satellites. The apparatus has both upward and downward looking views, and thus can observe both the atmosphere and land surface. The solar transmitted irradiance can be derived from the measured full spectral irradiance and diffused spectral irradiance of atmosphere within visible spectrum (0.4-1.0μm). A method similar to that of King et al. which originally intended to apply to multi-wavelength measurements, is adopted to determine absorptive gaseous columnar amount from hyper spectrum. The solar irradiance at top of atmosphere and absorption coefficients of water vapor (H2O), ozone (O3), oxygen (O2) and nitrogen dioxide (NO2) are recalculated at an instrumental spectral resolution by convolution method. Based on the gaseous characteristics of absorption, the total columnar amounts of water vapor and oxygen are first inferred from solar transmitted irradiance at strong absorption wavelength of 0.934μm and 0.763μm respectively. The total columnar amounts of ozone and nitrogen dioxide, together with aerosol optical depth, are determined by a nonlinear least distance fitting method which minimizes a χ2 statistic to obtain optimal solutions. ASRAI was deployed for observation in Dunhuang site in China in August of 2014. Our results demonstrate that the algorithm is reasonable. Although the validation is preliminary, the hyper spectrum measured by ASRAI exhibits good ability to retrieve the abundance of absorptive gases and aerosols.

  6. Optical response of columnar TiO{sub 2}:Co on Si substrate

    SciTech Connect

    Anggraeni, G. P.; Saripudin, A.; Rusydi, A.; Darma, Y.

    2015-09-30

    Vertically arranged columnar TiO{sub 2}:Co structure has been deposited on Si (100) substrate using the metal organic chemical vapor deposition (MOCVD) technique. SEM images confirm the columnar structure of the TiO{sub 2}:Co layer on Si (100). Concentration of the Co dopant has been defined by means of the energy dispersive x-ray (EDX) spectra. Co concentrations are varied at 0.18, 0.33, and 0.68 at. % using pure TiO{sub 2} as the reference. X-ray diffraction (XRD) spectra show that the TiO{sub 2}:Co layer have a rutile phase. Further analysis of this structure has been performed by using room temperature spectroscopic ellipsometry (SE) measurements in the energy range of 0.5 - 6.5 eV. This optical response shows the unique feature of significantly high density fringe especially below the band gap energy region (lower than 3.3 eV) in contrast to the conventional TiO{sub 2} thin film structure. This unique feature is interpreted as a dominant contribution of the vertical interfaces at columnar boundaries towards reflected light from the sample. The evolution of Ψ and Δ will be discussed as the function of Co concentration and some optical properties will be extracted after reasonably well data fitting by multilayer modelling. Furthermore, by comparing the SE data from different measurement orientations, it has been shown that TiO{sub 2}:Co tends to be anisotropic. This study enables us to further evaluate structural properties through optical responses given by SE measurement.

  7. The Solar Vortex: Electric Power Generation using Anchored, Buoyancy-Induced Columnar Vortices

    NASA Astrophysics Data System (ADS)

    Glezer, Ari

    2015-04-01

    Naturally-occurring, buoyancy-driven columnar vortices (``dust devils'') that are driven by the instability of thermally stratified air layers and sustained by the entrainment of ground- heated air, occur spontaneously in the natural environment with core diameters of 1-50 m and heights up to 1 km. These vortices convert low-grade waste heat in the air layer overlying the warm surface into a solar-induced wind with significant kinetic energy. Unlike dust devil vortices that are typically free to wander laterally, the Solar Vortex (SoV) is deliberately triggered and anchored within a cylindrical domain bounded by an azimuthal array of stationary ground-mounted vertical vanes and sustained by continuous entrainment of the ground-heated air through these vanes. The mechanical energy of the anchored vortex is exploited for power generation by coupling the vortex to a vertical-axis turbine. This simple, low-cost electric power generating unit is competitive in cost, intermittency, and capacity factor with traditional solar power technologies. The considerable kinetic energy of the vortex column cannot be explained by buoyancy alone, and the fundamental mechanisms associated with the formation, evolution, and dynamics of an anchored, buoyancy-driven columnar vortex were investigated experimentally and numerically with specific emphasis on flow manipulation for increasing the available kinetic energy and therefore the generated power. These investigations have also considered the dependence of the vortex scaling and strength on the thermal resources and on the flow enclosure in the laboratory and in the natural environment. Preliminary outdoor tests of a two-meter scale prototype successfully demonstrated the ability to engender and anchor a columnar vortex using only solar radiation and couple the flow to a vertical axis wind turbine. A kilowatt-scale outer door prototype will be tested during the summer of 2015.

  8. Experimental Study of Disruption of Columnar Grains During Rapid Solidification in Additive Manufacturing

    NASA Astrophysics Data System (ADS)

    Manogharan, Guha; Yelamanchi, Bharat; Aman, Ronald; Mahbooba, Zaynab

    2016-03-01

    Over the years, many studies have been conducted to study and analyze the grain structures of metal alloys during additive manufacturing to improve mechanical properties. In particular, columnar grains are observed predominantly during rapid solidification of molten metal. This leads to lower mechanical properties and requires expensive secondary heat-treatment processes. This study is aimed at disrupting the formation of columnar grain growth during rapid solidification using ultrasonic vibration and analyzes the effects on grain structure and mechanical properties. A gas-metal arc welder mounted on a Rep-Rap-based low-cost metal 3 Dimension printer was used to deposit ER70S-6 mild steel layers on a plate. A contact-type ultrasonic transducer with a control system to vary the frequency and power of the vibration was used. The effects of ultrasonic vibration were determined from the statistical analysis of microstructure and micro-indentation techniques on the deposited layer and heat-affected zone. It was found that both frequency and interaction between frequency and power had significant impact on the refinement of average grain size up to 10.64% and increased the number of grains by approximately 41.78%. Analysis of micro-indentation tests showed that there was an increase of approximately 14.30% in micro-hardness due to the applied frequency during rapid solidification. A pole diagram shows that application of vibration causes randomization of grain orientation. Along with the results from this study, further efforts in modeling and experimentation of multi-directional vibrations would lead to a better understanding of disrupting columnar grains in applications that use mechanical vibrations, such as welding, directed energy deposition, brazing, etc.

  9. Differential requirement for the ATPase domain of the Cockayne syndrome group B gene in the processing of UV-induced DNA damage and 8-oxoguanine lesions in human cells.

    PubMed

    Selzer, Rebecca R; Nyaga, Simon; Tuo, Jingsheng; May, Alfred; Muftuoglu, Meltem; Christiansen, Mette; Citterio, Elisabetta; Brosh, Robert M; Bohr, Vilhelm A

    2002-02-01

    Cockayne syndrome (CS) is a rare inherited human genetic disorder characterized by UV sensitivity, developmental abnormalities and premature aging. The cellular and molecular phenotypes of CS include increased sensitivity to oxidative and UV-induced DNA lesions. The CSB protein is thought to play a pivotal role in transcription-coupled repair and CS-B cells are defective in the repair of the transcribed strand of active genes, both after exposure to UV and in the presence of oxidative DNA lesions. A previous study has indicated that a conserved helicase ATPase motif II residue is essential for the function of the CSB protein in responding to UV-induced DNA damage in a hamster cell line. Due to the limitations in studying a complex human disorder in another species, this study introduced the site-directed mutation of the ATPase motif II in the human CSB gene in an isogenic human cell line. The CSB mutant allele was tested for genetic complementation of UV-sensitive phenotypes in the human CS-B cell line CS1AN.S3.G2. In addition, the incision of an 8-oxoguanine lesion by extracts of the CS-B cell lines stably transfected with the wild-type or ATPase mutant CSB gene has been investigated. The ATPase motif II point mutation (E646Q) abolished the function of the CSB protein to complement the UV-sensitive phenotypes of survival, RNA synthesis recovery and apoptosis. Interestingly, whole-cell extract prepared from these mutant cells retained wild-type incision activity on an oligonucleotide containing a single 8-oxoguanine lesion, whereas the absence of the CSB gene altogether resulted in reduced incision activity relative to wild-type. These results suggest damage-specific functional requirements for CSB in the repair of UV-induced and oxidative lesions in human cells. The transfection of the mutant or wild-type CSB gene into the CS1AN.S3.G2 cells did not alter the expression of the subset of genes examined by cDNA array analysis. PMID:11809892

  10. The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions.

    PubMed

    Maglietta, Antonella; Maglietta, Rosalia; Staiano, Teresa; Bertoni, Ramona; Ancona, Nicola; Marra, Giancarlo; Resta, Leonardo

    2016-01-01

    Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous

  11. Cumulative mechanical moments and microstructure deformation induced by growth shape in columnar solidification.

    PubMed

    Billia, Bernard; Bergeon, Nathalie; Thi, Henri Nguyen; Jamgotchian, Haïk; Gastaldi, Joseph; Grange, Gérard

    2004-09-17

    The dynamical interaction between columnar interface microstructure and self-stress, resulting in unforeseen mechanical deformation phenomena, is brought to light by means of in situ and real-time synchrotron x-ray topography during directional solidification of dilute aluminum alloys. Beyond long-known local mechanical stresses, global mechanical constraints are found to be active. In particular, column rotation results from deformation caused by the mechanical moments associated with the very growth shape, namely, the cumulative torque acting together with the cumulative bending moment under gravity. A basic model allowing for a qualitative explanation of the observed distinctive features of the self-stress effects on microstructure dynamics is proposed.

  12. Stable Isotopic Variations in Columnar Cacti: are Responses to Climate Recorded in Spines?

    NASA Astrophysics Data System (ADS)

    English, N. B.; Dettman, D. L.; Williams, D. G.

    2004-12-01

    The behavior of the North American monsoon (NAM), particularly with respect to times of continental drought and its relationship to the Pacific-North American (PNA) teleconnection pattern and the El Nino/Southern Oscillation (ENSO) is of great interest to paleoclimatologists and water managers. Long-term instrumental precipitation and tree ring records in the southwestern United States and northwestern Mexico at low elevations are sparse and this has hindered research on NAM variability at interannual timescales. Saguaro cacti (Carnegiea gigantea) and other columnar cacti in North and South America are long-lived and have the potential to record climate variability on land with high temporal and spatial resolution. The vertical sequence of spines on the saguaro's exterior represents a high resolution (4 to 6 per year), and long (over 150 years) record of environmental change. We present results from an experiment where we tracked the oxygen isotopic values in the source waters, stem tissue waters and spine tissue for three treatments over the course of three months. These data are then compared to a previously developed mechanistic model of isotopic variation that reflects the physiological responses of Saguaro to climate variation over seasonal to century long time-scales. We also present the rationale for a new method to determine the growth rate of columnar cacti using the radiocarbon bomb spike. Our measurements reveal that oxygen and hydrogen isotopic variation among the sequentially produced and persistent spines covering the saguaro body record fluctuations in saguaro water balance. The model successfully predicts isotopic variation in spines and constrains controlling variables, yielding a powerful and high-resolution stable isotope index of water stress in the low desert. The development and refinement of an isotopic model for saguaro will serve as the basis for models applied to other species of columnar cacti in North and South America. The role of the

  13. Columnar content measurements of the solar-wind turbulence near the sun

    NASA Technical Reports Server (NTRS)

    Callahan, P. S.

    1975-01-01

    Turbulence in the solar wind near the sun is investigated using records of changes in the integrated electron columnar content along the line of sight to Mariners 6, 7, and 9. The comoving turbulence spectrum is found to be well represented by a power law with an index of about 3.9. The turbulence is shown to decline with heliocentric distance, and the data suggest a region of enhanced turbulence near the sun. The Mariner-9 spectral amplitudes are found to correspond with Zurich sunspot numbers. Implications of the present observations are discussed for contemporary theories on solar-wind heating.

  14. Fine genetic mapping of the Co locus controlling columnar growth habit in apple.

    PubMed

    Bai, Tuanhui; Zhu, Yuandi; Fernández-Fernández, Felicidad; Keulemans, Johan; Brown, Susan; Xu, Kenong

    2012-05-01

    Tree architecture is an important, complex and dynamic trait affected by diverse genetic, ontogenetic and environmental factors. 'Wijcik McIntosh', a columnar (reduced branching) sport of 'McIntosh' and a valuable genetic resource, has been used intensively in apple-breeding programs for genetic improvement of tree architecture. The columnar growth habit is primarily controlled by the dominant allele of gene Co (columnar) on linkage group-10. But the Co locus is not well mapped and the Co gene remains unknown. To precisely map the Co locus and to identify candidate genes of Co, a sequence-based approach using both peach and apple genomes was used to develop new markers linked more tightly to Co. Five new simple sequence repeats markers were developed (C1753-3520, C18470-25831, C6536-31519, C7223-38004 and C7629-22009). The first four markers were obtained from apple genomic sequences on chromosome-10, whereas the last (C7629-22009) was from an unanchored apple contig that contains an apple expressed sequence tag CV082943, which was identified through synteny analysis between the peach and apple genomes. Genetic mapping of these five markers in four F(1) populations of 528 genotypes and 290 diverse columnar selections/cultivars (818 genotypes in total) delimited the Co locus in a genetic interval with 0.37 % recombination between markers C1753-3520 and C7629-22009. Marker C18470-25831 co-segregates with Co in the 818 genotypes studied. The Co region is estimated to be 193 kb and contains 26 predicted gene in the 'Golden Delicious' genome. Among the 26 genes, three are putative LATERAL ORGAN BOUNDARIES (LOB) DOMAIN (LBD) containing transcription factor genes known of essential roles in plant lateral organ development, and are therefore considered as strong candidates of Co, designated MdLBD1, MdLBD2, and MdLBD3. Although more comprehensive studies are required to confirm the function of MdLBD1-3, the present work represents an important step forward to better

  15. Preinvasive lesions

    Cancer.gov

    This definition is for allocation of lesions with preinvasive/borderline properties. It is currently aimed at newly identified neoplasms, which may be similar to those described in humans. In mouse pathology, many adenomas may be preinvasive/borderline lesions. However, their inclusion in the preinvasive category can be justified only upon development of better diagnostic criteria.

  16. Evidence for regulation of columnar habit in apple by a putative 2OG-Fe(II) oxygenase.

    PubMed

    Wolters, Pieter J; Schouten, Henk J; Velasco, Riccardo; Si-Ammour, Azeddine; Baldi, Paolo

    2013-12-01

    Understanding the genetic mechanisms controlling columnar-type growth in the apple mutant 'Wijcik' will provide insights on how tree architecture and growth are regulated in fruit trees. In apple, columnar-type growth is controlled by a single major gene at the Columnar (Co) locus. By comparing the genomic sequence of the Co region of 'Wijcik' with its wild-type 'McIntosh', a novel non-coding DNA element of 1956 bp specific to Pyreae was found to be inserted in an intergenic region of 'Wijcik'. Expression analysis of selected genes located in the vicinity of the insertion revealed the upregulation of the MdCo31 gene encoding a putative 2OG-Fe(II) oxygenase in axillary buds of 'Wijcik'. Constitutive expression of MdCo31 in Arabidopsis thaliana resulted in compact plants with shortened floral internodes, a phenotype reminiscent of the one observed in columnar apple trees. We conclude that MdCo31 is a strong candidate gene for the control of columnar growth in 'Wijcik'.

  17. Application of the Prague C and M criteria for endoscopic description of columnar-lined esophagus in South Korea

    PubMed Central

    Choe, Jung Wan; Kim, Young Choon; Joo, Moon Kyung; Kim, Hyo Jung; Lee, Beom Jae; Kim, Ji Hoon; Yeon, Jong Eun; Park, Jong-Jae; Kim, Jae Seon; Byun, Kwan Soo; Bak, Young-Tae

    2016-01-01

    AIM: To ascertain whether the Prague circumferential (C) length and maximal (M) length criteria for grading the extent of Barrett’s esophagus can be applied prior to its widespread application in South Korea. METHODS: Two hundred and thirteen consecutive cases with endoscopic columnar-lined esophagus (CLE) were included and classified according to the Prague C and M criteria. RESULTS: Of 213 cases with CLE, the distribution of maximum CLE lengths was: 0.5-0.9 cm in 99 cases (46.5%); 1.0-1.4 cm in 63 cases (29.6%); 1.5-1.9 cm in 15 cases (7.0%); 2.0-2.4 cm in 14 cases (6.6%); 2.5-2.9 cm in 1 case (0.5%); and 7.0 cm in 1 case (0.5%). Twenty cases (9.4%) had columnar islands alone. Two hundred and eight cases (97.7%) lacked the circumferential CLE component (C0Mx). Columnar islands were found in 70 cases (32.9%), of which 20 cases (9.4%) had columnar islands alone. CONCLUSION: In regions where most CLE patients display short or ultrashort tongue-like appearance, more detailed descriptions of CLE’s in < 1.0 cm lengths and columnar islands, as well as avoidance of repeating the prefix “C0” need to be considered in parallel with the widespread application of the Prague system in South Korea. PMID:27114749

  18. Preparation of High Silicon Electrical Steel Sheets with Strong {100} Recrystallization Texture by the Texture Inheritance of Initial Columnar Grains

    NASA Astrophysics Data System (ADS)

    Pan, Hongjiang; Zhang, Zhihao; Xie, Jianxin

    2016-05-01

    Texture evolutions and recrystallization texture features in warm- and cold-rolled sheets of high silicon electrical steel with two different initial microstructures (columnar-grained and equiaxed-grained microstructures) were investigated. The relationships between the recrystallization textures and the initial textures (the textures before rolling) of the samples were analyzed. The results showed that after annealing at 1073 K (800 °C) for 1 hour, strong {100} recrystallization textures with volume fractions of more than 47 pct were obtained in the columnar-grained samples fabricated by warm and cold rolling along the growing direction of the columnar grains. While after rolling and annealing in the same processes, only 12.8 pct volume fractions of {100} recrystallization texture were revealed in the equiaxed-grained samples. The formation of strong {100} recrystallization texture in the annealed sheets of high silicon electrical steel with initial columnar grains was attributed to the favorable texture inheritance of the initial texture during rolling and annealing. The columnar grains of strong near {100}<001> ({100}<001> {310}<001>) orientation in the samples before rolling were transferred into deformed grains with orientations such as {100}<011> and {100}<012>. after rolling. Afterwards, these deformed grains were further transferred into {100} oriented recrystallized grains, which formed strong {100} recrystallization texture in the annealed sheets and exhibited preferable soft magnetic properties.

  19. Effect of Column Disorder on Carrier Transport in Columnar Discotic Liquid Crystal Evaluated by Applying Precisely Controlled Shear Stress

    NASA Astrophysics Data System (ADS)

    Kim, Jaeki; Yamasaki, Naoyuki; Hayashi, Takeshi; Katayama, Mitsuyoshi; Yoshida, Hiroyuki; Moritake, Hiroshi; Fujii, Akihiko; Ozaki, Masanori

    2013-10-01

    The effect of column disorder on carrier drift mobility in columnar discotic liquid crystals has been investigated by applying a precisely controlled oscillating shear stress. Drift mobilities on the order of 10-1 cm2.V-1.s-1 were confirmed for positive and negative carriers in the columnar phase of 1,4,8,11,15,18,22,25-octahexylphthalocyanine in a well-aligned homeotropic geometry, in which the columnar axis was perfectly perpendicular to substrates with an electrode. A slight tilt of the columnar axis upon applying shear stress led to a marked decrease in electronic carrier mobility from 10-1 to less than 10-6 cm2.V-1.s-1, and transport was only confirmed for positive ion carriers. This result indicates that a uniform shear stress blocks the carrier transport path in the entire area of the electrode, and one-dimensional carrier transport path along the columns is easily hindered in columnar discotic liquid crystals.

  20. Specialization clines in the pollination systems of agaves (Agavaceae) and columnar cacti (Cactaceae): A phylogenetically controlled meta-analysis.

    PubMed

    Munguía-Rosas, Miguel A; Sosa, Vinicio J; Ojeda, Mario M; De-Nova, J Arturo

    2009-10-01

    The biogeography of plant-animal interactions is a novel topic on which many disciplines converge (e.g., reproductive biology, biogeography, and evolutionary biology). Narrative reviews have indicated that tropical columnar cacti and agaves have highly specialized pollination systems, while extratropical species have generalized systems. However, this dichotomy has never been quantitatively tested. We tested this hypothesis using traditional and phylogenetically informed meta-analysis. Three effect sizes were estimated from the literature: diurnal, nocturnal, and hand cross-pollination (an indicator of pollen limitation). Columnar cactus pollination systems ranged from purely bat-pollinated in the tropics to generalized pollination, with diurnal visitors as effective as nocturnal visitors in extratropical regions; even when phylogenetic relatedness among species is taken into account. Metaregressions identified a latitudinal increase in pollen limitation in columnar cacti, but this increase was not significant after correcting for phylogeny. The currently available data for agaves do not support any latitudinal trend. Nectar production of columnar cacti varied with latitude. Although this variation is positively correlated with pollination by diurnal visitors, it is influenced by phylogeny. The degree of specificity in the pollination systems of columnar cacti is heavily influenced by ecological factors and has a predictable geographic pattern.

  1. Imaging Pediatric Vascular Lesions

    PubMed Central

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  2. Kinetics and regulation of human keratinocyte stem cell growth in short-term primary ex vivo culture. Cooperative growth factors from psoriatic lesional T lymphocytes stimulate proliferation among psoriatic uninvolved, but not normal, stem keratinocytes.

    PubMed Central

    Bata-Csorgo, Z; Hammerberg, C; Voorhees, J J; Cooper, K D

    1995-01-01

    Flow cytometric analysis of primary ex vivo keratinocyte cultures demonstrated that stem cells, (beta 1 integrin+, keratin 1/keratin 10 [K1/K10-], proliferating cell nuclear antigen [PCNA-] [Bata-Csorgo, Zs., C. Hammerberg, J. J. Voorhees, and K. D. Cooper. 1993. J. Exp. Med. 178:1271-1281]) establish such cultures. This methodology also enabled the quantitation of synchronized recruitment of these cells from G0 into G1 of the cell cycle (PCNA expression), which preceded bright beta 1 integrin expression. (beta 1 integrinbright expression has been shown to be a characteristic feature of keratinocyte stem cells in culture (Jones, P. H., and F. M. Watt. 1993. Cell. 73:713-724). Using the above assay, we determined whether lesional T lymphocytes in psoriasis could be directly responsible for the induction of the stem cell hyperproliferation that is characteristic of this disease. Indeed, CD4+ T lymphocytes, cloned from lesional psoriatic skin and stimulated by immobilized anti-CD3 plus fibronectin, promoted psoriatic uninvolved keratinocyte stem cell proliferation via soluble factors. This induction appeared to be through accelerated recruitment of stem cells from their quiescent state (G0) into cell cycle. By contrast, normal keratinocyte stem cells exhibited no such growth stimulation. Supernatants exhibiting growth induction all contained high levels of GM-CSF and gamma-IFN, low IL-3 and TNF-alpha, and variable IL-4. Only anti-gamma-IFN antibody was able to neutralize growth stimulatory activity of the supernatants on psoriatic uninvolved keratinocyte stem cells. However, because recombinant gamma-IFN alone inhibited growth in this assay, these data suggest that, in psoriasis, gamma-IFN acts cooperatively with other growth factors in the immune induction of cell cycle progression by the normally quiescent stem cell keratinocytes. Images PMID:7529261

  3. Multiple lesion track structure model

    NASA Technical Reports Server (NTRS)

    Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.

    1992-01-01

    A multilesion cell kinetic model is derived, and radiation kinetic coefficients are related to the Katz track structure model. The repair-related coefficients are determined from the delayed plating experiments of Yang et al. for the C3H10T1/2 cell system. The model agrees well with the x ray and heavy ion experiments of Yang et al. for the immediate plat