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Sample records for oral epithelium regenerate

  1. Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

    PubMed

    Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

    2016-04-01

    Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells. PMID:26755348

  2. Gene Expression Profile of the Regeneration Epithelium during Axolotl Limb Regeneration

    PubMed Central

    Campbell, Leah J.; Suárez-Castillo, Edna C.; Ortiz-Zuazaga, Humberto; Knapp, Dunja; Tanaka, Elly M.; Crews, Craig M.

    2012-01-01

    Urodele amphibians are unique amongst adult vertebrates in their ability to regenerate missing limbs. The process of limb regeneration requires several key tissues including a regeneration-competent wound epidermis called the regeneration epithelium (RE). We used microarray analysis to profile gene expression of the RE in the axolotl, a Mexican salamander. A list of 125 genes and expressed sequence tags (ESTs) showed a ≥1.5 fold expression in the RE than in a wound epidermis covering a lateral cuff wound. A subset of the RE ESTs and genes were further characterized for expression level changes over the time-course of regeneration. This study provides the first large scale identification of specific gene expression in the RE. PMID:21648017

  3. Cytolethal Distending Toxin Damages the Oral Epithelium of Gingival Explants

    PubMed Central

    Damek-Poprawa, M.; Haris, M.; Volgina, A.; Korostoff, J.; DiRienzo, J.M.

    2011-01-01

    The cytolethal distending toxin (Cdt), expressed by the periodontal pathogen Aggregatibacter actinomycetemcomitans, inhibits the proliferation of cultured epithelial cells by arresting the cell cycle. The gingival epithelium is an early line of defense against microbial assault. When damaged, bacteria collectively gain entry into underlying connective tissue where microbial products can affect infiltrating inflammatory cells, leading to the destruction of the attachment apparatus. Histological evaluation of rat and healthy human gingival tissue exposed ex vivo to the Cdt for 36 and 18 hours, respectively, revealed extensive detachment of the keratinized outer layer and distention of spinous and basal cells in the oral epithelium. Treated human tissue also exhibited disruption of rete pegs and dissolution of cell junctions. Cells in the connective tissue appeared unaffected. Primary gingival epithelial cells, but not gingival fibroblasts, isolated from the same healthy human tissue were cell-cycle-arrested when treated with the toxin. These findings provide new evidence that the Cdt severely damages the oral epithelium, ex vivo, by specifically targeting epithelial cells, in situ. The Cdt shows preferential targeting of the epithelium as opposed to connective tissue in animal and human gingival explant models. Abbreviations: cytolethal distending toxin (Cdt), connective tissue (CT), 4′,6-diamidino-2-phenylindole (DAPI), human gingival epithelial cells (HGEC), human gingival explants (HGX), human gingival fibroblasts (HGF), junctional epithelium (JE), oral epithelium (OE), rete pegs (RP), sulcular epithelium (SE) PMID:21471326

  4. Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice.

    PubMed

    Ueha, Rumi; Ueha, Satoshi; Sakamoto, Takashi; Kanaya, Kaori; Suzukawa, Keigo; Nishijima, Hironobu; Kikuta, Shu; Kondo, Kenji; Matsushima, Kouji; Yamasoba, Tatsuya

    2016-08-01

    The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF-1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa. PMID:27003941

  5. Candida albicans Ultrastructure: Colonization and Invasion of Oral Epithelium

    PubMed Central

    Howlett, Julie A.; Squier, Christopher A.

    1980-01-01

    The colonization and invasion of various animal oral mucosae by Candida albicans were examined in an organ culture model. Scanning and transmission electron microscopy of the oral epithelium between 12 and 30 h after inoculation with the fungus revealed the morphological relationships between host and parasite. Examination of the fungi in thin sections showed five distinct layers in the cell wall of C. albicans within the epithelium, but changes were evident in the organization and definition of the outer cell wall layers in budding hyphae and in hyphae participating in colonization and invasion of the epithelial cells. Adherence of the fungus to the superficial cells of the oral mucosa appeared to involve intimate contact between the epithelial cell surface and the deeper layers of the fungal cell wall. During invasion a close seal was maintained between the invading hyphae and the surrounding epithelial cell envelope, there being no other evidence of damage to the host cell surface except at the site of entry. Within the epithelial cells there was only occasional loss of cytoplasmic components in the vicinity of the invading hyphae. These findings would suggest that enzymatic lysis associated with the invasive process is localized and that the mechanical support provided by surface adherence and the intimate association between the fungus and the epithelial cell envelope may permit growth of Candida on through the epithelium. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:6995338

  6. Developmental Plasticity of Patterned and Regenerating Oral Organs.

    PubMed

    Streelman, J Todd; Bloomquist, Ryan F; Fowler, Teresa E

    2015-01-01

    In many aquatic vertebrates, including bony and cartilaginous fishes, teeth and taste buds colocalize on jaw elements. In these animals, taste buds are renewed continuously throughout life, whereas teeth undergo cycled whole-organ replacement by various means. Recently, studies of cichlid fishes have yielded new insights into the development and regeneration of these dental and sensory oral organs. Tooth and taste bud densities covary positively across species with different feeding strategies, controlled by common regions of the genome and integrated molecular signals. Developing teeth and taste buds share a bipotent epithelium during early patterning stages, from which dental and taste fields are specified. Moreover, these organs share a common epithelial ribbon that supports label-retaining cells during later stages of regeneration. During both patterning and regeneration stages, dental organs can be converted to taste bud fate by manipulation of BMP signaling. These observations highlight a surprising long-term plasticity between dental and sensory organ types. Here, we review these findings and discuss the implications of developmental plasticity that spans the continuum of craniofacial organ patterning and regeneration. PMID:26589931

  7. Developmental plasticity of patterned and regenerating oral organs

    PubMed Central

    Streelman, J. Todd; Bloomquist, Ryan F.; Fowler, Teresa E.

    2015-01-01

    In many aquatic vertebrates, including bony and cartilaginous fishes, teeth and taste buds co-localize on jaw elements. In these animals, taste buds are renewed continuously throughout life, whereas teeth undergo cycled whole organ replacement by various means. Recently, studies of cichlid fishes have yielded new insights into the development and regeneration of these dental and sensory oral organs. Tooth and taste bud densities co-vary positively across species with different feeding strategies, controlled by common regions of the genome and integrated molecular signals. Developing teeth and taste buds share a bipotent epithelium during early patterning stages, from which dental and taste fields are specified. Moreover, these organs share a common epithelial ribbon that supports label-retaining cells during later stages of regeneration. During both patterning and regeneration stages, dental organs can be converted to taste bud fate by manipulation of BMP signaling. These observations highlight a surprising long-term plasticity between dental and sensory organ types. Here, we review these findings and discuss the implications of developmental plasticity that spans the continuum of craniofacial organ patterning and regeneration. PMID:26589931

  8. Epithelium

    MedlinePlus

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Epithelium. In: Kierszenbaum AL, Tres LL. Histology and Cell Biology - An Introduction to Pathology , 3rd ed. Philadelphia, ...

  9. DNA Methylation Dynamics Regulate the Formation of a Regenerative Wound Epithelium during Axolotl Limb Regeneration.

    PubMed

    Aguilar, Cristian; Gardiner, David M

    2015-01-01

    The formation of a blastema during regeneration of an axolotl limb involves important changes in the behavior and function of cells at the site of injury. One of the earliest events is the formation of the wound epithelium and subsequently the apical epidermal cap, which involves in vivo dedifferentiation that is controlled by signaling from the nerve. We have investigated the role of epigenetic modifications to the genome as a possible mechanism for regulating changes in gene expression patterns of keratinocytes of the wound and blastema epithelium that are involved in regeneration. We report a modulation of the expression DNMT3a, a de novo DNA methyltransferase, within the first 72 hours post injury that is dependent on nerve signaling. Treatment of skin wounds on the upper forelimb with decitabine, a DNA methyltransferase inhibitor, induced changes in gene expression and cellular behavior associated with a regenerative response. Furthermore, decitabine-treated wounds were able to participate in regeneration while untreated wounds inhibited a regenerative response. Elucidation of the specific epigenetic modifications that mediate cellular dedifferentiation likely will lead to insights for initiating a regenerative response in organisms that lack this ability. PMID:26308461

  10. Primary Cilia on Horizontal Basal Cells Regulate Regeneration of the Olfactory Epithelium

    PubMed Central

    Joiner, Ariell M.; Green, Warren W.; McIntyre, Jeremy C.; Allen, Benjamin L.; Schwob, James E.

    2015-01-01

    The olfactory epithelium (OE) is one of the few tissues to undergo constitutive neurogenesis throughout the mammalian lifespan. It is composed of multiple cell types including olfactory sensory neurons (OSNs) that are readily replaced by two populations of basal stem cells, frequently dividing globose basal cells and quiescent horizontal basal cells (HBCs). However, the precise mechanisms by which these cells mediate OE regeneration are unclear. Here, we show for the first time that the HBC subpopulation of basal stem cells uniquely possesses primary cilia that are aligned in an apical orientation in direct apposition to sustentacular cell end feet. The positioning of these cilia suggests that they function in the detection of growth signals and/or differentiation cues. To test this idea, we generated an inducible, cell type-specific Ift88 knock-out mouse line (K5rtTA;tetOCre;Ift88fl/fl) to disrupt cilia formation and maintenance specifically in HBCs. Surprisingly, the loss of HBC cilia did not affect the maintenance of the adult OE but dramatically impaired the regeneration of OSNs following lesion. Furthermore, the loss of cilia during development resulted in a region-specific decrease in neurogenesis, implicating HBCs in the establishment of the OE. Together, these results suggest a novel role for primary cilia in HBC activation, proliferation, and differentiation. SIGNIFICANCE STATEMENT We show for the first time the presence of primary cilia on a quiescent population of basal stem cells, the horizontal basal cells (HBCs), in the olfactory epithelium (OE). Importantly, our data demonstrate that cilia on HBCs are necessary for regeneration of the OE following injury. Moreover, the disruption of HBC cilia alters neurogenesis during the development of the OE, providing evidence that HBCs participate in the establishment of this tissue. These data suggest that the mechanisms of penetrance for ciliopathies in the OE extend beyond that of defects in olfactory sensory

  11. Expression of Nogo receptor 1 in the regeneration process of the mouse olfactory epithelium.

    PubMed

    Chen, He-Xin; Zeng, Xian-Ping; Sun, Yue-Qi; Fu, Qing-Ling

    2016-07-01

    Nogo receptor 1 (NgR1) is the most important Nogo-A receptor. By its interaction with myelin-associated inhibitory proteins, NgR1 inhibits the regeneration of axons and is extensively expressed in the central nervous system. However, the expression of NgR1 in regenerable neurons, such as olfactory neurons, and its expression in the regeneration progress of olfactory neurons have not been reported. In this study, we demonstrated that NgR1 was expressed in the cell bodies of certain mature olfactory receptor neurons (ORNs) but was not expressed in immature ORNs in the olfactory epithelium (OE) of normal adult mice. On day 21 after OE injury, NgR1 was expressed not only in the cell bodies of mature ORNs but also in the cell bodies of glial fibrillary acidic protein (GFAP)-positive cells in the top and submucosal layers of the OE. On day 48 after model establishment, NgR1 expression decreased in the cell bodies of the GFAP-positive cells. On day 56 after model establishment, no NgR1 expression was found in the cell bodies of the GFAP-positive cells, and NgR1 was again expressed only in the mature ORNs. Our results demonstrated that NgR1 expression is upregulated in the OE after injury, which suggests that NgR1 might be involved in the regeneration of the OE. PMID:27138950

  12. Defence mechanisms of olfactory neuro-epithelium: mucosa regeneration, metabolising enzymes and transporters.

    PubMed

    Watelet, J B; Strolin-Benedetti, M; Whomsley, R

    2009-01-01

    The olfactory neuro-epithelium is highly sensitive to chemicals and its direct microbiological environment. It also plays a role as an interface between the airways and the nervous system, and so it has developed several defence instruments for rapid regeneration or for the detoxification of the immediate environment. This review illustrates three of these defence mechanisms: regeneration of the epithelium, local production of metabolising enzymes and xenobiotic transporters. Toxicants can inflict damage by a direct toxic response. Alternatively, they may require metabolic activation to produce the proximate toxicant. In addition to detoxifying inhaled and systemically derived xenobiotics, the local olfactory metabolism may fulfil multiple functions such as the modification of inhaled odorant, the modulation of endogenous signalling molecules and the protection of other tissues such as the CNS and lungs from inhaled toxicants. Finally, the permeability of nasal and olfactory mucosa is an important efficacy parameter for some anti-allergic drugs delivered by intranasal administration or inhalation. Efflux or update transporters expressed in these tissues may therefore significantly influence the pharmacokinetics of drugs administered topically. PMID:20084803

  13. Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage

    PubMed Central

    Fernandez Vallone, Valeria; Leprovots, Morgane; Strollo, Sandra; Vasile, Gabriela; Lefort, Anne; Libert, Frederick; Vassart, Gilbert; Garcia, Marie-Isabelle

    2016-01-01

    ABSTRACT Mouse fetal intestinal progenitors lining the epithelium prior to villogenesis grow as spheroids when cultured ex vivo and express the transmembrane glycoprotein Trop2 as a marker. Here, we report the characterization of Trop2-expressing cells from fetal pre-glandular stomach, growing as immortal undifferentiated spheroids, and their relationship with gastric development and regeneration. Trop2+ cells generating gastric spheroids differed from adult glandular Lgr5+ stem cells, but appeared highly related to fetal intestinal spheroids. Although they shared a common spheroid signature, intestinal and gastric fetal spheroid-generating cells expressed organ-specific transcription factors and were committed to intestinal and glandular gastric differentiation, respectively. Trop2 expression was transient during glandular stomach development, being lost at the onset of gland formation, whereas it persisted in the squamous forestomach. Undetectable under homeostasis, Trop2 was strongly re-expressed in glands after acute Lgr5+ stem cell ablation or following indomethacin-induced injury. These highly proliferative reactive adult Trop2+ cells exhibited a transcriptome displaying similarity with that of gastric embryonic Trop2+ cells, suggesting that epithelium regeneration in adult stomach glands involves the partial re-expression of a fetal genetic program. PMID:26989172

  14. GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells

    PubMed Central

    Gao, Xia; Bali, Aman S.; Randell, Scott H.

    2015-01-01

    Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical–basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture. We also use CRISPR/Cas9 genome editing in primary human basal cells differentiating into organoids and mucociliary epithelium in vitro. Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2. PMID:26527742

  15. Cultivated Oral Mucosa Epithelium in Ocular Surface Reconstruction in Aniridia Patients

    PubMed Central

    Dobrowolski, Dariusz; Orzechowska-Wylegala, Boguslawa; Wowra, Bogumil; Wroblewska-Czajka, Ewa; Grolik, Maria; Szczubialka, Krzysztof; Nowakowska, Maria; Puzzolo, Domenico; Wylegala, Edward A.; Micali, Antonio; Aragona, Pasquale

    2015-01-01

    Purpose. Efficacy of cultivated oral mucosa epithelial transplantation (COMET) procedure in corneal epithelium restoration of aniridia patients. Methods. Study subjects were aniridia patients (13 patients; 17 eyes) with irregular, vascular conjunctival pannus involving visual axis who underwent autologous transplantation of cultivated epithelium. For the procedure oral mucosa epithelial cells were obtained from buccal mucosa with further enzymatic treatment. Suspension of single cells was seeded on previously prepared denuded amniotic membrane. Cultures were carried on culture dishes inserts in the presence of the inactivated with Mitomycin C monolayer of 3T3 fibroblasts. Cultures were carried for seven days. Stratified oral mucosa epithelium with its amniotic membrane carrier was transplanted on the surgically denuded corneal surface of aniridia patients with total or subtotal limbal stem cell deficiency. Outcome Measures. Corneal surface, epithelial regularity, and visual acuity improvement were evaluated. Results. At the end of the observation period, 76.4% of the eyes had regular transparent epithelium and 23.5% had developed epithelial defects or central corneal haze; in 88.2% of cases visual acuity had increased. VA range was from HM 0.05 before the surgery to HM up to 0.1 after surgery. Conclusion. Application of cultivated oral mucosa epithelium restores regular epithelium on the corneal surface with moderate improvement in quality of vision. PMID:26451366

  16. Effect of Atmospheric-Pressure Cold Plasma on Pathogenic Oral Biofilms and In Vitro Reconstituted Oral Epithelium.

    PubMed

    Delben, Juliana Aparecida; Zago, Chaiene Evelin; Tyhovych, Natalia; Duarte, Simone; Vergani, Carlos Eduardo

    2016-01-01

    Considering the ability of atmospheric-pressure cold plasma (ACP) to disrupt the biofilm matrix and rupture cell structure, it can be an efficient tool against virulent oral biofilms. However, it is fundamental that ACP does not cause damage to oral tissue. So, this study evaluated (1) the antimicrobial effect of ACP on single- and dual-species biofilms of Candida albicans and Staphylococcus aureus as well as (2) the biological safety of ACP on in vitro reconstituted oral epithelium. Standardized cell suspensions of each microorganism were prepared for biofilm culture on acrylic resin discs at 37°C for 48 hours. The biofilms were submitted to ACP treatment at 10 mm of plasma tip-to-sample distance during 60 seconds. Positive controls were penicillin G and fluconazole for S. aureus and C. albicans, respectively. The biofilms were analyzed through counting of viable colonies, confocal laser scanning microscopy, scanning electron microscopy and fluorescence microscopy for detection of reactive oxygen species. The in vitro reconstituted oral epithelium was submitted to similar ACP treatment and analyzed through histology, cytotoxocity test (LDH release), viability test (MTT assay) and imunnohistochemistry (Ki67 expression). All plasma-treated biofilms presented significant log10 CFU/mL reduction, alteration in microorganism/biofilm morphology, and reduced viability in comparison to negative and positive controls. In addition, fluorescence microscopy revealed presence of reactive oxygen species in all plasma-treated biofilms. Low cytotoxicity and high viability were observed in oral epithelium of negative control and plasma group. Histology showed neither sign of necrosis nor significant alteration in plasma-treated epithelium. Ki67-positive cells revealed maintenance of cell proliferation in plasma-treated epithelium. Atmospheric-pressure cold plasma is a promissing approach to eliminate single- and dual-species biofilms of C. albicans and S. aureus without having

  17. Effect of Atmospheric-Pressure Cold Plasma on Pathogenic Oral Biofilms and In Vitro Reconstituted Oral Epithelium

    PubMed Central

    Zago, Chaiene Evelin; Tyhovych, Natalia

    2016-01-01

    Considering the ability of atmospheric-pressure cold plasma (ACP) to disrupt the biofilm matrix and rupture cell structure, it can be an efficient tool against virulent oral biofilms. However, it is fundamental that ACP does not cause damage to oral tissue. So, this study evaluated (1) the antimicrobial effect of ACP on single- and dual-species biofilms of Candida albicans and Staphylococcus aureus as well as (2) the biological safety of ACP on in vitro reconstituted oral epithelium. Standardized cell suspensions of each microorganism were prepared for biofilm culture on acrylic resin discs at 37°C for 48 hours. The biofilms were submitted to ACP treatment at 10 mm of plasma tip-to-sample distance during 60 seconds. Positive controls were penicillin G and fluconazole for S. aureus and C. albicans, respectively. The biofilms were analyzed through counting of viable colonies, confocal laser scanning microscopy, scanning electron microscopy and fluorescence microscopy for detection of reactive oxygen species. The in vitro reconstituted oral epithelium was submitted to similar ACP treatment and analyzed through histology, cytotoxocity test (LDH release), viability test (MTT assay) and imunnohistochemistry (Ki67 expression). All plasma-treated biofilms presented significant log10 CFU/mL reduction, alteration in microorganism/biofilm morphology, and reduced viability in comparison to negative and positive controls. In addition, fluorescence microscopy revealed presence of reactive oxygen species in all plasma-treated biofilms. Low cytotoxicity and high viability were observed in oral epithelium of negative control and plasma group. Histology showed neither sign of necrosis nor significant alteration in plasma-treated epithelium. Ki67-positive cells revealed maintenance of cell proliferation in plasma-treated epithelium. Atmospheric-pressure cold plasma is a promissing approach to eliminate single- and dual-species biofilms of C. albicans and S. aureus without having

  18. BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors

    PubMed Central

    Tadokoro, Tomomi; Gao, Xia; Hong, Charles C.; Hotten, Danielle; Hogan, Brigid L. M.

    2016-01-01

    The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this brake is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair, the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal crucial roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium. PMID:26811382

  19. Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury.

    PubMed

    Vaughan, Andrew E; Brumwell, Alexis N; Xi, Ying; Gotts, Jeffrey E; Brownfield, Doug G; Treutlein, Barbara; Tan, Kevin; Tan, Victor; Liu, Feng Chun; Looney, Mark R; Matthay, Michael A; Rock, Jason R; Chapman, Harold A

    2015-01-29

    Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is both organ- and injury-specific. Current models in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers. By contrast, here we define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEP) cells present within normal distal lung. Quiescent LNEPs activate a ΔNp63 (a p63 splice variant) and cytokeratin 5 remodelling program after influenza or bleomycin injury in mice. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, at which point they differentiate towards mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single-cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signalling to activate the ΔNp63 and cytokeratin 5 program, and subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signalling after injury led to parenchymal 'micro-honeycombing' (alveolar cysts), indicative of failed regeneration. Lungs from patients with fibrosis show analogous honeycomb cysts with evidence of hyperactive Notch signalling. Our findings indicate that distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of the injury, and the outcomes of regeneration or fibrosis may depend in part on the dynamics of LNEP Notch signalling. PMID:25533958

  20. Lineage-negative Progenitors Mobilize to Regenerate Lung Epithelium after Major Injury

    PubMed Central

    Vaughan, Andrew E.; Brumwell, Alexis N.; Xi, Ying; Gotts, Jeffrey; Brownfield, Doug G.; Treutlein, Barbara; Tan, Kevin; Tan, Victor; Liu, Fengchun; Looney, Mark R.; Matthay, Michael; Rock, Jason R.; Chapman, Harold A.

    2014-01-01

    Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is both organ and injury-specific1–4. Current paradigms in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers5–8. In contrast we here define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEPs) cells present within normal distal lung. Quiescent LNEPs activate a ΔNp63/cytokeratin 5 (Krt5+) remodeling program after influenza or bleomycin injury. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, whereupon they differentiate toward mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signaling to activate the ΔNp63/Krt5+ program whereas subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signaling post-injury led to parenchymal micro-honeycombing, indicative of failed regeneration. Lungs from fibrosis patients show analogous honeycomb cysts with evidence of hyperactive Notch signaling. Our findings indicate distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of injury, and the outcomes of regeneration or fibrosis may ride in part on the dynamics of LNEP Notch signaling. PMID:25533958

  1. Candidates Cell Sources to Regenerate Alveolar Bone from Oral Tissue

    PubMed Central

    Nishimura, Masahiro; Takase, Kazuma; Suehiro, Fumio; Murata, Hiroshi

    2012-01-01

    Most of the cases of dental implant surgery, especially the bone defect extensively, are essential for alveolar ridge augmentation. As known as cell therapy exerts valuable effects on bone regeneration, numerous reports using various cells from body to regenerate bone have been published, including clinical reports. Mesenchymal cells that have osteogenic activity and have potential to be harvested from intra oral site might be a candidate cells to regenerate alveolar bone, even dentists have not been harvested the cells outside of mouth. This paper presents a summary of somatic cells in edentulous tissues which could subserve alveolar bone regeneration. The candidate tissues that might have differentiation potential as mesenchymal cells for bone regeneration are alveolar bone chip, bone marrow from alveolar bone, periosteal tissue, and gingival tissue. Understanding their phenotype consecutively will provide a rational approach for alveolar ridge augmentation. PMID:22505911

  2. Calcium transport across the isolated oral epithelium of scleractinian corals

    NASA Astrophysics Data System (ADS)

    Wright, O. P.; Marshall, A. T.

    1991-07-01

    Oral epithelia were isolated from Lobophyllia temprichii and Plerogyra sinuosa and placed in Ussing chambers. Calcium flux was measured under open circuit and short circuit conditions using 45Ca. Only a small transepithelial potential of 1.5 mV was recorded under open circuit conditions and no effect on flux rates were observed when the preparation was short circuited. Unidirectional fluxes in single and paired experiments were consistently greater in the ectoderm to gastroderm direction than from gastroderm to ectoderm with net flux of Ca2+ frequently being more than 3x10-4 μEq mm-2 min-1. A small number of paired experiments showed that net flux of Ca2+ was reduced by Sr2+ and sodium azide but not by dinitrophenol. Unidirectional fluxes from ectoderm to gastroderm appeared to have maxima in the early and late parts of the day when recorded between 0900 and 2100 hrs. It is concluded that active transport of Ca2+ occurs across the isolated oral epitheia and that this may be an initial step in the process of keletal Ca2+ deposition.

  3. Porphyromonas gingivalis infection of oral epithelium inhibits neutrophil transepithelial migration.

    PubMed Central

    Madianos, P N; Papapanou, P N; Sandros, J

    1997-01-01

    Periodontal diseases are inflammatory disorders caused by microorganisms of dental plaque that colonize the gingival sulcus and, subsequently, the periodontal pocket. As in other mucosal infections, the host response to plaque bacteria is characterized by an influx of polymorphonuclear leukocytes (PMNs) to the gingival crevice. Neutrophil migration through the epithelial lining of the gingival pocket is thought to be the first line of defense against plaque bacteria. In order to model this phenomenon in vitro, we used the oral epithelial cell line KB and human PMNs in the Transwell system and examined the impact of Porphyromonas gingivalis-epithelial cell interactions on subsequent PMN transepithelial migration. We demonstrate here that P. gingivalis infection of oral epithelial cells failed to trigger transmigration of PMNs. Furthermore, it significantly inhibited neutrophil transmigration actively induced by stimuli such as N-formylmethionyl leucyl phenylalanine, interleukin-8 (IL-8), and the intestinal pathogen enterotoxigenic Escherichia coli. The ability of P. gingivalis to block PMN transmigration was strongly positively correlated with the ability to adhere to and invade epithelial cells. In addition, P. gingivalis attenuated the production of IL-8 and the expression of intercellular adhesion molecule 1 by epithelial cells. The ability of P. gingivalis to block neutrophil migration across an intact epithelial barrier may critically impair the potential of the host to confront the bacterial challenge and thus may play an important role in the pathogenesis of periodontal disease. PMID:9316996

  4. Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

    PubMed Central

    Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

    2014-01-01

    Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the

  5. Effects of C-xylopyranoside derivative on epithelial regeneration in an in vitro 3D oral mucosa model.

    PubMed

    Uenoyama, Atsushi; Kakizaki, Ikuko; Shiomi, Aki; Saito, Naoaki; Hara, Yuko; Saito, Taro; Ohnuki, Hisashi; Kato, Hiroko; Takagi, Ritsuo; Maeda, Takeyasu; Izumi, Kenji

    2016-07-01

    Identifying substandard tissue-engineered oral mucosa grafts with a poor epithelium before clinical use is critical to ensure quality assurance/control in regenerative medicine, leading to success of grafting. This study investigated the effects of one of the C-xylopyranoside derivatives, β-D-xylopyranoside-n-propane-2-one (XPP), on oral epithelial regeneration. Using a three-dimensional oral mucosa model, we analyzed changes of the epithelial structure, glycosaminoglycan (GAG) synthesis, the expression levels of basement membrane zone markers, and substrates of Akt/mTOR signaling. Compared with the control, 2 mM XPP treatment increased the mean and minimal epithelial thickness, and reduced the variation of epithelial thickness. It also stimulated expressions of decorin and syndecan-1 with change of GAG amount and/or composition, and enhanced the expressions of integrin α6, CD44, and Akt/mTOR signaling substrates. These findings suggest that XPP supplementation contributes to consistent epithelial regeneration. Moreover, upregulation of those markers may play a role in increasing the quality of the oral mucosal epithelium. PMID:26966997

  6. Repair and regeneration of tracheal surface epithelium and submucosal glands in a mouse model of hypoxic-ischemic injury

    PubMed Central

    HEGAB, AHMED E.; NICKERSON, DEREK W.; HA, VI LUAN; DARMAWAN, DAPHNE O.; GOMPERTS, BRIGITTE N.

    2012-01-01

    Background and objective The heterotopic syngeneic tracheal transplant mouse model is an acute hypoxic-ischemic injury model that undergoes complete repair and regeneration. We hypothesized that the repair and regeneration process of the surface epithelium and submucosal glands would occur in a reproducible pattern that could be followed by the expression of specific markers of epithelial cell types. Methods We used the syngeneic heterotopic tracheal transplant model to develop a temporal and spatial map of cellular repair and regeneration by examining the tracheal grafts at post-transplant days 1, 3, 5, 7, 10 and 14. We used pulsed BrdU and immunofluorescent staining to identify and follow proliferating and repairing cell populations. Results We confirmed the reproducibility of the injury and repair in the model and we found a distinct sequence of reappearance of the various stem/ progenitor and differentiated cell populations of the tracheal surface epithelium and submucosal glands. In the initial phase, the basal and duct cells that survived the injury proliferated to re-epithelialize the basement membrane with K5 and K14 expressing cells. Then these cells proliferated further and differentiated to restore the function of the epithelium. During this repair process, TROP-2 marked all repairing submucosal gland tubules and ducts. Non-CCSP-expressing serous cells were found to differentiate 4–5 days before Clara, mucus and ciliated cells. Conclusions Improving our understanding of the reparative process of the airway epithelium will allow us to identify cell-specific mechanisms of repair that could be used as novel therapeutic approaches for abnormal repair leading to airway diseases. PMID:22617027

  7. Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells

    PubMed Central

    Fukahori, Mioko; Chitose, Shun-ichi; Sato, Kiminori; Sueyoshi, Shintaro; Kurita, Takashi; Umeno, Hirohito; Monden, Yu; Yamakawa, Ryoji

    2016-01-01

    Objectives Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells. Study Design Animal experiment using eight beagles (including three controls). Methods A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed. Results A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site. Conclusion The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds. PMID:26730600

  8. Proliferation of the intestinal epithelium and of the regenerating liver of rats with epidermal growth factor deficiency

    SciTech Connect

    Ivashchenko, Yu.D.; Gut, I.T.; Osipova, L.A.; Garmanchuk, L.V.; Khranovskaya, L.N.; Bykorez, A.I.

    1986-09-01

    The presence of specific receptors for epidermal growth factor (EGF) in hepatocytes and enterocytes, changes in their number during the period of postresection regeneration of the liver, and also the inexplicably high concentrations of this powerful growth factor in the saliva determined the main purpose of this investigation, which was to study the effect of EGF deficiency, produced by submandibular sialadenectomy, on proliferation of the intestinal and hepatic epithelium during postresection regeneration of these organs. The experiments were carried out on rats that received an intraperitoneal injection of /sup 3/H-thymidine. The specific activity of /sup 125/I-EGF was 12,000 cpm/ng. The EGF concentration in the rats' blood serum, saliva, and urine was determined by radioimmunoassay. Bound /sup 125/I-EGF was precipitated. Results indicate that EGF is a regulatory factor which modifies proliferation.

  9. Effects of oral contraceptive pill use on vaginal flora and vaginal epithelium.

    PubMed

    Eschenbach, D A; Patton, D L; Meier, A; Thwin, S S; Aura, J; Stapleton, A; Hooton, T M

    2000-09-01

    The objective of this study was to examine the effect of oral contraceptive (OC) use on vaginal discharge, epithelium, and flora. Thirty women who planned to use OC for contraception were evaluated before and 2 months after the start of OC use. At both visits, genital symptoms and exposures were assessed by questionnaire; vaginal signs were assessed by speculum examination and colposcopy; vaginal microflora was evaluated by quantitative culture; and a vaginal biopsy was obtained for histopathologic evaluation. Variables were compared between the initial visit and after 2 months of OC use. It was found that OC use did not change the gross, colposcopic, or histologic appearance of the vaginal epithelium or characteristics of vaginal or cervical discharge. Vaginal flora essentially remained unchanged after 2 months of OC use, except that a small decrease occurred in the number of subjects with > or =10(5) colony forming units/mL of H(2)O(2) producing Lactobacillus from 16 at baseline to 9 (p = 0.04) and in the total number of subjects with Ureaplasma urealyticum from 17 at baseline to 10 of 29 (p = 0.04). The results indicate minimal effect of OC use on the vaginal epithelium and vaginal and cervical discharge, and a small effect on vaginal flora. PMID:11124356

  10. A novel wounding device suitable for quantitative biochemical analysis of wound healing and regeneration of cultured epithelium.

    PubMed

    Lan, Rongpei; Geng, Hui; Hwang, Yoon; Mishra, Pramod; Skloss, Wayne L; Sprague, Eugene A; Saikumar, Pothana; Venkatachalam, Manjeri

    2010-01-01

    We describe the fabrication and use of an in vitro wounding device that denudes cultured epithelium in patterns designed to leave behind strips or islands of cells sufficiently narrow or small to ensure that all the remaining cells become rapidly activated and then migrate, dedifferentiate, and proliferate in near synchrony. The design ensures that signals specific to regenerating cells do not become diluted by quiescent differentiated cells that are not affected by wound-induced activation. The device consists of a flat circular disk of rubber, engraved to produce alternating ridges and grooves in patterns of concentric circles or parallel lines. The disk is mounted at the end of a pneumatically controlled piston assembly. Application of controlled pressure and circular or linear movement of the disk on cultures produced highly reproducible wounding patterns. The near-synchronous regenerative activity of cell bands or islands allowed the collection of samples large enough for biochemical studies to sensitively detect alterations involving mRNA for several early response genes and protein phosphorylation in major signaling pathways. The method is versatile, easy to use and reproducible, and should facilitate biochemical, proteomic, and genomic studies of wound-induced regeneration of cultured epithelium. PMID:20230600

  11. Expression and Localization of the Cell Adhesion Molecule SgIGSF during Regeneration of the Olfactory Epithelium in Mice

    PubMed Central

    Tsukioka, Fusae; Wakayama, Tomohiko; Tsukatani, Toshiaki; Miwa, Takaki; Furukawa, Mitsuru; Iseki, Shoichi

    2007-01-01

    Spermatogenic immunoglobulin superfamily (SgIGSF) is a cell adhesion molecule originally discovered in mouse testis. SgIGSF is expressed not only in spermatogenic cells but also in lung and liver epithelial cells and in neurons and glia of the central and peripheral nervous systems. In the present study, we examined the expression and localization of SgIGSF in mouse olfactory epithelium before and after transection of the olfactory nerves, by RT-PCR, Western blotting and immunohistochemistry. In normal olfactory mucosa, SgIGSF showed 100 kDa in molecular weight, which was identical with that in the lung but different from that in the brain. SgIGSF was expressed on the membrane of all olfactory, sustentacular and basal cells, but more abundantly in the apical portions of the olfactory epithelium where the dendrites of olfactory cells are in contact with sustentacular cells. After olfactory nerve transection, mature olfactory cells disappeared in 4 days but were regenerated around 7–15 days by proliferation and differentiation of basal cells into mature olfactory cells through the step of immature olfactory cells. During this period, both the mRNA and protein for SgIGSF showed a transient increase, with peak levels at 7 days and 11 days, respectively, after the transection. Immunohistochemistry showed that the enriched immunoreactivity for SgIGSF at 7–11 days was localized primarily to the membrane of immature olfactory cells. These results suggested that, during regeneration of the olfactory epithelium, the adhesion molecule SgIGSF plays physiological roles in differentiation, migration, and maturation of immature olfactory cells. PMID:17576432

  12. Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration.

    PubMed

    Vigneswara, Vasanthy; Esmaeili, Maryam; Deer, Louise; Berry, Martin; Logan, Ann; Ahmed, Zubair

    2015-09-01

    Axotomised retinal ganglion cells (RGCs) die rapidly by apoptosis and fail to regenerate because of the limited availability of neurotrophic factors and a lack of axogenic stimuli. However, we have recently showed that pigment epithelium-derived factor (PEDF) promotes RGC survival and axon regeneration after optic nerve crush injury. PEDF has multiple fragments of the native peptide that are neuroprotective, anti-angiogenic and anti-inflammatory. Here we investigated the neuroprotective and axogenic properties of a fragment of PEDF, PEDF-34, in retinal neurons in vitro and when delivered by intravitreal injection and eye drops in vivo. We found that PEDF-34 was 43% more neuroprotective and 52% more neuritogenic than PEDF-44 in vitro. Moreover, in vivo, intravitreal delivery of 1.88nM PEDF-34 was 71% RGC neuroprotective at 21days after optic nerve crush compared to intact controls, whilst daily eye drops containing 1.88nM PEDF-34 promoted 87% RGC survival. After topical eye drop delivery, PEDF-34 was detected in the vitreous body within 30min and attained physiologically relevant concentrations in the retina by 4h peaking at 1.4±0.05nM by 14days. In eye drop- compared to intravitreal-treated PEDF-34 animals, 55% more RGC axons regenerated 250μm beyond the optic nerve lesion. We conclude that daily topical eye drop application of PEDF-34 is superior to weekly intravitreal injections in promoting RGC survival and axon regeneration through both direct effects on retinal neurons and indirect effects on other retinal cells. PMID:26260110

  13. Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration

    PubMed Central

    Vigneswara, Vasanthy; Esmaeili, Maryam; Deer, Louise; Berry, Martin; Logan, Ann; Ahmed, Zubair

    2015-01-01

    Axotomised retinal ganglion cells (RGCs) die rapidly by apoptosis and fail to regenerate because of the limited availability of neurotrophic factors and a lack of axogenic stimuli. However, we have recently showed that pigment epithelium-derived factor (PEDF) promotes RGC survival and axon regeneration after optic nerve crush injury. PEDF has multiple fragments of the native peptide that are neuroprotective, anti-angiogenic and anti-inflammatory. Here we investigated the neuroprotective and axogenic properties of a fragment of PEDF, PEDF-34, in retinal neurons in vitro and when delivered by intravitreal injection and eye drops in vivo. We found that PEDF-34 was 43% more neuroprotective and 52% more neuritogenic than PEDF-44 in vitro. Moreover, in vivo, intravitreal delivery of 1.88 nM PEDF-34 was 71% RGC neuroprotective at 21 days after optic nerve crush compared to intact controls, whilst daily eye drops containing 1.88 nM PEDF-34 promoted 87% RGC survival. After topical eye drop delivery, PEDF-34 was detected in the vitreous body within 30 min and attained physiologically relevant concentrations in the retina by 4 h peaking at 1.4 ± 0.05 nM by 14 days. In eye drop- compared to intravitreal-treated PEDF-34 animals, 55% more RGC axons regenerated 250 μm beyond the optic nerve lesion. We conclude that daily topical eye drop application of PEDF-34 is superior to weekly intravitreal injections in promoting RGC survival and axon regeneration through both direct effects on retinal neurons and indirect effects on other retinal cells. PMID:26260110

  14. Collagenase-3 (matrix metalloproteinase-13) expression is induced in oral mucosal epithelium during chronic inflammation.

    PubMed Central

    Uitto, V. J.; Airola, K.; Vaalamo, M.; Johansson, N.; Putnins, E. E.; Firth, J. D.; Salonen, J.; López-Otín, C.; Saarialho-Kere, U.; Kähäri, V. M.

    1998-01-01

    Increased proliferation of mucosal epithelium during inflammation is associated with degradation of subepithelial connective tissue matrix and local invasion of the epithelial cells. Here we have studied, whether collagenase-3 (MMP-13), a collagenolytic matrix metalloproteinase with an exceptionally wide substrate specificity, is expressed in the epithelium of chronically inflamed mucosa. Examination of human gingival tissue sections from subjects with chronic adult periodontitis with in situ hybridization revealed marked expression of MMP-13 in basal cells of some epithelial rete ridges expanding into connective tissue. Immunohistochemical staining demonstrated that these cells also expressed strongly laminin-5, suggesting that they are actively migrating cells. A strong signal for MMP-13 mRNA was occasionally also noted in the suprabasal epithelial cells facing the gingival pocket, whereas no collagenase-1 (MMP-1) mRNA was detected in any areas of the epithelium. MMP-13 expression was also detected in fibroblast-like cells associated with collagen fibers of the inflamed subepithelial connective tissue. In organ culture of human oral mucosa, MMP-13 mRNA expression was observed in epithelial cells growing into connective tissue of the specimens. Regulation of MMP-13 expression was examined in cultured normal nonkeratinizing epithelial cells isolated from porcine periodontal ligament. In these cells, MMP-13 expression at the mRNA and protein level was potently enhanced (up to sixfold) by tumor necrosis factor-alpha, transforming growth factor-beta(1), and transforming growth factor-alpha and by keratinocyte growth factor in the presence of heparin. In addition, plating periodontal ligament epithelial cells on type I collagen stimulated MMP-13 expression (sevenfold) as compared with cells grown on tissue culture plastic. The results of this study show, that expression of MMP-13 is specifically induced in undifferentiated epithelial cells during chronic inflammation

  15. Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors.

    PubMed

    Ohigashi, Izumi; Zuklys, Saulius; Sakata, Mie; Mayer, Carlos E; Hamazaki, Yoko; Minato, Nagahiro; Hollander, Georg A; Takahama, Yousuke

    2015-11-17

    Medullary thymic epithelial cells (mTECs) play an essential role in establishing self-tolerance in T cells. mTECs originate from bipotent TEC progenitors that generate both mTECs and cortical TECs (cTECs), although mTEC-restricted progenitors also have been reported. Here, we report in vivo fate-mapping analysis of cells that transcribe β5t, a cTEC trait expressed in bipotent progenitors, during a given period in mice. We show that, in adult mice, most mTECs are derived from progenitors that transcribe β5t during embryogenesis and the neonatal period up to 1 week of age. The contribution of adult β5t(+) progenitors was minor even during injury-triggered regeneration. Our results further demonstrate that adult mTEC-restricted progenitors are derived from perinatal β5t(+) progenitors. These results indicate that the adult thymic medullary epithelium is maintained and regenerated by mTEC-lineage cells that pass beyond the bipotent stage during early ontogeny. PMID:26549457

  16. Mesenchymal to epithelial transition during tissue homeostasis and regeneration: Patching up the Drosophila midgut epithelium

    PubMed Central

    Antonello, Zeus A.; Reiff, Tobias; Dominguez, Maria

    2015-01-01

    Stem cells are responsible for preserving morphology and function of adult tissues. Stem cells divide to self-renew and to generate progenitor cells to sustain cell demand from the tissue throughout the organism's life. Unlike stem cells, the progenitor cells have limited proliferation potential but have the capacity to terminally differentiate and thereby to substitute older or damaged mature cells. Recent findings indicate that adult stem cells can adapt their division kinetics dynamically to match changes in tissue demand during homeostasis and regeneration. However, cell turnover not only requires stem cell division but also needs timed differentiation of the progenitor cells, which has been much less explored. In this Extra View article, we discuss the ability of progenitor cells to actively postpone terminal differentiation in the absence of a local demand and how tissue demand activates terminal differentiation via a conserved mesenchymal-epithelial transition program revealed in our recent EMBO J paper and other published and unpublished data. The extent of the significance of these results is discussed for models of tissue dynamics during both homeostasis and regeneration. PMID:26760955

  17. Stem Cell Therapy for Corneal Epithelium Regeneration following Good Manufacturing and Clinical Procedures

    PubMed Central

    Ramírez, Beatriz E.; Sánchez, Ana; Herreras, José M.; Fernández, Itziar; García-Sancho, Javier; Nieto-Miguel, Teresa; Calonge, Margarita

    2015-01-01

    Objective. To evaluate outcomes of cultivated limbal epithelial transplantation (CLET) for management of ocular surface failure due to limbal stem cell deficiency (LSCD). Design. Prospective, noncomparative, interventional case series and extensive comparison with recent similar studies. Participants. Twenty eyes with LSCD underwent CLET (11 autologous; 9 allogeneic) and were followed up for 3 years. Etiologies were divided into 3 prognostic categories: Group 1, chemical injuries (7 eyes); Group 2, immune-based inflammation (4 eyes); and Group 3, noninflammatory diseases (9 eyes). Intervention. Autologous and allogeneic limbal epithelial cells were cultivated on amniotic membranes and transplanted. Evaluations were based on clinical parameters, survival analysis, and in vivo confocal microscopy (IVCM). European Union Tissues/Cells Directive and good manufacturing procedures were followed. Main Outcome Measures. Improved clinical parameters, absence of epithelial defects, and improved central corneal epithelial phenotype. Results. Success rate was 80% at 1-2 years and 75% at 3 years. Autografts and allografts had similar survival. Success rate was significantly lower in prognostic Group 1 (42.9%) than in Groups 2-3 (100% each). All clinical parameters improved substantially. By IVCM, 80% of cases improved in epithelial status. Conclusions. CLET improved corneal epithelium quality, with subsequent improvement in symptoms, quality of life, and vision. These results confirm that CLET is a valid therapy for ocular surface failure. PMID:26451369

  18. The fine structure of the midgut epithelium in a centipede, Scolopendra cingulata (Chilopoda, Scolopendridae), with the special emphasis on epithelial regeneration.

    PubMed

    Chajec, Lukasz; Sonakowska, Lidia; Rost-Roszkowska, Magdalena M

    2014-01-01

    Scolopendra cingulata has a tube-shaped digestive system that is divided into three distinct regions: fore-, mid- and hindgut. The midgut is lined with a pseudostratified columnar epithelium which is composed of digestive, secretory and regenerative cells. Hemocytes also appear between the digestive cells of the midgut epithelium. The ultrastructure of three types of epithelial cells and hemocytes of the midgut has been described with the special emphasis on the role of regenerative cells in the protection of midgut epithelium. The process of midgut epithelium regeneration proceeds due to the ability of regenerative cells to proliferate and differentiate according to a circadian rhythm. The regenerative cells serve as unipotent stem cells that divide in an asymmetric manner. Additionally, two types of hemocytes have been distinguished among midgut epithelial cells. They enter the midgut epithelium from the body cavity. Because of the fact that numerous microorganisms occur in the cytoplasm of midgut epithelial cells, we discuss the role of hemocytes in elimination of pathogens from the midgut epithelium. The studies were conducted with the use of transmission electron microscope and immunofluorescent methods. PMID:23831526

  19. Regeneration of oral siphon pigment organs in the ascidian Ciona intestinalis

    PubMed Central

    Auger, Hélène; Sasakura, Yasunori; Joly, Jean-Stéphane; Jeffery, William R.

    2013-01-01

    Ascidians have powerful capacities for regeneration but the underlying mechanisms are poorly understood. Here we examine oral siphon regeneration in the solitary ascidian Ciona intestinalis. Following amputation, the oral siphon rapidly reforms oral pigment organs (OPO) at its distal margin prior to slower regeneration of proximal siphon parts. The early stages of oral siphon reformation include cell proliferation and re-growth of the siphon nerves, although the neural complex (adult brain and associated organs) is not required for regeneration. Young animals reform OPO more rapidly after amputation than old animals indicating that regeneration is age dependent. UV irradiation, microcautery, and cultured siphon explant experiments indicate that OPOs are replaced as independent units based on local differentiation of progenitor cells within the siphon, rather than by cell migration from a distant source in the body. The typical pattern of eight OPOs and siphon lobes is restored with fidelity after distal amputation of the oral siphon, but as many as 16 OPOs and lobes can be reformed following proximal amputation near the siphon base. Thus, the pattern of OPO regeneration is determined by cues positioned along the proximal distal axis of the oral siphon. A model is presented in which columns of siphon tissue along the proximal–distal axis below pre-existing OPO are responsible for reproducing the normal OPO pattern during regeneration. This study reveals previously unknown principles of oral siphon and OPO regeneration that will be important for developing Ciona as a regeneration model in urochordates, which may be the closest living relatives of vertebrates. PMID:20059994

  20. Regeneration, Stem Cells, and Aging in the Tunicate Ciona: Insights from the Oral Siphon.

    PubMed

    Jeffery, William R

    2015-01-01

    Regeneration studies in the tunicate Ciona intestinalis have recently been focused on the potential of adult stem cells to replace injured tissues and organs during the adult life cycle using the oral siphon (OS) as a model. The OS has oral siphon pigment organs (OPOs) along its rim and an underlying network of muscle fibers in its tube. Different regeneration processes are triggered by OS amputation at the tip, along the tube, or at the base. One process involves the replacement of OPOs without new cell division by direct differentiation of locally deployed stem cells or stem cells that migrate from the branchial sac. Another process involves blastema formation by the migration of progenitor cells produced from branchial sac stem cells. The capacity for complete and accurate OS regeneration declines continuously during the adult life cycle. Finally, after an age threshold is reached, OS regeneration ceases in old animals. The loss of regeneration capacity in old animals involves the depletion of stem cells in the branchial sac, the inability of branchial sac progenitor cells to migrate to the sites of regeneration, and defective oral pigment organ replacement. The significance of the OS model for studying regeneration, stem cells, and aging will be enhanced by the application of molecular methods. PMID:26404471

  1. Engineering Airway Epithelium

    PubMed Central

    Soleas, John P.; Paz, Ana; Marcus, Paula; McGuigan, Alison; Waddell, Thomas K.

    2012-01-01

    Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990). In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium. PMID:22523471

  2. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

    PubMed Central

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-01-01

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis. PMID:27025263

  3. Constitutively active mutation of ACVR1 in oral epithelium causes submucous cleft palate in mice.

    PubMed

    Noda, Kazuo; Mishina, Yuji; Komatsu, Yoshihiro

    2016-07-15

    Cleft palate is among the most common human birth defects. Submucous cleft palate (SMCP) is a subgroup of cleft palate, which may be as common as overt cleft palate. Despite the high frequency of SMCP in humans, only recently have several animal models of SMCP begun to provide insight into the mechanisms by which SMCP develops. In this study, we show that enhanced BMP signaling through constitutively active ACVR1 in palatal epithelium causes submucous cleft palate in mice. In these mutant mice, the fusion of both palatal mesenchyme in hard palate, and muscles in soft palate were hampered by epithelial tissue. During palatal fusion, enhanced SMAD-dependent BMP signaling impaired cell death and altered cell proliferation rate in medial edge epithelium (MEE), and resulted in MEE persistence. At the molecular level, downregulation of ΔNp63, which is crucial for normal palatal fusion, in MEE cells was impaired, leading to a reduction in caspase-3 activation. Our study provides a new insight into the etiology of SMCP caused by augmented BMP signaling. PMID:26116174

  4. A dielectrophoretic method of discrimination between normal oral epithelium, and oral and oropharyngeal cancer in a clinical setting.

    PubMed

    Graham, K A; Mulhall, H J; Labeed, F H; Lewis, M P; Hoettges, K F; Kalavrezos, N; McCaul, J; Liew, C; Porter, S; Fedele, S; Hughes, M P

    2015-08-01

    Despite the accessibility of the oral cavity to clinical examination, delays in diagnosis of oral and oropharyngeal carcinoma (OOPC) are observed in a large majority of patients, with negative impact on prognosis. Diagnostic aids might help detection and improve early diagnosis, but there remains little robust evidence supporting the use of any particular diagnostic technology at the moment. The aim of the present feasibility first-in-human study was to evaluate the preliminary diagnostic validity of a novel technology platform based on dielectrophoresis (DEP). DEP does not require labeling with antibodies or stains and it is an ideal tool for rapid analysis of cell properties. Cells from OOPC/dysplasia tissue and healthy oral mucosa were collected from 57 study participants via minimally-invasive brush biopsies and tested with a prototype DEP platform using median membrane midpoint frequency as main analysis parameter. Results indicate that the current DEP platform can discriminate between brush biopsy samples from cancerous and healthy oral tissue with a diagnostic sensitivity of 81.6% and a specificity of 81.0%. The present ex vivo results support the potential application of DEP testing for identification of OOPC. This result indicates that DEP has the potential to be developed into a low-cost, rapid platform as an assistive tool for the early identification of oral cancer in primary care; given the rapid, minimally-invasive and non-expensive nature of the test, dielectric characterization represents a promising platform for cost-effective early cancer detection. PMID:26086875

  5. Progenitor Epithelium

    PubMed Central

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

  6. Detection of molecular signatures of oral squamous cell carcinoma and normal epithelium - application of a novel methodology for unsupervised segmentation of imaging mass spectrometry data.

    PubMed

    Widlak, Piotr; Mrukwa, Grzegorz; Kalinowska, Magdalena; Pietrowska, Monika; Chekan, Mykola; Wierzgon, Janusz; Gawin, Marta; Drazek, Grzegorz; Polanska, Joanna

    2016-06-01

    Intra-tumor heterogeneity is a vivid problem of molecular oncology that could be addressed by imaging mass spectrometry. Here we aimed to assess molecular heterogeneity of oral squamous cell carcinoma and to detect signatures discriminating normal and cancerous epithelium. Tryptic peptides were analyzed by MALDI-IMS in tissue specimens from five patients with oral cancer. Novel algorithm of IMS data analysis was developed and implemented, which included Gaussian mixture modeling for detection of spectral components and iterative k-means algorithm for unsupervised spectra clustering performed in domain reduced to a subset of the most dispersed components. About 4% of the detected peptides showed significantly different abundances between normal epithelium and tumor, and could be considered as a molecular signature of oral cancer. Moreover, unsupervised clustering revealed two major sub-regions within expert-defined tumor areas. One of them showed molecular similarity with histologically normal epithelium. The other one showed similarity with connective tissue, yet was markedly different from normal epithelium. Pathologist's re-inspection of tissue specimens confirmed distinct features in both tumor sub-regions: foci of actual cancer cells or cancer microenvironment-related cells prevailed in corresponding areas. Hence, molecular differences detected during automated segmentation of IMS data had an apparent reflection in real structures present in tumor. PMID:27168173

  7. Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats.

    PubMed

    Okumura, Shinya; Teratani, Takumi; Fujimoto, Yasuhiro; Zhao, Xiangdong; Tsuruyama, Tatsuaki; Masano, Yuki; Kasahara, Naoya; Iida, Taku; Yagi, Shintaro; Uemura, Tadahiro; Kaido, Toshimi; Uemoto, Shinji

    2016-09-01

    Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD. PMID:27102080

  8. [Competence factors of retinal pigment epithelium cells for reprogramming in the neuronal direction during retinal regeneration in newts].

    PubMed

    Grigorian, E N

    2015-01-01

    Retinal pigment epithelium (RPE) cells that have the unique ability to reprogram retinal cells @in vivo@ were analyzed in the adult newt. Our own data and that available in the literature on the peculiarities of the biology of these cells (from morphology to molecular profile, which can be associated with the capability of phenotype change) were summarized: It was established that the molecular traits of specialized and poorly differentiated cells are combined in RPE of the adult newt. It was registered that persistent (at a low level) proliferation and rapid change of specific cytoskeleton proteins can contribute to the success of RPE cell reprogramming in the neuronal direction. Each of the considered factors of competence for reprogramming can be found for animal RPE, whose cells are not able @in vivo@ to change the phenotype to a neuronal one; however, their totality (supported by the epigenetic state permissive for conversion) is probably an internal property of only newt RPE. PMID:25872395

  9. Distinct mechanisms underlie oral vs aboral regeneration in the cnidarian Hydractinia echinata

    PubMed Central

    Bradshaw, Brian; Thompson, Kerry; Frank, Uri

    2015-01-01

    Cnidarians possess remarkable powers of regeneration, but the cellular and molecular mechanisms underlying this capability are unclear. Studying the hydrozoan Hydractinia echinata we show that a burst of stem cell proliferation occurs following decapitation, forming a blastema at the oral pole within 24 hr. This process is necessary for head regeneration. Knocking down Piwi1, Vasa, Pl10 or Ncol1 expressed by blastema cells inhibited regeneration but not blastema formation. EdU pulse-chase experiments and in vivo tracking of individual transgenic Piwi1+ stem cells showed that the cellular source for blastema formation is migration of stem cells from a remote area. Surprisingly, no blastema developed at the aboral pole after stolon removal. Instead, polyps transformed into stolons and then budded polyps. Hence, distinct mechanisms act to regenerate different body parts in Hydractinia. This model, where stem cell behavior can be monitored in vivo at single cell resolution, offers new insights for regenerative biology. DOI: http://dx.doi.org/10.7554/eLife.05506.001 PMID:25884246

  10. Oral Lesions Induced by Chronic Khat Use Consist Essentially of Thickened Hyperkeratinized Epithelium

    PubMed Central

    Lukandu, Ochiba Mohammed; Koech, Lionel Sang; Kiarie, Paul Ngugi

    2015-01-01

    Objectives. The habit of khat chewing is prevalent in many Middle Eastern and African cultures and has been associated with various adverse conditions in humans. This study aimed to describe histological changes induced by chronic khat chewing on the buccal mucosa. Methods. Biopsies of the buccal mucosa from 14 chronic khat chewers, 20 chronic khat chewers who also smoked tobacco, and 8 nonchewers were compared for epithelial thickness, degree and type of keratinization, and connective tissue changes. Results. Tissues from khat chewers depicted abnormal keratinization of the superficial cell layer and showed increased epithelial thickness affecting all layers. Epithelial thickness in control samples was 205 ± 26 μm whereas thickness in khat chewers and khat chewers who smoked tobacco was significantly higher measuring 330 ± 35 μm and 335 ± 19 μm, respectively. Tissues from khat chewers also showed increased intracellular edema, increased melanin pigment deposits, and increased number of rete pegs most of which were thin and deep. Conclusions. These results show that oral lesions induced by chronic chewing of khat in the buccal mucosa present with white and brown discoloration due to increased epithelial thickness, increased keratinization, and melanin deposition. PMID:26491446

  11. Characterization of Morphological and Cellular Events Underlying Oral Regeneration in the Sea Anemone, Nematostella vectensis.

    PubMed

    Amiel, Aldine R; Johnston, Hereroa T; Nedoncelle, Karine; Warner, Jacob F; Ferreira, Solène; Röttinger, Eric

    2015-01-01

    Cnidarians, the extant sister group to bilateria, are well known for their impressive regenerative capacity. The sea anemone Nematostella vectensis is a well-established system for the study of development and evolution that is receiving increased attention for its regenerative capacity. Nematostella is able to regrow missing body parts within five to six days after its bisection, yet studies describing the morphological, cellular, and molecular events underlying this process are sparse and very heterogeneous in their experimental approaches. In this study, we lay down the basic framework to study oral regeneration in Nematostella vectensis. Using various imaging and staining techniques we characterize in detail the morphological, cellular, and global molecular events that define specific landmarks of this process. Furthermore, we describe in vivo assays to evaluate wound healing success and the initiation of pharynx reformation. Using our described landmarks for regeneration and in vivo assays, we analyze the effects of perturbing either transcription or cellular proliferation on the regenerative process. Interestingly, neither one of these experimental perturbations has major effects on wound closure, although they slightly delay or partially block it. We further show that while the inhibition of transcription blocks regeneration in a very early step, inhibiting cellular proliferation only affects later events such as pharynx reformation and tentacle elongation. PMID:26633371

  12. Clinical Application of Mesenchymal Stem Cells and Novel Supportive Therapies for Oral Bone Regeneration

    PubMed Central

    O'Valle, Francisco; Lanis, Alejandro; Dohan Ehrenfest, David M.; Wang, Hom-Lay; Galindo-Moreno, Pablo

    2015-01-01

    Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality of the bone after infectious diseases, trauma, tumor, or congenital conditions. In these situations, cell transplantation technologies may help to overcome the limitations of autografts, xenografts, allografts, and alloplastic materials. A database search was conducted to include human clinical trials (randomized or controlled) and case reports/series describing the clinical use of mesenchymal stem cells (MSCs) in the oral cavity for bone regeneration only specifically excluding periodontal regeneration. Additionally, novel advances in related technologies are also described. 190 records were identified. 51 articles were selected for full-text assessment, and only 28 met the inclusion criteria: 9 case series, 10 case reports, and 9 randomized controlled clinical trials. Collectively, they evaluate the use of MSCs in a total of 290 patients in 342 interventions. The current published literature is very diverse in methodology and measurement of outcomes. Moreover, the clinical significance is limited. Therefore, the use of these techniques should be further studied in more challenging clinical scenarios with well-designed and standardized RCTs, potentially in combination with new scaffolding techniques and bioactive molecules to improve the final outcomes. PMID:26064899

  13. Characterization of Morphological and Cellular Events Underlying Oral Regeneration in the Sea Anemone, Nematostella vectensis

    PubMed Central

    Amiel, Aldine R.; Johnston, Hereroa T.; Nedoncelle, Karine; Warner, Jacob F.; Ferreira, Solène; Röttinger, Eric

    2015-01-01

    Cnidarians, the extant sister group to bilateria, are well known for their impressive regenerative capacity. The sea anemone Nematostella vectensis is a well-established system for the study of development and evolution that is receiving increased attention for its regenerative capacity. Nematostella is able to regrow missing body parts within five to six days after its bisection, yet studies describing the morphological, cellular, and molecular events underlying this process are sparse and very heterogeneous in their experimental approaches. In this study, we lay down the basic framework to study oral regeneration in Nematostella vectensis. Using various imaging and staining techniques we characterize in detail the morphological, cellular, and global molecular events that define specific landmarks of this process. Furthermore, we describe in vivo assays to evaluate wound healing success and the initiation of pharynx reformation. Using our described landmarks for regeneration and in vivo assays, we analyze the effects of perturbing either transcription or cellular proliferation on the regenerative process. Interestingly, neither one of these experimental perturbations has major effects on wound closure, although they slightly delay or partially block it. We further show that while the inhibition of transcription blocks regeneration in a very early step, inhibiting cellular proliferation only affects later events such as pharynx reformation and tentacle elongation. PMID:26633371

  14. Carbamazepine transbuccal delivery: the histo-morphological features of reconstituted human oral epithelium and buccal porcine mucosae in the transmucosal permeation.

    PubMed

    Campisi, G; Paderni, C; Saccone, R; Siragusa, M G; Lo Muzio, L; Tripodo, C; Giannola, L I; Florena, A M

    2008-01-01

    Transbuccal drug delivery is an attractive way of administration since several well-known advantages are provided, especially with respect to peroral management. Carbamazepine (CBZ) is an anticonvulsant which is useful in controlling neuropathic pain, and it is currently administered by peroral route, although its absorption and bioavailability is limited due to various factors. The oral cavity could be an interesting site for transbuccal CBZ delivery due to two properties: slow administration of constant low drug doses and less dose-related side effects. However, in transbuccal absorption a major limitation could be the low permeability of the mucosa which results in low drug bioavailability; thus the aptitude of the drug to penetrate the buccal mucosa has to be assessed by using tissue models resembling human normal mucosa. In our experience, CBZ well permeates mucosal membranes. In order to assess the efficacy of CBZ transbuccal delivery and to verify the reliability of these tissues in permeability testing before and after the passage of CBZ, the histo-morphological features of reconstituted human oral (RHO) epithelium (E) and buccal porcine mucosae were investigated. Significant histological changes due to CBZ passage were observed both in RHO-E and porcine mucosa. The main findings detected in RHO samples were cellular swellings with a signet ring-like appearance, nuclear swelling, prominent nucleoli lined against the nuclear membrane and the presence of keratohyalin granules. The most striking finding regarding porcine buccal mucosa was a cytoplasmic vacuolization, mainly involving the basal layer. PMID:19144275

  15. Neural Stem Cell-based Intraocular Administration of Pigment Epithelium-derived Factor Promotes Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Crush Injury in Rat: An Experimental Study

    PubMed Central

    Zhang, Wei-Min; Zhang, Zhi-Ren; Zhang, Yong-Gang; Gao, Yan-Sheng

    2016-01-01

    Background: Pigment epithelium-derived factor (PEDF) is regarded as a multifunctional protein possessing neurotrophic and neuroprotective properties. PEDF has a very short half-life, and it would require multiple injections to maintain a therapeutically relevant level without a delivery system. However, multiple injections are prone to cause local damage or infection. To overcome this, we chose a cell-based system that provided sustained delivery of PEDF and compared the effect of weekly injections of PEDF and neural stem cell (NSC)-based intraocular administration of PEDF on retinal ganglion cell (RGC) survival and axon regeneration after optic nerve injury. Methods: Seventy-two rats were randomly assigned to 3 groups: group with injections of phosphate buffered saline (PBS) (n=24), group with weekly injections of PEDF (n=24), and group with NSC-based administration of PEDF (n=24). Western blot was used to analyze the PEDF protein level 2 weeks after injection. Retinal flat mounts and immunohistochemistry were employed to analyze RGC survival and axon regeneration 2 weeks and 4 weeks after injection. The data were analyzed with one-way ANOVA in SPSS (version 19.0). A P<0.05 was considered significant. Results: The PEDF protein level in the group with NSC-based administration of PEDF increased compared with that in the groups with injections of PEDF and PBS (P<0.05). The PEDF-modified NSCs differentiated into GFAP-positive astrocytes andβ-tubulin-III-positive neurons. NSC-based administration of PEDF effectively increased RGC survival and improved the axon regeneration of the optic nerve compared with weekly injections of PEDF. Conclusion: Subretinal space transplantation of PEDF-secreting NSCs sustained high concentrations of PEDF, differentiated into neurons and astrocytes, and significantly promoted RGC survival and axon regeneration after optic nerve injury. PMID:27582587

  16. Nano-hydroxyapatite and nano-titanium dioxide exhibit different subcellular distribution and apoptotic profile in human oral epithelium.

    PubMed

    Tay, Chor Yong; Fang, Wanru; Setyawati, Magdiel Inggrid; Chia, Sing Ling; Tan, Kai Soo; Hong, Catherine Hsu Ling; Leong, David Tai

    2014-05-14

    Nanomaterials (NMs) such as titanium dioxide (nano-TiO2) and hydroxyapatite (nano-HA) are widely used in food, personal care, and many household products. Due to their extensive usage, the risk of human exposure is increased and may trigger NMs specific biological outcomes as the NMs interface with the cells. However, the interaction of nano-TiO2 and nano-HA with cells, their uptake and subcellular distribution, and the cytotoxic effects are poorly understood. Herein, we characterized and examined the cellular internalization, inflammatory response and cytotoxic effects of nano-TiO2 and nano-HA using TR146 human oral buccal epithelial cells as an in vitro model. We showed both types of NMs were able to bind to the cellular membrane and passage into the cells in a dose dependent manner. Strikingly, both types of NMs exhibited distinct subcellular distribution profile with nano-HA displaying a higher preference to accumulate near the cell membrane compared to nano-TiO2. Exposure to both types of NMs caused an elevated reactive oxygen species (ROS) level and expression of inflammatory transcripts with increasing NMs concentration. Although cells treated with nano-HA induces minimal apoptosis, nano-TiO2 treated samples displayed approximately 28% early apoptosis after 24 h of NMs exposure. We further showed that nano-TiO2 mediated cell death is independent of the classical p53-Bax apoptosis pathway. Our findings provided insights into the potential cellular fates of human oral epithelial cells as they interface with industrial grade nano-HA and nano-TiO2. PMID:24734929

  17. Light and electron microscopic studies of the intestinal epithelium in Notoplana humilis (Platyhelminthes, Polycladida): the contribution of mesodermal/gastrodermal neoblasts to intestinal regeneration.

    PubMed

    Okano, Daisuke; Ishida, Sachiko; Ishiguro, Sei-ichi; Kobayashi, Kazuya

    2015-12-01

    Some free-living flatworms in the phylum Platyhelminthes possess strong regenerative capability that depends on putative pluripotent stem cells known as neoblasts. These neoblasts are defined based on several criteria, including their proliferative capacity and the presence of cellular components known as chromatoid bodies. Polyclads, which are marine flatworms, have the potential to be a good model system for stem cell research, yet little information is available regarding neoblasts and regeneration. In this study, transmission electron microscopy and immunostaining analyses, using antibodies against phospho-histone H3 and BrdU, were used to identify two populations of neoblasts in the polyclad Notoplana humilis: mesodermal neoblasts (located in the mesenchymal space) and gastrodermal neoblasts (located within the intestine, where granular club cells and phagocytic cells are also located). Light and electron microscopic analyses also suggested that phagocytic cells and mesodermal/gastrodermal neoblasts, but not granular club cells, migrated into blastemas and remodeled the intestine during regeneration. Therefore, we suggest that, in polyclads, intestinal regeneration is accomplished by mechanisms underlying both morphallaxis (remodeling of pre-existing tissues) and epimorphosis (de novo tissue formation derived from mesodermal/gastrodermal neoblasts). Based on the assumption that gastrodermal neoblasts, which are derived from mesodermal neoblasts, are intestinal stem cells, we propose a model to study intestinal regeneration. PMID:26104134

  18. A single nucleotide polymorphism associated with isolated cleft lip and palate, thyroid cancer and hypothyroidism alters the activity of an oral epithelium and thyroid enhancer near FOXE1

    PubMed Central

    Lidral, Andrew C.; Liu, Huan; Bullard, Steven A.; Bonde, Greg; Machida, Junichiro; Visel, Axel; Uribe, Lina M. Moreno; Li, Xiao; Amendt, Brad; Cornell, Robert A.

    2015-01-01

    Three common diseases, isolated cleft lip and cleft palate (CLP), hypothyroidism and thyroid cancer all map to the FOXE1 locus, but causative variants have yet to be identified. In patients with CLP, the frequency of coding mutations in FOXE1 fails to account for the risk attributable to this locus, suggesting that the common risk alleles reside in nearby regulatory elements. Using a combination of zebrafish and mouse transgenesis, we screened 15 conserved non-coding sequences for enhancer activity, identifying three that regulate expression in a tissue specific pattern consistent with endogenous foxe1 expression. These three, located −82.4, −67.7 and +22.6 kb from the FOXE1 start codon, are all active in the oral epithelium or branchial arches. The −67.7 and +22.6 kb elements are also active in the developing heart, and the −67.7 kb element uniquely directs expression in the developing thyroid. Within the −67.7 kb element is the SNP rs7850258 that is associated with all three diseases. Quantitative reporter assays in oral epithelial and thyroid cell lines show that the rs7850258 allele (G) associated with CLP and hypothyroidism has significantly greater enhancer activity than the allele associated with thyroid cancer (A). Moreover, consistent with predicted transcription factor binding differences, the −67.7 kb element containing rs7850258 allele G is significantly more responsive to both MYC and ARNT than allele A. By demonstrating that this common non-coding variant alters FOXE1 expression, we have identified at least in part the functional basis for the genetic risk of these seemingly disparate disorders. PMID:25652407

  19. Calcium inhibits the damaging and compensatory proliferative effects of fatty acids on mouse colon epithelium.

    PubMed

    Wargovich, M J; Eng, V W; Newmark, H L

    1984-07-01

    Intrarectal instillations of the fatty acids (FA), lauric, linoleic or oleic acids induce inflammation and superficial lysis of the colon epithelium. This reaction is followed by increases in colonic mitotic activity and the number of cells engaged in DNA synthesis in compensatory regeneration for the cells that were lost. This explains, in part, the promotional effect of dietary fat in carcinogenesis. Concomitant oral administration of calcium salts, as CaCO3, largely reduced the mitogenic effects of fatty acids on colon epithelium, presumably by forming biologically inert calcium soaps. Calcium soap formation of dietary fatty acids may be one natural mechanism by which colon epithelium cells are protected hence reducing the impact of dietary fat on carcinogenesis for this organ. PMID:6744249

  20. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration

    PubMed Central

    2013-01-01

    Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

  1. An ultrastructural study of the effects of x-irradiation on the oral epithelium of the rat: qualitative aspects.

    PubMed

    Liu, H M; Meyer, J; Waterhouse, J P

    1976-07-01

    Adult male rats of Simonsen strain were given a dose of 5000 r at 50 peak KV of x-irradiation directed at the lower lip, which was everted through a hole in a lead rubber cylinder shielding the head and body of the animal. Light and electron microscopic observations were made on specimens of lip oral mucosa from animals killed at 2, 6, 26 and 50 h and at 12 days after irradiation. The experimental model met the aim of permitting the study of the sequential effects of high dose of irradiation without causing ulceration of the mucosa. Widespread degenerative changes were noted in the basal cells as early as 2 h after x-irradiation, increasing in degree up to 50 h. They included inflation of the outer nuclear envelope and rough endoplasmic reticulum (RER) with loss of ribosomes, swelling of mitochondria and disarrangement of cristae evident at 2 h, followed at 6 h by swelling of nucleus and cytoplasm and 26 h by frank membrane breaks. Irreversible degrees of damage were noted in a small though growing minority of cells. Immediate mobilization of the Golgi-lysosomal system was evident as an increase in size of the zone, maximal at 2 h, and subsequent autophagic activity. Signs of recovery, beginning at 26 h, were noted in nuclear envelope, RER, intercellular space, and in mitotic activity by 50 h. Virtually complete recovery was seen at 12 days. It is held that the successful confinement of irradiation to a small tissue volume, the effective activity of the lysosomal system and the short epithelial turnover time were important factors in limiting the damage and in permitting recovery. PMID:820842

  2. Carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) for corneal epithelium reconstruction: a histological study.

    PubMed

    Bardag-Gorce, Fawzia; Oliva, Joan; Wood, Andrew; Hoft, Richard; Pan, Derek; Thropay, Jacquelyn; Makalinao, Andrew; French, Samuel W; Niihara, Yutaka

    2015-04-01

    This study investigates the therapeutic effects of carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) transplantation for experimentally induced severe rabbit limbal stem cell deficiency (LSCD). Buccal biopsies were performed and CAOMECS were cultured and transplanted onto diseased corneas. Six-month follow-up examinations indicated that three out of four corneas with CAOMECS grafts showed a decrease in superficial vascularization, while almost all the sham corneas did not show a similar decrease. H&E staining of corneas showed that CAOMECS transplantation reduced blood vessel invasion of central cornea, reduced lymphocyte infiltration and fibrotic tissue formation. DeltaNp63 stained markedly in the grafted cornea and to a lesser extent in the sham corneas. PCNA and Ki-67 staining were much greater in the sham corneas than in the grafted and normal corneas. K3 and K13 staining demonstrated that CAOMECS transplanted corneas had much more K3- and less K13- positive cells compared to the sham corneas. Muc5AC was decreased in the central region of grafted corneas. Very little alpha-smooth muscle actin (aSMA) staining was detected in grafted corneas, while there was a greater amount of aSMA staining in sham corneas. Staining for anti-angiogenic factor TIMP -3 was also increased, and pro-angiogenic factor MMP-3 was decreased in grafted corneas compared to sham corneas. Our results indicate that CAOMECS grafts resulted in improved epithelialization of the corneal surface and decreased vascularization and fibrosis of the diseased corneas. PMID:25881998

  3. Improved peripheral nerve regeneration in streptozotocin-induced diabetic rats by oral lumbrokinase.

    PubMed

    Lee, Han-Chung; Hsu, Yuan-Man; Tsai, Chin-Chuan; Ke, Cherng-Jyh; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2015-01-01

    We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances. Immunohistochemical staining showed that lumbrokinase could dramatically promote calcitonin gene-related peptide (CGRP) expression in the lamina I-II regions in the dorsal horn ipsilateral to the injury and cause a marked increase in the number of macrophages recruited within the distal nerve stumps. In addition, the lumbrokinase could stimulate the secretion of interleukin-1 (IL-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) in dissected diabetic sciatic nerve segments. In conclusion, the administration of lumbrokinase after nerve repair surgery in diabetic rats was found to have remarkable effects on promoting peripheral nerve regeneration and functional recovery. PMID:25787300

  4. Experimental model for bone regeneration in oral and cranio-maxillo-facial surgery.

    PubMed

    Mardas, Nikos; Dereka, Xanthippi; Donos, Nikolaos; Dard, Michel

    2014-02-01

    Bone and tooth loss, as a result of trauma, anatomical or congenital reasons, cancer, and periodontal disease, is a common therapeutic problem in the fields of cranio-maxillo-facial surgery and periodontics. The proposed techniques for the treatment of various bone defects encountered include bone grafts, bone substitutes, guided tissue regeneration, and distraction osteogenesis as well as their combinations. In addition, dental implants have been successfully utilized for the restoration of full or partial edentulism. The introduction and development of new therapeutic approaches and devices demand the use of appropriate animal models that present bone anatomy and healing comparable to human. Among other animal models, the pig is extensively documented in several biomedical areas and has been largely used in maxillo-facial surgery and implants dentistry-related research. Anatomical and physiological similarities with human in size, physiology, and bone biology contribute to a successful involvement of this animal to understand and treat various osseous lesions. However, improvements and standardization are requested with respect to consistency and discrimination abilities. The aim of this review is to provide a critical appraisal of the literature related to swine models for the evaluation of cranio-maxillo-facial osseous defect healing, regeneration, and bone-implant interface. This review should assist researchers in the field to select the most appropriate model for each dedicated purpose and also contribute to stimulate an innovative thinking on the use of porcine models. PMID:23957784

  5. The junctional epithelium originates from the odontogenic epithelium of an erupted tooth

    PubMed Central

    Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

    2014-01-01

    The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period. PMID:24785116

  6. Tooth brushing, oil pulling and tissue regeneration: A review of holistic approaches to oral health

    PubMed Central

    Singh, Abhinav; Purohit, Bharathi

    2011-01-01

    Even though dentistry was not a specialized branch of Ayurveda, it is included in its Shalakya Tantra (system of surgery). Problems such as deformities of the oral cavity, plaques and infections were managed in ancient India. Traditional medicine can treat various infectious and chronic conditions. Research has shown that all kinds of chewing sticks described in ancient Ayurveda texts have medicinal and anti-cariogenic properties. Its oil pulling (Kaval, Gandush) practice is claimed to cure about 30 systemic diseases. Amla (Emblic myrobalan), is a general rebuilder of oral health. Bilberry fruit (Vaccinium myrtillus) and hawthorn berry (Crateagus oxycanthus) stabilize collagen, strengthening the gum tissue. Liquorice root (Glycyrrhiza glabral) promotes anti-cavity action, reduces plaque, and has an antibacterial effect. Use of safe, quality products and practices should be ensured based on available evidence if traditional medicine is to be acknowledged as part of primary health care. Scientific validations of the Ayurveda dental health practices could justify their incorporation into modern dental care. Publicity of these techniques using appropriate media would benefit the general population by giving more confidence in the ancient practices, thus preventing tooth decay and loss. PMID:21760690

  7. Tooth brushing, oil pulling and tissue regeneration: A review of holistic approaches to oral health.

    PubMed

    Singh, Abhinav; Purohit, Bharathi

    2011-04-01

    Even though dentistry was not a specialized branch of Ayurveda, it is included in its Shalakya Tantra (system of surgery). Problems such as deformities of the oral cavity, plaques and infections were managed in ancient India. Traditional medicine can treat various infectious and chronic conditions. Research has shown that all kinds of chewing sticks described in ancient Ayurveda texts have medicinal and anti-cariogenic properties. Its oil pulling (Kaval, Gandush) practice is claimed to cure about 30 systemic diseases. Amla (Emblic myrobalan), is a general rebuilder of oral health. Bilberry fruit (Vaccinium myrtillus) and hawthorn berry (Crateagus oxycanthus) stabilize collagen, strengthening the gum tissue. Liquorice root (Glycyrrhiza glabral) promotes anti-cavity action, reduces plaque, and has an antibacterial effect. Use of safe, quality products and practices should be ensured based on available evidence if traditional medicine is to be acknowledged as part of primary health care. Scientific validations of the Ayurveda dental health practices could justify their incorporation into modern dental care. Publicity of these techniques using appropriate media would benefit the general population by giving more confidence in the ancient practices, thus preventing tooth decay and loss. PMID:21760690

  8. Identification of Distinct Layers Within the Stratified Squamous Epithelium of the Adult Human True Vocal Fold

    PubMed Central

    Dowdall, Jayme R.; Sadow, Peter M.; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C.; Franco, Ramon A.; Rajagopal, Jayaraj

    2016-01-01

    Objectives/Hypothesis A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Study Design Qualitative study with adult human larynges. Methods Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). Results We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. Conclusion We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. Level of Evidence N/A. PMID:25988619

  9. Irf6 directly regulates Klf17 in zebrafish periderm and Klf4 in murine oral epithelium, and dominant-negative KLF4 variants are present in patients with cleft lip and palate

    PubMed Central

    Liu, Huan; Leslie, Elizabeth J.; Jia, Zhonglin; Smith, Tiffany; Eshete, Mekonen; Butali, Azeez; Dunnwald, Martine; Murray, Jeffrey; Cornell, Robert A.

    2016-01-01

    Non-syndromic (NS) cleft lip with or without cleft palate (CL/P) is a common disorder with a strong genetic underpinning. Genome-wide association studies have detected common variants associated with this disorder, but a large portion of the genetic risk for NSCL/P is conferred by unidentified rare sequence variants. Mutations in IRF6 (Interferon Regulatory Factor 6) and GRHL3 (Grainyhead-like 3) cause Van der Woude syndrome, which includes CL/P. Both genes encode members of a regulatory network governing periderm differentiation in model organisms. Here, we report that Krüppel-like factor 17 (Klf17), like Grhl3, acts downstream of Irf6 in this network in zebrafish periderm. Although Klf17 expression is absent from mammalian oral epithelium, a close homologue, Klf4, is expressed in this tissue and is required for the differentiation of epidermis. Chromosome configuration capture and reporter assays indicated that IRF6 directly regulates an oral-epithelium enhancer of KLF4. To test whether rare missense variants of KLF4 contribute risk for NSCL/P, we sequenced KLF4 in approximately 1000 NSCL/P cases and 300 controls. By one statistical test, missense variants of KLF4 as a group were enriched in cases versus controls. Moreover, two patient-derived KLF4 variants disrupted periderm differentiation upon forced expression in zebrafish embryos, suggesting that they have dominant-negative effect. These results indicate that rare NSCL/P risk variants can be found in members of the gene regulatory network governing periderm differentiation. PMID:26692521

  10. E-cadherin in non-tumor epithelium adjacent to oral cancer as risk marker for the development of multiple tumors.

    PubMed

    González-Moles, M A; Bravo, M; Ruiz-Avila, I; Gil-Montoya, J A; Acebal, F; Esteban, F

    2013-03-01

    Our aim was to find out whether the loss of E-cadherin is a risk factor for the development of multiple tumours in the oral cavity and whether it could serve as a diagnostic marker for oral premalignant fields. We studied 77 oral squamous cell carcinomas (SCC) with associated non-tumour epithelia from 61 patients. Immunohistochemical studies (antibody NHC-38) were used to investigate E-cadherin expression, which was completely lost in basal (48% of cases) and parabasal (43%) layers of non-tumour epithelia close to the tumour and in basal (47%) and parabasal (38%) layers of non-tumour epithelia distant from the tumour. In multiple tumours E-cadherin expression was significantly lower than in single tumours in the basal, parabasal layers, and the middle third of close (p=0.002, <0.001, <0.001) and distant (p=0.041, p<0.001, p=0.005) non-tumour epithelia, respectively. Downregulation of E-cadherin may be valuable as a risk marker for the development of multiple tumours in the oral cavity and for the diagnosis of premalignant fields. PMID:22658605

  11. Altered Immunohistochemical Expression of Mast Cell Tryptase and Chymase in the Pathogenesis of Oral Submucous Fibrosis and Malignant Transformation of the Overlying Epithelium

    PubMed Central

    Yadav, Archana; Desai, Rajiv S.; Bhuta, Bansari A.; Singh, Jatinder S.; Mehta, Reema; Nehete, Akash P.

    2014-01-01

    Mast cells (MCs) expressing serine proteases; tryptase and chymase, are associated with fibrosis in various diseases. However, little is known about their involvement in oral submucous fibrosis (OSF). Our goal was to evaluate the role of MC tryptase and chymase in the pathogenesis of OSF and its malignant transformation. Immunohistochemical expression of MC tryptase and chymase was evaluated in 20 cases of OSF, 10 cases of oral squamous cell carcinoma (OSCC) and 10 cases of healthy controls. Subepithelial zone of Stage 1 and 2 while deep zone of Stage 3 and 4 OSF demonstrated increased tryptase positive MCs. OSCC revealed a proportionate increase in tryptase and chymase positive MCs irrespective of areas of distribution. An altered balance in the subepithelial and deep distribution of tryptase and chymase positive MCs play an important role in the pathogenesis of OSF and its malignant transformation. PMID:24874976

  12. Effect of oral administration of mutagens found in food on the frequency of sister chromatid exchanges in the colonic epithelium of mice

    SciTech Connect

    Couch, D.B.; Stuart, E.; Heddle, J.A.

    1987-01-01

    Epidemiological studies indicate there is a link between dietary factors and the incidence of colon cancer, and it has been suggested mutagens in foods might be responsible for initiating the carcinogenic process. Some food mutagens are formed during the cooking process. For example, certain heterocyclic amines, including Trp-P-2 (3-amino-1-methyl-5H-pyrido(4,3-n) indole) and MeIQ (2-amino-3,4-dimethylimidazo(4,5-f)quinoline), which have been isolated from broiled meat and fish at low (ng/g) levels, are extremely potent mutagens in the Ames Salmonella/microsome test and can induce mutation in cultured mammalian cells as well. Other mutagens in foods are natural products; quercetin, a flavanoid widely distributed in plant products, is mutagenic to Salmonella and cultured mammalian cells. As most of the evidence implicating substance in food as mutagenic carcinogens comes from in vitro studies, it is of interest to determine whether these compounds can also exert genotoxic effects in vivo, particularly in colonic tissue. The ability to induce nuclear aberrations in vivo in murine colonic epithelial tissue has been suggested to be a property of colon carcinogens specifically, and several mutagens found in cooked food, including MeIQ and Trp-P-2, have been found to produce such nucleotoxicity. The authors report here tests of the ability of MeIQ, Trp-P-2, and quercetin to induce sister chromatid exchanges (SCEs) in the colonic epithelium of mice.

  13. Oral exposure to environmental pollutant benzo[a]pyrene impacts the intestinal epithelium and induces gut microbial shifts in murine model.

    PubMed

    Ribière, Céline; Peyret, Pierre; Parisot, Nicolas; Darcha, Claude; Déchelotte, Pierre J; Barnich, Nicolas; Peyretaillade, Eric; Boucher, Delphine

    2016-01-01

    Gut microbiota dysbiosis are associated with a wide range of human diseases, including inflammatory bowel diseases. The physiopathology of these diseases has multifactorial aetiology in which environmental factors, particularly pollution could play a crucial role. Among the different pollutants listed, Polycyclic Aromatic Hydrocarbons (PAHs) are subject to increased monitoring due to their wide distribution and high toxicity on Humans. Here, we used 16S rRNA gene sequencing to investigate the impact of benzo[a]pyrene (BaP, most toxic PAH) oral exposure on the faecal and intestinal mucosa-associated bacteria in C57BL/6 mice. Intestinal inflammation was also evaluated by histological observations. BaP oral exposure significantly altered the composition and the abundance of the gut microbiota and led to moderate inflammation in ileal and colonic mucosa. More severe lesions were observed in ileal segment. Shifts in gut microbiota associated with moderate inflammatory signs in intestinal mucosa would suggest the establishment of a pro-inflammatory intestinal environment following BaP oral exposure. Therefore, under conditions of genetic susceptibility and in association with other environmental factors, exposure to this pollutant could trigger and/or accelerate the development of inflammatory pathologies. PMID:27503127

  14. Oral exposure to environmental pollutant benzo[a]pyrene impacts the intestinal epithelium and induces gut microbial shifts in murine model

    PubMed Central

    Ribière, Céline; Peyret, Pierre; Parisot, Nicolas; Darcha, Claude; Déchelotte, Pierre J.; Barnich, Nicolas; Peyretaillade, Eric; Boucher, Delphine

    2016-01-01

    Gut microbiota dysbiosis are associated with a wide range of human diseases, including inflammatory bowel diseases. The physiopathology of these diseases has multifactorial aetiology in which environmental factors, particularly pollution could play a crucial role. Among the different pollutants listed, Polycyclic Aromatic Hydrocarbons (PAHs) are subject to increased monitoring due to their wide distribution and high toxicity on Humans. Here, we used 16S rRNA gene sequencing to investigate the impact of benzo[a]pyrene (BaP, most toxic PAH) oral exposure on the faecal and intestinal mucosa-associated bacteria in C57BL/6 mice. Intestinal inflammation was also evaluated by histological observations. BaP oral exposure significantly altered the composition and the abundance of the gut microbiota and led to moderate inflammation in ileal and colonic mucosa. More severe lesions were observed in ileal segment. Shifts in gut microbiota associated with moderate inflammatory signs in intestinal mucosa would suggest the establishment of a pro-inflammatory intestinal environment following BaP oral exposure. Therefore, under conditions of genetic susceptibility and in association with other environmental factors, exposure to this pollutant could trigger and/or accelerate the development of inflammatory pathologies. PMID:27503127

  15. Changes in the adult vertebrate auditory sensory epithelium after trauma.

    PubMed

    Oesterle, Elizabeth C

    2013-03-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

  16. Olfactory Epithelium Grafts in the Cerebral Cortex: An Immunohistochemical Analysis

    PubMed Central

    Holbrook, Eric H.; DiNardo, Laurence J.; Costanzo, Richard M.

    2009-01-01

    Objective To develop an alternative model for studying the regenerative capacity of olfactory neurons. Study Design An immunohistochemical analysis of mouse olfactory epithelium transplanted to the cerebral cortex. Methods Strips of olfactory epithelium removed from donor mice at postnatal day 5 to day 20 were inserted into the parietal cortex of adult mice. Recipient animals were allowed to survive for 25 to 120 days and then perfused with 4% paraformaldehyde 1 hour after bromodeoxyuridine injection. The brains were processed, and frozen sections were obtained. Sections through transplant tissue were analyzed using immunohistochemistry and compared with normal olfactory epithelium. Results Graft survival approached 85% with mature olfactory neurons detected in 35% of the transplants stained for olfactory marker protein. Transplant epithelium resembled normal olfactory epithelium containing mature olfactory neurons and axon bundles. Conclusions Studies of olfactory neuron regeneration have been limited by the inability to produce cultures with long-term viability. Olfactory epithelial grafts to the cerebral cortex provide an alternative approach to the study of olfactory neuron regeneration. PMID:11801979

  17. Examination of the reticular epithelium of the bovine pharyngeal tonsil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The nasopharyngeal tonsil (adenoid), located at the posterior of the nasopharynx is ideally positioned to sample antigens entering through the nasal cavity or oral cavity. Entering antigens will first contact tonsilar epithelium. To better understand the cellular composition of this important epithe...

  18. Regeneration inducers in limb regeneration.

    PubMed

    Satoh, Akira; Mitogawa, Kazumasa; Makanae, Aki

    2015-08-01

    Limb regeneration ability, which can be observed in amphibians, has been investigated as a representative phenomenon of organ regeneration. Recently, an alternative experimental system called the accessory limb model was developed to investigate early regulation of amphibian limb regeneration. The accessory limb model contributed to identification of limb regeneration inducers in urodele amphibians. Furthermore, the accessory limb model may be applied to other species to explore universality of regeneration mechanisms. This review aims to connect the insights recently gained to emboss universality of regeneration mechanisms among species. The defined molecules (BMP7 (or2) + FGF2 + FGF8) can transform skin wound healing to organ (limb) regeneration responses. The same molecules can initiate regeneration responses in some species. PMID:26100345

  19. Effects of female sex hormones on adhesion of Candida albicans yeast-like fungi to the buccal epithelium.

    PubMed

    Kravtsov, E G; Anokhina, I V; Rybas, Ya A; Sachivkina, N P; Ermolaev, A V; Brodskaya, S B

    2014-06-01

    Hormonal regulation of receptor expression and glycogen concentrations in the epithelial cells of the oral cavity remains poorly studied. Adhesion of microorganisms to the vaginal epithelium correlates with their adhesion to the buccal epithelium. Analysis of the correlation between Candida adhesion to the vaginal and buccal epithelium depending on the hormonal status has demonstrated that activity of Candida albicans strains in the buccal epithelium correlates with their adhesion activity in the vaginal epithelium, with the coefficient of correlations (r) reaching 0.76. PMID:24958376

  20. Characterization of side population cells from human airway epithelium.

    PubMed

    Hackett, Tillie-Louise; Shaheen, Furquan; Johnson, Andrew; Wadsworth, Samuel; Pechkovsky, Dmitri V; Jacoby, David B; Kicic, Anthony; Stick, Stephen M; Knight, Darryl A

    2008-10-01

    The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelial cells were obtained from seven nontransplantable healthy lungs and four asthmatic lungs by pronase digestion. SP cells were identified by verapamil-sensitive efflux of the DNA-binding dye Hoechst 33342. Using flow cytometry, CD45(-) SP, CD45(+) SP, and non-SP cells were isolated and sorted. CD45(-) SP cells made up 0.12% +/- 0.01% of the total epithelial cell population in normal airway but 4.1% +/- 0.06% of the epithelium in asthmatic airways. All CD45(-) SP cells showed positive staining for epithelial-specific markers cytokeratin-5, E-cadherin, ZO-1, and p63. CD45(-) SP cells exhibited stable telomere length and increased colony-forming and proliferative potential, undergoing population expansion for at least 16 consecutive passages. In contrast with non-SP cells, fewer than 100 CD45(-) SP cells were able to generate a multilayered and differentiated epithelium in air-liquid interface culture. SP cells are present in human tracheobronchial epithelium, exhibit both short- and long-term proliferative potential, and are capable of generation of differentiated epithelium in vitro. The number of SP cells is significantly greater in asthmatic airways, providing evidence of dysregulated resident SP cells in the asthmatic epithelium. Disclosure of potential conflicts of interest is found at the end of this article. PMID:18653771

  1. Denervation resulting in dento-alveolar ankylosis associated with decreased Malassez epithelium.

    PubMed

    Fujiyama, K; Yamashiro, T; Fukunaga, T; Balam, T A; Zheng, L; Takano-Yamamoto, T

    2004-08-01

    Inferior alveolar nerve denervation causes appreciable decreases in the distribution of epithelial rests of Malassez. To explore roles of the Malassez epithelium, we attempted to evaluate possible changes in dento-alveolar tissues surrounding this epithelium by experimental denervation. We found that denervation led to dento-alveolar ankylosis with a decrease in the width of the periodontal spaces. Interestingly, with regeneration of the Malassez epithelium 10 weeks after the denervation, the periodontal space width showed a correspondingly significant increase. These findings suggest that the Malassez epithelium may be involved in the maintenance of periodontal space and that sensory innervation might be indirectly associated with it. In addition, it is of interest that denervation activated root resorption of the coronal root surface and that the consequently resorbed lacunae were repaired by cellular cementum. It is suggested that Malassez epithelium may negatively regulate root resorption and induce acellular cementum formation. PMID:15271971

  2. [Tooth regeneration--dream to reality].

    PubMed

    Wang, Song-Ling; Wang, Xue-Jiu

    2008-04-01

    Tooth or dentition missing compromises human health physically and psychiatrically. Although several prosthesis methods are used to restore tooth loss, these restorations are still non-biological methods. It is a dream for human being to regenerate a real tooth for hundreds years. There are two ways to regenerate the tooth. One is application of conventional tissue engineering techniques including seed cells and scaffold. The other is regeneration tooth using dental epithelium and dental mesenchymal cells based on the knowledge of tooth initiation and development. Marked progress has been achieved in these two ways, while there is still a long way to go. Recently a new concept has been proposed for regeneration of a biological tooth root based on tooth-related stem cells and tissue engineering technique. A biological tooth root has been regenerated in swine. It may be a valuable method for restoration of tooth loss before successful whole tooth regeneration. A latest research showed that a subpopulation in bone marrow cells can give rise to ameloblast-like cells when mixed with embryonic epithelium and reassociation with integrated mesenchyme, which may provide a new seed cell source for tooth regeneration. PMID:18605442

  3. Lack of Dystrophin Affects Bronchial Epithelium in mdx Mice.

    PubMed

    Morici, Giuseppe; Rappa, Francesca; Cappello, Francesco; Pace, Elisabetta; Pace, Andrea; Mudò, Giuseppa; Crescimanno, Grazia; Belluardo, Natale; Bonsignore, Maria R

    2016-10-01

    Mild exercise training may positively affect the course of Duchenne Muscular Dystrophy (DMD). Training causes mild bronchial epithelial injury in both humans and mice, but no study assessed the effects of exercise in mdx mice, a well known model of DMD. The airway epithelium was examined in mdx (C57BL/10ScSn-Dmdmdx) mice, and in wild type (WT, C57BL/10ScSc) mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days of training (5 d/wk for 6 weeks), epithelial morphology and markers of regeneration, apoptosis, and cellular stress were assessed. The number of goblet cells in bronchial epithelium was much lower in mdx than in WT mice under all conditions. At 30 days, epithelial regeneration (PCNA positive cells) was higher in EX than SD animals in both groups; however, at 45 days, epithelial regeneration decreased in mdx mice irrespective of training, and the percentage of apoptotic (TUNEL positive) cells was higher in mdx-EX than in WT-EX mice. Epithelial expression of HSP60 (marker of stress) progressively decreased, and inversely correlated with epithelial apoptosis (r = -0.66, P = 0.01) only in mdx mice. Lack of dystrophin in mdx mice appears associated with defective epithelial differentiation, and transient epithelial regeneration during mild exercise training. Hence, lack of dystrophin might impair repair in bronchial epithelium, with potential clinical consequences in DMD patients. J. Cell. Physiol. 231: 2218-2223, 2016. © 2016 Wiley Periodicals, Inc. PMID:26868633

  4. Corneal cells for regeneration.

    PubMed

    Kinoshita, S; Nakamura, T

    2005-01-01

    In cases of corneal epithelial stem cell deficiency where ocular surface reconstruction is required, corneal epithelial replacement using a tissue engineering technique shows great potential. Autologous cultivated corneal epithelial stem cell sheets are the safest and most reliable forms of sheet we can use for such treatment; however, they are not useful for treating bilaterally affected ocular surface disorders. In order to treat such cases, we must choose either an allogeneic cultivated corneal epithelial sheet or an autologous cultivated oral mucosal epithelial sheet. If we use the former, the threat of immunological reaction must be dealt with. Therefore, it is imperative that we have a basic understanding of the immunological aspects of ocular surface reconstruction using allogeneic tissues. When using an autologous cultivated oral mucosal epithelial sheet, a basic understanding of ocular surface epithelial biology is required as the sheet is not exactly the same as corneal epithelium. PMID:16080287

  5. The art of fin regeneration in zebrafish

    PubMed Central

    Pfefferli, Catherine

    2015-01-01

    Abstract The zebrafish fin provides a valuable model to study the epimorphic type of regeneration, whereby the amputated part of the appendage is nearly perfectly replaced. To accomplish fin regeneration, two reciprocally interacting domains need to be established at the injury site, namely a wound epithelium and a blastema. The wound epithelium provides a supporting niche for the blastema, which contains mesenchyme‐derived progenitor cells for the regenerate. The fate of blastemal daughter cells depends on their relative position with respect to the fin margin. The apical compartment of the outgrowth maintains its undifferentiated character, whereas the proximal descendants of the blastema progressively switch from the proliferation program to the morphogenesis program. A delicate balance between self‐renewal and differentiation has to be continuously adjusted during the course of regeneration. This review summarizes the current knowledge about the cellular and molecular mechanisms of blastema formation, and discusses several studies related to the regulation of growth and morphogenesis during fin regeneration. A wide range of canonical signaling pathways has been implicated during the establishment and maintenance of the blastema. Epigenetic mechanisms play a crucial role in the regulation of cellular plasticity during the transition between differentiation states. Ion fluxes, gap‐junctional communication and protein phosphatase activity have been shown to coordinate proliferation and tissue patterning in the caudal fin. The identification of the downstream targets of the fin regeneration signals and the discovery of mechanisms integrating the variety of input pathways represent exciting future aims in this fascinating field of research. PMID:27499869

  6. Transcriptional regulatory network during development in the olfactory epithelium

    PubMed Central

    Im, SeungYeong; Moon, Cheil

    2015-01-01

    Regeneration, a process of reconstitution of the entire tissue, occurs throughout life in the olfactory epithelium (OE). Regeneration of OE consists of several stages: proliferation of progenitors, cell fate determination between neuronal and non-neuronal lineages, their differentiation and maturation. How the differentiated cell types that comprise the OE are regenerated, is one of the central questions in olfactory developmental neurobiology. The past decade has witnessed considerable progress regarding the regulation of transcription factors (TFs) involved in the remarkable regenerative potential of OE. Here, we review current state of knowledge of the transcriptional regulatory networks that are powerful modulators of the acquisition and maintenance of developmental stages during regeneration in the OE. Advance in our understanding of regeneration will not only shed light on the basic principles of adult plasticity of cell identity, but may also lead to new approaches for using stem cells and reprogramming after injury or degenerative neurological diseases. [BMB Reports 2015; 48(11): 599-608] PMID:26303973

  7. A Curriculum Vitae of Teeth: Evolution, Generation, Regeneration

    PubMed Central

    Koussoulakou, Despina S.; Margaritis, Lukas H.; Koussoulakos, Stauros L.

    2009-01-01

    The ancestor of recent vertebrate teeth was a tooth-like structure on the outer body surface of jawless fishes. Over the course of 500,000,000 years of evolution, many of those structures migrated into the mouth cavity. In addition, the total number of teeth per dentition generally decreased and teeth morphological complexity increased. Teeth form mainly on the jaws within the mouth cavity through mutual, delicate interactions between dental epithelium and oral ectomesenchyme. These interactions involve spatially restricted expression of several, teeth-related genes and the secretion of various transcription and signaling factors. Congenital disturbances in tooth formation, acquired dental diseases and odontogenic tumors affect millions of people and rank human oral pathology as the second most frequent clinical problem. On the basis of substantial experimental evidence and advances in bioengineering, many scientists strongly believe that a deep knowledge of the evolutionary relationships and the cellular and molecular mechanisms regulating the morphogenesis of a given tooth in its natural position, in vivo, will be useful in the near future to prevent and treat teeth pathologies and malformations and for in vitro and in vivo teeth tissue regeneration. PMID:19266065

  8. Human airway xenograft models of epithelial cell regeneration.

    PubMed

    Puchelle, E; Peault, B

    2000-01-01

    Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID) and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa. PMID:11667974

  9. Kidney Regeneration: Common Themes From the Embryo to the Adult

    PubMed Central

    Cirio, M. Cecilia; de Groh, Eric D.; de Caestecker, Mark P.; Davidson, Alan J.; Hukriede, Neil A.

    2013-01-01

    The vertebrate kidney has an inherent ability to regenerate following acute damage. Successful regeneration of the injured kidney requires the rapid replacement of damaged tubular epithelial cells and reconstitution of normal tubular function. Identifying the cells that participate in the regeneration process as well as the molecular mechanisms involved may reveal therapeutic targets for the treatment of kidney disease. Renal regeneration is associated with the expression of genetic pathways that are necessary for kidney organogenesis, suggesting that the regenerating tubular epithelium may be ‘reprogrammed’ to a less-differentiated, progenitor state. This review will highlight data from various vertebrate models supporting the hypothesis that nephrogenic genes are reactivated as part of the process of kidney regeneration following acute kidney injury (AKI). Emphasis will be placed on the reactivation of developmental pathways and how our understanding of the resulting regeneration process may be enhanced by lessons learned in the embryonic kidney. PMID:24005792

  10. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

    The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

  11. Unexpected regeneration in middle-aged mice.

    PubMed

    Reines, Brandon; Cheng, Lily I; Matzinger, Polly

    2009-02-01

    Complete regeneration of damaged extremities, including both the epithelium and the underlying tissues, is thought to occur mainly in embryos, fetuses, and juvenile mammals, but only very rarely in adult mammals. Surprisingly, we found that common strains of mice are able to regenerate all of the tissues necessary to completely fill experimentally punched ear holes, but only if punched at middle age. Although young postweaning mice regrew the epithelium without typical pre-scar granulation tissue, they showed only minimal regeneration of connective tissues. In contrast, mice punched at 5-11 months of age showed true amphibian-like blastema formation and regrowth of cartilage, fat, and dermis, with blood vessels, sebaceous glands, hair follicles, and, in black mice, melanocytes. These data suggest that at least partial appendage regeneration may be more common in adult mammals than previously thought and call into question the common view that regenerative ability is lost with age. The data suggest that the age at which various inbred mouse strains become capable of epimorphic regeneration may be correlated with adult body weight. PMID:19226206

  12. Liver Regeneration

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

    Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other. PMID:17559071

  13. Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.

    PubMed

    Jiang, Nan; Zhou, Jian; Chen, Mo; Schiff, Michael D; Lee, Chang H; Kong, Kimi; Embree, Mildred C; Zhou, Yanheng; Mao, Jeremy J

    2014-02-01

    Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4-5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed towards bioengineered tooth regeneration. PMID:24345734

  14. Cartilage Regeneration

    PubMed Central

    Tuan, Rocky S.; Chen, Antonia F.; Klatt, Brian A.

    2016-01-01

    Cartilage damaged by trauma has a limited capacity to regenerate. Current methods for treating small chondral defects include palliative treatment with arthroscopic debridement and lavage, reparative treatment with marrow stimulation techniques (e.g. microfracture), and restorative treatment, including osteochondral grafting and autologous chondrocyte implantation. Larger defects are treated by osteochondral allografting or total joint replacements. However, the future of treating cartilage defects lies in providing biologic solutions through cartilage regeneration. Laboratory and clinical studies have examined the treatment of larger lesions using tissue engineered cartilage. Regenerated cartilage can be derived from various cell types, including chondrocytes, mesenchymal stem cells, and pluripotent stem cells. Common scaffolding materials include proteins, carbohydrates, synthetic materials, and composite polymers. Scaffolds may be woven, spun into nanofibers, or configured as hydrogels. Chondrogenesis may be enhanced with the application of chondroinductive growth factors. Finally, bioreactors are being developed to enhance nutrient delivery and provide mechanical stimulation to tissue-engineered cartilage ex vivo. The multi-disciplinary approaches currently being developed to produce cartilage promise to bring the dream of cartilage regeneration in clinical use to reality. PMID:23637149

  15. Cell Signaling Pathways in Vertebrate Lens Regeneration. Published in “New Perspectives in Regeneration” (E. Heber-Katz and D. L. Stocum, eds)

    PubMed Central

    Henry, Jonathan J.; Thomas, Alvin G.; Hamilton, Paul W.; Moore, Lisa; Perry, Kimberly J.

    2015-01-01

    Certain vertebrates are capable of regenerating parts of the eye, including the lens. Depending on the species, two principal forms of in vivo lens regeneration have been described wherein the new lens arises from either the pigmented epithelium of the dorsal iris or the cornea epithelium. These forms of lens regeneration are triggered by retinal factors present in the eye. Studies have begun to illuminate the nature of the signals that support lens regeneration. This review describes evidence for the involvement of specific signaling pathways in lens regeneration, including the FGF, retinoic acid, TGF-beta, Wnt and hedgehog pathways. PMID:23224710

  16. Role of GATA factors in development, differentiation, and homeostasis of the small intestinal epithelium

    PubMed Central

    Aronson, Boaz E.; Stapleton, Kelly A.

    2014-01-01

    The small intestinal epithelium develops from embryonic endoderm into a highly specialized layer of cells perfectly suited for the digestion and absorption of nutrients. The development, differentiation, and regeneration of the small intestinal epithelium require complex gene regulatory networks involving multiple context-specific transcription factors. The evolutionarily conserved GATA family of transcription factors, well known for its role in hematopoiesis, is essential for the development of endoderm during embryogenesis and the renewal of the differentiated epithelium in the mature gut. We review the role of GATA factors in the evolution and development of endoderm and summarize our current understanding of the function of GATA factors in the mature small intestine. We offer perspective on the application of epigenetics approaches to define the mechanisms underlying context-specific GATA gene regulation during intestinal development. PMID:24436352

  17. Endometrial regeneration and endometrial stem/progenitor cells.

    PubMed

    Gargett, Caroline E; Nguyen, Hong P T; Ye, Louie

    2012-12-01

    The functional layer of the human endometrium is a highly regenerative tissue undergoing monthly cycles of growth, differentiation and shedding during a woman's reproductive years. Fluctuating levels of circulating estrogen and progesterone orchestrate this dramatic remodeling of human endometrium. The thin inactive endometrium of postmenopausal women which resembles the permanent basal layer of cycling endometrium retains the capacity to respond to exogenous sex steroid hormones to regenerate into a thick functional endometrium capable of supporting pregnancy. Endometrial regeneration also follows parturition and endometrial resection. In non menstruating rodents, endometrial epithelium undergoes rounds of proliferation and apoptosis during estrus cycles. The recent identification of adult stem cells in both human and mouse endometrium suggests that epithelial progenitor cells and the mesenchymal stem/stromal cells have key roles in the cyclical regeneration of endometrial epithelium and stroma. This review will summarize the evidence for endometrial stem/progenitor cells, examine their role in mouse models of endometrial epithelial repair and estrogen-induced endometrial regeneration, and also describe the generation of endometrial-like epithelium from human embryonic stem cells. With markers now available for identifying endometrial mesenchymal stem/stromal cells, their possible role in gynecological diseases associated with abnormal endometrial proliferation and their potential application in cell-based therapies to regenerate reproductive and other tissues will be discussed. PMID:22847235

  18. Histology, Immunohistochemistry and Ultrastructure of the Bovine Palatine Tonsil with Special Emphasis on Reticular Epithelium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The paired palatine tonsils are located at the junction of the nasopharynx and oropharynx; ideally positioned to sample antigens entering through either the nasal cavity or oral cavity. Entering antigens will first contact tonsilar epithelium. To better understand the cellular and functional composi...

  19. Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium

    PubMed Central

    Horvay, Katja; Jardé, Thierry; Casagranda, Franca; Perreau, Victoria M; Haigh, Katharina; Nefzger, Christian M; Akhtar, Reyhan; Gridley, Thomas; Berx, Geert; Haigh, Jody J; Barker, Nick; Polo, Jose M; Hime, Gary R; Abud, Helen E

    2015-01-01

    Snail family members regulate epithelial-to-mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote an undifferentiated state. Here, we demonstrate that conditional knockout of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snai1 conditional knockout mice also undergo apoptosis when Snai1 is deleted. Conversely, ectopic expression of Snai1 in the intestinal epithelium in vivo results in the expansion of the crypt base columnar cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following conditional deletion of Snai1, the intestinal epithelium fails to produce a proliferative response following radiation-induced damage indicating a fundamental requirement for Snai1 in epithelial regeneration. These results demonstrate that Snai1 is required for regulation of lineage choice, maintenance of CBC stem cells and regeneration of the intestinal epithelium following damage. PMID:25759216

  20. Regenerator seal

    NASA Technical Reports Server (NTRS)

    Davis, Leonard C. (Inventor); Pacala, Theodore (Inventor); Sippel, George R. (Inventor)

    1981-01-01

    A method for manufacturing a hot side regenerator cross arm seal assembly having a thermally stablilized wear coating with a substantially flat wear surface thereon to seal between low pressure and high pressure passages to and from the hot inboard side of a rotary regenerator matrix includes the steps of forming a flat cross arm substrate member of high nickel alloy steel; fixedly securing the side edges of the substrate member to a holding fixture with a concave surface thereacross to maintain the substrate member to a slightly bent configuration on the fixture surface between the opposite ends of the substrate member to produce prestress therein; applying coating layers on the substrate member including a wear coating of plasma sprayed nickel oxide/calcium flouride material to define a wear surface of slightly concave form across the restrained substrate member between the free ends thereon; and thereafter subjecting the substrate member and the coating thereon to a heat treatment of 1600.degree. F. for sixteen hours to produce heat stabilizing growth in the coating layers on the substrate member and to produce a thermally induced growth stress in the wear surface that substantially equalizes the prestress in the substrate whereby when the cross arm is removed from the fixture surface following the heat treatment step a wear face is formed on the cross arm assembly that will be substantially flat between the ends.

  1. Heart regeneration.

    PubMed

    Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

    2016-07-01

    Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26597703

  2. Etiology and pathogenesis of oral lichen planus: an overview.

    PubMed

    Kurago, Zoya B

    2016-07-01

    Oral lichen planus is a noninfectious, chronic inflammatory condition that involves the oral mucosal stratified squamous epithelium and the underlying lamina propria and may be accompanied by skin lesions. This overview describes the current understanding of the immunopathologic mechanisms implicated in oral lichen planus. PMID:27260276

  3. One-step treatment of proximal hypospadias by the autologous graft of cultured urethral epithelium.

    PubMed

    Romagnoli, G; De Luca, M; Faranda, F; Franzi, A T; Cancedda, R

    1993-10-01

    Surgical management of severe proximal hypospadias or long strictures of the posterior urethra is a difficult clinical task. Often, the therapeutic approach involves the autologous graft of free flaps of bladder or oral mucosa. We recently reported the use of autologous graft of cultured squamous urethral epithelium during urethroplasty in patients with severe proximal hypospadias. The main limitation to the widespread use of cultured epithelium was the long hospitalization due to the requirement of 2 surgical steps. We now report a substantial modification of the surgical procedure which allows for rapid 1-step urethroplasty. Cultured squamous urethral epithelium is tubularized in vitro with the aid of a tubular polytetrafluoroethylene (Gore-Tex) support and 1-step urethroplasty is performed within 30 minutes. Results obtained in 8 patients are presented. PMID:8371392

  4. Maintenance of sweat glands by stem cells located in the acral epithelium.

    PubMed

    Ohe, Shuichi; Tanaka, Toshihiro; Yanai, Hirotsugu; Komai, Yoshihiro; Omachi, Taichi; Kanno, Shohei; Tanaka, Kiyomichi; Ishigaki, Kazuhiko; Saiga, Kazuho; Nakamura, Naohiro; Ohsugi, Haruyuki; Tokuyama, Yoko; Atsumi, Naho; Hisha, Hiroko; Yoshida, Naoko; Kumano, Keiki; Yamazaki, Fumikazu; Okamoto, Hiroyuki; Ueno, Hiroo

    2015-10-23

    The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1-positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexal epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1-positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes. PMID:26362184

  5. Mesenchymal stem cells for repair of the airway epithelium in asthma.

    PubMed

    Knight, Darryl A; Rossi, Fabio M; Hackett, Tillie-Louise

    2010-12-01

    The airway epithelium is constantly faced with inflammatory and potentially injurious stimuli. Following damage, rapid repair mechanisms involving proliferation and differentiation of resident progenitor and stem cell pools are necessary in order to maintain a protective barrier. In asthma, evidence pointing to a compromised ability of the epithelium to properly repair and regenerate is rapidly accumulating. The consequences of this are presently unknown but are likely to have a significant impact on lung function. Mesenchymal stem cells have the potential to serve as a universal source for replacement of specific cells in several diseases and thus offer hope as a potential therapeutic intervention for the treatment of the chronic remodeling changes that occur in the asthmatic epithelium. However, controversy exists regarding whether these cells can actually home to and engraft within the airways and contribute to tissue function or whether this mechanism is necessary, since they can have potent paracrine immunomodulatory effects. This article focuses on the current knowledge about specific stem cell populations that may contribute to airway epithelial regeneration and discusses the use of mesenchymal stem cells as a potential therapeutic intervention. PMID:21128750

  6. Lesion of the Olfactory Epithelium Accelerates Prion Neuroinvasion and Disease Onset when Prion Replication Is Restricted to Neurons

    PubMed Central

    Crowell, Jenna; Wiley, James A.; Bessen, Richard A.

    2015-01-01

    Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain. PMID:25822718

  7. Dkk2/Frzb in the dermal papillae regulates feather regeneration.

    PubMed

    Chu, Qiqi; Cai, Linyan; Fu, Yu; Chen, Xi; Yan, Zhipeng; Lin, Xiang; Zhou, Guixuan; Han, Hao; Widelitz, Randall B; Chuong, Cheng-ming; Wu, Wei; Yue, Zhicao

    2014-03-15

    Avian feathers have robust growth and regeneration capability. To evaluate the contribution of signaling molecules and pathways in these processes, we profiled gene expression in the feather follicle using an absolute quantification approach. We identified hundreds of genes that mark specific components of the feather follicle: the dermal papillae (DP) which controls feather regeneration and axis formation, the pulp mesenchyme (Pp) which is derived from DP cells and nourishes the feather follicle, and the ramogenic zone epithelium (Erz) where a feather starts to branch. The feather DP is enriched in BMP/TGF-β signaling molecules and inhibitors for Wnt signaling including Dkk2/Frzb. Wnt ligands are mainly expressed in the feather epithelium and pulp. We find that while Wnt signaling is required for the maintenance of DP marker gene expression and feather regeneration, excessive Wnt signaling delays regeneration and reduces pulp formation. Manipulating Dkk2/Frzb expression by lentiviral-mediated overexpression, shRNA-knockdown, or by antibody neutralization resulted in dual feather axes formation. Our results suggest that the Wnt signaling in the proximal feather follicle is fine-tuned to accommodate feather regeneration and axis formation. PMID:24463139

  8. Poly(amido amine) dendrimers in oral delivery.

    PubMed

    Yellepeddi, Venkata K; Ghandehari, Hamidreza

    2016-01-01

    Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed. PMID:27358755

  9. Differential Expression Patterns of EGF, EGFR, and ERBB4 in Nasal Polyp Epithelium

    PubMed Central

    Zhao, Li; Subramaniam, Somasundaram; Yu, Xue Min; Li, Ying Ying; Chen, De Hua; Li, Tian Ying; Shen, Liang; Shi, Li; Wang, De Yun

    2016-01-01

    Epidermal growth factor receptors play an important role in airway epithelial cell growth and differentiation. The current study investigates the expression profiles of EGF, EGFR and ERBB4 in patients with nasal polyps (NP), and their response to glucocorticosteroid (GC) treatment. Fifty patients with NP (40 without GC treatment and 10 with oral GC) and 20 control subjects with septal deviation were recruited into the study. Protein levels of EGF, EGFR, and ERBB4 were evaluated by immune-staining. In healthy nasal epithelium, EGF and EGFR localized within p63+ basal cells, while ERBB4 localized within ciliated cells. GC-naïve NP epithelium showed weak expression of EGF in 90% of samples versus 5% of controls. EGFR was significantly increased in the epithelium with basal cell hyperplasia from GC-naïve NPs (78%, 31/40) compared to controls (23%, 4/17). EGFR was also found in some degranulating goblet cells. ERBB4 expression was significantly higher in hyperplastic epithelium from GC-naïve NPs (65%, 26/40) than in controls (6%, 1/17). GC treatment restored the EGF expression and normalized the EGFR and ERBB4 expression in NPs. Differential expression patterns of EGF, EGFR, and ERBB4 are essential in epithelial restitution and remodeling in nasal epithelium. PMID:27285994

  10. Periodontal regeneration in gingival recession defects.

    PubMed

    Trombelli, L

    1999-02-01

    Surgical treatment of gingival recession defects aims at obtaining soft tissue coverage of exposed root surfaces and/or augmentation of gingival tissue dimensions. A variety of protocols have been developed to manage these clinical problems. Since one goal of periodontal therapy is the regeneration of the lost attachment apparatus of the tooth, full restoration of defect should be accomplished following mucogingival procedures. This implies regeneration of all periodontal structures, including formation of new cementum with inserting connective tissue fibers, alveolar bone regeneration and recreation of a functional and aesthetic morphology of the mucogingival complex. Animal and human histological studies have shown that healing at gingiva-root interface following pedicle flaps or free soft tissue grafts generally includes a long junctional epithelium with varying amounts of a new connective tissue attachment in the most apical aspect of the covered root surface. Limited bone regeneration has been observed. Adjunctive use of root conditioning agents and cell excluding, wound-stabilizing devices may amplify regenerative outcomes. Changes in the amount of keratinized tissue, which can significantly affect the aesthetic outcome of treatment, have been shown to depend on the interactions among various tissues involved in the healing process and the selected surgical procedure. PMID:10321221

  11. Active magnetic regenerator

    DOEpatents

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  12. The coelomic epithelium transcriptome from a clonal sea star, Coscinasterias muricata.

    PubMed

    Gabre, Jonatan L; Martinez, Pedro; Nilsson Sköld, Helen; Ortega-Martinez, Olga; Abril, Josep F

    2015-12-01

    Coscinasterias is a cosmopolitan genus of large asteroid sea stars with the ability of somatic fission as a clonal reproductive strategy. During fission, the animals tear themselves apart across their central disc, where the lost body parts are regenerated afterwards. Here, we have sequenced and subsequently analysed the transcriptome of the coelomic epithelium of a clonal Coscinasterias muricata specimen from New Zealand. Out of the total 389,768 raw reads, 11,344 contigs were assembled and grouped into functions. Raw read and assembled contig sequences are available at NCBI (BioSample: SAMN03371637), while the annotated assembly can be accessed through the project transcriptome browser (compgen.bio.ub.edu/gbrowse/starfish_transcriptome/). Our data is valuable for future detailed exploration of the coelomic epithelium functions as well as for a better understanding of sea star physiology. PMID:26321383

  13. Olfactory epithelium changes in germfree mice

    PubMed Central

    François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

    2016-01-01

    Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

  14. STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation

    PubMed Central

    Hiraoka, Takehiro; Hirota, Yasushi; Saito-Fujita, Tomoko; Matsuo, Mitsunori; Egashira, Mahiro; Matsumoto, Leona; Haraguchi, Hirofumi; Dey, Sudhansu K.; Furukawa, Katsuko S.; Fujii, Tomoyuki; Osuga, Yutaka

    2016-01-01

    Although a close connection between uterine regeneration and successful pregnancy in both humans and mice has been consistently observed, its molecular basis remains unclear. We here established a mouse model of decellularized uterine matrix (DUM) transplantation. Resected mouse uteri were processed with SDS to make DUMs without any intact cells. DUMs were transplanted into the mouse uteri with artificially induced defects, and all the uterine layers were recovered at the DUM transplantation sites within a month. In the regenerated uteri, normal hormone responsiveness in early pregnancy was observed, suggesting the regeneration of functional uteri. Uterine epithelial cells rapidly migrated and formed a normal uterine epithelial layer within a week, indicating a robust epithelial-regenerating capacity. Stromal and myometrial regeneration occurred following epithelial regeneration. In ovariectomized mice, uterine regeneration of the DUM transplantation was similarly observed, suggesting that ovarian hormones are not essential for this regeneration process. Importantly, the regenerating epithelium around the DUM demonstrated heightened STAT3 phosphorylation and cell proliferation, which was suppressed in uteri of Stat3 conditional knockout mice. These data suggest a key role of STAT3 in the initial step of the uterine regeneration process. The DUM transplantation model is a powerful tool for uterine regeneration research. PMID:27358915

  15. IL-17 and VEGF are necessary for efficient corneal nerve regeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) yo T cells, neutrophils, and platelets in t...

  16. EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila

    PubMed Central

    Jiang, Huaqi; Grenley, Marc O.; Bravo, Maria-Jose; Blumhagen, Rachel Z.; Edgar, Bruce A.

    2010-01-01

    Many tissues in higher animals undergo dynamic homeostatic growth, wherein damaged or aged cells are replaced by the progeny of resident stem cells. To maintain homeostasis, stem cells must respond to tissue needs. Here we show that in response to damage or stress in the intestinal (midgut) epithelium of adult Drosophila, multiple EGFR ligands and rhomboids (intramembrane proteases that activate some EGFR ligands) are induced, leading to the activation of EGFR signaling in intestinal stem cells (ISCs). Activation of EGFR signaling promotes ISC division and midgut epithelium regeneration, thus maintaining tissue homeostasis. ISCs defective in EGFR signaling cannot grow or divide, are poorly maintained, and cannot support midgut epithelium regeneration following enteric infection by the bacterium, Pseudomonas entomophila. Furthermore, ISC proliferation induced by Jak/Stat signaling is dependent upon EGFR signaling. Thus the EGFR/Ras/MAPK signaling pathway plays central, essential roles in ISC maintenance and the feedback system that mediates intestinal homeostasis. PMID:21167805

  17. Alcohol and oral squamous cell carcinoma.

    PubMed

    Feller, L; Chandran, R; Khammissa, R A G; Meyerov, R; Lemmer, J

    2013-05-01

    Alcohol is a risk factor for oral squamous cell carcinoma. It enhances the permeability of the oral epithelium, acts as a solvent for tobacco carcinogens, induces basal-cell proliferation, and generates free radicals and acetaldehyde, which have the capacity to cause DNA damage. Alcohol-associated malnutrition and immune suppression may further promote carcinogenesis. However, acetaldehyde, the first metabolite of ethanol, is the critical agent by which prolonged and excessive consumption of alcoholic beverages increases the risk of oral squamous cell carcinoma. Alcohol also acts synergistically with the products of tobacco combustion in the pathogenesis of oral squamous cell carcinoma. PMID:23971298

  18. Similar Squamous Cell Carcinoma Epithelium microRNA Expression in Never Smokers and Ever Smokers

    PubMed Central

    Kolokythas, Antonia; Zhou, Yalu; Schwartz, Joel L.; Adami, Guy R.

    2015-01-01

    The incidence of oral tumors in patients who never used mutagenic agents such as tobacco is increasing. In an effort to better understand these tumors we studied microRNA (miRNA) expression in tumor epithelium of never tobacco users, tumor epithelium of ever tobacco users, and nonpathological control oral epithelium. A comparison of levels among 372 miRNAs in 12 never tobacco users with oral squamous cell carcinoma (OSCC) versus 10 healthy controls was made using the reverse transcription quantitative polymerase chain reaction. A similar analysis was done with 8 ever tobacco users with OSCC. These comparisons revealed miR-10b-5p, miR-196a-5p, and miR-31-5p as enriched in the tumor epithelium in OSCC of both never and ever tobacco users. Examination of The Cancer Genome Atlas (TCGA) project miRNA data on 305 OSCCs and 30 controls revealed 100% of those miRNAs enriched in never smoker OSCCs in this patient group were also enriched in ever smoker OSCCs. Nonsupervised clustering of TCGA OSCCs was suggestive of two or four subgroups of tumors based on miRNA levels with limited evidence for differences in tobacco exposure among the groups. Results from both patient groups together stress the importance of miR196a-5p in OSCC malignancy in both never and ever smokers, and emphasize the overall similarity of miRNA expression in OSCCs in these two risk groups. It implies that there may be great similarity in etiology of OSCC in never and ever smokers and that classifying OSCC based on tobacco exposure may not be helpful in the clinic. PMID:26544609

  19. Identification and molecular regulation of neural stem cells in the olfactory epithelium

    SciTech Connect

    Beites, Crestina L.; Kawauchi, Shimako; Crocker, Candice E.; Calof, Anne L. . E-mail: alcalof@uci.edu

    2005-06-10

    The sensory neurons that subserve olfaction, olfactory receptor neurons (ORNs), are regenerated throughout life, making the neuroepithelium in which they reside [the olfactory epithelium (OE)] an excellent model for studying how intrinsic and extrinsic factors regulate stem cell dynamics and neurogenesis during development and regeneration. Numerous studies indicate that transcription factors and signaling molecules together regulate generation of ORNs from stem and progenitor cells during development, and work on regenerative neurogenesis indicates that these same factors may operate at postnatal ages as well. This review describes our current knowledge of the identity of the OE neural stem cell; the different cell types that are thought to be the progeny (directly or indirectly) of this stem cell; and the factors that influence cell differentiation in the OE neuronal lineage. We review data suggesting that (1) the ORN lineage contains three distinct proliferating cell types-a stem cell and two populations of transit amplifying cells; (2) in established OE, these three cell types are present within the basal cell compartment of the epithelium; and (3) the stem cell that gives rise ultimately to ORNs may also generate two glial cell types of the primary olfactory pathway: sustentacular cells (SUS), which lie within OE proper; and olfactory ensheathing cells (OEC), which envelope the olfactory nerve. In addition, we describe factors that are both made by and found within the microenvironment of OE stem and progenitor cells, and which exert crucial growth regulatory effects on these cells. Thus, as with other regenerating tissues, the basis of regeneration in the OE appears be a population of stem cells, which resides within a microenvironment (niche) consisting of factors crucial for maintenance of its capacity for proliferation and differentiation.

  20. Inexhaustible hair-cell regeneration in young and aged zebrafish

    PubMed Central

    Pinto-Teixeira, Filipe; Viader-Llargués, Oriol; Torres-Mejía, Elen; Turan, Melissa; González-Gualda, Estela; Pola-Morell, Laura; López-Schier, Hernán

    2015-01-01

    ABSTRACT Animals have evolved two general strategies to counter injury and maintain physiological function. The most prevalent is protection by isolating vital organs into body cavities. However, protection is not optimal for sensory systems because their external components need to be exposed to the environment to fulfill their receptive function. Thus, a common strategy to maintain sensory abilities against persistent environmental insult involves repair and regeneration. However, whether age or frequent injuries affect the regenerative capacity of sensory organs remains unknown. We have found that neuromasts of the zebrafish lateral line regenerate mechanosensory hair cells after recurrent severe injuries and in adulthood. Moreover, neuromasts can reverse transient imbalances of Notch signaling that result in defective organ proportions during repair. Our results reveal inextinguishable hair-cell regeneration in the lateral line, and suggest that the neuromast epithelium is formed by plastic territories that are maintained by continuous intercellular communication. PMID:26002931

  1. Oscarella lobularis (Homoscleromorpha, Porifera) Regeneration: Epithelial Morphogenesis and Metaplasia

    PubMed Central

    Ereskovsky, Alexander V.; Borisenko, Ilya E.; Lapébie, Pascal; Gazave, Eve; Tokina, Daria B.; Borchiellini, Carole

    2015-01-01

    Sponges are known to possess remarkable reconstitutive and regenerative abilities ranging from common wounding or body part regeneration to more impressive re-building of a functional body from dissociated cells. Among the four sponge classes, Homoscleromorpha is notably the only sponge group to possess morphologically distinct basement membrane and specialized cell-junctions, and is therefore considered to possess true epithelia. The consequence of this peculiar organization is the predominance of epithelial morphogenesis during ontogenesis of these sponges. In this work we reveal the underlying cellular mechanisms used during morphogenesis accompanying ectosome regeneration in the homoscleromorph sponge model: Oscarella lobularis. We identified three main sources of novel exopinacoderm during the processes of its regeneration and the restoration of functional peripheral parts of the aquiferous system in O. lobularis: (1) intact exopinacoderm surrounding the wound surface, (2) the endopinacoderm from peripheral exhalant and inhalant canals, and (3) the intact choanoderm found on the wound surface. The basic morphogenetic processes during regeneration are the spreading and fusion of epithelial sheets that merge into one continuous epithelium. Transdifferentiation of choanocytes into exopinacocytes is also present. Epithelial-mesenchymal transition is absent during regeneration. Moreover, we cannot reveal any other morphologically distinct pluripotent cells. In Oscarella, neither blastema formation nor local dedifferentiation and proliferation have been detected, which is probably due to the high morphogenetic plasticity of the tissue. Regeneration in O. lobularis goes through cell transdifferentiation and through the processes, when lost body parts are replaced by the remodeling of the remaining tissue. Morphogenesis during ectosome regeneration in O. lobularis is correlated with its true epithelial organization. Knowledge of the morphological basis of

  2. Oscarella lobularis (Homoscleromorpha, Porifera) Regeneration: Epithelial Morphogenesis and Metaplasia.

    PubMed

    Ereskovsky, Alexander V; Borisenko, Ilya E; Lapébie, Pascal; Gazave, Eve; Tokina, Daria B; Borchiellini, Carole

    2015-01-01

    Sponges are known to possess remarkable reconstitutive and regenerative abilities ranging from common wounding or body part regeneration to more impressive re-building of a functional body from dissociated cells. Among the four sponge classes, Homoscleromorpha is notably the only sponge group to possess morphologically distinct basement membrane and specialized cell-junctions, and is therefore considered to possess true epithelia. The consequence of this peculiar organization is the predominance of epithelial morphogenesis during ontogenesis of these sponges. In this work we reveal the underlying cellular mechanisms used during morphogenesis accompanying ectosome regeneration in the homoscleromorph sponge model: Oscarella lobularis. We identified three main sources of novel exopinacoderm during the processes of its regeneration and the restoration of functional peripheral parts of the aquiferous system in O. lobularis: (1) intact exopinacoderm surrounding the wound surface, (2) the endopinacoderm from peripheral exhalant and inhalant canals, and (3) the intact choanoderm found on the wound surface. The basic morphogenetic processes during regeneration are the spreading and fusion of epithelial sheets that merge into one continuous epithelium. Transdifferentiation of choanocytes into exopinacocytes is also present. Epithelial-mesenchymal transition is absent during regeneration. Moreover, we cannot reveal any other morphologically distinct pluripotent cells. In Oscarella, neither blastema formation nor local dedifferentiation and proliferation have been detected, which is probably due to the high morphogenetic plasticity of the tissue. Regeneration in O. lobularis goes through cell transdifferentiation and through the processes, when lost body parts are replaced by the remodeling of the remaining tissue. Morphogenesis during ectosome regeneration in O. lobularis is correlated with its true epithelial organization. Knowledge of the morphological basis of

  3. Desulfurization sorbent regeneration

    DOEpatents

    Jalan, V.M.; Frost, D.G.

    1982-07-07

    A spent solid sorbent resulting from the removal of hydrogen sulfide from a fuel gas flow is regenerated with a steam-air mixture. The mixture of steam and air may also include additional nitrogen or carbon dioxide. The gas mixture contacts the spent sorbent containing metal sulfide at a temperature above 500/sup 0/C to regenerate the sulfide to metal oxide or carbonate. Various metal species including the period four transition metals and the lanthanides are suitable sorbents that may be regenerated by this method. In addition, the introduction of carbon dioxide gas permits carbonates such as those of strontium, barium and calcium to be regenerated. The steam permits regeneration of spent sorbent without formation of metal sulfate. Moreover, the regeneration will proceed with low oxygen concentrations and will occur without the increase in temperature to minimize the risk of sintering and densification of the sorbent. This method may be used for high-temperature fuel cells.

  4. Regeneration Heat Exchange

    SciTech Connect

    J. Lin

    2003-07-30

    The original project goals were to establish the viability of the proposed gas turbine regenerator concept by performing the following tasks: (1) Perform detailed design of a working model of the regenerator concept. (2) Construct a ''bench-top'' model of the regenerator concept based upon the detail design. (3) Test the bench-top model and gather data to support the concept's viability. The project funding was used to acquire the tools and material to perform the aforementioned tasks.

  5. Visualization of retinoic acid signaling in transgenic axolotls during limb development and regeneration

    PubMed Central

    Monaghan, James R.; Maden, Malcolm

    2012-01-01

    Retinoic acid (RA) plays a necessary role in limb development and regeneration, but the precise mechanism by which it acts during these processes is unclear. The role of RA in limb regeneration was first highlighted by the remarkable effect that it has on respecifying the proximodistal axis of the regenerating limb so that serially repeated limbs are produced. To facilitate the study of RA signaling during development and then during regeneration of the same structure we have turned to the axolotl, the master of vertebrate regeneration, and generated transgenic animals that fluorescently report RA signaling in vivo. Characterization of these animals identified an anterior segment of the developing embryo where RA signaling occurs revealing conserved features of the early vertebrate embryo. During limb development RA signaling was present in the developing forelimb bud mesenchyme, but was not detected during hindlimb development. During limb regeneration, RA signaling was surprisingly almost exclusively observed in the apical epithelium suggesting a different role of RA during limb regeneration. After the addition of supplemental RA to regenerating limbs that leads to pattern duplications, the fibroblast stem cells of the blastema responded showing that they are capable of transcriptionally responding to RA. These findings are significant because it means that RA signaling may play a multifunctional role during forelimb development and regeneration and that the fibroblast stem cells that regulate proximodistal limb patterning during regeneration are targets of RA signaling. PMID:22627291

  6. Cell signaling and ion transport across the fish gill epithelium.

    PubMed

    Evans, David H

    2002-08-01

    A large array of circulating and local signaling agents modulate transport of ions across the gill epithelium of fishes by either affecting transport directly or by altering the size and distribution of transporting cells in the epithelium. In some cases, these transport effects are in addition to cardiovascular effects of the same agents, which may affect the perfusion pathways in the gill vasculature and, in turn, affect epithelial transport indirectly. Prolactin is generally considered to function in freshwater, because it is the only agent that allows survival of some hypophysectomized fish species in freshwater. It appears to function by either reducing branchial permeability, Na,K-activated ATPase activity, or reducing the density of chloride cells. Cortisol was initially considered to produce virtually opposite effects (e.g., stimulation of Na,K-activated ATPase and of chloride cell size and density), but more recent studies have found that this steroid stimulates ionic uptake in freshwater fishes, as well as the activity of H-ATPase, an enzyme thought to be central to ionic uptake. Thus, cortisol may function in both high and low salinities. Growth hormone and insulin-like growth factor appear to act synergistically to affect ion regulation in seawater fishes, stimulating both Na,K-activated ATPase and Na-K-2Cl co-transporter activity, and chloride cell size, independent of their effects on growth. Some of the effects of the GH-IGF axis may be via stimulation of the number of cortisol receptors. Thyroid hormones appear to affect seawater ion regulation indirectly, by stimulating the GH-IGF axis. Natriuretic peptides were initially thought to stimulate gill ionic extrusion, but recent studies have not corroborated this finding, so it appears that the major mode of action of these peptides may be reduction of salt loading by inhibition of oral ingestion and intestinal ionic uptake. Receptors for both arginine vasotocin and angiotensin have been described in

  7. Porphyromonas gingivalis invades human pocket epithelium in vitro.

    PubMed

    Sandros, J; Papapanou, P N; Nannmark, U; Dahlén, G

    1994-01-01

    The present study examined the adhesive and invasive potential of Porphyromonas gingivalis interacting with human pocket epithelium in vitro. Pocket epithelial tissue, obtained during periodontal surgery of patients with advanced periodontal disease, generated a stratified epithelium in culture. P. gingivalis strains W50 and FDC 381 (laboratory strains), OMGS 712, 1439, 1738, 1739 and 1743 (clinical isolates) as well as Escherichia coli strain HB101 (non-adhering control) were tested with respect to epithelial adhesion and invasion. Adhesion was quantitated by scintillation spectrometry after incubation of radiolabeled bacteria with epithelial cells. The invasive ability of P. gingivalis was measured by means of an antibiotic protection assay. The epithelial multilayers were infected with the test and control strains and subsequently incubated with an antibiotic mixture (metronidazole 0.1 mg/ml and gentamicin 0.5 mg/ml). The number of internalized bacteria surviving the antibiotic treatment was assessed after plating lyzed epithelial cells on culture media. All tested P. gingivalis strains adhered to and entered pocket epithelial cells. However, considerable variation in their adhesive and invasive potential was observed. E. coli strain HB101 did not adhere or invade. Transmission electron microscopy revealed that internalization of P. gingivalis was preceded by formation of microvilli and coated pits on the epithelial cell surfaces. Intracellular bacteria were most frequently surrounded by endosomal membranes; however, bacteria devoid of such membranes were also seen. Release of outer membrane vesicles (blebs) by internalized P. gingivalis was observed. These results support and extend previous work from this laboratory which demonstrated invasion of a human oral epithelial cell-line (KB) by P. gingivalis. PMID:8113953

  8. Epithelium-Derived Wnt Ligands Are Essential for Maintenance of Underlying Digit Bone.

    PubMed

    Takeo, Makoto; Hale, Christopher S; Ito, Mayumi

    2016-07-01

    Clinically, many nail disorders accompany bone deformities, but whether the two defects are causally related is under debate. To investigate the potential interactions between the two tissue types, we analyzed epithelial-specific β-catenin-deficient mice, in which nail differentiation is abrogated. These mice showed regression of not only the nail plate but also of the underlying digit bone. Characterization of these bone defects revealed active bone resorption, which is suppressed by Wnt activation in osteoblast and osteoclast precursors. Furthermore, we found that Wntless expression, essential for Wnt ligand secretion, was lacking in the β-catenin-deficient nail epithelium and that genetic deletion of Wntless (Wls) in the nail epithelium led to the lack of Wnt activation in osteoblast and osteoclast precursors and subsequently led to defective regression of the underlying digit bone. Together, these data show that epithelial Wnt ligands can ultimately regulate Wnt signaling in osteoblast and osteoclast precursors, known to regulate bone homeostasis. These results reveal a critical role for the nail epithelium on the digit bone during homeostatic regeneration and show that Wnt/β-catenin signaling is critical for this interaction. PMID:27021406

  9. Odors Discrimination by Olfactory Epithelium Biosensor

    NASA Astrophysics Data System (ADS)

    Liu, Qingjun; Hu, Ning; Ye, Weiwei; Zhang, Fenni; Wang, Hua; Wang, Ping

    2011-09-01

    Humans are exploring the bionic biological olfaction to sense the various trace components of gas or liquid in many fields. For achieving the goal, we endeavor to establish a bioelectronic nose system for odor detection by combining intact bioactive function units with sensors. The bioelectronic nose is based on the olfactory epithelium of rat and microelectrode array (MEA). The olfactory epithelium biosensor generates extracellular potentials in presence of odor, and presents obvious specificity under different odors condition. The odor response signals can be distinguished with each other effectively by signal sorting. On basis of bioactive MEA hybrid system and the improved signal processing analysis, the bioelectronic nose will realize odor discrimination by the specific feature of signals response to various odors.

  10. Retinal pigment epithelium in incontinentia pigmenti.

    PubMed

    Mensheha-Manhart, O; Rodrigues, M M; Shields, J A; Shannon, G M; Mirabelli, R P

    1975-04-01

    An 18-month-old white girl with incontinentia pigmenti presented clinically with leukokoria of the right eye. B-scan ultrasound demonstrated a retrolental mass consistent with a detached retina. Histologic examination of the skin revealed changes compatible with the intermediate verrucous phase of the disease. Microscopic examination of the right eye showed retinal detachment and nodular proliferation of the retinal pigment epithelium. The nodules contained macrophages laden with melanin and lipofuscin. An unusually large amount of lipofuscin was present for a child of this age. The basic pigmentary abnormality may affect the retinal pigment epithelium, resulting in changes in the overlying neurosensory retina that may lead to the retinal dysplasia or retinal detachemnt often associated with this condition. PMID:1119517

  11. Mechanically patterning the embryonic airway epithelium

    PubMed Central

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  12. Mechanically patterning the embryonic airway epithelium.

    PubMed

    Varner, Victor D; Gleghorn, Jason P; Miller, Erin; Radisky, Derek C; Nelson, Celeste M

    2015-07-28

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  13. Retinoic acid regulation by CYP26 in vertebrate lens regeneration

    PubMed Central

    Thomas, Alvin G; Henry, Jonathan J

    2014-01-01

    Xenopus laevis is among the few species that are capable of fully regenerating a lost lens de novo. This occurs upon removal of the lens, when secreted factors from the retina are permitted to reach the cornea epithelium and trigger it to form a new lens. Although many studies have investigated the retinal factors that initiate lens regeneration, relatively little is known about what factors support this process and make the cornea competent to form a lens. We presently investigate the role of Retinoic acid (RA) signaling in lens regeneration in Xenopus. RA is a highly important morphogen during vertebrate development, including the development of various eye tissues, and has been previously implicated in several regenerative processes as well. For instance, Wolffian lens regeneration in the newt requires active RA signaling. In contrast, we provide evidence here that lens regeneration in Xenopus actually depends on the attenuation of RA signaling, which is regulated by the RA-degrading enzyme CYP26. Using RTPCR we examined the expression of RA synthesis and metabolism related genes within ocular tissues. We found expression of aldh1a1, aldh1a2, and aldh1a3, as well as cyp26a1 and cyp26b1 in both normal and regenerating corneal tissue. On the other hand, cyp26c1 does not appear to be expressed in either control or regenerating corneas, but it is expressed in the lens. Additionally in the lens, we found expression of aldh1a1 and aldh1a2, but not aldh1a3. Using an inhibitor of CYP26, and separately using exogenous retinoids, as well as RA signaling inhibitors, we demonstrate that CYP26 activity is necessary for lens regeneration to occur. We also find using phosphorylated Histone H3 labeling that CYP26 antagonism reduces cell proliferation in the cornea, and using qPCR we find that exogenous retinoids alter the expression of putative corneal stem cell markers. Furthermore, the Xenopus cornea is composed of an outer layer and inner basal epithelium, as well as a

  14. Primary Air-Liquid Interface Culture of Nasal Epithelium for Nasal Drug Delivery.

    PubMed

    Ong, Hui Xin; Jackson, Claire L; Cole, Janice L; Lackie, Peter M; Traini, Daniela; Young, Paul M; Lucas, Jane; Conway, Joy

    2016-07-01

    Nasal drug administration is a promising alternative to oral and parenteral administration for both local and systemic delivery of drugs. The benefits include its noninvasive nature, rapid absorption, and circumvention of first pass metabolism. Hence, the use of an in vitro model using human primary nasal epithelial cells could be key to understanding important functions and parameters of the respiratory epithelium. This model will enable investigators to address important and original research questions using a biologically relevant in vitro platform that mimics the in vivo nasal epithelial physiology. The purpose of this study was to establish, systematically characterize, and validate the use of a primary human nasal epithelium model cultured at the air-liquid interface for the study of inflammatory responses and drug transport and to simultaneously quantify drug effects on ciliary activity. PMID:27223825

  15. Ceramic regenerator program

    NASA Technical Reports Server (NTRS)

    Franklin, Jerrold E.

    1991-01-01

    The feasibility of fabricating an Air Turbo Ramjet (ATR) regenerator containing intricate hydraulic passages from a ceramic material in order to allow operation with high temperature combustion gas and to reduce weight as compared with metallic materials was demonstrated. Platelet technology, ceramic tape casting, and multilayer ceramic packaging techniques were used in this fabrication of subscale silicon nitride components. Proof-of-concept demonstrations were performed to simulate a methane cooled regenerator for an ATR engine. The regenerator vane was designed to operate at realistic service conditions, i.e., 600 psi in a 3500 R (3040 F), 500 fps combustion gas environment. A total of six regenerators were fabricated and tested. The regenerators were shown to be able to withstand internal pressurization to 1575 psi. They were subjected to testing in 500 fps, 3560 R (3100 F) air/propane combustion products and were operated satisfactorily for an excess of 100 hr and 40 thermal cycles which exceeded 2460 R (2000 F).

  16. Specialized progenitors and regeneration

    PubMed Central

    Reddien, Peter W.

    2013-01-01

    Planarians are flatworms capable of regenerating all body parts. Planarian regeneration requires neoblasts, a population of dividing cells that has been studied for over a century. Neoblast progeny generate new cells of blastemas, which are the regenerative outgrowths at wounds. If the neoblasts comprise a uniform population of cells during regeneration (e.g. they are all uncommitted and pluripotent), then specialization of new cell types should occur in multipotent, non-dividing neoblast progeny cells. By contrast, recent data indicate that some neoblasts express lineage-specific transcription factors during regeneration and in uninjured animals. These observations raise the possibility that an important early step in planarian regeneration is the specialization of neoblasts to produce specified rather than naïve blastema cells. PMID:23404104

  17. Remodeling of the Fetal Collecting Duct Epithelium

    PubMed Central

    Hiatt, Michael J.; Ivanova, Larissa; Toran, Nuria; Tarantal, Alice F.; Matsell, Douglas G.

    2010-01-01

    Congenital urinary tract obstruction induces changes to the renal collecting duct epithelium, including alteration and depletion of intercalated cells. To study the effects of obstruction on the ontogeny of intercalated cell development, we examined normal and obstructed human fetal and postnatal kidneys. In the normal human fetal kidney, intercalated cells originated in the medullary collecting duct at 8 weeks gestation and remained most abundant in the inner medulla throughout gestation. In the cortex, intercalated cells were rare at 18 and 26 weeks gestation and observed at low abundance at 36 weeks gestation. Although early intercalated cells exhibit an immature phenotype, Type A intercalated cells predominated in the inner and outer medullae at 26 and 36 weeks gestation with other intercalated cell subtypes observed rarely. Postnatally, the collecting duct epithelium underwent a remodeling whereby intercalated cells become abundant in the cortex yet absent from the inner medulla. In 18-week obstructed kidneys with mild to moderate injury, the intercalated cells became more abundant and differentiated than the equivalent age-matched normal kidney. In contrast, more severely injured ducts of the late obstructed kidney exhibited a significant reduction in intercalated cells. These studies characterize the normal ontogeny of human intercalated cell development and suggest that obstruction induces premature remodeling and differentiation of the fetal collecting duct epithelium. PMID:20035053

  18. Development of the ovarian follicular epithelium.

    PubMed

    Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

    1999-05-25

    A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women. PMID:10411332

  19. Confocal fluorescence microendoscopy of bronchial epithelium

    NASA Astrophysics Data System (ADS)

    Lane, Pierre M.; Lam, Stephen; McWilliams, Annette; Leriche, Jean C.; Anderson, Marshall W.; Macaulay, Calum E.

    2009-03-01

    Confocal microendoscopy permits the acquisition of high-resolution real-time confocal images of bronchial mucosa via the instrument channel of an endoscope. We report here on the construction and validation of a confocal fluorescence microendoscope and its use to acquire images of bronchial epithelium in vivo. Our objective is to develop an imaging method that can distinguish preneoplastic lesions from normal epithelium to enable us to study the natural history of these lesions and the efficacy of chemopreventive agents without biopsy removal of the lesion that can introduce a spontaneous regression bias. The instrument employs a laser-scanning engine and bronchoscope-compatible confocal probe consisting of a fiber-optic image guide and a graded-index objective lens. We assessed the potential of topical application of physiological pH cresyl violet (CV) as a fluorescence contrast-enhancing agent for the visualization of tissue morphology. Images acquired ex vivo with the confocal microendoscope were first compared with a bench-top confocal fluorescence microscope and conventional histology. Confocal images from five sites topically stained with CV were then acquired in vivo from high-risk smokers and compared to hematoxylin and eosin stained sections of biopsies taken from the same site. Sufficient contrast in the confocal imagery was obtained to identify cells in the bronchial epithelium. However, further improvements in the miniature objective lens are required to provide sufficient axial resolution for accurate classification of preneoplastic lesions.

  20. Oral epithelial stem cells – implications in normal development and cancer metastasis

    PubMed Central

    Papagerakis, Silvana; Pannone, Giuseppe; Zheng, Li; About, Imad; Taqi, Nawar; Nguyen, Nghia P.T.; Matossian, Margarite; McAlpin, Blake; Santoro, Angela; McHugh, Jonathan; Prince, Mark E.; Papagerakis, Petros

    2014-01-01

    Oral mucosa is continuously exposed to environmental forces and has to be constantly renewed. Accordingly, the oral mucosa epithelium contains a large reservoir of epithelial stem cells necessary for tissue homeostasis. Despite considerable scientific advances in stem cell behavior in a number of tissues, fewer studies have been devoted to the stem cells in the oral epithelium. Most of oral mucosa stem cells studies are focused on identifying cancer stem cells (CSC) in oral squamous cell carcinomas (OSCCs) among other head and neck cancers. OSCCs are the most prevalent epithelial tumors of the head and neck region, marked by their aggressiveness and invasiveness. Due to their highly tumorigenic properties, it has been suggested that CSC may be the critical population of cancer cells in the development of OSCC metastasis. This review presents a brief overview of epithelium stem cells with implications in oral health, and the clinical implications of the CSC concept in OSCC metastatic dissemination. PMID:24803391

  1. Epithelial Wnt ligand secretion is required for adult hair follicle growth and regeneration

    PubMed Central

    Myung, Peggy; Takeo, Makoto; Ito, Mayumi; Atit, Radhika

    2012-01-01

    β-catenin, a key transducer molecule of Wnt signaling, is required for adult hair follicle growth and regeneration. However, the cellular source of Wnt ligands required for Wnt/β-catenin activation during anagen induction is unknown. In this study, we genetically deleted Wntless, a gene required for Wnt ligand secretion by Wnt-producing cells, specifically in the hair follicle epithelium during telogen phase. We show that epithelial Wnt ligands are required for anagen, as loss of Wntless in the follicular epithelium resulted in a profound hair cycle arrest. Both the follicular epithelium and dermal papilla showed markedly decreased Wnt/β-catenin signaling during anagen induction compared to control hair follicles. Surprisingly, hair follicle stem cells that are responsible for hair regeneration maintained expression of stem cell markers but exhibited significantly reduced proliferation. Finally, we demonstrate that epidermal Wnt ligands are critical for adult wound-induced de novo hair formation. Collectively, these data show that Wnt ligands secreted by the hair follicle epithelium are required for adult hair follicle regeneration and provide new insight into potential cellular targets for the treatment of hair disorders such as alopecia. PMID:22810306

  2. Expression of complement 3 and complement 5 in newt limb and lens regeneration.

    PubMed

    Kimura, Yuko; Madhavan, Mayur; Call, Mindy K; Santiago, William; Tsonis, Panagiotis A; Lambris, John D; Del Rio-Tsonis, Katia

    2003-03-01

    Some urodele amphibians possess the capacity to regenerate their body parts, including the limbs and the lens of the eye. The molecular pathway(s) involved in urodele regeneration are largely unknown. We have previously suggested that complement may participate in limb regeneration in axolotls. To further define its role in the regenerative process, we have examined the pattern of distribution and spatiotemporal expression of two key components, C3 and C5, during limb and lens regeneration in the newt Notophthalmus viridescens. First, we have cloned newt cDNAs encoding C3 and C5 and have generated Abs specifically recognizing these molecules. Using these newt-specific probes, we have found by in situ hybridization and immunohistochemical analysis that these molecules are expressed during both limb and lens regeneration, but not in the normal limb and lens. The C3 and C5 proteins were expressed in a complementary fashion during limb regeneration, with C3 being expressed mainly in the blastema and C5 exclusively in the wound epithelium. Similarly, during the process of lens regeneration, C3 was detected in the iris and cornea, while C5 was present in the regenerating lens vesicle as well as the cornea. The distinct expression profile of complement proteins in regenerative tissues of the urodele lens and limb supports a nonimmunologic function of complement in tissue regeneration and constitutes the first systematic effort to dissect its involvement in regenerative processes of lower vertebrate species. PMID:12594255

  3. Oral Cancer

    MedlinePlus

    ... HUMAN SERVICES National Institutes of Health About Oral Cancer Oral cancer includes cancers of the mouth and pharynx (the back of the throat). Oral cancer accounts for roughly two percent of all cancers ...

  4. Interleukin-22 Promotes Intestinal Stem Cell-Mediated Epithelial Regeneration

    PubMed Central

    Dudakov, Jarrod A.; Jenq, Robert R.; Velardi, Enrico; Young, Lauren F.; Smith, Odette M.; Lawrence, Gillian; Ivanov, Juliet A.; Fu, Ya-Yuan; Takashima, Shuichiro; Hua, Guoqiang; Martin, Maria L.; O'Rourke, Kevin P.; Lo, Yuan-Hung; Mokry, Michal; Romera-Hernandez, Monica; Cupedo, Tom; Dow, Lukas; Nieuwenhuis, Edward E.; Shroyer, Noah F.; Liu, Chen; Kolesnick, Richard

    2015-01-01

    Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch, and epidermal growth factor (EGF) signals supporting Lgr5+ crypt base columnar ISCs for normal epithelial maintenance1,2. However, little is known about the regulation of the ISC compartment after tissue damage. Utilizing ex vivo organoid cultures, we provide evidence that innate lymphoid cells (ILCs), potent producers of Interleukin-22 (IL-22) after intestinal injury3,4, increased the growth of murine small intestine (SI) organoids in an IL-22-dependent fashion. Recombinant IL-22 directly targeted ISCs, augmenting the growth of both murine and human intestinal organoids, increasing proliferation, and promoting ISC expansion. IL-22 induced Stat3 phosphorylation in Lgr5+ ISCs, and Stat3 was critical for both organoid formation and IL-22-mediated regeneration. Treatment with IL-22 in vivo after murine allogeneic bone marrow transplantation (BMT) enhanced recovery of ISCs, increased epithelial regeneration, and reduced intestinal pathology and mortality from graft vs. host disease (GVHD). Atoh1-deficient organoid culture demonstrated that IL-22 induced epithelial regeneration independent of the Paneth cell niche. Our findings reveal a fundamental mechanism by which the immune system is able to support intestinal epithelium, activating ISCs to promote regeneration. PMID:26649819

  5. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration.

    PubMed

    Lindemans, Caroline A; Calafiore, Marco; Mertelsmann, Anna M; O'Connor, Margaret H; Dudakov, Jarrod A; Jenq, Robert R; Velardi, Enrico; Young, Lauren F; Smith, Odette M; Lawrence, Gillian; Ivanov, Juliet A; Fu, Ya-Yuan; Takashima, Shuichiro; Hua, Guoqiang; Martin, Maria L; O'Rourke, Kevin P; Lo, Yuan-Hung; Mokry, Michal; Romera-Hernandez, Monica; Cupedo, Tom; Dow, Lukas E; Nieuwenhuis, Edward E; Shroyer, Noah F; Liu, Chen; Kolesnick, Richard; van den Brink, Marcel R M; Hanash, Alan M

    2015-12-24

    Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) signals supporting Lgr5(+) crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regulation of the ISC compartment after tissue damage. Using ex vivo organoid cultures, here we show that innate lymphoid cells (ILCs), potent producers of interleukin-22 (IL-22) after intestinal injury, increase the growth of mouse small intestine organoids in an IL-22-dependent fashion. Recombinant IL-22 directly targeted ISCs, augmenting the growth of both mouse and human intestinal organoids, increasing proliferation and promoting ISC expansion. IL-22 induced STAT3 phosphorylation in Lgr5(+) ISCs, and STAT3 was crucial for both organoid formation and IL-22-mediated regeneration. Treatment with IL-22 in vivo after mouse allogeneic bone marrow transplantation enhanced the recovery of ISCs, increased epithelial regeneration and reduced intestinal pathology and mortality from graft-versus-host disease. ATOH1-deficient organoid culture demonstrated that IL-22 induced epithelial regeneration independently of the Paneth cell niche. Our findings reveal a fundamental mechanism by which the immune system is able to support the intestinal epithelium, activating ISCs to promote regeneration. PMID:26649819

  6. Oral Myiasis

    PubMed Central

    Saravanan, Thalaimalai; Mohan, Mathan A; Thinakaran, Meera; Ahammed, Saneem

    2015-01-01

    Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy. PMID:25709196

  7. Enamel Regeneration - Current Progress and Challenges

    PubMed Central

    Baswaraj; H.K, Navin; K.B, Prasanna

    2014-01-01

    Dental Enamel is the outermost covering of teeth. It is hardest mineralized tissue present in the human body. Enamel faces the challenge of maintaining its integrity in a constant demineralization and remineralization within the oral environment and it is vulnerable to wear, damage, and decay. It cannot regenerate itself, because it is formed by a layer of cells that are lost after the tooth eruption. Conventional treatment relies on synthetic materials to restore lost enamel that cannot mimic natural enamel. With advances in material science and understanding of basic principles of organic matrix mediated mineralization paves a way for formation of synthetic enamel. The knowledge of enamel formation and understanding of protein interactions and their gene products function along with the isolation of postnatal stem cells from various sources in the oral cavity, and the development of smart materials for cell and growth factor delivery, makes possibility for biological based enamel regeneration. This article will review the recent endeavor on biomimetic synthesis and cell based strategies for enamel regeneration. PMID:25386548

  8. Human turbinate mesenchymal stromal cell sheets with bellows graft for rapid tracheal epithelial regeneration.

    PubMed

    Park, Jeong Hun; Park, Ju Young; Nam, Inn-Chul; Hwang, Se-Hwan; Kim, Choung-Soo; Jung, Jin Woo; Jang, Jinah; Lee, Hyungseok; Choi, Yeongjin; Park, Sun Hwa; Kim, Sung Won; Cho, Dong-Woo

    2015-10-01

    Rapid functional epithelial regeneration on the luminal surface is essential when using artificial tracheal grafts to repair tracheal defects. In this study, we imposed human turbinate mesenchymal stromal cell (hTMSC) sheets for tracheal epithelial regeneration, and then assessed their potential as a new clinical cell source. In vitro, hTMSCs sheets showed high capacity to differentiate into tracheal epithelium. We fabricated a poly(ε-caprolactone) (PCL) tracheal graft by indirect three-dimensional (3D) printing technique and created a composite construct by transplanting the hTMSC sheets to its luminal surface of the tracheal graft, then applied this tissue-engineered tracheal graft to non-circumferential tracheal reconstruction in a rabbit model. 4 weeks after implantation, the luminal surface of tissue-engineered tracheal graft was covered by a mature and highly-ciliated epithelium, whereas tracheal grafts without hTMSC sheets were covered by only a thin, immature epithelium. Therefore, hTMSC sheets on the luminal surface of a tissue-engineered tracheal graft can accelerate the tracheal epithelial regeneration, and the tissue-engineered tracheal graft with hTMSC sheets provides a useful clinical alternative for tracheal epithelial regeneration. PMID:26163763

  9. Notch Signaling and Atoh1 Expression During Hair Cell Regeneration in the Mouse Utricle

    PubMed Central

    Wang, Guo-Peng; Chatterjee, Ishani; Batts, Shelley A.; Wong, Hiu Tung; Gong, Tzy-Wen; Gong, Shu-Sheng; Raphael, Yehoash

    2010-01-01

    The mammalian vestibular epithelium has a limited capacity for spontaneous hair cell regeneration. The mechanism underlying the regeneration is not well understood. Because the Notch signaling pathway mediates the formation of the sensory epithelial mosaic patterning during ear development, it may also play a role in hair cell regeneration in the mature mammalian vestibular epithelium after a lesion. To investigate the process of spontaneous regeneration in the vestibular epithelium vis-à-vis changes in Notch signaling, we induced a unilateral lesion by infusing streptomycin into the mouse posterior semicircular canal, and examined Notch signaling molecules and their mRNA expression levels by immunohistochemistry and quantitative real-time polymerase chain reaction (qRTPCR), respectively. We detected Jagged1 in supporting cells in both normal and lesioned utricles. Atoh1, a marker for early developing hair cells, was absent in the intact mature tissue, but re-appeared after the lesion. Many cells were either positive for both Atoh1 and myosin VIIa, or for one of them. qRTPCR data showed a post trauma decrease of Hes5 and an increase in Atoh1. Atoh1 up-regulation may either be a result of Hes5 down-regulation or mediated by another signaling pathway. PMID:20433915

  10. The microbial challenge to pulp regeneration.

    PubMed

    Fouad, A F

    2011-07-01

    Pulp regeneration is considered in cases where the dental pulp has been destroyed because of microbial irritation. Diverse oral and food-borne micro-organisms are able to invade the pulp space, form biofilm on canal walls, and infiltrate dentinal tubules. Prior to pulp regeneration procedures, the pulp space and dentinal walls need to be sufficiently disinfected to allow for and promote regeneration. The necessary level of disinfection is likely higher than that accepted for traditional endodontic therapy, because in traditional techniques the mere lowering of bacterial loads and prevention of bacterial access to periapical tissues is conducive to healing. Moreover, several of the non-specific antimicrobials used in traditional endodontic therapy may cause significant changes in remaining dentin that interfere with its inherent potential to mediate regeneration. Non-specific antimicrobials also suppress all microbial taxa, which may allow residual virulent micro-organisms to preferentially repopulate the pulp space. Therefore, it is important for endodontic pathogens to be studied by molecular methods that allow for a broad depth of coverage. It is then essential to determine the most effective protocols to disinfect the pulp space, with minimal disruption of remaining dentin. These protocols include the topical use of effective antibiotics, including newer agents that have demonstrated efficacy against endodontic pathogens. PMID:21677080

  11. Defective Barrier Function in Neosquamous Epithelium

    PubMed Central

    Jovov, Biljana; Shaheen, Nicholas J; Orlando, Geraldine S.; Djukic, Zorka; Orlando, Roy C.

    2013-01-01

    BACKGROUND Radiofrequency ablation (RFA) of Barrett’s esophagus (BE) is a common strategy for the prevention of esophageal adenocarcinoma (EAC). After RFA, the ablated esophagus heals on acid suppressive therapy, and is re-populated with a stratified squamous epithelium, referred to as ‘neosquamous epithelium (NSE).’ Because the ability of the NSE to protect the underlying tissue from recurrent insult by reflux is unclear, we assessed the barrier function of NSE by comparing it to that of the native upper squamous epithelium (USE) in subjects having undergone RFA. METHODS At varying intervals following RFA, the barrier function of NSE and USE were assessed in endoscopic biopsies by light and electron microscopy, and by measurement of electrical resistance (RT) and fluorescein flux in mini-Ussing chambers. Chamber results were further compared with results from control biopsies (healthy distal esophagus). A claudin expression profile in the tight junctions (TJ) of NSE and USE was determined using qRT-PCR. Differential expression of claudin 4 between NSE and USE was assayed by immunoblots. RESULTS USE was histologically normal while NSE showed dilated intercellular spaces and marked eosinophilia. NSE was also more permeable than USE and healthy controls, having lower mean RT and higher fluorescein fluxes. Abnormally low RT values for NSE were unrelated to the time period following RFA (or number of prior RFA sessions), being abnormal even 26 months after RFA. Abnormal permeability in NSE was associated with significantly lower values for claudin-4 and claudin-10 than in USE. CONCLUSIONS NSE commonly exhibits defective barrier function. Since this defect will make it vulnerable to injury, inflammation and destruction by acidic and weakly acidic refluxates, it may in part explain incidences of recurrence of BE following ablation. PMID:23318477

  12. Potential of pigment epithelium-derived factor (PEDF) as a bone regenerative biopharmaceutical.

    PubMed

    Lee, P X; Dass, C R

    2016-04-01

    Bone is very much a dynamic tissue, capable of various functions not limited to protection of the marrow, serving as a reservoir for calcium, maintaining posture and facilitating mobility. It is also a tissue that is fully capable of regenerating itself at most stages of life, with a diminishing capacity with increasing age. Bone defects can arise from a variety of factors not limited to bone tumours and fractures. At present, clinically, most diseased bone is removed and the patient fitted with prosthetics, with use of certain factors such as bone morphogenetic proteins (BMPs) to aid healing. Recently, the protein pigment epithelium-derived factor (PEDF) has been found to have favourable effects on bone regeneration, which is reviewed here. Numerous studies have shown the potential of PEDF in vitro, with increasing reports of success in small animal models of bone trauma. This review puts forward the advantages, and some disadvantages, in the use of PEDF as a biopharmaceutical for bone regeneration. PMID:27209693

  13. Nanomaterials and bone regeneration

    PubMed Central

    Gong, Tao; Xie, Jing; Liao, Jinfeng; Zhang, Tao; Lin, Shiyu; Lin, Yunfeng

    2015-01-01

    The worldwide incidence of bone disorders and conditions has been increasing. Bone is a nanomaterials composed of organic (mainly collagen) and inorganic (mainly nano-hydroxyapatite) components, with a hierarchical structure ranging from nanoscale to macroscale. In consideration of the serious limitation in traditional therapies, nanomaterials provide some new strategy in bone regeneration. Nanostructured scaffolds provide a closer structural support approximation to native bone architecture for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. In this article, we focused on reviewing the classification and design of nanostructured materials and nanocarrier materials for bone regeneration, their cell interaction properties, and their application in bone tissue engineering and regeneration. Furthermore, some new challenges about the future research on the application of nanomaterials for bone regeneration are described in the conclusion and perspectives part. PMID:26558141

  14. [Relative biological effectiveness of accelerated heavy ions and fast neutrons estimated from frequency of aberration mytoses in the retinal epithelium].

    PubMed

    Vorozhtsova, S V; Shafirkin, A V; Fedorenko, B S

    2006-01-01

    Analyzed was the literature and authors' experimental data concerning lesion and recovery of epithelium cells of mice retina immediately and long after irradiation at different sources including single and partly fractionated irradiation by gamma- and X-rays, accelerated protons, helium, carbon and boron ions, and fast neutrons of the reactor range in a large spectrum of doses and LET. Reviewed are some new techniques of determining the RBE coefficient for these types of radiation; large values of the RBE coefficients for accelerated ions and neutrons (5-10 times higher than RBE coefficients calculated for the next day following irradiation) are a result of integration into calculation of the available data about the delayed disorders in retinal epithelium cell regeneration. PMID:17193969

  15. Histatin-1 Expression in Human Lacrimal Epithelium

    PubMed Central

    Pasha, Zeeshan; Jaboori, Assraa Jassim; Jassim, Sarmad H.; Jain, Sandeep; Aakalu, Vinay K.

    2016-01-01

    Background Study of human lacrimal cell biology is limited by poor access to tissue samples, heterogeneous cell composition of tissue and a lack of established lacrimal epithelial markers. In order to further our understanding of lacrimal cell biology, we sought to find a better marker for human lacrimal epithelial cells, compared to what has been reported in the literature. Methods We utilized human Muller’s muscle conjunctival resection (MMCR) specimens containing accessory lacrimal gland (ALG) and cadaveric main lacrimal gland (MLG) as sources of lacrimal tissue. Candidate markers were sought using human ALG tissue from MMCR specimens, isolated by laser capture microdissection (LCM). Affymetrix® analysis was performed on total RNA isolated from FFPE samples to profile transcription in ALG. MMCR tissue sections were assessed by immunofluorescence using antibodies for histatin-1, lactoferrin, E-cadherin (E-cad) and alpha-smooth muscle actin (ASMA). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was performed to analyze the expression of histatin-1, E-cad and lactoferrin from cadaveric MLG. Results Histatin-1 is expressed in ALG and MLG, localizes to lacrimal epithelium, and to a greater degree than do other putative lacrimal epithelial markers. Conclusions Histatin-1 is a good marker for human lacrimal epithelium in ALG and MLG and can be used to identify lacrimal cells in future studies. PMID:26824896

  16. The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns.

    PubMed

    Cejka, Cestmir; Holan, Vladimir; Trosan, Peter; Zajicova, Alena; Javorkova, Eliska; Cejkova, Jitka

    2016-01-01

    The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties. PMID:27057279

  17. Evolution of the chordate regeneration blastema: Differential gene expression and conserved role of notch signaling during siphon regeneration in the ascidian Ciona.

    PubMed

    Hamada, Mayuko; Goricki, Spela; Byerly, Mardi S; Satoh, Noriyuki; Jeffery, William R

    2015-09-15

    The regeneration of the oral siphon (OS) and other distal structures in the ascidian Ciona intestinalis occurs by epimorphosis involving the formation of a blastema of proliferating cells. Despite the longstanding use of Ciona as a model in molecular developmental biology, regeneration in this system has not been previously explored by molecular analysis. Here we have employed microarray analysis and quantitative real time RT-PCR to identify genes with differential expression profiles during OS regeneration. The majority of differentially expressed genes were downregulated during OS regeneration, suggesting roles in normal growth and homeostasis. However, a subset of differentially expressed genes was upregulated in the regenerating OS, suggesting functional roles during regeneration. Among the upregulated genes were key members of the Notch signaling pathway, including those encoding the delta and jagged ligands, two fringe modulators, and to a lesser extent the notch receptor. In situ hybridization showed a complementary pattern of delta1 and notch gene expression in the blastema of the regenerating OS. Chemical inhibition of the Notch signaling pathway reduced the levels of cell proliferation in the branchial sac, a stem cell niche that contributes progenitor cells to the regenerating OS, and in the OS regeneration blastema, where siphon muscle fibers eventually re-differentiate. Chemical inhibition also prevented the replacement of oral siphon pigment organs, sensory receptors rimming the entrance of the OS, and siphon muscle fibers, but had no effects on the formation of the wound epidermis. Since Notch signaling is involved in the maintenance of proliferative activity in both the Ciona and vertebrate regeneration blastema, the results suggest a conserved evolutionary role of this signaling pathway in chordate regeneration. The genes identified in this investigation provide the foundation for future molecular analysis of OS regeneration. PMID:26206613

  18. Ultra structural study of the rat cheek epithelium treated with Neem extract.

    PubMed

    Azmi, Muhammad Arshad; Khatoon, Nasira; Ghaffar, Rizwana Abdul

    2015-11-01

    The purpose of this study was to investigate the effects of neem extract (Azadirachta indica A. Juss) on the ultrastructure of the rat oral epithelium, because neem extract has been added in the tooth paste as an anti-plaque-forming substance in Asian countries. The non-toxic dose of 2000 mg/kg body weight of Neem extract (NBE) was applied daily to the surface of buccal epithelium for four weeks and controls did not receive Neem extract. After four weeks cheek epithelial tissues were excised and processed for light microscopy, scanning and transmission electron microscopy. Light microscopy did not show significant differences between NBE-treated and control epithelium. Difference between control and treated rats weight was non-significant. Moreover, time period was also non-significant. Irregular cell surfaces were noticed when compared to control specimens when examined by scanning electron microscopy. Under transmission electron microscopy, wider intercellular spaces were observed in the treated epithelial spinous cellular layers when compared to control. Further, more keratohyalin granules were present in experimental granular cells. It was concluded that present study showed differences between Neem-treated and control in epithelial tissues but these structural differences may not be related to adverse side effects of the Neem extract. PMID:26639494

  19. Specific-sized hyaluronan fragments promote expression of human β-defensin 2 in intestinal epithelium.

    PubMed

    Hill, David R; Kessler, Sean P; Rho, Hyunjin K; Cowman, Mary K; de la Motte, Carol A

    2012-08-31

    Hyaluronan (HA) is a glycosaminoglycan polymer found in the extracellular matrix of virtually all mammalian tissues. Recent work has suggested a role for small, fragmented HA polymers in initiating innate defense responses in immune cells, endothelium, and epidermis through interaction with innate molecular pattern recognition receptors, such as TLR4. Despite these advances, little is known regarding the effect of fragmented HA at the intestinal epithelium, where numerous pattern recognition receptors act as sentinels of an innate defense response that maintains epithelial barrier integrity in the presence of abundant and diverse microbial challenges. Here we report that HA fragments promote expression of the innate antimicrobial peptide human β-defensin 2 (HβD2) in intestinal epithelial cells. Treatment of HT-29 colonic epithelial cells with HA fragment preparations resulted in time- and dose-dependent up-regulated expression of HβD2 protein in a fragment size-specific manner, with 35-kDa HA fragment preparations emerging as the most potent inducers of intracellular HβD2. Furthermore, oral administration of specific-sized HA fragments promotes the expression of an HβD2 ortholog in the colonic epithelium of both wild-type and CD44-deficient mice but not in TLR4-deficient mice. Together, our observations suggest that a highly size-specific, TLR4-dependent, innate defense response to fragmented HA contributes to intestinal epithelium barrier defense through the induction of intracellular HβD2 protein. PMID:22761444

  20. Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration.

    PubMed

    Farkas, Johanna E; Freitas, Polina D; Bryant, Donald M; Whited, Jessica L; Monaghan, James R

    2016-08-01

    The Mexican axolotl (Ambystoma mexicanum) is capable of fully regenerating amputated limbs, but denervation of the limb inhibits the formation of the post-injury proliferative mass called the blastema. The molecular basis behind this phenomenon remains poorly understood, but previous studies have suggested that nerves support regeneration via the secretion of essential growth-promoting factors. An essential nerve-derived factor must be found in the blastema, capable of rescuing regeneration in denervated limbs, and its inhibition must prevent regeneration. Here, we show that the neuronally secreted protein Neuregulin-1 (NRG1) fulfills all these criteria in the axolotl. Immunohistochemistry and in situ hybridization of NRG1 and its active receptor ErbB2 revealed that they are expressed in regenerating blastemas but lost upon denervation. NRG1 was localized to the wound epithelium prior to blastema formation and was later strongly expressed in proliferating blastemal cells. Supplementation by implantation of NRG1-soaked beads rescued regeneration to digits in denervated limbs, and pharmacological inhibition of NRG1 signaling reduced cell proliferation, blocked blastema formation and induced aberrant collagen deposition in fully innervated limbs. Taken together, our results show that nerve-dependent NRG1/ErbB2 signaling promotes blastemal proliferation in the regenerating limb and may play an essential role in blastema formation, thus providing insight into the longstanding question of why nerves are required for axolotl limb regeneration. PMID:27317805

  1. KRT14 marks a subpopulation of bladder basal cells with pivotal role in regeneration and tumorigenesis

    PubMed Central

    Papafotiou, George; Paraskevopoulou, Varvara; Vasilaki, Eleni; Kanaki, Zoi; Paschalidis, Nikolaos; Klinakis, Apostolos

    2016-01-01

    The urothelium is a specialized epithelium that lines the urinary tract. It consists of three different cell types, namely, basal, intermediate and superficial cells arranged in relatively distinct cell layers. Normally, quiescent, it regenerates fast upon injury, but the regeneration process is not fully understood. Although several reports have indicated the existence of progenitors, their identity and exact topology, as well as their role in key processes such as tissue regeneration and carcinogenesis have not been clarified. Here we show that a minor subpopulation of basal cells, characterized by the expression of keratin 14, possesses self-renewal capacity and also gives rise to all cell types of the urothelium during natural and injury-induced regeneration. Moreover, these cells represent cells of origin of urothelial cancer. Our findings support the hypothesis of basally located progenitors with profound roles in urothelial homoeostasis. PMID:27320313

  2. In goldfish the discriminative ability for odours persists after reduction of the olfactory epithelium, and rapidly returns after olfactory nerve axotomy and crossing bulbs.

    PubMed

    Zippel, H P

    2000-09-29

    Goldfish are ideal vertebrates for the study of regeneration within the peripheral and the central olfactory system. The present behavioural investigations studied the effects of bilateral lesions on the animals' ability to qualitatively discriminate two amino acids (10(-6) M) and their performance in two more difficult tasks: (i) rewarded amino acid applied in a lower concentration, and (ii) rewarded stimulus contaminated. A 50 and 85% reduction of the olfactory epithelium resulted in no recordable behavioural deficit. After axotomy of olfactory nerves and lateral olfactory tractotomy, fishes were anosmic for seven to ten days. Following replacement of sensory cells in the epithelium, and after regeneration of olfactory tract fibres a full functional recovery i.e. a highly specific regeneration, was recorded. After three surgical modifications of the olfactory bulbs' position, (i) crossing olfactory tracts and bulbs, (ii) crossing tracts and turning bulbs, and (iii) turning bulbs upside down, a full functional recovery was recorded for amino-acid discrimination in a similar concentration. A permanent, and similar slight deficit was, however, found during application of different concentrations, and of contaminated stimuli when medial lateral halves of the bulb were in 'incorrect' position (i) and (ii), or olfactory bulbs were positioned in the vicinity of the contralateral epithelium (i) and (ii). PMID:11079402

  3. Chronic inflammation imposes aberrant cell fate in regenerating epithelia through mechanotransduction.

    PubMed

    Nowell, Craig S; Odermatt, Pascal D; Azzolin, Luca; Hohnel, Sylke; Wagner, Erwin F; Fantner, Georg E; Lutolf, Matthias P; Barrandon, Yann; Piccolo, Stefano; Radtke, Freddy

    2016-02-01

    Chronic inflammation is associated with a variety of pathological conditions in epithelial tissues, including cancer, metaplasia and aberrant wound healing. In relation to this, a significant body of evidence suggests that aberration of epithelial stem and progenitor cell function is a contributing factor in inflammation-related disease, although the underlying cellular and molecular mechanisms remain to be fully elucidated. In this study, we have delineated the effect of chronic inflammation on epithelial stem/progenitor cells using the corneal epithelium as a model tissue. Using a combination of mouse genetics, pharmacological approaches and in vitro assays, we demonstrate that chronic inflammation elicits aberrant mechanotransduction in the regenerating corneal epithelium. As a consequence, a YAP-TAZ/β-catenin cascade is triggered, resulting in the induction of epidermal differentiation on the ocular surface. Collectively, the results of this study demonstrate that chronic inflammation and mechanotransduction are linked and act to elicit pathological responses in regenerating epithelia. PMID:26689676

  4. Dpp signaling determines regional stem cell identity in the regenerating adult Drosophila gastrointestinal tract

    PubMed Central

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2013-01-01

    Summary The gastrointestinal tract is lined by a series of epithelia that share functional requirements, but also have distinct, highly specialized roles. Distinct populations of somatic stem cells (SCs) regenerate these epithelia, yet the mechanisms that maintain regional identities of these SCs are not well understood. Here, we identify a role for the BMP-like Dpp signaling pathway in diversifying regenerative processes in the adult gastrointestinal tract of Drosophila. Dpp secreted from enterocytes at the boundary between the posterior midgut (PM) and the middle midgut (MM) sets up a morphogen gradient that selectively directs copper cell (CC) regeneration from gastric SCs in the MM and thus determines the size of the CC region. In vertebrates, deregulation of BMP signaling has been associated with Barrett’s metaplasia, where the squamous esophageal epithelium is replaced by a columnar epithelium, suggesting that the maintenance of regional SC identities by BMP is conserved. PMID:23810561

  5. Neuropilins: expression and roles in the epithelium.

    PubMed

    Wild, Jonathan R L; Staton, Carolyn A; Chapple, Keith; Corfe, Bernard M

    2012-04-01

    Initially found expressed in neuronal and then later in endothelial cells, it is well established that the transmembrane glycoproteins neuropilin-1 (NRP1) and neuropilin-2 (NRP2) play essential roles in axonal growth and guidance and in physiological and pathological angiogenesis. Neuropilin expression and function in epithelial cells has received little attention when compared with neuronal and endothelial cells. Overexpression of NRPs is shown to enhance growth, correlate with invasion and is associated with poor prognosis in various tumour types, especially those of epithelial origin. The contribution of NRP and its ligands to tumour growth and metastasis has spurred a strong interest in NRPs as novel chemotherapy drug targets. Given NRP's role as a multifunctional co-receptor with an ability to bind with disparate ligand families, this has sparked new areas of research implicating NRPs in diverse biological functions. Here, we review the growing body of research demonstrating NRP expression and role in the normal and neoplastic epithelium. PMID:22414290

  6. Adenocarcinoma of the pigmented ciliary epithelium

    PubMed Central

    Sukeda, Aoi; Mori, Taisuke; Suzuki, Shigenobu; Ochiai, Atsushi

    2014-01-01

    Adenocarcinoma of the pigmented ciliary epithelium is an exceptionally rare eye tumour, with only a few cases reported to date. We encountered such a case in a 50-year-old woman who reported seeing floaters in her right eye. Fundus examination and MRI revealed an elevated lesion located in the ciliary body compressing the lens. The ciliary body was resected under the diagnosis of ciliary adenoma. On histological examination, the tumour exhibited epithelial features with glandular formation and moderate nuclear pleomorphism. The tumour invaded the subepithelial stroma of the ciliary body. Immunohistochemical findings were positive for cytokeratin OSCAR, AE1/AE3, CK7, EMA, S100, Melan A, HMB45, and microphthalmia-associated transcription factor. PMID:25015166

  7. Ultrastructure of gingival epithelium in chronic gingivitis.

    PubMed

    Lushnikova, E L; Nepomnyashchikh, L M; Oskolsky, G I; Jurkevich, N V

    2012-03-01

    We studied ultrastructural reorganization of the gingival mucosa in chronic gingivitis. It was found that chronic inflammation leads to significant intracellular reorganization of epitheliocytes in the basal and prickle cell layers of gingival epithelium and their pronounced structural and functional heterogeneity. The main ultrastructural alterations of epitheliocytes in the basal and prickle cell layers include pronounced vacuolization of the perinuclear zone (partial necrosis), formation of thick tonofilament bundles, focal lysis and sequestration of glycogen, and destruction and reduction of intracellular junctions in some cases accompanied by acantholytic alterations. Chronic inflammation in the gingival mucosa induced extensive remodeling of the lamina propria manifested in multiplication of the basement membrane and obturation of blood vessels with collagen fibrils. PMID:22803154

  8. Microgravity effects on neural retina regeneration in the newt

    NASA Astrophysics Data System (ADS)

    Grigoryan, E. N.; Anton, H. J.; Mitashov, V. I.

    Data on forelimb and eye lens regenerationin in urodeles under spaceflight conditions (SFC) have been obtained in our previous studies. Today, evidence is available that SFC stimulate regeneration in experimental animals rather than inhibit it. The results of control on-ground experiments with simulated microgravity suggest that the stimulatory effect of SFC is due largely to weightlessness. An original experimental model is proposed, which is convenient for comprehensively analyzing neural regeneration under SFC. The initial results described here concern regeneration of neural retina in Pleurodeles waltl newts exposed to microgravity simulated in radial clinostat. After clinorotation for seven days (until postoperation day 16), a positive effect of altered gravity on structural restoration of detached neural retina was confirmed by a number of criteria. Specifically, an increased number of Müllerian glial cells, an increased relative volume of the plexiform layers, reduced cell death, advanced redifferentiation of retinal pigment epithelium, and extended areas of neural retina reattachment were detected in experimental newts. Moreover, cell proliferation in the inner nuclear layer of neural retina increased as compared with control. Thus, low gravity appears to intensify natural cytological and molecular mechanisms of neural retina regeneration in lower vertebrates.

  9. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology. PMID:16277953

  10. Atlas Regeneration, Inc.

    PubMed

    Makarev, Eugene; Isayev, Olexandr; Atala, Anthony

    2016-03-01

    Atlas Regeneration is dedicated to the development of novel data-driven solutions for regenerative medicine, adapting proven technologies, and analysis strategies to take a multiomics-wide view of stem cell quality and cell fate design. Our core offering is a global comprehensive map of stem cell differentiation, Universal Signalome Atlas for Regenerative Medicine, reflecting the pathway activation states across all characterized stem cells and their differentiated products. Key applications of Universal Signalome Atlas for Regenerative Medicine will include quality assurance for engineered cell products, and directed regeneration pharmacology, where we will screen and identify compounds that can efficiently convert pluripotent cells into desired subtypes. Another marketable piece of IP is development of specialized signaling pathway analysis systems Regeneration Intelligence which supposed to target the unmet needs of determination and prediction of stem cell signaling pathway activation to govern cell differentiation in specific directions. PMID:26925598

  11. Nanostructured Biomaterials for Regeneration**

    PubMed Central

    Wei, Guobao; Ma, Peter X.

    2009-01-01

    Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/dysfunctional tissues or organs. Biomaterials (scaffolds) serve as temporary 3D substrates to guide neo tissue formation and organization. It is often beneficial for a scaffolding material to mimic the characteristics of extracellular matrix (ECM) at the nanometer scale and to induce certain natural developmental or/and wound healing processes for tissue regeneration applications. This article reviews the fabrication and modification technologies for nanofibrous, nanocomposite, and nanostructured drug-delivering scaffolds. ECM-mimicking nanostructured biomaterials have been shown to actively regulate cellular responses including attachment, proliferation, differentiation and matrix deposition. Nano-scaled drug delivery systems can be successfully incorporated into a porous 3D scaffold to enhance the tissue regeneration capacity. In conclusion, nano-structured biomateials are a very exciting and rapidly expanding research area, and are providing new enabling technologies for regenerative medicine. PMID:19946357

  12. Velocity fields in a collectively migrating epithelium.

    PubMed

    Petitjean, L; Reffay, M; Grasland-Mongrain, E; Poujade, M; Ladoux, B; Buguin, A; Silberzan, P

    2010-05-19

    We report quantitative measurements of the velocity field of collectively migrating cells in a motile epithelium. The migration is triggered by presenting free surface to an initially confluent monolayer by using a microstencil technique that does not damage the cells. To avoid the technical difficulties inherent in the tracking of single cells, the field is mapped using the technique of particle image velocimetry. The main relevant parameters, such as the velocity module, the order parameter, and the velocity correlation function, are then extracted from this cartography. These quantities are dynamically measured on two types of cells (collectively migrating Madin-Darby canine kidney (MDCK) cells and fibroblastlike normal rat kidney (NRK) cells), first as they approach confluence, and then when the geometrical constraints are released. In particular, for MDCK cells filling up the patterns, we observe a sharp decrease in the average velocity after the point of confluence, whereas the densification of the monolayer is much more regular. After the peeling off of the stencil, a velocity correlation length of approximately 200 microm is measured for MDCK cells versus only approximately 40 microm for the more independent NRK cells. Our conclusions are supported by parallel single-cell tracking experiments. By using the biorthogonal decomposition of the velocity field, we conclude that the velocity field of MDCK cells is very coherent in contrast with the NRK cells. The displacements in the fingers arising from the border of MDCK epithelia are very oriented along their main direction. They influence the velocity field in the epithelium over a distance of approximately 200 microm. PMID:20441742

  13. Chemosensory Brush Cells of the Trachea. A Stable Population in a Dynamic Epithelium

    PubMed Central

    Reynolds, Susan D.; Finger, Thomas E.

    2013-01-01

    Tracheal brush cells (BCs) are specialized epithelial chemosensors that use the canonical taste transduction cascade to detect irritants. To test whether BCs are replaced at the same rate as other cells in the surrounding epithelium of adult mice, we used 5-bromo-2′-deoxyuridine (BrdU) to label dividing cells. Although scattered BrdU-labeled epithelial cells are present 5–20 days after BrdU, no BCs are labeled. These data indicate that BCs comprise a relatively static population. To determine how BCs are generated during development, we injected 5-day-old mice with BrdU and found labeled BCs and non-BC epithelial cells 5 days after BrdU. During the next 60 days, the percentage of labeled BCs increased, whereas the percentage of other labeled cell types decreased. These data suggest that BCs are generated from non-BC progenitor cells during postnatal tracheal growth. To test whether the adult epithelium retains the capacity to generate BCs, tracheal epithelial cells were recovered from adult mice and grown in an air–liquid interface (ALI) culture. After transition to differentiation conditions, BCs are detected, and comprise 1% of the total cell population by Day 14. BrdU added to cultures before the differentiation of BCs was chased into BCs, indicating that the increase in BC density is attributable to the proliferation of a non-BC progenitor. We conclude that: (1) BCs are normally a static population in adult mice; (2) BC progenitors proliferate and differentiate during neonatal development; and (3) BCs can be regenerated from a proliferative population resident in adult epithelium. PMID:23526223

  14. Electrochemically regenerable carbon dioxide absorber

    NASA Technical Reports Server (NTRS)

    Woods, R. R.; Marshall, R. D.; Schubert, F. H.; Heppner, D. B.

    1979-01-01

    Preliminary designs were generated for two electrochemically regenerable carbon dioxide absorber concepts. Initially, an electrochemically regenerable absorption bed concept was designed. This concept incorporated the required electrochemical regeneration components in the absorber design, permitting the absorbent to be regenerated within the absorption bed. This hardware was identified as the electrochemical absorber hardware. The second hardware concept separated the functional components of the regeneration and absorption process. This design approach minimized the extravehicular activity component volume by eliminating regeneration hardware components within the absorber. The electrochemical absorber hardware was extensively characterized for major operating parameters such as inlet carbon dioxide partial pressure, process air flow rate, operational pressure, inlet relative humidity, regeneration current density and absorption/regeneration cycle endurance testing.

  15. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

  16. Human milk hyaluronan enhances innate defense of the intestinal epithelium.

    PubMed

    Hill, David R; Rho, Hyunjin K; Kessler, Sean P; Amin, Ripal; Homer, Craig R; McDonald, Christine; Cowman, Mary K; de la Motte, Carol A

    2013-10-01

    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

  17. Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*

    PubMed Central

    Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.

    2013-01-01

    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

  18. Supercritical fluid regeneration of adsorbents

    NASA Astrophysics Data System (ADS)

    Defilippi, R. P.; Robey, R. J.

    1983-05-01

    The results of a program to perform studies supercritical (fluid) carbon dioxide (SCF CO2) regeneration of adsorbents, using samples of industrial wastewaters from manufacturing pesticides and synthetic solution, and to estimate the economics of the specific wastewater treatment regenerations, based on test data are given. Processing costs for regenerating granular activated carbon GAC) for treating industrial wastewaters depend on stream properties and regeneration throughput.

  19. The cell biology of regeneration

    PubMed Central

    King, Ryan S.

    2012-01-01

    Regeneration of complex structures after injury requires dramatic changes in cellular behavior. Regenerating tissues initiate a program that includes diverse processes such as wound healing, cell death, dedifferentiation, and stem (or progenitor) cell proliferation; furthermore, newly regenerated tissues must integrate polarity and positional identity cues with preexisting body structures. Gene knockdown approaches and transgenesis-based lineage and functional analyses have been instrumental in deciphering various aspects of regenerative processes in diverse animal models for studying regeneration. PMID:22391035

  20. [Regeneration of the ocular surface: stem cells and reconstructive techniques].

    PubMed

    Fernández, A; Moreno, J; Prósper, F; García, M; Echeveste, J

    2008-01-01

    The cornea is a transparent tissue microscopically constituted by 5 well differentiated layers. The corneal epithelium is essential for corneal transparency and is found in a state of constant renovation throughout life on the basis of the population of limbocorneal stem cells. The localisation of these limbocorneal stem cells seems to be in the basal layers of the limbocorneal epithelium, of vital importance for maintaining the micro-environment of these limbocorneal stem cells, which depend on a variety of intrinsic and extrinsic factors. Limbic insufficiency occurs when there is a partial or total loss of these limbocorneal stem cells. These clinical features lead to a corneal clouding with a resulting loss of vision. In these cases, corneal transplant only represents a temporary replacement of the corneal epithelium; it is necessary to carry out a prior treatment involving transplant of the autologous or allogeneic limbus, which enables regeneration of the population of damaged limbocorneal cells. To reduce the risk involved in the transplant of the limbus of the donor eye, techniques of cultivation of limbocorneal cells on the basis of small limbocorneal biopsies are proposed. PMID:18496580

  1. Oral Insulin

    PubMed Central

    2010-01-01

    Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation. PMID:21059246

  2. Regeneration: rewarding, but potentially risky.

    PubMed

    Egger, Bernhard

    2008-12-01

    Some bilaterally symmetric animals, such as flatworms, annelids, and nemerteans, are renowned for their outstanding regeneration capacity-even a fraction of the body can give rise to a complete new animal. However, not all species of these taxa can regenerate equally well-some cannot regenerate at all. If regeneration was purely beneficial, why cannot all of members of the flat, round, and ribbon worms regenerate? At that, why cannot all other bilaterians, including humans, regenerate as well? Regeneration capacity is an obvious advantage in accidental, predatory, and parasitic loss of body parts and is also closely intertwined with asexual reproduction strategies. Regeneration is suspected to play a role in life span extension or even rejuvenation. An answer for reduced or missing regeneration capacity in many species may be found in limitations of the body plan, high costs, and inherent dangers of regeneration. Defects in adults and juveniles are shown, and similarities between development and regeneration are pointed out. With a focus on some worms, but also highlighting comparisons with other animal taxa, putative reasons for a limited and an advanced regeneration capacity are discussed in this article. PMID:19067421

  3. Regenerator seal design

    DOEpatents

    Eckart, Francis H.

    1982-01-01

    A rotary regenerator disc matrix has a face seal with a cross arm and arcuate rim segments joined by prestress clamps to prestrain the arcuate rim seals so as to compensate seal rim twisting or coning and resultant disc face seal leakage as produced by operating thermal gradients across the seal.

  4. Regenerated Fe is tasty!

    NASA Astrophysics Data System (ADS)

    Nuester, J.; Twining, B. S.

    2012-12-01

    Bioavailability of nutrients is an essential factor controlling primary productivity in the ocean. In addition to macronutrients such as nitrogen and phosphorous, availability of the trace element iron unequivocally affects growth rates and community structure of phytoplankton and thereby primary productivity in many ocean regions. External sources of iron such as Aeolian dust, upwelling of Fe-rich waters, and hydrothermal are reduced in high-nutrient low-chlorophyll regions, and most Fe used by phytoplankton has been regenerated by zooplankton. While zooplankton regeneration of Fe was first shown two decades ago, major factors controlling this process such as chemical composition of prey and grazer taxonomy are not well constrained. As pH varies significantly in digestive systems between protozoa and mesozooplankton, we hypothesize that the extent and the bioavailability of regenerated Fe is a function of the digestive physiology. Furthermore, major element components such as silica for diatoms and calcium carbonate for cocolithophores may be able to buffer the pH of digestive systems of different grazer taxa. Such effects may further influence the magnitude and bioavailability of regenerated Fe. In order to constrain the effect of grazer taxonomy and chemical composition of prey on Fe bioavailability, 55Fe-labeled phytoplankton were fed to different grazers and unlabeled phytoplankton were subsequently inoculated to the filtrate of the grazing experiment in the regrowth phase of the experiment, and the uptake of 55Fe into the phytoplankton biomass was monitored over time. A parallel uptake experiment using inorganic 55Fe was used to compare the bioavailability of regenerated and inorganic Fe to the same phytoplankton species. Furthermore, some samples of the inorganic and the regenerated uptake experiments were treated with an oxalate rinse to remove any adsorbed Fe. This allowed us to estimate the adsorption of 55Fe from either source to the cell walls of

  5. Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity

    PubMed Central

    Kawamoto, Kohei; Izumikawa, Masahiko; Beyer, Lisa A.; Atkin, Graham M.; Raphael, Yehoash

    2010-01-01

    Whereas most epithelial tissues turn-over and regenerate after a traumatic lesion, this restorative ability is diminished in the sensory epithelia of the inner ear; it is absent in the cochlea and exists only in a limited capacity in the vestibular epithelium. The extent of regeneration in vestibular hair cells has been characterized for several mammalian species including guinea pig, rat, and chinchilla, but not yet in mouse. As the fundamental model species for investigating hereditary disease, the mouse can be studied using a wide variety of genetic and molecular tools. To design a mouse model for vestibular hair cell regeneration research, an aminoglycoside-induced method of complete hair cell elimination was developed in our lab and applied to the murine utricle. Loss of utricular hair cells was observed using scanning electron microscopy, and corroborated by a loss of fluorescent signal in utricles from transgenic mice with GFP-positive hair cells. Regenerative capability was characterized at several time points up to six months following insult. Using scanning electron microscopy, we observed that as early as two weeks after insult, a few immature hair cells, demonstrating the characteristic immature morphology indicative of regeneration, could be seen in the utricle. As time progressed, larger numbers of immature hair cells could be seen along with some mature cells resembling surface morphology of type II hair cells. By six months post-lesion, numerous regenerated hair cells were present in the utricle, however, neither their number nor their appearance was normal. A BrdU assay suggested that at least some of the regeneration of mouse vestibular hair cells involved mitosis. Our results demonstrate that the vestibular sensory epithelium in mice can spontaneously regenerate, elucidate the time course of this process, and identify involvement of mitosis in some cases. These data establish a road map of the murine vestibular regenerative process, which can be

  6. Oral Insulin Delivery: How Far Are We?

    PubMed Central

    Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

    2013-01-01

    Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

  7. Oral insulin delivery: how far are we?

    PubMed

    Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

    2013-01-01

    Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The mainbarriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

  8. Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates

    PubMed Central

    Lachaud, Christian Claude; Rodriguez-Campins, Berta; Hmadcha, Abdelkrim; Soria, Bernat

    2015-01-01

    Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities (peritoneal, pericardial, and pleural) and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold (biocompatible, degradable, and non-immunogenic) may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions. PMID:26347862

  9. Cell Jamming in the Airway Epithelium.

    PubMed

    Park, Jin-Ah; Fredberg, Jeffrey J

    2016-03-01

    Hallmarks of asthma include chronic airway inflammation, progressive airway remodeling, and airway hyperresponsiveness. The initiation and perpetuation of these processes are attributable at least in part to critical events within the airway epithelium, but the underlying mechanisms remain poorly understood. New evidence now suggests that epithelial cells derived from donors without asthma versus donors with asthma, even in the absence of inflammatory cells or mediators, express modes of collective migration that innately differ not only in the amount of migration but also in the kind of migration. The maturing cell layer tends to undergo a transition from a hypermobile, fluid-like, unjammed phase in which cells readily rearrange, exchange places, and flow, to a quiescent, solid-like, jammed phase in which cells become virtually frozen in place. Moreover, the unjammed phase defines a phenotype that can be perpetuated by the compressive stresses caused by bronchospasm. Importantly, in cells derived from donors with asthma versus donors without asthma, this jamming transition becomes substantially delayed, thus suggesting an immature or dysmature epithelial phenotype in asthma. PMID:27027955

  10. Glucose metabolism in rat retinal pigment epithelium.

    PubMed

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2006-01-01

    The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress. PMID:16475003

  11. Stroma–epithelium crosstalk in prostate cancer

    PubMed Central

    Niu, Yi-Nong; Xia, Shu-Jie

    2009-01-01

    The critical role played by stroma–epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells. In human prostate cancer, reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis. Permanent genetic mutations have been reported in stromal cells as well as in tumour cells. Transforming growth factor-β, vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth factor-1, epidermal growth factor, CXC12 and Interleukin-6 play active roles in the progression, androgen-independent conversion and distal metastasis of prostate cancer. Some soluble factors have reciprocal interactions with androgens and the androgen receptor (AR), and can even activate AR in the absence of the androgen ligand. In this article, we review the complex interactions between cancer cells and the surrounding microenvironment, and discuss the potential therapeutic targets in the stromal compartment of prostate cancer. PMID:19098934

  12. Biochemical studies of the tracheobronchial epithelium

    SciTech Connect

    Mass, M.J.; Kaufman, D.G.

    1984-06-01

    Tracheobronchial epithelium has been a focus of intense investigation in the field of chemical carcinogenesis. We have reviewed some biochemical investigations that have evolved through linkage with carcinogenesis research. These areas of investigation have included kinetics of carcinogen metabolism, identification of carcinogen metabolites, levels of carcinogen binding to DNA, and analysis of carcinogen-DNA adducts. Such studies appear to have provided a reasonable explanation for the susceptibilities of the respiratory tracts of rats and hamsters to carcinogenesis by benzo(a)pyrene. Coinciding with the attempts to understand the initiation of carcinogenesis in the respiratory tract has also been a major thrust aimed at effecting its prevention both in humans and in animal models for human bronchogenic carcinoma. These studies have concerned the effects of derivatives of vitamin A (retinoids) and their influence on normal cell biology and biochemistry of this tissue. Recent investigations have included the effects of retinoid deficiency on the synthesis of RNA and the identification of RNA species associated with this biological state, and also have included the effects of retinoids on the synthesis of mucus-related glycoproteins. Tracheal organ cultures from retinoid-deficient hamsters have been used successfully to indicate the potency of synthetic retinoids by monitoring the reversal of squamous metaplasia. Techniques applied to this tissue have also served to elucidate features of the metabolism of retinoic acid using high pressure liquid chromatography. 94 references, 9 figures, 2 tables.

  13. Human vomeronasal epithelium development: An immunohistochemical overview.

    PubMed

    Dénes, Lóránd; Pap, Zsuzsanna; Szántó, Annamária; Gergely, István; Pop, Tudor Sorin

    2015-06-01

    The vomeronasal organ (VNO) is the receptor structure of the vomeronasal system (VNS) in vertebrates. It is found bilaterally in the submucosa of the inferior part of the nasal septum. There are ongoing controversies regarding the functionality of this organ in humans. In this study we propose the immunohistochemical evaluation of changes in components of the human vomeronasal epithelium during foetal development. We used 45 foetuses of different age, which were included in three age groups. After VNO identification immunohistochemical reactions were performed using primary antibodies against the following: neuron specific enolase, calretinin, neurofilament, chromogranin, synaptophysin, cytokeratin 7, pan-cytokeratin and S100 protein. Digital slides were obtained and following colorimetric segmentation, surface area measurements were performed. The VNO was found in less than half of the studied specimens (42.2%). Neuron specific enolase and calretinin immunoexpression showed a decreasing trend with foetal age, while the other neural/neuroendocrine markers were negative in all specimens. Cytokeratin 7 expression increased with age, while Pan-Ctk had no significant variations. S100 protein immunoexpression also decreased around the VNO. The results of the present work uphold the theory of regression of the neuroepithelium that is present during initial stages of foetal development. PMID:26132837

  14. Reconstituted Human Upper Airway Epithelium as 3-D In Vitro Model for Nasal Polyposis

    PubMed Central

    de Borja Callejas, Francisco; Martínez-Antón, Asunción; Alobid, Isam; Fuentes, Mireya; Cortijo, Julio; Picado, César

    2014-01-01

    Background Primary human airway epithelial cells cultured in an air-liquid interface (ALI) develop a well-differentiated epithelium. However, neither characterization of mucociliar differentiation overtime nor the inflammatory function of reconstituted nasal polyp (NP) epithelia have been described. Objectives 1st) To develop and characterize the mucociliar differentiation overtime of human epithelial cells of chronic rhinosinusitis with nasal polyps (CRSwNP) in ALI culture system; 2nd) To corroborate that 3D in vitro model of NP reconstituted epithelium maintains, compared to control nasal mucosa (NM), an inflammatory function. Methods Epithelial cells were obtained from 9 NP and 7 control NM, and differentiated in ALI culture for 28 days. Mucociliary differentiation was characterized at different times (0, 7, 14, 21, and 28 days) using ultrastructure analysis by electron microscopy; ΔNp63 (basal stem/progenitor cell), β-tubulin IV (cilia), and MUC5AC (goblet cell) expression by immunocytochemistry; and mucous (MUC5AC, MUC5B) and serous (Lactoferrin) secretion by ELISA. Inflammatory function of ALI cultures (at days 0, 14, and 28) through cytokine (IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70) and chemokine (RANTES, MIG, MCP-1, IP-10, eotaxin-1, and GM-CSF) production was analysed by CBA (Cytometric Bead Array). Results In both NP and control NM ALI cultures, pseudostratified epithelium with ciliated, mucus-secreting, and basal cells were observed by electron microscopy at days 14 and 28. Displaying epithelial cell re-differentation, β-tubulin IV and MUC5AC positive cells increased, while ΔNp63 positive cells decreased overtime. No significant differences were found overtime in MUC5AC, MUC5B, and lactoferrin secretions between both ALI cultures. IL-8 and GM-CSF were significantly increased in NP compared to control NM regenerated epithelia. Conclusion Reconstituted epithelia from human NP epithelial cells cultured in ALI system provides a 3D in vitro model

  15. Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo

    PubMed Central

    YUAN, FENG-NING F.; VALIYAPARAMBIL, JAYASANKER; WOODS, MICHAEL C.; TRAN, HUY; PANT, RIMA; ADAMS, JOHN S.; MALLYA, SANJAY M.

    2014-01-01

    The secosteroidal hormone 1,25-dihyroxyvitamin D [1,25(OH)2D3] and its receptor, the vitamin D receptor (VDR), are crucial regulators of epidermal proliferation and differentiation. However, the effects of 1,25(OH)2D3-directed signaling on oral keratinocyte pathophysiology have not been well studied. We examined the role of 1,25(OH)2D3 in regulating proliferation and differentiation in cultured oral keratinocytes and on the oral epithelium in vivo. Using lentiviral-mediated shRNA to silence VDR, we generated an oral keratinocyte cell line with stable knockdown of VDR expression. VDR knockdown significantly enhanced proliferation and disrupted calcium- and 1,25(OH)2D3-induced oral keratinocyte differentiation, emphasizing the anti-proliferative and pro-differentiation effects of 1,25(OH)2D3 in oral keratinocytes. Using vitamin D3-deficient diets, we induced chronic vitamin D deficiency in mice as evidenced by decreased serum 25-hydroxyvitamin D (25OHD) concentrations. The vitamin D-deficient mice manifested increased proliferation of the tongue epithelium, but did not develop any morphological or histological abnormalities in the oral epithelium, suggesting that vitamin D deficiency alone is insufficient to alter oral epithelial homeostasis and provoke carcinogenesis. Immunohistochemical analyses of human and murine oral squamous cell carcinomas showed increased VDR expression. Overall, our results provide strong support for a crucial role for vitamin D signaling in oral keratinocyte pathophysiology. PMID:24626468

  16. Desmosomal component expression in normal, dysplastic, and oral squamous cell carcinoma.

    PubMed

    Narayana, Nagamani; Gist, Julie; Smith, Tyler; Tylka, Daniel; Trogdon, Gavin; Wahl, James K

    2010-01-01

    Squamous cell carcinoma (oral SCC) is the most common oral cancer in the U.S., affecting nearly 30,000 Americans each year. Despite recent advances in detection and treatment, there has been little improvement in the five-year survival rate for this devastating disease. Oral cancer may be preceded by premalignant disease that appears histologically as dysplasia. Identification of molecular markers for cellular change would assist in determining the risk of dysplasia progressing to oral squamous cell carcinoma. The goal of this study was to determine if any correlation exists between histological diagnosed dysplasia and OSCC lesions and altered expression of desmosomal cell-cell adhesion molecules in the oral epithelium. Our data showed that oral SCC tissue samples showed decreased immunoreactivity of both desmoplakin and plakophilin-1 proteins compared to normal oral epithelium. Furthermore, significant decrease in desmoplakin immunoreactivity was observed in dysplastic tissue compared to normal oral epithelium. In contrast, the level of desmoglein-1 staining was unchanged between samples however desmoglein-1 was found localized to cell borders in oral SCC samples. These data suggest that changes in expression of desmoplakin and plakophilin-1 may prove to be a useful marker for changes in tissue morphology and provide a tool for identifying pre-neoplastic lesions of the oral cavity. PMID:20585603

  17. Tissue regeneration with photobiomodulation

    NASA Astrophysics Data System (ADS)

    Tang, Elieza G.; Arany, Praveen R.

    2013-03-01

    Low level light therapy (LLLT) has been widely reported to reduce pain and inflammation and enhance wound healing and tissue regeneration in various settings. LLLT has been noted to have both stimulatory and inhibitory biological effects and these effects have been termed Photobiomodulation (PBM). Several elegant studies have shown the key role of Cytochrome C oxidase and ROS in initiating this process. The downstream biological responses remain to be clearly elucidated. Our work has demonstrated activation of an endogenous latent growth factor complex, TGF-β1, as one of the major biological events in PBM. TGF-β1 has critical roles in various biological processes especially in inflammation, immune responses, wound healing and stem cell biology. This paper overviews some of the studies demonstrating the efficacy of PBM in promoting tissue regeneration.

  18. HIV is inactivated after transepithelial migration via adult oral epithelial cells but not fetal epithelial cells

    PubMed Central

    Tugizov, Sharof M.; Herrera, Rossana; Veluppillai, Piri; Greenspan, Deborah; Soros, Vanessa; Greene, Warner C.; Levy, Jay A.; Palefsky, Joel M.

    2010-01-01

    Oral transmission of human immunodeficiency virus (HIV) in adult populations is rare. However, HIV spread across fetal/neonatal oropharyngeal epithelia could be important in mother-to-child transmission. Analysis of HIV transmission across polarized adult and fetal oral epithelial cells revealed that HIV transmigrates through both adult and fetal cells. However, only virions that passed through the fetal cells – and not those that passed through the adult cells – remained infectious. Analysis of expression of anti-HIV innate proteins beta-defensins 2 and 3, and secretory leukocyte protease inhibitor in adult, fetal, and infant oral epithelia showed that their expression is predominantly in the adult oral epithelium. Retention of HIV infectivity after transmigration correlated inversely with the expression of these innate proteins. Inactivation of innate proteins in adult oral keratinocytes restored HIV infectivity. These data suggest that high-level innate protein expression may contribute to the resistance of the adult oral epithelium to HIV transmission. PMID:21056450

  19. Reprogramming for cardiac regeneration

    PubMed Central

    Raynaud, Christophe Michel; Ahmad, Faizzan Syed; Allouba, Mona; Abou-Saleh, Haissam; Lui, Kathy O.; Yacoub, Magdi

    2014-01-01

    Treatment of cardiovascular diseases remains challenging considering the limited regeneration capacity of the heart muscle. Developments of reprogramming strategies to create in vitro and in vivo cardiomyocytes have been the focus point of a considerable amount of research in the past decades. The choice of cells to employ, the state-of-the-art methods for different reprogramming strategies, and their promises and future challenges before clinical entry, are all discussed here. PMID:25763379

  20. Regenerable adsorption system

    NASA Technical Reports Server (NTRS)

    Roychoudhury, Subir (Inventor); Perry, Jay (Inventor); Walsh, Dennis (Inventor)

    2006-01-01

    A method for regenerable adsorption includes providing a substrate that defines at least one layer of ultra short channel length mesh capable of conducting an electrical current therethrough, coating at least a portion of the substrate with a desired sorbent for trace contaminant control or CO.sub.2 sorption, resistively heating the substrate, and passing a flowstream through the substrate and in contact with the sorbent.

  1. Can MMP-9 be a Prognosticator Marker for Oral Squamous Cell Carcinoma?

    PubMed Central

    Basu, Shiva Kumar; Kumar, Manish

    2016-01-01

    Introduction Invasion and metastasis of malignant tumours severely endanger the life of cancer patients. Squamous cell carcinoma is one of the commonly found malignancies in the oral cavity and its survival rate has not improved from past few decades. Since an important risk factor for oral squamous cell carcinoma is the presence of epithelial dysplasia, it is necessary to check the presence of a prognosticator marker in both of them. As matrix metalloproteinase’s (MMP’s) are involved in degradation of type IV collagen, which are one of the important components of extracellular matrix components which play a relevant role in several steps of tumour progression such as invasion and metastasis. We have studied MMP-9 expression to evaluate its prognostic potential in oral cancers as well as oral epithelial dysplasia along with tissues of normal oral epithelium. Materials and Methods The expression was examined using immunohistochemistry procedure with MMP-9 in 100 samples including cases of epithelium from normal oral mucosa, oral dysplastic lesions and oral squamous cell carcinoma. One set of formalin fixed, paraffin embedded sections of the three categories were stained by haematoxylin and eosin. The sections were then evaluated under microscope. Data was examined for statistical significance using SPSS 13.0 by Mann-Whitney Test and Kruskal-Wallis Test. Results With MMP-9 gain of expression was noted from Control group to oral squamous cell carcinoma. Cytoplasmic staining was seen with MMP-9. Statistically highly significant differences were seen between oral epithelial dysplasia and oral squamous cell carcinoma and statistically significant differences were found between the control group and the oral squamous cell carcinoma group. Conclusion This study suggested that oral squamous cell carcinoma shows higher MMP-9 expression as compared to oral epithelial dysplasia followed by epithelium from normal oral mucosa. However, no correlation was found among the

  2. THE ROLE OF EPITHELIUM IN EXPERIMENTAL IMMUNIZATION.

    PubMed

    Sewall, H

    1925-10-01

    When a small amount of blood serum is dropped into the nose of a guinea pig the serum is absorbed by the mucous membrane and, after a definite period of incubation, the animal can be shown to have become profoundly changed. Depending upon the number of instillations, the interval between them and, especially, the quantity of serum instilled, the animal becomes either highly hypersensitive or strongly resistant to a toxic injection given by the vein. This resistance withstands a considerable series of increasing toxic injections and is strengthened with lapse of time,-contrary to the state of tolerance produced by traumatic methods. It is inferred that the absorption of foreign protein by the nose causes the formation of two different antibodies. One of these is allergic and excites to anaphylaxis; the other is protective and leads to true immuuity. The relative amount of either antibody can be regulated by modifying the amount of serum instilled. Added to a state of general allergy it is easy to produce, in the guinea pig, a special sensitization of the respiratory apparatus which leads, under appropriate stimulation, to attacks resembling those of bronchial asthma in man. No conclusion can be drawn at present concerning the nature or mode of action of the protective or immunizing antibody; but the indications are that its relations to the circulation and to tissue fixation resemble those which have been developed by other investigators in regard to the anaphylactic antibody. Evidence has been submitted that the living epithelium mediates between foreign protein and the organism in a way to favor specifically the elaboration of true immunity. PMID:17748743

  3. Transcriptome analysis of the planarian eye identifies ovo as a specific regulator of eye regeneration

    PubMed Central

    Lapan, Sylvain W.; Reddien, Peter W.

    2013-01-01

    Summary Among the millions of invertebrate species with visual systems, the genetic basis of eye development and function is well understood only in Drosophila melanogaster. We describe an eye transcriptome for the planarian Schmidtea mediterranea. Planarian photoreceptors expressed orthologs of genes required for phototransduction and microvillus structure in Drosophila and vertebrates, and optic pigment cells expressed solute transporters and melanin synthesis enzymes similar to those active in the vertebrate retinal pigment epithelium. Orthologs of several planarian eye genes, such as bestrophin-1 and Usher syndrome genes, cause eye defects in mammals when perturbed and were not previously described to have roles in invertebrate eyes. Five previously undescribed planarian eye transcription factors were required for normal eye formation during head regeneration. In particular, a conserved, transcription factor-encoding ovo gene was expressed from the earliest stages of eye regeneration and was required for regeneration of all cell types of the eye. PMID:22884275

  4. The role of the epithelium in airway remodeling in asthma.

    PubMed

    Davies, Donna E

    2009-12-01

    The bronchial epithelium is the barrier to the external environment and plays a vital role in protection of the internal milieu of the lung. It functions within the epithelial-mesenchymal trophic unit to control the local microenvironment and help maintain tissue homeostasis. However, in asthma, chronic perturbation of these homeostatic mechanisms leads to alterations in the structure of the airways, termed remodeling. Damage to the epithelium is now recognized to play a key role in driving airway remodeling. We have postulated that epithelial susceptibility to environmental stress and injury together with impaired repair responses results in generation of signals that act on the underlying mesenchyme to propagate and amplify inflammatory and remodeling responses in the submucosa. Many types of challenges to the epithelium, including pathogens, allergens, environmental pollutants, cigarette smoke, and even mechanical forces, can elicit production of mediators by the epithelium, which can be translated into remodeling responses by the mesenchyme. Several important mediators of remodeling have been identified, most notably transforming growth factor-beta, which is released from damaged/repairing epithelium or in response to inflammatory mediators, such as IL-13. The cross talk between the epithelium and the underlying mesenchyme to drive remodeling responses is considered in the context of subepithelial fibrosis and potential pathogenetic mechanisms linked to the asthma susceptibility gene, a disintegrin and metalloprotease (ADAM)33. PMID:20008875

  5. Bone morphogenetic protein signaling promotes morphogenesis of blood vessels, wound epidermis, and actinotrichia during fin regeneration in zebrafish.

    PubMed

    Thorimbert, Valentine; König, Désirée; Marro, Jan; Ruggiero, Florence; Jaźwińska, Anna

    2015-10-01

    Zebrafish fin regeneration involves initial formation of the wound epidermis and the blastema, followed by tissue morphogenesis. The mechanisms coordinating differentiation of distinct tissues of the regenerate are poorly understood. Here, we applied pharmacologic and transgenic approaches to address the role of bone morphogenetic protein (BMP) signaling during fin restoration. To map the BMP transcriptional activity, we analyzed the expression of the evolutionarily conserved direct phospho-Smad1 target gene, id1, and its homologs id2a and id3. This analysis revealed the BMP activity in the distal blastema, wound epidermis, osteoblasts, and blood vessels of the regenerate. Blocking the BMP function with a selective chemical inhibitor of BMP type I receptors, DMH1, suppressed id1 and id3 expression and arrested regeneration after blastema formation. We identified several previously uncharacterized functions of BMP during fin regeneration. Specifically, BMP signaling is required for remodeling of plexus into structured blood vessels in the rapidly growing regenerate. It organizes the wound epithelium by triggering wnt5b expression and promoting Collagen XIV-A deposition into the basement membrane. BMP represents the first known signaling that induces actinotrichia formation in the regenerate. Our data reveal a multifaceted role of BMP for coordinated morphogenesis of distinct tissues during regeneration of a complex vertebrate appendage. PMID:26148971

  6. Biological activity of celecoxib in the bronchial epithelium of current and former smokers.

    PubMed

    Kim, Edward S; Hong, Waun K; Lee, J Jack; Mao, Li; Morice, Rodolfo C; Liu, Diane D; Jimenez, Carlos A; Eapen, Georgie A; Lotan, Reuben; Tang, Ximing; Newman, Robert A; Wistuba, Ignacio I; Kurie, Jonathan M

    2010-02-01

    Non-small cell lung cancer is the primary cause of cancer-related death in Western countries. One important approach taken to address this problem is the development of effective chemoprevention strategies. In this study, we examined whether the cyclooxygenase-2 inhibitor celecoxib, as evidenced by decreased cell proliferation, is biologically active in the bronchial epithelium of current and former smokers. Current or former smokers with at least a 20 pack-year (pack-year = number of packs of cigarettes per day times number of years smoked) smoking history were randomized into one of four treatment arms (3-month intervals of celecoxib then placebo, celecoxib then celecoxib, placebo then celecoxib, or placebo then placebo) and underwent bronchoscopies with biopsies at baseline, 3 months, and 6 months. The 204 patients were primarily (79.4%) current smokers: 81 received either low-dose celecoxib or placebo and 123 received either high-dose celecoxib or placebo. Celecoxib was originally administered orally at 200 mg twice daily and the protocol subsequently increased the dose to 400 mg twice daily. The primary end point was change in Ki-67 labeling (from baseline to 3 months) in bronchial epithelium. No cardiac toxicities were observed in the participants. Although the effect of low-dose treatment was not significant, high-dose celecoxib decreased Ki-67 labeling by 3.85% in former smokers and by 1.10% in current smokers-a significantly greater reduction (P = 0.02) than that seen with placebo after adjusting for metaplasia and smoking status. A 3- to 6-month celecoxib regimen proved safe to administer. Celecoxib (400 mg twice daily) was biologically active in the bronchial epithelium of current and former smokers; additional studies on the efficacy of celecoxib in non-small cell lung cancer chemoprevention may be warranted. PMID:20103722

  7. Gene-expression analysis of hair cell regeneration in the zebrafish lateral line.

    PubMed

    Jiang, Linjia; Romero-Carvajal, Andres; Haug, Jeff S; Seidel, Christopher W; Piotrowski, Tatjana

    2014-04-01

    Deafness caused by the terminal loss of inner ear hair cells is one of the most common sensory diseases. However, nonmammalian animals (e.g., birds, amphibians, and fish) regenerate damaged hair cells. To understand better the reasons underpinning such disparities in regeneration among vertebrates, we set out to define at high resolution the changes in gene expression associated with the regeneration of hair cells in the zebrafish lateral line. We performed RNA-Seq analyses on regenerating support cells purified by FACS. The resulting expression data were subjected to pathway enrichment analyses, and the differentially expressed genes were validated in vivo via whole-mount in situ hybridizations. We discovered that cell cycle regulators are expressed hours before the activation of Wnt/β-catenin signaling following hair cell death. We propose that Wnt/β-catenin signaling is not involved in regulating the onset of proliferation but governs proliferation at later stages of regeneration. In addition, and in marked contrast to mammals, our data clearly indicate that the Notch pathway is significantly down-regulated shortly after injury, thus uncovering a key difference between the zebrafish and mammalian responses to hair cell injury. Taken together, our findings lay the foundation for identifying differences in signaling pathway regulation that could be exploited as potential therapeutic targets to promote either sensory epithelium or hair cell regeneration in mammals. PMID:24706903

  8. Posterior regeneration following fission in the holothurian Cladolabes schmeltzii (Dendrochirotida: Holothuroidea).

    PubMed

    Kamenev, Yaroslav O; Dolmatov, Igor Yu

    2015-07-01

    The regeneration of the posterior portion of the body after fission was studied in the holothurian Cladolabes schmeltzii using electron microscopy methods. Following fission, the aquapharyngeal complex, gonad and anterior portion of the first descending part of the intestine remain in the anterior fragment of the body. The entire regeneration process is divided into five stages. In the first three stages, the digestive system and damaged ends of the longitudinal muscle bands regenerate. The intestine is formed through the rearrangement and growth of the remaining portion of the first descending part of the intestine. The gut anlage grows down the mesentery and joins the regenerating cloaca. The cloaca is formed from two sources: its posterior portion appears as a result of immersion of the epidermis, while the anterior portion develops from the terminal segment of the growing intestine. Regeneration of muscles progresses in the typical manner for echinoderms: through immersion and myogenic transformation of the coelomic epithelium. Respiratory trees appear in animals when the growth of the external part of the body has begun (fourth stage). They are formed as an outgrowth of the dorsal wall of the anterior portion of the cloaca. It was concluded that regeneration of the posterior portion of the body in the holothurian C. schmeltzii following fission is realized through morphallactic rearrangements of the remaining parts of organs. The main mechanism through which the digestive, respiratory, and contractile systems are formed is epithelial morphogenesis. PMID:25921295

  9. Effortless effort in bone regeneration: a review.

    PubMed

    Nazirkar, Girish; Singh, Shailendra; Dole, Vinaykumar; Nikam, Akhilesh

    2014-06-01

    Since the beginning of the 20th century, the concept of osteoconduction in bony changes in the oral cavity showed a wide range of biomaterials and their osteoinductive potential that emerged gradually and has to a large extent improved the quality of the bone prior to the placement of an implant. Alveolar bone loss is a major concern after tooth extraction in patients and therefore atraumatic extraction procedures should be followed to avoid further bone loss. To overcome the alveolar bone loss and to augment support for placing dental implants, many bone regenerative substitutes are available such as allografts, autografts, xenografts, synthetic biomaterials and osteoactive agents. In light of the steady progress in bone grafting techniques and graft materials, it has become possible to improve the volume, width, and height of bone in deficient areas of the oral cavity. These advances in regenerative dentistry thus facilitate an easy and convenient placement of an implant in an ideal position and angulations resulting in superior esthetics and function. Bone grafting materials and their substitutes are the alternative filler materials, which facilitate to reduce additional surgical procedures, risks, chances of cross infection involved in placing autografts and allografts into the bony structures. This review literature highlights various biomaterials that are helpful in bone healing and thus create an anatomically favorable base for ideal implant placement. How to cite the article: Nazirkar G, Singh S, Dole V, Nikam A. Effortless effort in bone regeneration: A review. J Int Oral Health 2014;6(3):120-4. PMID:25083047

  10. Effortless Effort in Bone Regeneration: A Review

    PubMed Central

    Nazirkar, Girish; Singh, Shailendra; Dole, Vinaykumar; Nikam, Akhilesh

    2014-01-01

    Since the beginning of the 20th century, the concept of osteoconduction in bony changes in the oral cavity showed a wide range of biomaterials and their osteoinductive potential that emerged gradually and has to a large extent improved the quality of the bone prior to the placement of an implant. Alveolar bone loss is a major concern after tooth extraction in patients and therefore atraumatic extraction procedures should be followed to avoid further bone loss. To overcome the alveolar bone loss and to augment support for placing dental implants, many bone regenerative substitutes are available such as allografts, autografts, xenografts, synthetic biomaterials and osteoactive agents. In light of the steady progress in bone grafting techniques and graft materials, it has become possible to improve the volume, width, and height of bone in deficient areas of the oral cavity. These advances in regenerative dentistry thus facilitate an easy and convenient placement of an implant in an ideal position and angulations resulting in superior esthetics and function. Bone grafting materials and their substitutes are the alternative filler materials, which facilitate to reduce additional surgical procedures, risks, chances of cross infection involved in placing autografts and allografts into the bony structures. This review literature highlights various biomaterials that are helpful in bone healing and thus create an anatomically favorable base for ideal implant placement. How to cite the article: Nazirkar G, Singh S, Dole V, Nikam A. Effortless effort in bone regeneration: A review. J Int Oral Health 2014;6(3):120-4. PMID:25083047

  11. Live imaging of baculovirus infection of midgut epithelium cells: a functional assay of per os infectivity factors.

    PubMed

    Mu, Jingfang; van Lent, Jan W M; Smagghe, Guy; Wang, Yun; Chen, Xinwen; Vlak, Just M; van Oers, Monique M

    2014-11-01

    The occlusion-derived viruses (ODVs) of baculoviruses are responsible for oral infection of insect hosts, whereas budded viruses (BVs) are responsible for systemic infection within the host. The ODV membrane proteins play crucial roles in mediating virus entry into midgut epithelium cells to initiate infection and are important factors in host-range determination. For Autographa californica multiple nucleopolyhedrovirus (AcMNPV), seven conserved ODV membrane proteins have been shown to be essential for oral infectivity and are called per os infectivity factors (PIFs). Information on the function of the individual PIF proteins in virus entry is limited, partly due to the lack of a good in vitro system for monitoring ODV entry. Here, we constructed a baculovirus with EGFP fused to the nucleocapsid to monitor virus entry into primary midgut epithelium cells ex vivo using confocal fluorescence microscopy. The EGFP-labelled virus showed similar BV virulence and ODV infectivity as WT virus. The ability to bind and enter host cells was then visualized for WT AcMNPV and viruses with mutations in P74 (PIF0), PIF1 or PIF2, showing that P74 is required for ODV binding, whilst PIF1 and PIF2 play important roles in the entry of ODV after binding to midgut cells. This is the first live imaging of ODV entry into midgut cells and complements the genetic and biochemical evidence for the role of PIFs in the oral infection process. PMID:25006078

  12. Dynamic Regulation of Wnt7a Expression in the Primate Endometrium: Implications for Postmenstrual Regeneration and Secretory Transformation

    PubMed Central

    Fan, Xiujun; Krieg, Sacha; Hwang, Jong Yun; Dhal, Sabita; Kuo, Calvin J.; Lasley, Bill L.; Brenner, Robert M.

    2012-01-01

    Despite the vital physiological role of endometrial regeneration during the menstrual cycle and the various pathological implications of abnormal growth of endometrial epithelial cells, the local factors and regulatory mechanisms involved in endometrial regeneration and growth have not been well characterized. Here, we examine the pattern, hormone dependence, and potential functions of Wnt7a (wingless-type MMTV integration site family member 7a), which is known to play a critical role in the formation of the mouse endometrial epithelium during embryonic development, in both human and artificially cycling rhesus macaque endometrium, and using a potent Wnt-antagonist in a mouse model of endometrial regeneration. Wnt7a transcript levels were examined using quantitative real-time PCR and in situ hybridization, and immunohistochemistry was performed to detect Ki-67 and 3,5-bromodeoxyuridine. Stringent, fully conditional Wnt inhibition was achieved by adenoviral expression of Dickkopf-1 during artificial endometrial regeneration in mice. In macaques, Wnt7a expression was confined to the newly formed luminal epithelium (LE) and upper glands during the postmenstrual repair phase. The signal increased in the LE during the proliferative phase but decreased in the upper glands and was undetectable in the glands by the late proliferative phase. Interestingly, Wnt7a was completely suppressed in the LE and remained undetectable in other cell types after 7 d of progesterone treatment. The pattern of Wnt7a expression in the human endometrium was similar to that in macaques. Blockade of Wnt signaling during endometrial regeneration in mice resulted in a dramatic delay in reepithelialization and degeneration of glands and LE. These results strongly suggest, for the first time, a role for Wnt7a in postmenstrual regeneration and proliferation of endometrial glands and LE in primates, and its dramatic suppression by progesterone is likely essential for secretory transformation of the

  13. Regenerating Water-Sterilizing Resins

    NASA Technical Reports Server (NTRS)

    Colombo, G. V.; Putnam, D. F.

    1982-01-01

    Iodine-dispensing resin can be regenerated after iodine content has been depleted, without being removed from water system. Resin is used to make water potable by killing bacteria, fungi, and viruses. Regeneration technique may be come basis of water purifier for very long space missions. Enough crystalline iodine for multiple regenerations during mission can be stored in one small cartridge. Cartridge could be inserted in waterline as necessary on signal from iodine monitor or timer.

  14. Intrinsic Control of Axon Regeneration.

    PubMed

    He, Zhigang; Jin, Yishi

    2016-05-01

    A determinant of axon regeneration is the intrinsic growth ability of injured neurons, which dictates a battery of injury responses in axons and cell bodies. While some of these regulatory mechanisms are evolutionarily conserved, others are unique to the mammalian central nervous system (CNS) where spontaneous regeneration usually does not occur. Here we examine our current understanding of these mechanisms at cellular and molecular terms and discuss their potential implications for promoting axon regeneration and functional recovery after nerve injury. PMID:27151637

  15. M cell-depletion blocks oral prion disease pathogenesis.

    PubMed

    Donaldson, D S; Kobayashi, A; Ohno, H; Yagita, H; Williams, I R; Mabbott, N A

    2012-03-01

    Many prion diseases are orally acquired. Our data show that after oral exposure, early prion replication upon follicular dendritic cells (FDC) in Peyer's patches is obligatory for the efficient spread of disease to the brain (termed neuroinvasion). For prions to replicate on FDC within Peyer's patches after ingestion of a contaminated meal, they must first cross the gut epithelium. However, the mechanism through which prions are conveyed into Peyer's patches is uncertain. Within the follicle-associated epithelium overlying Peyer's patches are microfold cells (M cells), unique epithelial cells specialized for the transcytosis of particles. We show that following M cell-depletion, early prion accumulation upon FDC in Peyer's patches is blocked. Furthermore, in the absence of M cells at the time of oral exposure, neuroinvasion and disease development are likewise blocked. These data suggest M cells are important sites of prion uptake from the gut lumen into Peyer's patches. PMID:22294048

  16. Oral heparins.

    PubMed

    Hiebert, Linda M

    2002-01-01

    The antithrombotic drug heparin is administered parenterally and believed not effective orally. Oral heparin would be most suitable for long term administration, often required for the prevention of thrombosis. Following parenteral administration, heparin is taken up by endothelial cells. Our laboratory has shown that heparin is similarly taken up by endothelium following oral administration, despite low plasma heparin concentrations. In a twenty-four hour period, endothelial heparin concentrations are greatest within 15 minutes of oral dosing although plasma levels never exceed one percent of dose. Endothelial uptake accounts for a considerable amount of absorption if the total body endothelium is considered. In support of oral heparin absorption, we demonstrated a dose-dependent decrease in thrombosis incidence in a rat jugular vein model following single oral doses of unfractionated heparins (bovine and porcine) or low molecular weight heparins (reviparin, logiparin and ardeparin). Low molecular weight heparins were effective at lower doses than unfractionated heparins where a fifty percent reduction in thrombosis was observed with 0.025 mg/kg reviparin, 0.1 mg/kg logiparin, versus 7.5 mg/kg bovine unfractionated heparin. These studies support the work of others demonstrating measurable systemic changes following oral heparin administration and suggest that heparin may be effective when administered by the oral route. It also indicates that the presence of heparin in plasma likely reflects a much greater amount associated with endothelium. PMID:11934211

  17. Oral Cancer

    MedlinePlus

    ... Main Content National Institute of Dental and Craniofacial Research (NIDCR) Improving the Nation's Oral Health National Institutes of Health Español Staff Directory A–Z Index Search Text size: Website Contents NIDCR Home Oral Health Diseases and Conditions Gum ...

  18. Oral Herpes

    MedlinePlus

    ... Main Content National Institute of Dental and Craniofacial Research (NIDCR) Improving the Nation's Oral Health National Institutes of Health Español Staff Directory A–Z Index Search Text size: Website Contents NIDCR Home Oral Health Diseases and Conditions Gum ...

  19. Oral cysticercosis.

    PubMed

    Chunduri, Nagendra S; Goteki, Venkateswarulu; Gelli, Vamsi; Madasu, Krishnaveni

    2013-03-01

    Cysticercosis is a common disease in developing countries, but oral lesions caused by this parasitic infestation are rare. We report here a rare case of oral cysticercosis in a 17 year old male who sought treatment for an asymptomatic nodule of the lower lip that had previously been diagnosed as a mucocele. PMID:23691623

  20. Oral Testing.

    ERIC Educational Resources Information Center

    de Charruf, Laurie Frey

    1984-01-01

    Oral tests for speaking skills evaluate two major skills: linguistic competence, including accuracy of pronunciation, vocabulary, and structure, and communication ease. Four factors affect students' oral performance: verbal intelligence, short-term auditory and visual memory, sound-symbol association skill, and grammatical analysis. Personality…

  1. Synthetic Phage for Tissue Regeneration

    PubMed Central

    Merzlyak, Anna; Lee, Seung-Wuk

    2014-01-01

    Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy. PMID:24991085

  2. Understanding Urban Regeneration in Turkey

    NASA Astrophysics Data System (ADS)

    Candas, E.; Flacke, J.; Yomralioglu, T.

    2016-06-01

    In Turkey, rapid population growth, informal settlements, and buildings and infrastructures vulnerable to natural hazards are seen as the most important problems of cities. Particularly disaster risk cannot be disregarded, as large parts of various cities are facing risks from earthquakes, floods and landslides and have experienced loss of lives in the recent past. Urban regeneration is an important planning tool implemented by local and central governments in order to reduce to disaster risk and to design livable environments for the citizens. The Law on the Regeneration of Areas under Disaster Risk, commonly known as the Urban Regeneration Law, was enacted in 2012 (Law No.6306, May 2012). The regulation on Implementation of Law No. 6306 explains the fundamental steps of the urban regeneration process. The relevant institutions furnished with various authorities such as expropriation, confiscation and changing the type and place of your property which makes urban regeneration projects very important in terms of property rights. Therefore, urban regeneration projects have to be transparent, comprehensible and acceptable for all actors in the projects. In order to understand the urban regeneration process, the legislation and projects of different municipalities in Istanbul have been analyzed. While some steps of it are spatial data demanding, others relate to land values. In this paper an overview of the urban regeneration history and activities in Turkey is given. Fundamental steps of the urban regeneration process are defined, and particularly spatial-data demanding steps are identified.

  3. Oral cenesthopathy.

    PubMed

    Umezaki, Yojiro; Miura, Anna; Watanabe, Motoko; Takenoshita, Miho; Uezato, Akihito; Toriihara, Akira; Nishikawa, Toru; Toyofuku, Akira

    2016-01-01

    Cenesthopathy is characterized by abnormal and strange bodily sensations and is classified as a 'delusional disorder, somatic type' or 'somatoform disorder' according to the DSM 5. The oral cavity is one of the frequent sites of cenesthopathy, thus the term 'oral cenesthopathy.' Patients with oral cenesthopathy complain of unusual sensations without corresponding abnormal findings in the oral area, such as excessive mucus secretion, a slimy sensation, or a feeling of coils or wires being present within the oral region. They usually visit multiple dentists rather than psychiatrists. Without a proper diagnosis, they repeatedly pursue unnecessary surgical procedures to remove their 'foreign body'. This sometimes creates a dilemma between the dentists and patients. The nosography of oral cenesthopathy has been discussed in some case reports and reviews but is overlooked in mainstream medicine. This review focuses on the various aspects of oral cenesthopathy. The estimated prevalence of cenesthopathy was 0.2 to 1.9 % in a study done at a Japanese university psychiatry clinic and 27 % in a study done at a Japanese psychosomatic dentistry clinic. Oral cenesthopathy do not have clear disposition, while some studies reported that elderly women were most commonly affected. Its pathophysiology has not been fully elucidated. However, recent studies have suggested a right > left asymmetrical pattern of the cerebral blood flow of patients with oral cenesthopathy. Antidepressants, antipsychotic drugs, electroconvulsive therapy, and psychotherapy might be effective in some cases, though it is known to be intractable. To date, the epidemiology, pathophysiology, etiology, classification and treatment of oral cenesthopathy are unknown due to the few reports on the disorder, though there are a few case reports. To overcome this difficult medical condition, clinico-statistical and case-control studies done under rigorous criteria and with a large sample size are required. PMID

  4. Closed end regeneration method

    DOEpatents

    Yang, Arthur Jing-Min; Zhang, Yuehua

    2006-06-27

    A nanoporous reactive adsorbent incorporates a relatively small number of relatively larger reactant, e.g. metal, enzyme, etc. particles (10) forming a discontinuous or continuous phase interspersed among and surrounded by a continuous phase of smaller adsorbent particles (12) and connected interstitial pores (14) therebetween. The reactive adsorbent can effectively remove inorganic or organic impurities in a liquid by causing the liquid to flow through the adsorbent. For example, silver ions may be adsorbed by the adsorbent particles (12) and reduced to metallic silver by reducing metal, such as irons, as the reactant particles (10). The column can be regenerated by backwashing with the liquid effluent containing, for example, acetic acid.

  5. Regenerable solid imine sorbents

    DOEpatents

    Gray, McMahan; Champagne, Kenneth J.; Fauth, Daniel; Beckman, Eric

    2013-09-10

    Two new classes of amine-based sorbents are disclosed. The first class comprises new polymer-immobilized tertiary amine sorbents; the second class new polymer-bound amine sorbents. Both classes are tailored to facilitate removal of acid anhydrides, especially carbon dioxide (CO.sub.2), from effluent gases. The amines adsorb acid anhydrides in a 1:1 molar ratio. Both classes of amine sorbents adsorb in the temperature range from about 20.degree. C. upwards to 90.degree. C. and can be regenerated by heating upwards to 100.degree. C.

  6. Novel ebullated bed catalyst regeneration technology improves regenerated catalyst quality

    SciTech Connect

    Neuman, D.J.

    1995-09-01

    Regeneration of spent hydroprocessing catalysts has long been practiced by the refining industry. With increased pressures on refiners to reduce catalyst expenditures and waste generation, refiners are more frequently reusing spent hydroprocessing catalysts after ex-situ regeneration to restore catalytic activity. By reusing regenerated catalyst for at least two cycles, the refiner reduces catalyst waste by at least one-half. As environmental laws become more restrictive, spent hydroprocessing catalyst is more likely to be classified as hazardous waste. Disposal of spent catalyst, which was previously accomplished by landfilling, now requires more expensive reclamation techniques. TRICAT has introduced the TRICAT Regeneration Process (TRP), a novel ebullated bed regeneration plant, to improve the catalyst regeneration process. The ebullated bed design allows for better control of heat release during the regeneration process. As a result, the regeneration can be accomplished in a single-pass, with improved catalyst activity retention. Catalyst losses are also minimized due to reduced catalyst handling. Commercial results from the TRP have demonstrated successful scale-up of the technology from pilot scale. The plant has achieved complete recovery of the available catalyst activity with little or no losses in catalyst yield or extrudate length. The flexibility of the TRP to process a variety of catalysts is also discussed.

  7. Regeneration of desiccants with solar energy

    SciTech Connect

    Ghate, S.R.; Butts, C.L.; Lown, J.B.

    1985-01-01

    Saturated silica gel was regenerated with solar energy. This paper describes the experimental set-up for silica gel regeneration and data collection. The regenerated silica gel can be used to dry high moisture in-shell pecans.

  8. Evaluation of cell proliferation in malignant and potentially malignant oral lesions

    PubMed Central

    Madan, Mani; Chandra, Shaleen; Raj, Vineet; Madan, Rohit

    2015-01-01

    Aims: To evaluate the cell proliferation rate by the expression of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizing region (AgNOR) counts and to assess its usefulness as a marker for malignant potential in oral epithelial lesions. Materials and Methods: The study group included 30 cases of leukoplakia, 15 nondysplastic (NDL), 15 dysplastic (DL), 15 cases of oral squamous cell carcinoma (OSCC) and 5 cases of normal oral mucosa. Formalin fixed paraffin embedded tissues were subjected to immunohistochemical staining for PCNA and AgNOR technique. The PCNA labeling index (LI) and the AgNOR dots were evaluated for the entire sample. Statistical Analysis Used: ANOVA, Tukey honestly significant difference, Pearson's correlation. Results: In this study, the AgNOR count of OSCC was lower than the DL lesions moreover the AgNOR counts were found to be higher in normal mucosa as compared to the DL and the NDL epithelium. The study results also showed that the mean AgNOR count failed to distinguish between DL and NDL lesions. Overall we observed increased PCNA expression from normal epithelium to NDL to DL lesion. Conclusions: Based on the findings of the present study on oral epithelial precancerous and cancerous lesions we conclude that mean AgNOR count alone cannot be a valuable parameter to distinguish between the normal, NDL, DL epithelium and OSCC but, on the other hand, we found out that PCNA can be a useful biomarker for delineating normal epithelium from DL epithelium and OSCC. PMID:26980956

  9. Meckel's diverticulum and ectopic epithelium: Evaluation of a complex relationship

    PubMed Central

    Burjonrappa, Sathyaprasad; Khaing, Phue

    2014-01-01

    Introduction: Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract. Currently, for any incidentally discovered Meckel's diverticulum, the management approach is based on weighing the statistical odds of future complications against the risks of a diverticulectomy. Materials and Methods: The temporal relationship between age at Meckel's diverticulectomy and the presence of ectopic epithelium was evaluated in our series. A meta-analysis of all reported recent literature on this condition was subsequently performed to evaluate the strength of the relationship between ectopic epithelium and symptomatic Meckel's diverticulum. Results: There was a paucity of ectopic epithelium in Meckel's diverticulectomy specimens in infants operated on at less than 1 year of age. Having two or more ectopic epithelia in a diverticulum does not appear to carry an additive risk for complications. The meta-analysis confirmed that ectopic epithelium was the most significant factor that influenced surgical intervention in all series of Meckel's diverticulum. Conclusion: The relationship between ectopic epithelium and the development of symptomatic Meckel's diverticulum is complex. Further understanding of the development of ectopic rests in the diverticulum will facilitate elucidating the pathophysiology in symptomatic cases. PMID:24741211

  10. Histopathological study on changes of bronchial epithelium among chromate workers

    SciTech Connect

    Mikami, H.

    1982-09-01

    There have been many reports on lung cancer among chromate workers. Chromate compounds are thought to be a carcinogen and lung cancer among chromate workers is considered one of the occupational lung cancers. Recently, it is debated that metaplastic and hyperplastic changes of bronchial epithelium are revealed or not to the development of bronchogenic carcinoma. Histopathological study on changes of bronchial epithelium among chromate workers was performed in order to clarify the effect of chromate compounds to bronchial epithelium. The subjects were 14 cases of lung cancer among chromate workers. As a control, 18 cases of non cancer among chromate workers. Lung tissue which was obtained at necropsy or surgery was fixed by formalin and was produced cross-sections and was stained on Haematoxylin-Eosin. The results were as follows. 1. Of examined 235 cross-sections, basal cell hyperplasia of bronchial epithelium was found in 13 per cent. Squamous metaplasia was found in 29 per cent, on the contrary, atypical metaplastic changes were observed in 34 per cent. 2. Of four cases of carcinoma in situ and two cases of small invasive carcinoma, four cases revealed development from atypical squamous metaplasia to precancerous changes. 3. These cases developed invasive carcinoma from atypical squamous metaplasia for a long period, of which were found by successive exfoliative cytology of sputum. From these findings, it was concluded that inhalation of chromate dust affected bronchial epithelium and caused highly atypical squamous metaplasia which developed to carcinoma in situ and finally to invasive carcinoma.

  11. Regenerable Iodine Water-Disinfection System

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L.; Colombo, Gerald V.; Jolly, Clifford D.

    1994-01-01

    Iodinated resin bed for disinfecting water regenerated to extend useful life. Water flows through regeneration bed of crystalline iodine during regeneration. At other times, flow diverted around regeneration bed. Although regeneration cycle manually controlled readily automated to start and stop according to signals from concentration sensors. Further benefit of regeneration is bed provides highly concentrated biocide source when needed. Concentrated biocide used to superiodinate system after contamination from routine maintenance or unexpected introduction of large concentration of microbes.

  12. Bone Repair Cells for Craniofacial Regeneration

    PubMed Central

    Pagni, G; Kaigler, D; Rasperini, G; Avila-Ortiz, G; Bartel, R; Giannobile, WV

    2012-01-01

    Reconstruction of complex craniofacial deformities is a clinical challenge in situations of injury, congenital defects or disease. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound healing. Both Somatic and Stem Cells have been adopted in the treatment of complex osseous defects and advances have been made in finding the most adequate scaffold for the delivery of cell therapies in human regenerative medicine. As an example of such approaches for clinical application for craniofacial regeneration, Ixmyelocel-T or bone repair cells are a source of bone marrow derived stem and progenitor cells. They are produced through the use of single pass perfusion bioreactors for CD90+ mesenchymal stem cells and CD14+ monocyte/macrophage progenitor cells. The application of ixmyelocel-T has shown potential in the regeneration of muscular, vascular, nervous and osseous tissue. The purpose of this manuscript is to highlight cell therapies used to repair bony and soft tissue defects in the oral and craniofacial complex. The field at this point remains at an early stage, however this review will provide insights into the progress being made using cell therapies for eventual development into clinical practice. PMID:22433781

  13. Minor Salivary Gland Changes in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma - A Histopathological Study

    PubMed Central

    Chitturi, Ravi Teja; Ragunathan, Yoithapprabhunath Thukanayakanpalayam; Lakshmi, Suman Jhansi; Nallusamy, Jaisanghar; Joseph, Isaac

    2016-01-01

    Introduction The most common etiology for Oral Squamous Cell Carcinoma (OSCC) is tobacco and tobacco related products which cause nuclear damage to the keratinocytes. The chemical carcinogens not only affect the lining of oral epithelium but also affect the lining epithelium of the excretory ducts of the salivary glands. Thus, there is a possibility of epithelial dysplasia of the salivary duct epithelium which may lead to potential malignant transformation. Aim The study was performed to see the changes in the minor salivary glands and excretory ducts in cases of oral epithelial dysplasia and OSCC. Materials and Methods A total of 278 archival cases of mild, moderate and severe epithelial dysplasia, carcinoma in situ, OSCC including verrucous carcinoma were histopathologically evaluated to observe changes in the excretory ducts and the minor salivary glands. Results In the study there were 56.5% males and 43.5% females. The age group that was most commonly affected in both the sexes was 50-60 yr old. Buccal mucosa was the most common site of involvement. Ductal changes observed in the excretory duct include simple hyperplasia, metaplastic changes such as mucous, oncocytic & squamous, and infiltration of inflammatory cells and malignant cells. Acinar changes observed were degeneration, squamous metaplasia, myoepithelial cell proliferation and inflammatory cell infiltration. Both the excretory ducts and ducts within the gland showed dysplasia. Conclusion According to observations in our study it is suggested that histopathological interpretation for oral mucosal lesions especially oral epithelial dysplasias and OSCC should also include changes related to salivary gland tissue to provide a better treatment plan and prevent recurrence of the malignant tumours.

  14. [Mucoepidermoid carcinoma of maxillofacial and oral cavity].

    PubMed

    Byung, M

    1990-11-01

    Authors experienced a case of low grade mucoepidermoid carcinoma in 48-year-old female and a case of low grade central mucoepidermoid carcinoma in 51-year-old female, respectively. The former occurred in right mandibular angle and showed multilocular radiolucent area surrounded by sclerotic rim but perforation of cortical bone connected with tumor mass in oral cavity radiographically. The latter occurred in left mandibular angle and ramus. Radiographic feature showed large radiolucent area in left mandibular angle and ramus, and destruction of coronoid process but intact condylar process. The origin of the latter might be mucus secreting cells of lined epithelium in dentigerous epithelium. In two cases metastases were not found. PMID:2130125

  15. Divergent requirements for FGF signaling in zebrafish maxillary barbel and caudal fin regeneration

    PubMed Central

    Duszynski, Robert J.; Topczewski, Jacek; LeClair, Elizabeth E.

    2013-01-01

    The zebrafish maxillary barbel is an integumentary organ containing skin, glands, pigment cells, taste buds, nerves, and endothelial vessels. The maxillary barbel can regenerate (LeClair & Topczewski, 2010); however, little is know about its molecular regulation. We have studied FGF-related signaling molecules during barbel regeneration, comparing these to a well-known regenerating appendage, the zebrafish caudal fin. Multiple FGF ligands (fgf20a, fgf24), receptors (fgfr1–4) and downstream targets (pea3, il17d) are expressed in normal and regenerating barbel tissue, confirming FGF activation. To test if specific FGF pathways were required for barbel regeneration, we performed simultaneous barbel and caudal fin amputations in two temperature-dependent zebrafish lines. Zebrafish homozygous for a point mutation in fgf20a, a factor essential for caudal fin blastema formation, regrew maxillary barbels normally, indicating that the requirement for this ligand is appendage-specific. Global overexpression of a dominant negative FGF receptor, Tg(hsp70l:dn-fgfr1:EGFP)pd1 completely blocked fin outgrowth but only partially inhibited barbel outgrowth, suggesting reduced requirements for FGFs in barbel tissue. Maxillary barbels expressing dn-fgfr1 regenerated peripheral nerves, dermal connective tissue, endothelial tubes, and a glandular epithelium; in contrast to a recent report in which dn-fgfr1 overexpression blocks pharyngeal taste bud formation in zebrafish larvae (Kapsimali et al., 2011), we observed robust formation of calretinin-positive tastebuds. These are the first experiments to explore the molecular mechanisms of maxillary barbel regeneration. Our results suggest heterogeneous requirements for FGF signaling in the regeneration of different zebrafish appendages (caudal fin vs. maxillary barbel) and taste buds of different embryonic origin (pharyngeal endoderm vs. barbel ectoderm). PMID:23350700

  16. Oral Cancer Exam

    MedlinePlus Videos and Cool Tools

    ... Dental Research See All Continuing Education Practical Oral Care for People With Developmental Disabilities – This booklet presents ... developmental disabilities and offers strategies for providing oral care. NIDCR > OralHealth > Topics > Oral Cancer > Oral Cancer Exam ...

  17. Oral cancer

    MedlinePlus

    ... is advanced Other symptoms may include: Chewing problems Mouth sores that may bleed Pain with swallowing Speech difficulties ... Your doctor or dentist will examine your mouth area. The exam may ... bleeding Tests used to confirm oral cancer include: Gum biopsy ...

  18. Oral Health

    MedlinePlus

    ... its box has the American Dental Association's (ADA) seal of acceptance, it is good for your oral ... dispensed solutions have the American Dental Association (ADA) seal. Other over-the-counter whitening products include whitening ...

  19. Oral Cancer

    MedlinePlus

    ... use. Some oral cancers are linked to human papilloma virus (HPV) infections of the mouth and throat. ... The number of oropharyngeal cancers linked to human papilloma virus (HPV) has risen dramatically over the past ...

  20. Herpes - oral

    MedlinePlus

    ... virus type 2 (HSV-2) most often causes genital herpes . However, sometimes HSV-2 is spread to the ... the virus to the genitals. Both oral and genital herpes viruses can sometimes be spread, even when you ...

  1. Methylprednisolone Oral

    MedlinePlus

    ... Nizoral), oral contraceptives, phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), theophylline (Theo-Dur), and vitamins.if you have a ... stomach irritation vomiting headache dizziness insomnia restlessness depression anxiety acne increased hair growth easy bruising irregular or ...

  2. Dexamethasone Oral

    MedlinePlus

    ... Nizoral), oral contraceptives, phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), theophylline (Theo-Dur), and vitamins.if you have a ... stomach irritation vomiting headache dizziness insomnia restlessness depression anxiety acne increased hair growth easy bruising irregular or ...

  3. Hydrocortisone Oral

    MedlinePlus

    ... Nizoral), oral contraceptives, phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), theophylline (Theo-Dur), and vitamins.if you have a ... stomach irritation vomiting headache dizziness insomnia restlessness depression anxiety acne increased hair growth easy bruising irregular or ...

  4. Properties of odour-binding glycoproteins from rat olfactory epithelium.

    PubMed

    Fesenko, E E; Novoselov, V I; Bystrova, M F

    1988-01-22

    The specific membrane glycoproteins with high affinity for camphor and decanal were isolated from rat olfactory epithelium. Antibodies to these glycoproteins inhibited both the electroolfactogram and the binding of odorants. The enzyme immunoassay has shown these glycoproteins to be present in the olfactory epithelium of rat, mouse, guinea-pig and hamster but not in that of frog and carp. The molecular mass of the odour-binding glycoproteins from rat olfactory epithelium solubilized by Triton X-100 was approx. 140 kDa. They consisted of two subunits (88 and 55 kDa). The 88 kDa subunit was capable of binding odorants. The data obtained suggest that the glycoproteins isolated have some properties that make them plausible candidates for olfactory receptor molecules. PMID:3337807

  5. In vivo survival and stratification of cultured limbal epithelium.

    PubMed

    Fatima, Anees; Vemuganti, Geeta K; Iftekhar, Ghazala; Rao, Gullapalli N; Sangwan, Virender S

    2007-01-01

    A 6-year-old Bangladeshi girl presented with total limbal stem cell deficiency in the left eye, secondary to a 6-month-old chemical injury. The patient had also previously undergone two limbal transplantation surgeries. At the authors' centre the child underwent autologous cultured limbal epithelium transplantation, on human amniotic membrane, without the use of air-lift technique. Symptomatic relief, re-epithelialization of the ocular surface, regression of corneal pannus and slight improvement in vision were all noted. The corneal button obtained at the time of keratoplasty (performed 4 months later) revealed stratified epithelium with basement membrane. Thirty-seven months post keratoplasty, the best-corrected visual acuity was 6/15 with clear graft and stable ocular surface. Herein, a case of limbal stem cell deficiency successfully managed by monolayer of cultured limbal epithelium is presented. PMID:17300583

  6. Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

    NASA Astrophysics Data System (ADS)

    Knowles, M. R.; Stutts, M. J.; Spock, A.; Fischer, N.; Gatzy, J. T.; Boucher, R. C.

    1983-09-01

    The epithelium of nasal tissue excised from subjects with cystic fibrosis exhibited higher voltage and lower conductance than tissue from control subjects. Basal sodium ion absorption by cystic fibrosis and normal nasal epithelia equaled the short-circuit current and was amiloride-sensitive. Amiloride induced chloride ion secretion in normal but not cystic fibrosis tissue and consequently was more effective in inhibiting the short-circuit current in cystic fibrosis epithelia. Chloride ion-free solution induced a smaller hyperpolarization of cystic fibrosis tissue. The increased voltage and amiloride efficacy in cystic fibrosis reflect absorption of sodium ions across an epithelium that is relatively impermeable to chloride ions.

  7. Nanocomposites and bone regeneration

    NASA Astrophysics Data System (ADS)

    James, Roshan; Deng, Meng; Laurencin, Cato T.; Kumbar, Sangamesh G.

    2011-12-01

    This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

  8. Spontaneous oral chytridiomycosis in wild bullfrog tadpoles in Japan.

    PubMed

    Kadekaru, Sho; Tamukai, Ken-Ichi; Tominaga, Atsushi; Goka, Koichi; Une, Yumi

    2016-05-01

    Batrachochytrium dendrobatidis (Bd) infects Anuran larvae (tadpole) mouthparts and causes oral chytridiomycosis, which can be diagnosed in tadpoles by detecting mouthparts deformities. However, oral chytridiomycosis may or may not be observable, depending on species, tadpole stage and season, and has never been reported in Japan. We aimed to observe oral chytridiomycosis characteristics in bullfrog (Lithobates catesbeiana) tadpoles, determine associated pathologic features and investigate the usability of bullfrog tadpoles in Japanese Bd field surveys. Wild-captured bullfrog tadpole mouthparts were examined macroscopically, histopathologically and by molecular biological examination. Macroscopic lesions were observed in 21 of 59 tadpole mouthparts. Lesions were most frequently located in the lower jaw sheaths and were mainly recognized by partial depigmentation (11 tadpoles; some were completely depigmented) and thinning of the pigmented layer (10 tadpoles). Partial defects of the tips and blunt cutting edges of the jaw sheaths were observed with severe jaw sheath depigmentation. Whitened tooth rows were observed in 7 tadpoles. Histologically, the stratified epithelium (pigmented epithelium) showed partial or diffuse hypopigmentation or pigment loss. Irregular stratified epithelium thickening with hyperkeratosis or parakeratosis was observed in the jaw sheaths. Bd infection was confirmed in 20 of 21 tadpoles presenting jaw sheath deformities, by histopathological examination and/or nested polymerase chain reaction. Depigmentation and thinning of the pigmented layers of jaw sheaths were associated with Bd infection. Thus, diagnosis of Bd infection by macroscopic observation of bullfrog tadpole mouthparts is feasible. This is the first report of oral chytridiomycosis in wild bullfrog tadpoles in Japan. PMID:26685882

  9. Spontaneous oral chytridiomycosis in wild bullfrog tadpoles in Japan

    PubMed Central

    KADEKARU, Sho; TAMUKAI, Ken-ichi; TOMINAGA, Atsushi; GOKA, Koichi; UNE, Yumi

    2015-01-01

    Batrachochytrium dendrobatidis (Bd) infects Anuran larvae (tadpole) mouthparts and causes oral chytridiomycosis, which can be diagnosed in tadpoles by detecting mouthparts deformities. However, oral chytridiomycosis may or may not be observable, depending on species, tadpole stage and season, and has never been reported in Japan. We aimed to observe oral chytridiomycosis characteristics in bullfrog (Lithobates catesbeiana) tadpoles, determine associated pathologic features and investigate the usability of bullfrog tadpoles in Japanese Bd field surveys. Wild-captured bullfrog tadpole mouthparts were examined macroscopically, histopathologically and by molecular biological examination. Macroscopic lesions were observed in 21 of 59 tadpole mouthparts. Lesions were most frequently located in the lower jaw sheaths and were mainly recognized by partial depigmentation (11 tadpoles; some were completely depigmented) and thinning of the pigmented layer (10 tadpoles). Partial defects of the tips and blunt cutting edges of the jaw sheaths were observed with severe jaw sheath depigmentation. Whitened tooth rows were observed in 7 tadpoles. Histologically, the stratified epithelium (pigmented epithelium) showed partial or diffuse hypopigmentation or pigment loss. Irregular stratified epithelium thickening with hyperkeratosis or parakeratosis was observed in the jaw sheaths. Bd infection was confirmed in 20 of 21 tadpoles presenting jaw sheath deformities, by histopathological examination and/or nested polymerase chain reaction. Depigmentation and thinning of the pigmented layers of jaw sheaths were associated with Bd infection. Thus, diagnosis of Bd infection by macroscopic observation of bullfrog tadpole mouthparts is feasible. This is the first report of oral chytridiomycosis in wild bullfrog tadpoles in Japan. PMID:26685882

  10. Glutamine synthetase gene expression during the regeneration of the annelid Enchytraeus japonensis.

    PubMed

    Niva, Cintia Carla; Lee, Jae Min; Myohara, Maroko

    2008-01-01

    Enchytraeus japonensis is a highly regenerative oligochaete annelid that can regenerate a complete individual from a small body fragment in 4-5 days. In our previous study, we performed complementary deoxyribonucleic acid subtraction cloning to isolate genes that are upregulated during E. japonensis regeneration and identified glutamine synthetase (gs) as one of the most abundantly expressed genes during this process. In the present study, we show that the full-length sequence of E. japonensis glutamine synthetase (EjGS), which is the first reported annelid glutamine synthetase, is highly similar to other known class II glutamine synthetases. EjGS shows a 61-71% overall amino acid sequence identity with its counterparts in various other animal species, including Drosophila and mouse. We performed detailed expression analysis by in situ hybridization and reveal that strong gs expression occurs in the blastemal regions of regenerating E. japonensis soon after amputation. gs expression was detectable at the cell layer covering the wound and was found to persist in the epidermal cells during the formation and elongation of the blastema. Furthermore, in the elongated blastema, gs expression was detectable also in the presumptive regions of the brain, ventral nerve cord, and stomodeum. In the fully formed intact head, gs expression was also evident in the prostomium, brain, the anterior end of the ventral nerve cord, the epithelium of buccal and pharyngeal cavities, the pharyngeal pad, and in the esophageal appendages. In intact E. japonensis tails, gs expression was found in the growth zone in actively growing worms but not in full-grown individuals. In the nonblastemal regions of regenerating fragments and in intact worms, gs expression was also detected in the nephridia, chloragocytes, gut epithelium, epidermis, spermatids, and oocytes. These results suggest that EjGS may play roles in regeneration, nerve function, cell proliferation, nitrogenous waste excretion

  11. Biomaterial Selection for Tooth Regeneration

    PubMed Central

    Yuan, Zhenglin; Nie, Hemin; Wang, Shuang; Lee, Chang Hun; Li, Ang; Fu, Susan Y.; Zhou, Hong

    2011-01-01

    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or synthetic polymers, three-dimensional scaffold fabrication, stem cell transplantation, and stem cell homing. A tooth is a complex biological organ. Tooth loss represents the most common organ failure. Tooth regeneration encompasses not only regrowth of an entire tooth as an organ, but also biological restoration of individual components of the tooth including enamel, dentin, cementum, or dental pulp. Regeneration of tooth root represents perhaps more near-term opportunities than the regeneration of the whole tooth. In the adult, a tooth owes its biological vitality, arguably more, to the root than the crown. Biomaterials are indispensible for the regeneration of tooth root, tooth crown, dental pulp, or an entire tooth. PMID:21699433

  12. Cardiac Regeneration and Stem Cells.

    PubMed

    Zhang, Yiqiang; Mignone, John; MacLellan, W Robb

    2015-10-01

    After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world. PMID:26269526

  13. Lgr6 marks nail stem cells and is required for digit tip regeneration

    PubMed Central

    Lehoczky, Jessica A.; Tabin, Clifford J.

    2015-01-01

    The tips of the digits of some mammals, including human infants and mice, are capable of complete regeneration after injury. This process is reliant on the presence of the overlaying nail organ and is mediated by a proliferative blastema. Epithelial Wnt/β-catenin signaling has been shown to be necessary for mouse digit tip regeneration. Here, we report on Lgr5 and Lgr6 (leucine-rich repeat-containing G protein-coupled receptor 5 and 6), two important agonists of the Wnt pathway that are known to be markers of several epithelial stem cell populations. We find that Lgr5 is expressed in a dermal population of cells adjacent to the specialized epithelia surrounding the keratinized nail plate. Moreover, Lgr5-expressing cells contribute to this dermis, but not the blastema, during digit tip regeneration. In contrast, we find that Lgr6 is expressed within cells of the nail matrix portion of the nail epithelium, as well as in a subset of cells in the bone and eccrine sweat glands. Genetic lineage analysis reveals that Lgr6-expressing cells give rise to the nail during homeostatic growth, demonstrating that Lgr6 is a marker of nail stem cells. Moreover, Lgr6-expressing cells contribute to the blastema, suggesting a potential direct role for Lgr6-expressing cells during digit tip regeneration. This role is confirmed by analysis of Lgr6-deficient mice, which have both a nail and bone regeneration defect. PMID:26460010

  14. Vasa, PL10, and Piwi gene expression during caudal regeneration of the polychaete annelid Alitta virens.

    PubMed

    Kozin, Vitaly V; Kostyuchenko, Roman P

    2015-06-01

    Polychaetes are famous for their outstanding ability to regenerate lost body parts. Moreover, these worms possess a number of ancestral features in anatomy, development, and genetics, making them particularly suitable for comparative studies. Thus, fundamental as well as new undisclosed so far features of regenerative processes may be revealed, using polychaetes as a model. In the present work, we aimed to analyze the molecular basis of caudal regeneration in the nereid polychaete Alitta virens (formerly Nereis virens). We focused on homologues genes of RNA helicases Vasa and PL10 and ncRNA-binding proteins Piwi. These markers are suggested to play a significant role in maintenance of undifferentiated state of primordial germ cells and multipotent stem cells across invertebrates. In normal conditions, A. virens homologues of Vasa, PL10, and Piwi were differentially expressed in the subterminal growth zone and germline cells. Caudal amputation induced expression of studied genes de novo, which further accompanies all steps of regeneration. An early appearance of the transcripts in wound epithelium and internal blastemal cells suggests involvement of these genes in the well-known cell dedifferentiation events that assure polychaete regeneration. Provided interpretation of the gene expression dynamics implies the primary restoration of the pygidium and growth zone, which promotes following segment formation. Obtained results are valuable as a molecular fingerprint of the alterations occurring in regulatory state of locally regenerating tissues. PMID:25772273

  15. Lgr6 marks nail stem cells and is required for digit tip regeneration.

    PubMed

    Lehoczky, Jessica A; Tabin, Clifford J

    2015-10-27

    The tips of the digits of some mammals, including human infants and mice, are capable of complete regeneration after injury. This process is reliant on the presence of the overlaying nail organ and is mediated by a proliferative blastema. Epithelial Wnt/β-catenin signaling has been shown to be necessary for mouse digit tip regeneration. Here, we report on Lgr5 and Lgr6 (leucine-rich repeat-containing G protein-coupled receptor 5 and 6), two important agonists of the Wnt pathway that are known to be markers of several epithelial stem cell populations. We find that Lgr5 is expressed in a dermal population of cells adjacent to the specialized epithelia surrounding the keratinized nail plate. Moreover, Lgr5-expressing cells contribute to this dermis, but not the blastema, during digit tip regeneration. In contrast, we find that Lgr6 is expressed within cells of the nail matrix portion of the nail epithelium, as well as in a subset of cells in the bone and eccrine sweat glands. Genetic lineage analysis reveals that Lgr6-expressing cells give rise to the nail during homeostatic growth, demonstrating that Lgr6 is a marker of nail stem cells. Moreover, Lgr6-expressing cells contribute to the blastema, suggesting a potential direct role for Lgr6-expressing cells during digit tip regeneration. This role is confirmed by analysis of Lgr6-deficient mice, which have both a nail and bone regeneration defect. PMID:26460010

  16. Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

    PubMed Central

    2012-01-01

    Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

  17. The Effect of Plasma Exposure on Tail Regeneration of Tadpoles Xenopus Laevis

    NASA Astrophysics Data System (ADS)

    June, Joyce; Rivie, Adonis; Ezuduemoih, Raphael; Menon, Jaishri; Martus, Kevin

    2014-03-01

    Wound healing requires a balanced combination of nutrients and growth factors for healing and tissue regeneration. The effect of plasma exposure on tail regeneration of tadpoles, Xenopus laevis is investigated. The exposure of the wound to the helium plasma immediately followed the amputation of 40% of the tail. Amputation of the tail initiates regeneration of spinal cord, muscle, notochord, skin and connective tissues. By 24 h, the wound was covered by wound epithelium and blastema was formed by day 5. There was increased angiogenesis in plasma exposed tail regenerate compared to the control following 5 d post amputation. Observed was an increase in NO production in the regenerate of plasma exposed tadpoles was derived from increased activity of nNOS and iNOS. Western blot analysis for vascular endothelial growth factor showed stronger bands for the protein in amputated tadpoles of both the groups. Analysis of the composition and characteristics of the plasma using optical emission spectroscopy indicates excited state species consisting of N2, N2+,and OH is present in the plasma. This study was supported, in part, by the NSF Grant 1040108.

  18. Evaluation of advanced regenerator systems

    NASA Technical Reports Server (NTRS)

    Cook, J. A.; Fucinari, C. A.; Lingscheit, J. N.; Rahnke, C. J.

    1978-01-01

    The major considerations are discussed which will affect the selection of a ceramic regenerative heat exchanger for an improved 100 HP automotive gas turbine engine. The regenerator considered for this application is about 36cm in diameter. Regenerator comparisons are made on the basis of material, method of fabrication, cost, and performance. A regenerator inlet temperature of 1000 C is assumed for performance comparisons, and laboratory test results are discussed for material comparisons at 1100 and 1200 C. Engine test results using the Ford 707 industrial gas turbine engine are also discussed.

  19. Cigarette smoke inhibition of ion transport in canine tracheal epithelium

    SciTech Connect

    Welsh, M.J.

    1983-06-01

    To determine the effect of cigarette smoke on airway epithelial ion transport, the electrical properties and transepithelial Na and Cl fluxes were measured in canine tracheal epithelium. In vivo, the inhalation of the smoke from one cigarette acutely and reversibly decreased the electrical potential difference across the tracheal epithelium. In vitro, exposure of the mucosal surface of the epithelium to cigarette smoke decreased the short circuit current and transepithelial resistance. The decrease in short circuit current was due to an inhibition of the rate of Cl secretion with minimal effect on the rate of Na absorption. The effect of cigarette smoke was reversible, was not observed upon exposure of the submucosal surface to smoke, and was most pronounced when secretion was stimulated. The particulate phase of smoke was largely responsible for the inhibitory effect, since filtering the smoke minimized the effect. The effect of cigarette smoke was not prevented by addition of antioxidants to the bathing solutions, suggesting that the inhibition of Cl secretion cannot be entirely attributed to an oxidant mechanism. These results indicate that cigarette smoke acutely inhibits active ion transport by tracheal epithelium, both in vivo and in vitro. This effect may explain, in part, both the abnormal mucociliary clearance and the airway disease observed in cigarette smokers.

  20. Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

    NASA Astrophysics Data System (ADS)

    Garzotto, D.; De Marchis, S.

    2010-10-01

    Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

  1. Coelomic epithelium-derived cells in visceral morphogenesis.

    PubMed

    Ariza, Laura; Carmona, Rita; Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón

    2016-03-01

    Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. PMID:26638186

  2. Epithelial expression of keratinocytes growth factor in oral precancer lesions

    PubMed Central

    Jimson, Sudha; Murali, S.; Zunt, Susan L.; Goldblatt, Lawrence I.; Srinivasan, Mythily

    2016-01-01

    Background: Keratinocyte growth factor (KGF) is a potent epithelial mitogen that acts by binding the KGF receptors (KGFRs) expressed on epithelial cells and regulates proliferation and differentiation. The objective of this study was to investigate the expression of KGF in the epithelium in oral precancer. Materials and Methods: Archival tissues of oral submucous fibrosis (SMF) and leukoplakia were assessed for epithelial KGF expression by immunohistochemistry and real-time quantitative polymerase chain reaction. Results: KGF was predominantly expressed in the basal and parabasal cells in the epithelium of SMF tissues. KGF transcript in the epithelial cells increased with increasing severity of epithelial dysplasia in oral leukoplakia. Conclusion: Although widely reported as a product secreted by the mesenchymal cells, our data suggest that the KGF is also expressed in oral epithelial cells much like the expression in ovarian epithelial cells. Based on the localization of KGF in cells at the epithelial mesenchymal junction and that of the reported presence of KGFR in oral keratinocytes, a potential mechanism involving paracrine and autocrine interactions of KGF and KGFR in early stages of oral precancer is postulated. PMID:27274338

  3. Establishment of a Novel Lingual Organoid Culture System: Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells

    NASA Astrophysics Data System (ADS)

    Hisha, Hiroko; Tanaka, Toshihiro; Kanno, Shohei; Tokuyama, Yoko; Komai, Yoshihiro; Ohe, Shuichi; Yanai, Hirotsugu; Omachi, Taichi; Ueno, Hiroo

    2013-11-01

    Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.

  4. Purinergic signaling in retinal degeneration and regeneration.

    PubMed

    Reichenbach, Andreas; Bringmann, Andreas

    2016-05-01

    Purinergic signaling is centrally involved in mediating the degeneration of the injured and diseased retina, the induction of retinal gliosis, and the protection of the retinal tissue from degeneration. Dysregulated calcium signaling triggered by overactivation of P2X7 receptors is a crucial step in the induction of neuronal and microvascular cell death under pathogenic conditions like ischemia-hypoxia, elevated intraocular pressure, and diabetes, respectively. Overactivation of P2X7 plays also a pathogenic role in inherited and age-related photoreceptor cell death and in the age-related dysfunction and degeneration of the retinal pigment epithelium. Gliosis of micro- and macroglial cells, which is induced and/or modulated by purinergic signaling and associated with an impaired homeostatic support to neurons, and the ATP-mediated propagation of retinal gliosis from a focal injury into the surrounding noninjured tissue are involved in inducing secondary cell death in the retina. On the other hand, alterations in the glial metabolism of extracellular nucleotides, resulting in a decreased level of ATP and an increased level of adenosine, may be neuroprotective in the diseased retina. Purinergic signals stimulate the proliferation of retinal glial cells which contributes to glial scarring which has protective effects on retinal degeneration and adverse effects on retinal regeneration. Pharmacological modulation of purinergic receptors, e.g., inhibition of P2X and activation of adenosine receptors, may have clinical importance for the prevention of photoreceptor, neuronal, and microvascular cell death in diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration, and glaucoma, respectively, for the clearance of retinal edema, and the inhibition of dysregulated cell proliferation in proliferative retinopathies. This article is part of a Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:25998275

  5. Regenerable Iodine Water-Disinfection System

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L.; Colombo, Gerald V.; Jolly, Clifford D.

    1994-01-01

    Iodinated resin bed for disinfecting water regenerated to extend its useful life. Water flows through regeneration bed of crystalline iodine during regeneration. At other times, flow diverted around regeneration bed. Although regeneration cycle was manually controlled in demonstration, readily automated to start and stop according to signals and stop according to signals from concentration sensors. Further benefit of regeneration is that regeneration bed provides highly concentrated biocide source (200 mg/L) when needed. Concentrated biocide used to superiodinate system after contamination from routine maintenance or unexpected introduction of large concentration of microbes.

  6. Pigmented epithelium induces complete retinal reconstitution from dispersed embryonic chick retinae in reaggregation culture.

    PubMed Central

    Rothermel, A; Willbold, E; Degrip, W J; Layer, P G

    1997-01-01

    Reaggregation of dispersed retinal cells of the chick embryo leads to histotypic retinospheroids in which the laminar organization remains incomplete: photoreceptors form rosettes which are surrounded by constituents of the other retinal layers. Here, for the first time, a complete arrangement of layers is achieved in cellular spheres (stratoids), provided that fully dispersed retinal cells are younger than embryonic day E6, and are reaggregated in the presence of a monolayer of retinal pigmented epithelium (RPE). A remarkable mechanism of stratoid formation from 1 to 15 days in vitro is revealed by the establishment of a radial Müller glia scaffold and of photoreceptors. During the first two days of reaggregation on RPE, rosettes are still observed. At this stage immunostaining with vimentin and F11 antibodies for radial Müller glia reveal a disorganized pattern. Subsequently, radial glia processes organize into long parallel fibre bundles which are arranged like spokes to stabilize the surface and centre of the stratoid. The opsin-specific antibody CERN 901 detects photoreceptors as they gradually build up an outer nuclear layer at the surface. These findings assign to the RPE a decisive role for the genesis and regeneration of a vertebrate retina. PMID:9332014

  7. A novel Bruch's membrane-mimetic electrospun substrate scaffold for human retinal pigment epithelium cells.

    PubMed

    Xiang, Ping; Wu, Kun-Chao; Zhu, Ying; Xiang, Lue; Li, Chong; Chen, Deng-Long; Chen, Feng; Xu, Guotong; Wang, Aijun; Li, Min; Jin, Zi-Bing

    2014-12-01

    Various artificial membranes have been used as scaffolds for retinal pigment epithelium cells (RPE) for monolayer reconstruction, however, long-term cell viability and functionality are still largely unknown. This study aimed to construct an ultrathin porous nanofibrous film to mimic Bruch's membrane, and in particular to investigate human RPE cell responses to the resultant substrates. An ultrathin porous nanofibrous membrane was fabricated by using regenerated wild Antheraea pernyi silk fibroin (RWSF), polycaprolactone (PCL) and gelatin (Gt) and displayed a thickness of 3-5 μm, with a high porosity and an average fiber diameter of 166 ± 85 nm. Human RPE cells seeded on the RWSF/PCL/Gt membranes showed a higher cell growth rate (p < 0.05), and a typical expression pattern of RPE signature genes, with reduced expression of inflammatory mediators. With long-term cultivation on the substrates, RPE cells exhibited characteristic polygonal morphology and development of apical microvilli. Immunocytochemisty demonstrated RPE-specific expression profiles in cells after 12-weeks of co-culture on RWSF/PCL/Gt membranes. Interestingly, the cells on the RWSF/PCL/Gt membranes functionally secreted polarized PEDF and phagocytosed labeled porcine POS. Furthermore, RWSF/PCL/Gt membranes transplanted subsclerally exhibited excellent biocompatibility without any evidence of inflammation or rejection. In conclusion, we established a novel RWSF-based substrate for growth of RPE cells with excellent cytocompatibility in vitro and biocompatibility in vivo for potential use as a prosthetic Bruch's membrane for RPE transplantation. PMID:25220295

  8. Conditioning the cochlea to facilitate survival and integration of exogenous cells into the auditory epithelium.

    PubMed

    Park, Yong-Ho; Wilson, Kevin F; Ueda, Yoshihisa; Tung Wong, Hiu; Beyer, Lisa A; Swiderski, Donald L; Dolan, David F; Raphael, Yehoash

    2014-04-01

    The mammalian auditory epithelium (AE) cannot replace supporting cells and hair cells once they are lost. Therefore, sensorineural hearing loss associated with missing cells is permanent. This inability to regenerate critical cell types makes the AE a potential target for cell replacement therapies such as stem cell transplantation. Inserting stem cells into the AE of deaf ears is a complicated task due to the hostile, high potassium environment of the scala media in the cochlea, and the robust junctional complexes between cells in the AE that resist stem cell integration. Here, we evaluate whether temporarily reducing potassium levels in the scala media and disrupting the junctions in the AE make the cochlear environment more receptive and facilitate survival and integration of transplanted cells. We used sodium caprate to transiently disrupt the AE junctions, replaced endolymph with perilymph, and blocked stria vascularis pumps with furosemide. We determined that these three steps facilitated survival of HeLa cells in the scala media for at least 7 days and that some of the implanted cells formed a junctional contact with native AE cells. The data suggest that manipulation of the cochlear environment facilitates survival and integration of exogenously transplanted HeLa cells in the scala media. PMID:24394296

  9. Transgenic BDNF induces nerve fiber regrowth into the auditory epithelium in deaf cochleae.

    PubMed

    Shibata, Seiji B; Cortez, Sarah R; Beyer, Lisa A; Wiler, James A; Di Polo, Adriana; Pfingst, Bryan E; Raphael, Yehoash

    2010-06-01

    Sensory organs typically use receptor cells and afferent neurons to transduce environmental signals and transmit them to the CNS. When sensory cells are lost, nerves often regress from the sensory area. Therapeutic and regenerative approaches would benefit from the presence of nerve fibers in the tissue. In the hearing system, retraction of afferent innervation may accompany the degeneration of auditory hair cells that is associated with permanent hearing loss. The only therapy currently available for cases with severe or complete loss of hair cells is the cochlear implant auditory prosthesis. To enhance the therapeutic benefits of a cochlear implant, it is necessary to attract nerve fibers back into the cochlear epithelium. Here we show that forced expression of the neurotrophin gene BDNF in epithelial or mesothelial cells that remain in the deaf ear induces robust regrowth of nerve fibers towards the cells that secrete the neurotrophin, and results in re-innervation of the sensory area. The process of neurotrophin-induced neuronal regeneration is accompanied by significant preservation of the spiral ganglion cells. The ability to regrow nerve fibers into the basilar membrane area and protect the auditory nerve will enhance performance of cochlear implants and augment future cell replacement therapies such as stem cell implantation or induced transdifferentiation. This model also provides a general experimental stage for drawing nerve fibers into a tissue devoid of neurons, and studying the interaction between the nerve fibers and the tissue. PMID:20109446

  10. Transgenic BDNF induces nerve fiber regrowth into the auditory epithelium in deaf cochleae

    PubMed Central

    Shibata, Seiji B.; Cortez, Sarah R.; Beyer, Lisa A.; Wiler, Jim A.; Di Polo, Adriana; Pfingst, Bryan E.; Raphael, Yehoash

    2010-01-01

    Sensory organs typically use receptor cells and afferent neurons to transduce environmental signals and transmit them to the CNS. When sensory cells are lost, nerves often regress from the sensory area. Therapeutic and regenerative approaches would benefit from the presence of nerve fibers in the tissue. In the hearing system, retraction of afferent innervation may accompany the degeneration of auditory hair cells that is associated with permanent hearing loss. The only therapy currently available for cases with severe or complete loss of hair cells is the cochlear implant auditory prosthesis. To enhance the therapeutic benefits of a cochlear implant, it is necessary to attract nerve fibers back into the cochlear epithelium. Here we show that forced expression of the neurotrophin gene BDNF in epithelial or mesothelial cells that remain in the deaf ear, induces robust regrowth of nerve fibers towards the cells that secrete the neurotrophin, and results in re-innervation of the sensory area. The process of neurotrophin-induced neuronal regeneration is accompanied by significant preservation of the spiral ganglion cells. The ability to regrow nerve fibers into the basilar membrane area and protect the auditory nerve will enhance performance of cochlear implants and augment future cell replacement therapies such as stem cell implantation or induced transdifferentiation. This model also provides a general experimental stage for drawing nerve fibers into a tissue devoid of neurons, and studying the interaction between the nerve fibers and the tissue. PMID:20109446

  11. Endogenous Mechanisms of Cardiac Regeneration.

    PubMed

    Xiang, M S W; Kikuchi, K

    2016-01-01

    Zebrafish possess a remarkable capacity for cardiac regeneration throughout their lifetime, providing a model for investigating endogenous cellular and molecular mechanisms regulating myocardial regeneration. By contrast, adult mammals have an extremely limited capacity for cardiac regeneration, contributing to mortality and morbidity from cardiac diseases such as myocardial infarction and heart failure. However, the viewpoint of the mammalian heart as a postmitotic organ was recently revised based on findings that the mammalian heart contains multiple undifferentiated cell types with cardiogenic potential as well as a robust regenerative capacity during a short period early in life. Although it occurs at an extremely low level, continuous cardiomyocyte turnover has been detected in adult mouse and human hearts, which could potentially be enhanced to restore lost myocardium in damaged human hearts. This review summarizes and discusses recent advances in the understanding of endogenous mechanisms of cardiac regeneration. PMID:27572127

  12. Oral candidiasis.

    PubMed

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options. PMID:27343964

  13. Esophageal melanocytosis in oral opium consumption.

    PubMed

    Geramizadeh, Bita; Asadian, Fatemeh; Taghavi, Alireza

    2014-01-01

    Esophageal melanocytosis is a rare and benign condition, characterized by melanocytic proliferation of the esophageal squamous epithelium with heavy melanin deposition. The etiology and pathogenesis has not been exactly known but it seems to be a chronic stimulus such as gastroesophageal reflux. This condition is very rare and about 35 cases have been reported so far, most of which have been from India and Japan. Herein, we present a case of esophageal melanocytosis in a patient with long history of oral opium consumption. To the best of our knowledge, such a history has not been reported. PMID:24719715

  14. Hairpin Vortex Regeneration Threshold

    NASA Astrophysics Data System (ADS)

    Sabatino, Daniel; Maharjan, Rijan

    2015-11-01

    A free surface water channel is used to study hairpin vortex formation created by fluid injection through a narrow slot into a laminar boundary layer. Particle image velocimetry is used to calculate the circulation of the primary hairpin vortex head which is found to monotonically decrease in strength with downstream distance. When a secondary hairpin vortex is formed upstream of the primary vortex, the circulation strength of the head is comparable to the strength of the primary head at the time of regeneration. However, the legs of the primary vortex strengthen up to the moment the secondary hairpin is generated. Although the peak circulation in the legs is not directly correlated to the strength of the original elongated ring vortex, when the circulation is scaled with the injection momentum ratio it is linearly related to scaled injection time. It is proposed that the injection momentum ratio and nondimensionalized injection time based on the wall normal penetration time can be used to identify threshold conditions which produce a secondary vortex. Supported by the National Science Foundation under Grant CBET- 1040236.

  15. Biomaterials for periodontal regeneration

    PubMed Central

    Shue, Li; Yufeng, Zhang; Mony, Ullas

    2012-01-01

    Periodontal disease is characterized by the destruction of periodontal tissues. Various methods of regenerative periodontal therapy, including the use of barrier membranes, bone replacement grafts, growth factors and the combination of these procedures have been investigated. The development of biomaterials for tissue engineering has considerably improved the available treatment options above. They fall into two broad classes: ceramics and polymers. The available ceramic-based materials include calcium phosphate (eg, tricalcium phosphate and hydroxyapatite), calcium sulfate and bioactive glass. The bioactive glass bonds to the bone with the formation of a layer of carbonated hydroxyapatite in situ. The natural polymers include modified polysaccharides (eg, chitosan,) and polypeptides (collagen and gelatin). Synthetic polymers [eg, poly(glycolic acid), poly(L-lactic acid)] provide a platform for exhibiting the biomechanical properties of scaffolds in tissue engineering. The materials usually work as osteogenic, osteoconductive and osteoinductive scaffolds. Polymers are more widely used as a barrier material in guided tissue regeneration (GTR). They are shown to exclude epithelial downgrowth and allow periodontal ligament and alveolar bone cells to repopulate the defect. An attempt to overcome the problems related to a collapse of the barrier membrane in GTR or epithelial downgrowth is the use of a combination of barrier membranes and grafting materials. This article reviews various biomaterials including scaffolds and membranes used for periodontal treatment and their impacts on the experimental or clinical management of periodontal defect. PMID:23507891

  16. Regenerable biocide delivery unit

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L. (Inventor); Colombo, Gerald V. (Inventor); Jolly, Clifford D. (Inventor)

    1993-01-01

    A method and apparatus are disclosed for maintaining continuous, long-term microbial control in the water supply for potable, hygiene, and experimental water for space activities, as well as treatment of water supplies on Earth. The water purification is accomplished by introduction of molecular iodine into the water supply to impart a desired iodine residual. The water is passed through an iodinated anion exchange resin bed. The iodine is bound as I-(sub n) at the anion exchange sites and releases I(sub 2) into the water stream flowing through the bed. The concentration of I(sub 2) in the flowing water gradually decreases and, in the prior art, the ion-exchange bed has had to be replaced. In a preferred embodiment, a bed of iodine crystals is provided with connections for flowing water therethrough to produce a concentrated (substantially saturated) aqueous iodine solution which is passed through the iodinated resin bed to recharge the bed with bound iodine. The bed of iodine crystals is connected in parallel with the iodinated resin bed and is activated periodically (e.g., by timer, by measured flow of water, or by iodine residual level) to recharge the bed. Novelty resides in the capability of inexpensively and repeatedly regenerating the ion-exchange bed in situ.

  17. c-Src drives intestinal regeneration and transformation

    PubMed Central

    Cordero, Julia B; Ridgway, Rachel A; Valeri, Nicola; Nixon, Colin; Frame, Margaret C; Muller, William J; Vidal, Marcos; Sansom, Owen J

    2014-01-01

    The non-receptor tyrosine kinase c-Src, hereafter referred to as Src, is overexpressed or activated in multiple human malignancies. There has been much speculation about the functional role of Src in colorectal cancer (CRC), with Src amplification and potential activating mutations in up to 20%of the human tumours, although this has never been addressed due to multiple redundant family members. Here, we have used the adult Drosophila and mouse intestinal epithelium as paradigms to define a role for Src during tissue homeostasis, damage-induced regeneration and hyperplasia. Through genetic gain and loss of function experiments, we demonstrate that Src is necessary and sufficient to drive intestinal stem cell (ISC) proliferation during tissue self-renewal, regeneration and tumourigenesis. Surprisingly, Src plays a non-redundant role in the mouse intestine, which cannot be substituted by the other family kinases Fyn and Yes. Mechanistically, we show that Src drives ISC proliferation through upregulation of EGFR and activation of Ras/MAPK and Stat3 signalling. Therefore, we demonstrate a novel essential role for Src in intestinal stem/progenitor cell proliferation and tumourigenesis initiation in vivo. PMID:24788409

  18. Enhancement of skeletal muscle regeneration.

    PubMed

    Bischoff, R; Heintz, C

    1994-09-01

    We have studied the effect of adding extra satellite cells or soluble factors from crushed muscle on regeneration of minced fragments from rat tibialis muscle. The muscle mince was wrapped in an artificial epimysium to prevent adhesions and cell immigration from adjacent muscles. Regeneration was quantitatively assessed by electrophoretic determination of the muscle-specific form of creatine kinase. Control minces exhibited three periods of change in creatine kinase activity during a 7-week regeneration period. Activity fell rapidly during the first week, then rose gradually from 1-3 weeks and increased more rapidly from 3-7 weeks. To augment the original complement of myogenic cells, satellite cells were isolated from the contralateral muscle, purified by density gradient centrifugation, and expanded in culture for 3 days before adding to the muscle mince. The added cells resulted in a 3-fold enhancement of creatine kinase activity throughout the regeneration period. Soluble muscle extract incorporated into a collagen matrix also stimulated regeneration when added to muscle mince. The extract accelerated the rate of creatine kinase increase during the 1-3 week period beyond that observed in the control or cell augmented mince, suggesting that factors in the extract may facilitate revascularization or reinnervation. The specific activity of creatine kinase was increased in regenerates augmented with both cells and extract, indicating that the effects enhance primarily myogenic processes. PMID:7803846

  19. Oral exposure to polystyrene nanoparticles affects iron absorption

    NASA Astrophysics Data System (ADS)

    Mahler, Gretchen J.; Esch, Mandy B.; Tako, Elad; Southard, Teresa L.; Archer, Shivaun D.; Glahn, Raymond P.; Shuler, Michael L.

    2012-04-01

    The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron transport in an in vitro model of the intestinal epithelium and an in vivo chicken intestinal loop model. Intestinal cells that are exposed to high doses of nanoparticles showed increased iron transport due to nanoparticle disruption of the cell membrane. Chickens acutely exposed to carboxylated particles (50 nm in diameter) had a lower iron absorption than unexposed or chronically exposed birds. Chronic exposure caused remodelling of the intestinal villi, which increased the surface area available for iron absorption. The agreement between the in vitro and in vivo results suggests that our in vitro intestinal epithelium model is potentially useful for toxicology studies.

  20. Lung development: orchestrating the generation and regeneration of a complex organ

    PubMed Central

    Herriges, Michael; Morrisey, Edward E.

    2014-01-01

    The respiratory system, which consists of the lungs, trachea and associated vasculature, is essential for terrestrial life. In recent years, extensive progress has been made in defining the temporal progression of lung development, and this has led to exciting discoveries, including the derivation of lung epithelium from pluripotent stem cells and the discovery of developmental pathways that are targets for new therapeutics. These discoveries have also provided new insights into the regenerative capacity of the respiratory system. This Review highlights recent advances in our understanding of lung development and regeneration, which will hopefully lead to better insights into both congenital and acquired lung diseases. PMID:24449833

  1. Oral Cancer

    MedlinePlus

    ... What are the effects of oral cancer on speech and swallowing? The effects of cancer on speech and swallowing depend on the location and size ... movement. This could result in unclear production of speech sounds made with the lips such as /p/, / ...

  2. Oral Warts

    MedlinePlus

    ... Title: Oral Warts Description: Warts are small, white, gray, or pinkish rough bumps that look like cauliflower. They can appear inside the lips and on other parts of the mouth. Credit: NIDCR publication: Mouth Problems + HIV Download: Low-Resolution Image High- ...

  3. Oral Cancer

    MedlinePlus

    ... won't heal Bleeding in your mouth Loose teeth Problems or pain with swallowing A lump in your neck An earache Oral cancer treatments may include surgery, radiation therapy or chemotherapy. Some patients have a combination of treatments. NIH: National Cancer Institute

  4. Distal Airway Stem Cells Render Alveoli in Vitro and During Lung Regeneration Following H1N1 Influenza Infection

    PubMed Central

    Kumar, Pooja A.; Hu, Yuanyu; Yamamoto, Yusuke; Hoe, Neo Boon; Wei, Tay Seok; Mu, Dakai; Sun, Yan; Joo, Lim Siew; Dagher, Rania; Zielonka, Elisabeth; Wang, De Yun; Chow, Vincent T.; Crum, Christopher P.; Xian, Wa; McKeon, Frank

    2011-01-01

    SUMMARY The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel finding that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease. PMID:22036562

  5. Oral care.

    PubMed

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable. PMID:21325845

  6. Oral Health and Aging

    MedlinePlus

    ... please turn JavaScript on. Feature: Oral Health and Aging Oral Health and Aging Summer 2016 Table of Contents Jerrold H. Epstein, ... they may need. Read More "Oral Health and Aging" Articles Oral Health and Aging / 4 Myths About ...

  7. Oral Cancer Screening

    MedlinePlus

    ... Prevention Oral Cavity and Oropharyngeal Cancer Screening Research Oral Cavity and Oropharyngeal Cancer Screening (PDQ®)–Patient Version What ... These are called diagnostic tests . General Information About Oral Cavity and Oropharyngeal Cancer Key Points Oral cavity and ...

  8. In vitro preparation of newt inner ear sensory epithelia as a model for repair and regeneration.

    PubMed

    Taylor, Ruth R

    2015-01-01

    The sensory "hair" cells of the inner ear transform sound energy into electrical signals, but are readily lost through aging, excessive noise, and ototoxic agents. The newt provides an excellent model in which to explore regeneration and whilst loss of hair cells from inner ear epithelia does not require whole organ regeneration, new hair cells are generated from differentiated supporting cells that transdifferentiate without an intervening mitotic event. Here we describe the methods for maintaining the sensory epithelia in long term culture; for the use of the aminoglycoside, gentamicin, to kill the hair cells; and for the examination of the tissue by electron microscopy or fluorescence microscopy. Demembranation of the epithelium reveals the underlying ultrastructure of the tissue for examination by scanning electron microscopy (SEM) and is a technique that can be utilized with immunogold labelling. PMID:25740492

  9. Matrix metalloproteinase expression and function during fin regeneration in zebrafish: analysis of MT1-MMP, MMP2 and TIMP2.

    PubMed

    Bai, Shan; Thummel, Ryan; Godwin, Alan R; Nagase, Hideaki; Itoh, Yoshifumi; Li, Li; Evans, Richard; McDermott, Jeffrey; Seiki, Motoharu; Sarras, Michael P

    2005-06-01

    Matrix metalloproteinases (MMPs) play key roles in the turnover of extracellular matrix (ECM) and, thereby, function as key regulators of cell-ECM interactions during development. In spite of their importance during developmental processes, relatively little has been reported about the role of these metalloproteinases during limb development and regeneration. To approach the problem of cell-ECM interactions during limb (fin) regeneration, we have utilized zebrafish as an experimental model. Based on previous MMP cloning studies from our laboratory, the current study has focused on the expression of membrane-type 1 metalloproteinase (MT1-MMP), gelatinase A (MMP-2) and endogenous tissue inhibitor 2 of metalloproteinases (TIMP-2) during fin regeneration in adult zebrafish. In situ analysis indicated co-expression of zmt1-mmp, zmmp-2, and ztimp-2 mRNA transcripts in regenerating caudal fins. In situ gelatin-zymography confirmed the presence of active metalloproteinases in regenerating fins. zmt1-mmp, zmmp-2, and ztimp-2 mRNA transcripts were expressed in the blastema and basal epithelium during caudal fin regeneration while expression of type IV collagen [zcol-IV(a5)] transcripts (a basal lamina component) was restricted to the basal epithelium. Fin outgrowth was greatly reduced in the presence of GM6001 (an inhibitor of MMP activity) indicating the importance of these enzymes during fin regeneration. Previous studies by Itoh (EMBO, 2001) indicated that expression of a vertebrate MT1-MMP construct containing only the hemopexin-transmembrane-cytoplasmic domains (MT1HPX) resulted in blockage of MT1-MMP homophilic complex formation and subsequent inhibition of pro-MMP-2 activation. Interference with homophilic complex formation was attributed to expression of the hemopexin domain at the cell surface. Building upon these earlier findings, the current study found that ectopic expression of MT1HPX in fin regenerates inhibited the regeneration process and resulted in a

  10. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth. PMID:14521517

  11. Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

    PubMed Central

    Schnittke, Nikolai; Herrick, Daniel B.; Lin, Brian; Peterson, Jesse; Coleman, Julie H.; Packard, Adam I.; Jang, Woochan; Schwob, James E.

    2015-01-01

    Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs. PMID:26305958

  12. Expression of Two Classes of Pax6 Transcripts in Reprogramming Retinal Pigment Epithelium Cells of the Adult Newt.

    PubMed

    Inami, Wataru; Islam, Md Rafiqul; Nakamura, Kenta; Yoshikawa, Taro; Yasumuro, Hirofumi; Casco-Robles, Martin Miguel; Toyama, Fubito; Maruo, Fumiaki; Chiba, Chikafumi

    2016-02-01

    The adult newt has the remarkable ability to regenerate a functional retina from retinal pigment epithelium (RPE) cells, even when the neural retina (NR) is completely lost from the eye. In this system, RPE cells are reprogrammed into a unique state of multipotent cells, named RPESCs, in an early phase of retinal regeneration. However, the signals that trigger reprogramming remain unknown. Here, to approach this issue we focused on Pax6, a transcription factor known to be expressed in RPESCs. We first identified four classes (v1, v2, v3 and v4) of Pax6 variants in the eye of adult newt, Cynops pyrrhogaster. These variants were expressed in most tissues of the intact eye in different combinations but not in the RPE, choroid or sclera. On the basis of this information, we investigated the expression of Pax6 in RPE cells after the NR was removed from the eye by surgery (retinectomy), and found that two classes (v1 and v2) of Pax6 variants were newly expressed in RPE cells 10 days after retinectomy, both in vivo and in vitro (RLEC system). In the RLEC system, we found that Pax6 expression is mediated through a pathway separate from the MEK-ERK pathway, which is required for cell cycle re-entry of RPE cells. These results predict the existence of a pathway that may be of fundamental importance to a better understanding of the reprogramming of RPE cells in vivo. PMID:26853865

  13. African Swine Fever Virus Replication in the Midgut Epithelium Is Required for Infection of Ornithodoros Ticks

    PubMed Central

    Kleiboeker, S. B.; Scoles, G. A.; Burrage, T. G.; Sur, J.-H.

    1999-01-01

    Although the Malawi Lil20/1 (MAL) strain of African swine fever virus (ASFV) was isolated from Ornithodoros sp. ticks, our attempts to experimentally infect ticks by feeding them this strain failed. Ten different collections of Ornithodorus porcinus porcinus ticks and one collection of O. porcinus domesticus ticks were orally exposed to a high titer of MAL. At 3 weeks postinoculation (p.i.), <25% of the ticks contained detectable virus, with viral titers of <4 log10 50% hemadsorbing doses/ml. Viral titers declined to undetectability in >90% of the ticks by 5 weeks p.i. To further study the growth defect, O. porcinus porcinus ticks were orally exposed to MAL and assayed at regular intervals p.i. Whole-tick viral titers dramatically declined (>1,000-fold) between 2 and 6 days p.i., and by 18 days p.i., viral titers were below the detection limit. In contrast, viral titers of ticks orally exposed to a tick-competent ASFV isolate, Pretoriuskop/96/4/1 (Pr4), increased 10-fold by 10 days p.i. and 50-fold by 14 days p.i. Early viral gene expression, but not extensive late gene expression or viral DNA synthesis, was detected in the midguts of ticks orally exposed to MAL. Ultrastructural analysis demonstrated that progeny virus was rarely present in ticks orally exposed to MAL and, when present, was associated with extensive cytopathology of phagocytic midgut epithelial cells. To determine if viral replication was restricted only in the midgut epithelium, parenteral inoculations into the hemocoel were performed. With inoculation by this route, a persistent infection was established although a delay in generalization of MAL was detected and viral titers in most tissues were typically 10- to 1,000-fold lower than those of ticks injected with Pr4. MAL was detected in both the salivary secretion and coxal fluid following feeding but less frequently and at a lower titer compared to Pr4. Transovarial transmission of MAL was not detected after two gonotrophic cycles

  14. ORAL LICHEN PLANUS AND ORAL LICHENOID REACTION--AN UPDATE.

    PubMed

    Rotim, Zeljko; Bolanca, Zeljana; Rogulj, Ana Andabak; Andabak, Matej; Boras, Vanja Vucićević; Vrdoljak, Danko Velimir

    2015-12-01

    Oral lichen planus (OLP) and oral lichenoid reaction (OLR) are clinically and histopathologically similar diseases. Whereas OLP is a consequence of T cell mediated autoinflammatory process to a still unknown antigen, OLR might be caused by drugs, dental restorative materials and dental plaque. Pubmed was searched and 24 publications published over the last three years regarding etiology, diagnosis and malignant alteration were included in this study. Patients with OLR who have amalgam fillings near lesions should have them replaced, i.e. when possible they should be referred to patch test, as well as when drug-induced OLR are suspected. OLR lesions induced by drugs should disappear when the offending drug has been discontinued. Histology finding in OLR consists of more eosinophils, plasma cells and granulocytes in comparison to OLP lesions. Furthermore, OLP lesions showed more p53, bcl-2 and COX-2 positivity when compared to OLR. OLP is characterized by infiltration, atrophic epithelium, rete pegs and Max Joseph spaces, while deep infiltration into connective tissue and hyperkeratosis were the criteria for making the diagnosis of OLR. The number of degranulated mastocytes in the reticular layer, as well as the number of capillaries was higher in OLR in comparison to OLP. It seems that OLR are more prone to malignant alteration in comparison to OLP. PMID:27017728

  15. Frenum-like oral synechiae of the lip and vestibule.

    PubMed

    Mishima, Katsuaki; Shiraishi, Mami; Kawai, Yui; Harada, Koji; Ueyama, Yoshiya

    2016-06-01

    Two cases where aberrant tissue was attached to the lower lip mimicking the inferior labial frenum were reported. The frenum-like tissue extended from the gingival margin between the lower left deciduous central and lateral incisors in case 1 and between the lower right deciduous central and lateral incisors in case 2, to the dry lower lip. Histologically, the resected specimen was regarded as normal oral mucosa covered with stratified squamous epithelium, without a clear amniotic band. The frenum-like tissue of the lower lip found in both our patients was diagnosed as a category of oral synechiae, of unknown origin. PMID:26780195

  16. Oral insulin-delivery system for diabetes mellitus.

    PubMed

    Kanzarkar, Minakshi; Pathak, Prem Prakash; Vaidya, Mandar; Brumlik, Charles; Choudhury, Abhishek

    2015-01-01

    Current insulin therapy for diabetes mellitus involves frequent dosing of subcutaneous injections, causing local discomfort, patient noncompliance, hypoglycemia and hyperinsulinemia, among others. While noninvasive therapy through oral delivery is greatly desired, there are challenges that include low bioavailability due to rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen, poor permeability across the intestinal epithelium and poor stability. This article reviews patents that provide novel approaches for oral insulin delivery to the bloodstream through the GI tract. PMID:25565158

  17. Identification of Human Fibroblast Cell Lines as a Feeder Layer for Human Corneal Epithelial Regeneration

    PubMed Central

    Lu, Rong; Bian, Fang; Lin, Jing; Su, Zhitao; Qu, Yangluowa; Pflugfelder, Stephen C.; Li, De-Quan

    2012-01-01

    There is a great interest in using epithelium generated in vitro for tissue bioengineering. Mouse 3T3 fibroblasts have been used as a feeder layer to cultivate human epithelia including corneal epithelial cells for more than 3 decades. To avoid the use of xeno-components, we evaluated human fibroblasts as an alternative feeder supporting human corneal epithelial regeneration. Five human fibroblast cell lines were used for evaluation with mouse 3T3 fibroblasts as a control. Human epithelial cells isolated from fresh corneal limbal tissue were seeded on these feeders. Colony forming efficiency (CFE) and cell growth capacity were evaluated on days 5–14. The phenotype of the regenerated epithelia was evaluated by morphology and immunostaining with epithelial markers. cDNA microarray was used to analyze the gene expression profile of the supportive human fibroblasts. Among 5 strains of human fibroblasts evaluated, two newborn foreskin fibroblast cell lines, Hs68 and CCD1112Sk, were identified to strongly support human corneal epithelial growth. Tested for 10 passages, these fibroblasts continually showed a comparative efficiency to the 3T3 feeder layer for CFE and growth capacity of human corneal epithelial cells. Limbal epithelial cells seeded at 1×104 in a 35-mm dish (9.6 cm2) grew to confluence (about 1.87–2.41×106 cells) in 12–14 days, representing 187–241 fold expansion with over 7–8 doublings on these human feeders. The regenerated epithelia expressed K3, K12, connexin 43, p63, EGFR and integrin β1, resembling the phenotype of human corneal epithelium. DNA microarray revealed 3 up-regulated and 10 down-regulated genes, which may be involved in the functions of human fibroblast feeders. These findings demonstrate that commercial human fibroblast cell lines support human corneal epithelial regeneration, and have potential use in tissue bioengineering for corneal reconstruction. PMID:22723892

  18. [Hormone-mediated reactions in the endosalpinx epithelium].

    PubMed

    Glukhovets, B I; Ukhov, Iu I; Lebedev, S S; Plastun, G A; Bulaeva, V P

    1983-07-01

    The epithelium of normal uterine tubes resected in 38 young women of the child-bearing age during the periods of the maximal physiological fluctuations of the ovarian steroid hormones levels has been studied. The correlative dependence between the morphometrical data and the results of quanitative biochemical analysis of the estrogen excretion has been investigated. The morphometric method reliably reflects the hormone-dependent variabilities of the oviduct epithelium and makes it possible to perform an objective morphological evaluation of the ovarian functional activity. The height and specific density of cells in the epithelial layer, portion of the aciliary cells and nuclear volume of the ciliary cells are the most important for diagnosis as compared to the excretory level of the estrogenic hormones. PMID:6625907

  19. Responses of the rat olfactory epithelium to retronasal air flow.

    PubMed

    Scott, John W; Acevedo, Humberto P; Sherrill, Lisa; Phan, Maggie

    2007-03-01

    Responses of the rat olfactory epithelium were assessed with the electroolfactogram while odorants were presented to the external nares with an artificial sniff or to the internal nares by positive pressure. A series of seven odorants that varied from very polar, hydrophilic odorants to very nonpolar, hydrophobic odorants were used. Although the polar odorants activated the dorsal olfactory epithelium when presented by the external nares (orthonasal presentation), they were not effective when forced through the nasal cavity from the internal nares (retronasal presentation). However, the nonpolar odorants were effective in both stimulus modes. These results were independent of stimulus concentration or of humidity of the carrier air. Similar results were obtained with multiunit recordings from olfactory bulb. These results help to explain why human investigations often report differences in the sensation or ability to discriminate odorants presented orthonasally versus retronasally. The results also strongly support the importance of odorant sorption in normal olfactory processes. PMID:17215498

  20. Odorant-evoked potassium changes in the frog olfactory epithelium.

    PubMed

    Khayari, A; Math, F; Trotier, D

    1991-01-18

    Electroolfactogram (EOG) and extracellular potassium activity (aK) measurements were carried out in frog olfactory epithelia in vivo. Odorant-evoked changes in aK were characterized on the basis of depth profile analysis. Following an olfactory stimulation with butanol vapours, an increase in aK was measured in the mucus and the proximal part of the epithelium; this response started after the beginning of the EOG and was proportional to the amplitude of the latter. In the deeper part of the epithelium, the aK response had complex waveforms showing an initial K decrease which was suppressed by local application of ouabain, suggesting the existence of a pumping mechanism at this level. The results are discussed in terms of extracellular accumulation of K ions following neuroreceptor activation with respect to EOG generation theories. PMID:2015495

  1. Responses of the Rat Olfactory Epithelium to Retronasal Air Flow

    PubMed Central

    Scott, John W.; Acevedo, Humberto P.; Sherrill, Lisa; Phan, Maggie

    2008-01-01

    Responses of the rat olfactory epithelium were assessed with the electroolfactogram while odorants were presented to the external nares with an artificial sniff or to the internal nares by positive pressure. A series of seven odorants that varied from very polar, hydrophilic odorants to very non-polar, hydrophobic odorants were used. While the polar odorants activated the dorsal olfactory epithelium when presented by the external nares (orthonasal presentation), they were not effective when forced through the nasal cavity from the internal nares (retronasal presentation). However, the non-polar odorants were effective in both stimulus modes. These results were independent of stimulus concentration or of humidity of the carrier air. Similar results were obtained with multiunit recording from olfactory bulb. These results help to explain why human investigations often report differences in the sensation or ability to discriminate odorants presented orthonasally vs. retronasally. The results also strongly support the importance of odorant sorption in normal olfactory processes. PMID:17215498

  2. Hydrodynamics of stratified epithelium: Steady state and linearized dynamics

    NASA Astrophysics Data System (ADS)

    Yeh, Wei-Ting; Chen, Hsuan-Yi

    2016-05-01

    A theoretical model for stratified epithelium is presented. The viscoelastic properties of the tissue are assumed to be dependent on the spatial distribution of proliferative and differentiated cells. Based on this assumption, a hydrodynamic description of tissue dynamics at the long-wavelength, long-time limit is developed, and the analysis reveals important insights into the dynamics of an epithelium close to its steady state. When the proliferative cells occupy a thin region close to the basal membrane, the relaxation rate towards the steady state is enhanced by cell division and cell apoptosis. On the other hand, when the region where proliferative cells reside becomes sufficiently thick, a flow induced by cell apoptosis close to the apical surface enhances small perturbations. This destabilizing mechanism is general for continuous self-renewal multilayered tissues; it could be related to the origin of certain tissue morphology, tumor growth, and the development pattern.

  3. Morphological study of fetal nasopharyngeal epithelium in man.

    PubMed

    Gulisano, M; Montella, A; Orlandini, S Z; Pacini, P

    1992-01-01

    In 30 human fetuses between 8 and 13 weeks of intrauterine life the lateral wall of the nasopharynx was examined by light microscopy and transmission and scanning electron microscopy. In the subjects between 8 and 9 weeks in utero the mucosa displays still an immature appearance, being mono- or bistratified and lacking the characteristic structures of the respiratory epithelium. Nevertheless, signs of differentiation are to be noticed, with the presence of two distinct cellular types that, in the later periods, will give rise to ciliated cells and microvillus-provided cells. An almost complete differentiation will be reached at 12-13 weeks in utero, even if goblet cells are still lacking in the examined zone during the considered period. Nonrespiratory types of epithelium, such as transitional or squamous, were never found in the studied subjects. PMID:1514372

  4. Nested expression domains for odorant receptors in zebrafish olfactory epithelium.

    PubMed

    Weth, F; Nadler, W; Korsching, S

    1996-11-12

    The mapping of high-dimensional olfactory stimuli onto the two-dimensional surface of the nasal sensory epithelium constitutes the first step in the neuronal encoding of olfactory input. We have used zebrafish as a model system to analyze the spatial distribution of odorant receptor molecules in the olfactory epithelium by quantitative in situ hybridization. To this end, we have cloned 10 very divergent zebrafish odorant receptor molecules by PCR. Individual genes are expressed in sparse olfactory receptor neurons. Analysis of the position of labeled cells in a simplified coordinate system revealed three concentric, albeit overlapping, expression domains for the four odorant receptors analyzed in detail. Such regionalized expression should result in a corresponding segregation of functional response properties. This might represent the first step of spatial encoding of olfactory input or be essential for the development of the olfactory system. PMID:8917589

  5. Liquid Movement Across the Surface Epithelium of Large Airways

    PubMed Central

    Chambers, Lucy A.; Rollins, Brett M.; Tarran, Robert

    2009-01-01

    The cystic fibrosis conductance regulator CFTR gene is found on chromosome 7 (Kerem et al., 1989; Riordan et al., 1989) and encodes for a 1,480 amino acid protein which is present in the plasma membrane of epithelial cells (Anderson et al., 1992). This protein appears to have many functions, but a unifying theme is that it acts as a protein kinase C- and cyclic AMP-regulated Cl- channel (Winpenny et al., 1995; Jia et al., 1997). In the superficial epithelium of the conducting airways, CFTR is involved in Cl- secretion (Boucher, 2003) and also acts as a regulator of the epithelial Na+ channel (ENaC) and hence Na+ absorption (Boucher et al., 1986; Stutts et al., 1995). In this chapter, we will discuss the regulation of these two ion channels, and how they can influence liquid movement across the superficial airway epithelium. PMID:17692578

  6. Cell Therapy for Cardiovascular Regeneration

    PubMed Central

    2013-01-01

    A great numbers of cardiovascular disease patients all over the world are suffering in the poor outcomes. Under this situation, cardiac regeneration therapy to reorganize the postnatal heart that is defined as a terminal differentiated-organ is a very important theme and mission for human beings. However, the temporary success of several clinical trials using usual cell types with uncertain cell numbers has provided the transient effect of cell therapy to these patients. We therefore should redevelop the evidence of cell-based cardiovascular regeneration therapy, focusing on targets (disease, patient’s status, cardiac function), materials (cells, cytokines, genes), and methodology (transplantation route, implantation technology, tissue engineering). Meanwhile, establishment of the induced pluripotent stem (iPS) cells is an extremely innovative technology which should be proposed as embryonic stem (ES) cellularization of post natal somatic cells, and this application have also showed the milestones of the direct conversion to reconstruct cardiomyocyte from the various somatic cells, which does not need the acquisition of the re-pluripotency. This review discusses the new advance in cardiovascular regeneration therapy from cardiac regeneration to cardiac re-organization, which is involved in recent progress of on-going clinical trials, basic research in cardiovascular regeneration, and the possibility of tissue engineering technology. PMID:23825492

  7. Hindlimb suspension reduces muscle regeneration

    NASA Technical Reports Server (NTRS)

    Mozdziak, P. E.; Truong, Q.; Macius, A.; Schultz, E.

    1998-01-01

    Exposure of juvenile skeletal muscle to a weightless environment reduces growth and satellite cell mitotic activity. However, the effect of a weightless environment on the satellite cell population during muscle repair remains unknown. Muscle injury was induced in rat soleus muscles using the myotoxic snake venom, notexin. Rats were placed into hindlimb-suspended or weightbearing groups for 10 days following injury. Cellular proliferation during regeneration was evaluated using 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and image analysis. Hindlimb suspension reduced (P < 0.05) regenerated muscle mass, regenerated myofiber diameter, uninjured muscle mass, and uninjured myofiber diameter compared to weightbearing rats. Hindlimb suspension reduced (P < 0.05) BrdU labeling in uninjured soleus muscles compared to weight-bearing muscles. However, hindlimb suspension did not abolish muscle regeneration because myofibers formed in the injured soleus muscles of hindlimb-suspended rats, and BrdU labeling was equivalent (P > 0.10) on myofiber segments isolated from the soleus muscles of hindlimb-suspended and weightbearing rats following injury. Thus, hindlimb suspension (weightlessness) does not suppress satellite cell mitotic activity in regenerating muscles before myofiber formation, but reduces growth of the newly formed myofibers.

  8. Anti-inflammatory and protective effects of 2-methacryloyloxyethyl phosphorylcholine polymer on oral epithelial cells.

    PubMed

    Yumoto, Hiromichi; Hirota, Katsuhiko; Hirao, Kouji; Miyazaki, Tsuyoshi; Yamamoto, Nobuyuki; Miyamoto, Koji; Murakami, Keiji; Fujiwara, Natsumi; Matsuo, Takashi; Miyake, Yoichiro

    2015-02-01

    Periodontitis is a chronic inflammatory disease initiated by a microbial biofilm formed in the periodontal pocket. Gingival epithelium plays important roles as the first physical barrier to bacterial invasion and in orchestrating the innate immune reaction via toll-like receptors (TLRs), which recognize various bacterial products, and maintaining its function. Newly developed oral care products to inhibit bacterial adherence, subsequent inflammatory reaction and protect the gingival epithelium are expected. We previously reported that 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer coating decreased bacterial adhesion to human oral keratinocytes, RT-7, and mouth-rinsing with MPC-polymer inhibited the increase of oral bacteria. In this study, regarding the possibility of MPC-polymer application for preventing the adherence of periodontal pathogen, subsequent inflammatory reaction and protection of gingival epithelium, we examined the effects of MPC-polymer on the adherence of Porphyromonas gingivalis, major periodontitis-related pathogen, and TLR2 ligand to RT-7 and subsequent interleukin (IL)-8 production. MPC-polymer treatment significantly reduced P. gingivalis adherence by 44% and TLR2-mediated IL-8 production by blocking the binding of its specific-ligand in a concentration-dependent manner. Furthermore, MPC-polymer pretreatment protected RT-7 from injury by chemical irritants, cetylpyridinium chloride. These findings suggest that MPC-polymer is potentially useful for oral care to prevent oral infection and to maintain oral epithelial function. PMID:24753309

  9. The expression profile of filaggrin-2 in the normal and pathologic human oral mucosa.

    PubMed

    Makino, Teruhiko; Mizawa, Megumi; Inoue, Sayaka; Noguchi, Makoto; Shimizu, Tadamichi

    2016-04-01

    The epithelial cells of the oral cavity show a remarkable degree of regional variation with respect to their morphology and keratinization status. In the oral cavity, the tongue and palate contain keratinizing stratified epithelia, while the buccal mucosa contains non-keratinizing stratified epithelia. We herein examined the expression of filaggrin-2, a member of the S100 fused-type protein family, in the oral mucosa. Filaggrin-2 was weakly expressed in the normal epithelium of the palate, but not in the buccal mucosa or tongue, although filaggrin protein was observed in the epithelium of the buccal mucosa and the palate. We next examined the expression of filaggrin-2 in the oral mucosa of subjects with hyperkeratotic diseases. The expression of filaggrin-2 was markedly increased in the epithelium of the oral mucosa in patients with lichen planus, leukokeratosis and leukoplakia. Filaggrin-2 positivity was observed in granules, some of which were co-localized with those of filaggrin. These results indicate that filaggrin-2 was expressed in the oral mucosa under certain pathological conditions, demonstrating that an aberrant protein expression, together with filaggrin, indicates the altered differentiation program including hyperkeratosis that occurs in these diseases. PMID:26858109

  10. Cell proliferation in the human gallbladder epithelium: effect of distension.

    PubMed Central

    Putz, P; Willems, G

    1979-01-01

    DNA synthesis activity in the epithelium of the human gallbladder was studied through in vitro labelling of mucosal specimens with 3H-thymidine and autoradiography. The specimens were taken at the time of a surgical operation. Eight 'normal' gallbladders and six distended gallbladders from patients with carcinomatous obstruction of the common bile duct were examined. Proliferative activity was very low in the normal and significantly higher in the distended gallbladders. Images Figure PMID:437558

  11. Intraocular involvement with subretinal pigment epithelium infiltrates by mycosis fungoides.

    PubMed Central

    Erny, B. C.; Egbert, P. R.; Peat, I. M.; Shorrock, K.; Rosenthal, A. R.

    1991-01-01

    We report a case of intraocular mycosis fungoides in a 48-year-old man. The patient presented with decreased visual acuity, white subretinal lesions, and vitritis. Post-mortem histopathology revealed malignant T cell infiltrates consistent with mycosis fungoides in the retina, vitreous, and between the retinal pigment epithelium (RPE) and Bruch's membrane Focal atrophy of the RPE, along with the sub-RPE infiltrates, correlated with the clinically visible fundus lesions. Images PMID:1751471

  12. Primary adenocarcinoma of pigmented ciliary epithelium in a phthisical eye.

    PubMed

    Kumar, Jaya B; Proia, Alan D; Mruthyunjaya, Prithvi; Sharma, Sumit

    2016-01-01

    We report a case of adenocarcinoma of the pigmented ciliary epithelium arising in a phthisical eye. A 92-year-old man who initially presented with severe ocular pain had calcification extending from the posterior pole to ciliary body on B-scan ultrasonography to a degree not previously reported. We highlight the importance of screening for intraocular neoplasms in adults with a long-standing phthisical eye. PMID:26597037

  13. Zinc uptake in vitro by human retinal pigment epithelium

    SciTech Connect

    Newsome, D.A.; Rothman, R.J.

    1987-11-01

    Zinc, an essential trace element, is present in unusually high concentrations in the chorioretinal complex relative to most other tissues. Because little has been known about the interactions between the retinal pigment epithelium and free or protein-associated zinc, we studied /sup 65/Zn uptake by human retinal pigment epithelium in vitro. When monolayers were exposed to differing concentrations from 0 to 30 microM /sup 65/Zn in Dulbecco's modified Eagle's medium with 5.4 gm/l glucose at 37 degrees C and 4 degrees C, we observed a temperature-dependent saturable accumulation of the radiolabel. With 15 microM /sup 65/Zn, we saw a biphasic pattern of uptake with a rapid first phase and a slower second phase over 120 min. Uptake of /sup 65/Zn was inhibited by iodacetate and cold, and reduced approximately 50% by the addition of 2% albumin to the labelling medium. Neither ouabain nor 2-deoxyglucose inhibited uptake. Cells previously exposed to /sup 65/Zn retained approximately 70% of accumulated /sup 65/Zn 60 min after being changed to radiolabel-free medium. Following removal of cells from the extracellular matrix adherent to the dish bottom, a variable amount of nonspecific binding of /sup 65/Zn to the residual matrix was demonstrated. These observations are consistent with a facilitated type of transport and demonstrate the ability of human retinal pigment epithelium in vitro to accumulate and retain zinc.

  14. Expression of cytokeratins in the epithelium of canine odontogenic tumours.

    PubMed

    Arzi, B; Murphy, B; Nemec, A; Vapniarsky, N; Naydan, D K; Verstraete, F J M

    2011-11-01

    Odontogenic tumours are considered to be relatively rare; however, several histologically distinct types have been identified in dogs. The more common canine odontogenic tumours are peripheral odontogenic fibroma and canine acanthomatous ameloblastoma. The expression of cytokeratins (CKs) has been established for the human dental germ and odontogenic tumours. The aim of the present study was to describe the immunohistochemical expression of a panel of CKs in the epithelium of the canine dental germ, normal gingiva and odontogenic tumours arising in this species. Samples from 20 odontogenic tumours, 12 tooth germs and three normal gingival tissues were obtained. Each sample was stained with haematoxylin and eosin and subjected to immunohistochemistry for CK expression. The typical expression pattern of CKs in the odontogenic epithelium and gingiva of dogs was CK14 and CK5/6. CKs 7, 8, 18 and 20 were generally absent from the canine dental germ, gingiva and odontogenic tumours. Dogs and man therefore exhibit similar CK expression in the odontogenic epithelium. PMID:21511272

  15. Biomechanics of liquid-epithelium interactions in pulmonary airways.

    PubMed

    Ghadiali, Samir N; Gaver, Donald P

    2008-11-30

    The delicate structure of the lung epithelium makes it susceptible to surface tension induced injury. For example, the cyclic reopening of collapsed and/or fluid-filled airways during the ventilation of injured lungs generates hydrodynamic forces that further damage the epithelium and exacerbate lung injury. The interactions responsible for epithelial injury during airway reopening are fundamentally multiscale, since air-liquid interfacial dynamics affect global lung mechanics, while surface tension forces operate at the molecular and cellular scales. This article will review the current state-of-knowledge regarding the effect of surface tension forces on (a) the mechanics of airway reopening and (b) epithelial cell injury. Due to the complex nature of the liquid-epithelium system, a combination of computational and experimental techniques are being used to elucidate the mechanisms of surface-tension induced lung injury. Continued research is leading to an integrated understanding of the biomechanical and biological interactions responsible for cellular injury during airway reopening. This information may lead to novel therapies that minimize ventilation induced lung injury. PMID:18511356

  16. Pathohistological changes of tracheal epithelium in laryngectomized patients.

    PubMed

    Rosso, Marinela; Prgomet, Drago; Marjanović, Ksenija; Pušeljić, Silvija; Kraljik, Nikola

    2015-11-01

    Total laryngectomy results in a permanent disconnection of the upper and lower airways. Thus, the upper airways are bypassed and can no longer condition, humidify, and filter the inhaled air, leading to damage of the tracheobronchial epithelium. There is little scientific information available about the effects of tracheostoma breathing and the degree of mucosal damage in laryngectomized patients. The aims of this study were to determine the histopathologic findings and investigate the potential impact of using a heat and moisture exchanger (HME) on the tracheal epithelium in long-term tracheostomy patients. Tracheal mucosal biopsies were taken from a total of 70 patients. Specimens were stained with hematoxylin and eosin and examined by a light microscope. Normal pseudostratified ciliated columnar epithelium was found in only 9 (12.9%) cases; while, 17 (24.3%) cases had some degree of basal cell hyperplasia. Squamous metaplasia was the most common finding (50%). Pre-invasive lesions (mild and moderate squamous dysplasia) were found in only one patient who used an HME, and in eight (11.4%) non-users. Although the HME cannot completely restore the physiological functions of the upper respiratory track, it delivers a better quality of air to the lower airways and has a positive effect on tracheal mucosa. PMID:25399353

  17. Cultured lung epithelium: A cellular model for lung preservation.

    PubMed

    Lee, C Y; Matsumoto-Pon, J; Widdicombe, J H

    1997-11-01

    Cellular models have helped with the development of conditions needed for hypothermic preservation of kidney, liver, and heart. Recently, highly differentiated cultured lung epithelial cell lines grown with basolateral side feeding technique have become available that can mimic airspace, epithelium, and interstitium of lung parenchyma. Cultured lung epithelium coupled with Ussing's short-circuit current technique was used as a cellular model system for lung preservation. A parametric study was conducted to correlate the effects of luminal fluid composition (University of Wisconsin (UW) solution and phosphate-buffered saline) and storage gas (air vs nitrogen) at 4 degrees C for 24 h on postischemic electrogenic properties (transepithelial ion transport and resistance). The results showed that cells were better preserved with the UW solution on both sides as measured by their transepithelial resistance, an indicator of tight junction integrity (Rte approximately 65% of control values approximately 135 Omega cm2). In addition, they responded better to mediators that stimulate chloride secretion than cells preserved with other conditions. Cells preserved with no additional fluid on the apical side had substantially lowered Rte (<20%) than those preserved with an additional thin layer of fluid ( approximately 35-65%). This cellular model system is a realistic representation of lung epithelium and can provide an accurate assessment of preservation quality through the measurements of tight junction integrity and active ion transport. PMID:9367609

  18. In vitro biology of corneal epithelium and endothelium.

    PubMed Central

    Yanoff, M

    1975-01-01

    Four main areas are explored: (1) the proper culture medium for corneal tissue; (2) the effect of serum on in vitro tissue growth; (3) the in vitro interrelationships between corneal epithelium and endothelium; and (4) the biology of cultures of whole corneas (organ cultures). Modified Eagle's minimal essential medium (MEM) proved to be an excellent culture fluid. Corneal tissue could be grown in MEM without serum or clot, thus providing a defined culture medium. The in vitro biology of outgrowths of multilayered corneal epithelium and monolayered corneal endothelium are discussed. Contact inhibition between epithelium and endothelium is demonstrated in whole corneal (organ) cultures. Images FIGURE 5 A FIGURE 5 B FIGURE 10 A FIGURE 10 B FIGURE 1 A FIGURE 1 B FIGURE 1 C FIGURE 2 A FIGURE 2 B FIGURE 3 A FIGURE 3 B FIGURE 4 A FIGURE 4 B FIGURE 6 A FIGURE 6 B FIGURE 7 A FIGURE 7 B FIGURE 8 A FIGURE 8 B FIGURE 9 A FIGURE 9 B FIGURE 11 A FIGURE 11 B FIGURE 12 A FIGURE 12 B FIGURE 12 C FIGURE 13 FIGURE 14 A FIGURE 14 B FIGURE 15 A FIGURE 15 B FIGURE 16 A FIGURE 16 B FIGURE 17 A FIGURE 17 B FIGURE 17 C FIGURE 18 A FIGURE 18 B PMID:1246815

  19. Oral malignant melanoma: Report of three cases with literature review

    PubMed Central

    Gupta, Shalini; Tandon, Ankita; Ram, Hari; Gupta, O. P.

    2015-01-01

    Primary oral melanoma is known to be an extremely rare and aggressive neoplasm arising from the mucosal epithelium of the oral cavity especially upper jaw (palate or alveolar gingivae). Malignant melanoma that does not originate in the skin is a very rare disease and is considered one of the most deadly of all human neoplasms. Oral malignant melanoma (OMM) represents about 1% of all melanomas and approximately 0.5% of all oral malignancies. OMM has been reported in patients aged 20 to 80 years and has a male predilection. Because most mucosal melanotic lesions are painless in their early stages, so delayed recognition and subsequent treatment result in worst prognosis. Here, we report three cases with significant heterogeneity in morphological features and biologic behavior. PMID:26668465

  20. The use of platelet rich plasma with guided tissue regeneration in defects caused by periodontal diseases.

    PubMed

    Holly, D; Mracna, J

    2009-01-01

    The goal of periodontal treatment in not only the stabilization of disease but also the regeneration of the destructed tissue. In the past few years various procedures have been created to achieve this. The guided tissue regeneration is a surgical procedure developed on the basis of experimental studies. It enables the creation of periodontal tissues affected by periodontitis, the so called reattachment. It stands for formation of new attachment--meaning the regeneration of cementum, alveolar bone and periodontal ligament. This surgical procedure of the treatment of periodontitis is based on the principle of exclusion of the epithelium and also the gingival connective tissue from the root surface so the precursor cells (desmodontal cells) can occupy the defect and pursue their differentiation. Periodontal ligament containing cells with regenerative potential are the exclusive ones to have the ability to regenerate structures affected by periodontitis. The use of growth factors offer new aspects to the therapy (Fig. 7, Ref. 11). Full Text (Free, PDF) www.bmj.sk. PMID:20017463

  1. Current strategies for the protection, regeneration, and replacement of cochlear hair cells.

    PubMed

    Perde-Schrepler, Maria; Maniu, Alma; Cosgarea, Marcel

    2012-08-01

    Sensorineural hearing loss, which is often caused by degeneration of hair cells in the auditory epithelium, is permanent because lost hair cells cannot be replaced in mammals. In recent years, important progress has been made in understanding the mechanisms involved in hair cell damage and, more importantly, the reasons why hair cells cannot be regenerated spontaneously in mammals. The knowledge of the factors implicated in hair cell fate determination and of the mechanisms of hair cell regeneration in birds could help in the effort to find a treatment for hearing loss. Although cochlear implant technology is advanced, it still provides only moderate hearing capacity in sensorineural deaf individuals. Inducible stem cells and molecular therapies are appealing alternatives to the cochlear implant as they hold the promise of a cure. It is important to develop a safe and effective means to deliver stem cells or genes to the correct sites to stimulate regeneration in the right place. This review aims to synthesize the present knowledge in the field of sensorineural hearing loss, focusing on the mechanisms involved in hair cell development and regeneration, with the specific purpose of identifying new therapeutic strategies. Despite tremendous progress in this field, most of the concepts discussed in this review are still in the experimental stage. PMID:22935173

  2. Distribution and time course of hair cell regeneration in the pigeon utricle

    NASA Technical Reports Server (NTRS)

    Dye, B. J.; Frank, T. C.; Newlands, S. D.; Dickman, J. D.

    1999-01-01

    Vestibular and cochlear regeneration following ototoxic insult from aminoglycoside antibiotics has been well documented, particularly in birds. In the present study, intraotic application of a 2 mg streptomycin paste was used to achieve complete vestibular hair cell destruction in pigeons (Columba livia) while preserving regenerative ability. Scanning electron microscopy was used to quantify hair cell density longitudinally during regeneration in three different utricular macula locations, including the striola, central and peripheral regions. The utricular epithelium was void of stereocilia (indicating hair cell loss) at 4 days after intraotic treatment with streptomycin. At 2 weeks the stereocilia began to appear randomly and mostly in an immature form. However, when present most kinocilia were polarized toward the developing striola. Initially, regeneration occurred more rapidly in the central and peripheral regions of the utricle as compared to the striola. As regeneration proceeded from 2 to 12 weeks, hair cell density in the striola region equaled the density noted in the central and peripheral regions. At 24 weeks, hair cell density of the central and peripheral regions was equal to normal values, however the striola region had a slightly greater hair cell density than that observed for normal animals.

  3. The regeneration blastema of lizards: an amniote model for the study of appendage replacement

    PubMed Central

    Gilbert, E. A. B.; Delorme, S. L.

    2015-01-01

    Abstract Although amniotes (reptiles, including birds, and mammals) are capable of replacing certain tissues, complete appendage regeneration is rare. Perhaps the most striking example is the lizard tail. Tail loss initiates a spontaneous epimorphic (blastema‐mediated) regenerative program, resulting in a fully functional but structurally non‐identical replacement. Here we review lizard tail regeneration with a particular focus on the blastema. In many lizards, the original tail has evolved a series of fracture planes, anatomical modifications that permit the tail to be self‐detached or autotomized. Following tail loss, the wound site is covered by a specialized wound epithelium under which the blastema develops. An outgrowth of the spinal cord, the ependymal tube, plays a key role in governing growth (and likely patterning) of the regenerate tail. In some species (e.g., geckos), the blastema forms as an apical aggregation of proliferating cells, similar to that of urodeles and teleosts. For other species (e.g., anoles) the identification of a proliferative blastema is less obvious, suggesting an unexpected diversity in regenerative mechanisms among tail‐regenerating lizards. PMID:27499867

  4. Molecular Sieve Regeneration System (MSRS)

    SciTech Connect

    Nasise, J.E.; Anderson, J.L. ); Naruse, Y. )

    1992-01-01

    A Molecular Sieve Regeneration System (MSRS) was added to the existing Tritium Waste Treatment system (TWT) within the Tritium Systems Test Assembly (TSTA) at Los Alamos National Laboratory. The Department of Energy (DOE) no longer allows inventory by difference'' for radioactive wastes that are to be buried. The MSRS was designed and built to comply with this requirement. Within the TWT, water is generated by the catalytic conversion of hydrogen isotopes and removed by molecular sieve trapping prior to release to the environment. Molecular sieve regeneration is required to remove the trapped water and to rejuvenate the beds. The MSRS permits the collection and direct tritium assay of regenerated tritiated water from molecular sieve beds. This paper describes the MSRS in detail and how it is interfaced with the TWT.

  5. Molecular Sieve Regeneration System (MSRS)

    SciTech Connect

    Nasise, J.E.; Anderson, J.L.; Naruse, Y.

    1992-03-01

    A Molecular Sieve Regeneration System (MSRS) was added to the existing Tritium Waste Treatment system (TWT) within the Tritium Systems Test Assembly (TSTA) at Los Alamos National Laboratory. The Department of Energy (DOE) no longer allows ``inventory by difference`` for radioactive wastes that are to be buried. The MSRS was designed and built to comply with this requirement. Within the TWT, water is generated by the catalytic conversion of hydrogen isotopes and removed by molecular sieve trapping prior to release to the environment. Molecular sieve regeneration is required to remove the trapped water and to rejuvenate the beds. The MSRS permits the collection and direct tritium assay of regenerated tritiated water from molecular sieve beds. This paper describes the MSRS in detail and how it is interfaced with the TWT.

  6. Regenerator cross arm seal assembly

    DOEpatents

    Jackman, Anthony V.

    1988-01-01

    A seal assembly for disposition between a cross arm on a gas turbine engine block and a regenerator disc, the seal assembly including a platform coextensive with the cross arm, a seal and wear layer sealingly and slidingly engaging the regenerator disc, a porous and compliant support layer between the platform and the seal and wear layer porous enough to permit flow of cooling air therethrough and compliant to accommodate relative thermal growth and distortion, a dike between the seal and wear layer and the platform for preventing cross flow through the support layer between engine exhaust and pressurized air passages, and air diversion passages for directing unregenerated pressurized air through the support layer to cool the seal and wear layer and then back into the flow of regenerated pressurized air.

  7. Self-regenerating column chromatography

    SciTech Connect

    Park, Woo K.

    1994-12-31

    The present invention provides a process for treating both cations and anions by using a self-regenerating, multi-ionic exchange resin column system which requires no separate regeneration steps. The process involves alternation ion-exchange chromatography for cations and anions in a multi-ionic exchange column packed with a mixture of cation and anion exchange resins. The multi-ionic mixed-charge resin column works as a multifunction column, capable of independently processing either cationic or anionic exchange, or simultaneously processing both cationic and anionic exchanges. The major advantage offered by the alternating multifunction ion exchange process is the self-regeneration of the resins. Applications are to separation of nitrogen and sulfur isotopes.

  8. Ceramic regenerator systems development program

    NASA Technical Reports Server (NTRS)

    Fucinari, C. A.; Rahnke, C. J.; Rao, V. D. N.; Vallance, J. K.

    1980-01-01

    The DOE/NASA Ceramic Regenerator Design and Reliability Program aims to develop ceramic regenerator cores that can be used in passenger car and industrial/truck gas turbine engines. The major cause of failure of early gas turbine regenerators was found to be chemical attack of the ceramic material. Improved materials and design concepts aimed at reducing or eliminating chemical attack were placed on durability test in Ford 707 industrial gas turbine engines late in 1974. Results of 53,065 hours of turbine engine durability testing are described. Two materials, aluminum silicate and magnesium aluminum silicate, show promise. Five aluminum silicate cores attained the durability objective of 10,000 hours at 800 C (1472 F). Another aluminum silicate core shows minimal evidence of chemical attack after 8071 hours at 982 C (1800 F). Results obtained in ceramic material screening tests, aerothermodynamic performance tests, stress analysis, cost studies, and material specifications are included.

  9. Self-regenerating column chromatography

    DOEpatents

    Park, W.K.

    1995-05-30

    The present invention provides a process for treating both cations and anions by using a self-regenerating, multi-ionic exchange resin column system which requires no separate regeneration steps. The process involves alternating ion-exchange chromatography for cations and anions in a multi-ionic exchange column packed with a mixture of cation and anion exchange resins. The multi-ionic mixed-charge resin column works as a multi-function column, capable of independently processing either cationic or anionic exchange, or simultaneously processing both cationic and anionic exchanges. The major advantage offered by the alternating multi-function ion exchange process is the self-regeneration of the resins.

  10. Cardiac regeneration: epicardial mediated repair

    PubMed Central

    2015-01-01

    The hearts of lower vertebrates such as fish and salamanders display scarless regeneration following injury, although this feature is lost in adult mammals. The remarkable capacity of the neonatal mammalian heart to regenerate suggests that the underlying machinery required for the regenerative process is evolutionarily retained. Recent studies highlight the epicardial covering of the heart as an important source of the signalling factors required for the repair process. The developing epicardium is also a major source of cardiac fibroblasts, smooth muscle, endothelial cells and stem cells. Here, we examine animal models that are capable of scarless regeneration, the role of the epicardium as a source of cells, signalling mechanisms implicated in the regenerative process and how these mechanisms influence cardiomyocyte proliferation. We also discuss recent advances in cardiac stem cell research and potential therapeutic targets arising from these studies. PMID:26702046

  11. Raman microspectroscopic study of oral buccal mucosa

    NASA Astrophysics Data System (ADS)

    Behl, Isha; Mamgain, Hitesh; Deshmukh, Atul; Kukreja, Lekha; Hole, Arti R.; Krishna, C. Murali

    2014-03-01

    Oral cancer is the most common cancer among Indian males, with 5-year- survival-rates of less than 50%. Efficacy of Raman spectroscopic methods in non-invasive and objective diagnosis of oral cancers and confounding factors has already been demonstrated. The present Raman microspectroscopic study was undertaken for in-depth and site-specific analysis of normal and tumor tissues. 10 normal and 10 tumors unstained sections from 20 tissues were accrued. Raman data of 160 x 60 μm and 140 x 140 μm in normal and tumor sections, respectively, were acquired using WITec alpha 300R equipped with 532 nm laser, 50X objective and 600 gr/mm grating. Spectral data were corrected for CCDresponse, background. First-derivitized and vector-normalized data were then subjected to K-mean cluster analysis to generate Raman maps and correlated with their respective histopathology. In normal sections, stratification among epithelial layers i.e. basal, intermediate, superficial was observed. Tumor, stromal and inflammatory regions were identified in case of tumor section. Extracted spectra of the pathologically annotated regions were subjected to Principal component analysis. Findings suggest that all three layers of normal epithelium can be differentiated against tumor cells. In epithelium, basal and superficial layers can be separated while intermediate layer show misclassifications. In tumors, discrimination of inflammatory regions from tumor cells and tumor-stroma regions were observed. Finding of the study indicate Raman mapping can lead to molecular level insights of normal and pathological states.

  12. Hyaluronic acid production and hyaluronidase activity in the newt iris during lens regeneration

    SciTech Connect

    Kulyk, W.M.; Zalik, S.E.; Dimitrov, E.

    1987-09-01

    The process of lens regeneration in newts involves the dedifferentiation of pigmented iris epithelial cells and their subsequent conversion into lens fibers. In vivo this cell-type conversion is restricted to the dorsal region of the iris. We have examined the patterns of hyaluronate accumulation and endogenous hyaluronidase activity in the newt iris during the course of lens regeneration in vivo. Accumulation of newly synthesized hyaluronate was estimated from the uptake of (/sup 3/H)glucosamine into cetylpyridinium chloride-precipitable material that was sensitive to Streptomyces hyaluronidase. Endogenous hyaluronidase activity was determined from the quantity of reducing N-acetylhexosamine released upon incubation of iris tissue extract with exogenous hyaluronate substrate. We found that incorporation of label into hyaluronate was consistently higher in the regeneration-activated irises of lentectomized eyes than in control irises from sham-operated eyes. Hyaluronate labeling was higher in the dorsal (lens-forming) region of the iris than in ventral (non-lens-forming) iris tissue during the regeneration process. Label accumulation into hyaluronate was maximum between 10 and 15 days after lentectomy, the period of most pronounced dedifferentiation in the dorsal iris epithelium. Both normal and regenerating irises demonstrated a high level of endogenous hyaluronidase activity with a pH optimum of 3.5-4.0. Hyaluronidase activity was 1.7 to 2 times higher in dorsal iris tissue than in ventral irises both prior to lentectomy and throughout the regeneration process. We suggest that enhanced hyaluronate accumulation may facilitate the dedifferentiation of iris epithelial cells in the dorsal iris and prevent precocious withdrawal from the cell cycle. The high level of hyaluronidase activity in the dorsal iris may promote the turnover and remodeling of extracellular matrix components required for cell-type conversion.

  13. Ceramic regenerator systems development program

    NASA Technical Reports Server (NTRS)

    Cook, J. A.; Fucinari, C. A.; Lingscheit, J. N.; Rahnke, C. J.; Rao, V. D.

    1978-01-01

    Ceramic regenerator cores are considered that can be used in passenger car gas turbine engines, Stirling engines, and industrial/truck gas turbine engines. Improved materials and design concepts aimed at reducing or eliminating chemical attack were placed on durability tests/in industrial gas turbine engines. A regenerator core made from aluminum silicate shows minimal evidence of chemical attack damage after 7804 hours of engine test at 800 C and another showed little distress after 4983 hours at 982 C. The results obtained in ceramic material screening tests, aerothermodynamic performance tests, stress analysis, cost studies, and material specifications are also included.

  14. A model regenerator for a Stirling cycle

    NASA Astrophysics Data System (ADS)

    Carolan, James

    2001-05-01

    An essential feature of the engine patented by Robert Stirling in 1817 was the careful description of the idea of regeneration. In the standard thermodynamic cycle representation of the engine, regeneration is the storing and the reusing of the thermal energy released in the constant volume cooling part of the cycle. Due to the difficulty in treating regeneration quantitatively, introductory physics texts generally either ignore the concept or assume the regeneration to be perfect. As a result students obtain little or no understanding of regeneration. In addition there seem to be differing views in various texts about the efficiency of Stirling engines. In this work a simple finite element model regenerator is presented with which one can do simple calculations. The model does not accurately represent actual regeneration in a practical engine. But the model might help students gain better insight into Stirling engine efficiency and the idea of regeneration.

  15. Regulation of crustacean molting and regeneration

    SciTech Connect

    Skinner, D.M.; Graham, D.E.; Holland, C.A.; Soumoff, C.; Mykles, D.L.

    1981-01-01

    The regulation of molting and regeneration by two antagonistic hormones is discussed. The time course of ecdysteroid titers in crustacean tissues has been followed during molt and regeneration cycles. (ACR)

  16. Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune/epithelial cell interaction

    SciTech Connect

    Pellegrina, Chiara Dalla; Perbellini, Omar; Scupoli, Maria Teresa; Tomelleri, Carlo; Zanetti, Chiara; Zoccatelli, Gianni; Fusi, Marina; Peruffo, Angelo; Rizzi, Corrado; Chignola, Roberto

    2009-06-01

    Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed, among many others, by human gastrointestinal epithelial and immune cells. WGA is a toxic compound and an anti-nutritional factor, but recent works have shown that it may have potential as an anti-tumor drug and as a carrier for oral drugs. To quantitate the toxicity threshold for WGA on normal epithelial cells we previously investigated the effects of the lectin on differentiated Caco2 cells, and showed that in the micromolar range of concentrations WGA could alter the integrity of the epithelium layer and increase its permeability to both mannitol and dextran. WGA was shown to be uptaken by Caco2 cells and only {approx} 0.1% molecules were observed to cross the epithelium layer by transcytosis. Here we show that at nanomolar concentrations WGA is unexpectedly bioactive on immune cells. The supernatants of WGA-stimulated peripheral blood mononuclear cells (PBMC) can alter the integrity of the epithelium layer when administered to the basolateral side of differentiated Caco2 cells and the effects can be partially inhibited by monoclonal antibodies against IL1, IL6 and IL8. At nanomolar concentrations WGA stimulates the synthesis of pro-inflammatory cytokines and thus the biological activity of WGA should be reconsidered by taking into account the effects of WGA on the immune system at the gastrointestinal interface. These results shed new light onto the molecular mechanisms underlying the onset of gastrointestinal disorders observed in vivo upon dietary intake of wheat-based foods.

  17. Effects of wheat germ agglutinin on human gastrointestinal epithelium: insights from an experimental model of immune/epithelial cell interaction.

    PubMed

    Dalla Pellegrina, Chiara; Perbellini, Omar; Scupoli, Maria Teresa; Tomelleri, Carlo; Zanetti, Chiara; Zoccatelli, Gianni; Fusi, Marina; Peruffo, Angelo; Rizzi, Corrado; Chignola, Roberto

    2009-06-01

    Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed, among many others, by human gastrointestinal epithelial and immune cells. WGA is a toxic compound and an anti-nutritional factor, but recent works have shown that it may have potential as an anti-tumor drug and as a carrier for oral drugs. To quantitate the toxicity threshold for WGA on normal epithelial cells we previously investigated the effects of the lectin on differentiated Caco2 cells, and showed that in the micromolar range of concentrations WGA could alter the integrity of the epithelium layer and increase its permeability to both mannitol and dextran. WGA was shown to be uptaken by Caco2 cells and only approximately 0.1% molecules were observed to cross the epithelium layer by transcytosis. Here we show that at nanomolar concentrations WGA is unexpectedly bioactive on immune cells. The supernatants of WGA-stimulated peripheral blood mononuclear cells (PBMC) can alter the integrity of the epithelium layer when administered to the basolateral side of differentiated Caco2 cells and the effects can be partially inhibited by monoclonal antibodies against IL1, IL6 and IL8. At nanomolar concentrations WGA stimulates the synthesis of pro-inflammatory cytokines and thus the biological activity of WGA should be reconsidered by taking into account the effects of WGA on the immune system at the gastrointestinal interface. These results shed new light onto the molecular mechanisms underlying the onset of gastrointestinal disorders observed in vivo upon dietary intake of wheat-based foods. PMID:19332085

  18. An ancient dental gene set governs development and continuous regeneration of teeth in sharks.

    PubMed

    Rasch, Liam J; Martin, Kyle J; Cooper, Rory L; Metscher, Brian D; Underwood, Charlie J; Fraser, Gareth J

    2016-07-15

    The evolution of oral teeth is considered a major contributor to the overall success of jawed vertebrates. This is especially apparent in cartilaginous fishes including sharks and rays, which develop elaborate arrays of highly specialized teeth, organized in rows and retain the capacity for life-long regeneration. Perpetual regeneration of oral teeth has been either lost or highly reduced in many other lineages including important developmental model species, so cartilaginous fishes are uniquely suited for deep comparative analyses of tooth development and regeneration. Additionally, sharks and rays can offer crucial insights into the characters of the dentition in the ancestor of all jawed vertebrates. Despite this, tooth development and regeneration in chondrichthyans is poorly understood and remains virtually uncharacterized from a developmental genetic standpoint. Using the emerging chondrichthyan model, the catshark (Scyliorhinus spp.), we characterized the expression of genes homologous to those known to be expressed during stages of early dental competence, tooth initiation, morphogenesis, and regeneration in bony vertebrates. We have found that expression patterns of several genes from Hh, Wnt/β-catenin, Bmp and Fgf signalling pathways indicate deep conservation over ~450 million years of tooth development and regeneration. We describe how these genes participate in the initial emergence of the shark dentition and how they are redeployed during regeneration of successive tooth generations. We suggest that at the dawn of the vertebrate lineage, teeth (i) were most likely continuously regenerative structures, and (ii) utilised a core set of genes from members of key developmental signalling pathways that were instrumental in creating a dental legacy redeployed throughout vertebrate evolution. These data lay the foundation for further experimental investigations utilizing the unique regenerative capacity of chondrichthyan models to answer evolutionary

  19. Cryogenic regenerator including sarancarbon heat conduction matrix

    NASA Technical Reports Server (NTRS)

    Jones, Jack A. (Inventor); Petrick, S. Walter (Inventor); Britcliffe, Michael J. (Inventor)

    1989-01-01

    A saran carbon matrix is employed to conduct heat through the heat storing volume of a cryogenic regenerator. When helium is adsorbed into the saran carbon matrix, the combination exhibits a volumetric specific heat much higher than previously used lead balls. A helium adsorbed saran regenerator should allow much lower refrigerator temperatures than those practically obtainable with lead based regenerators for regenerator type refrigeration systems.

  20. Patterned substrates and methods for nerve regeneration

    DOEpatents

    Mallapragada, Surya K.; Heath, Carole; Shanks, Howard; Miller, Cheryl A.; Jeftinija, Srdija

    2004-01-13

    Micropatterned substrates and methods for fabrication of artificial nerve regeneration conduits and methods for regenerating nerves are provided. Guidance compounds or cells are seeded in grooves formed on the patterned substrate. The substrates may also be provided with electrodes to provide electrical guidance cues to the regenerating nerve. The micropatterned substrates give physical, chemical, cellular and/or electrical guidance cues to promote nerve regeneration at the cellular level.

  1. Mesenchymal-epithelial interactions during digestive tract development and epithelial stem cell regeneration.

    PubMed

    Le Guen, Ludovic; Marchal, Stéphane; Faure, Sandrine; de Santa Barbara, Pascal

    2015-10-01

    The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior-posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal-epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal-epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal-epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration. PMID:26126787

  2. Survivin expression in oral lichen planus: Role in malignant transformation

    PubMed Central

    Suganya, G; Bavle, Radhika M; Paremala, K; Makarla, Soumya; Sudhakar, M; Reshma, V

    2016-01-01

    Context: Oral lichen planus (OLP) is a potentially malignant disease with a prevalence rate of 0.5–2.2%. It is a T-cell-mediated autoimmune disease, in which cytotoxic CD8+ T-cells trigger apoptosis of the basal cells of oral epithelium. The reported progression of OLP to oral squamous cell carcinoma (OSCC) ranges from 0.4% to 6.5%. Apoptosis plays a major role in the maintenance of tissue homeostasis. The evasion of apoptosis in the form of dysregulation of inhibitors of apoptosis proteins (IAPs) may lead to malignant transformation. Survivin belongs to the second gene family of IAPs, which is overexpressed in many tumors such as OSCC and gastric carcinomas, and its expression is widely involved in apoptosis as well as in tumor metastasis. Materials and Methods: Sections were obtained from the paraffin-embedded archival blocks of patients diagnosed histologically as OLP, and cases with normal epithelium were used for comparison whereas cases with OSCC were used as positive control. Results: We analyzed the expression of survivin in OLP and normal epithelium. Survivin expression with moderate intensity was seen in the cells of basal layer with nuclear positivity in cases of OLP, whereas mild to nil expression was seen in normal epithelium with nuclear and cytoplasmic positivity in different layers. Conclusions: Survivin positivity was seen predominantly in the basal cells of OLP suggesting increased longevity of these cells which in turn might acquire dysplastic changes leading to increased risk of malignant transformation of this premalignant condition. Although the conversion rate may be low, the potential exists in the indolent course of the disease. PMID:27601815

  3. Regeneration: New Neurons Wire Up.

    PubMed

    Raymond, Pamela A

    2016-09-12

    Functional repair of damage in the nervous system requires re-establishment of precise patterns of synaptic connectivity. A new study shows that after selective ablation, zebrafish retinal neurons regenerate and reconstruct some, although not all, of their stereotypic wiring. PMID:27623258

  4. Increasing FCC regenerator catalyst level

    SciTech Connect

    Wong, R.F. )

    1993-11-01

    A Peruvian FCC unit's operations were improved by increasing the regenerator's catalyst level. This increase resulted in lower stack losses, an improved temperature profile, increased catalyst activity and a lower catalyst consumption rate. A more stable operation saved this Peruvian refiner over $131,000 per year in catalyst alone. These concepts and data may be suitable for your FCC unit as well.

  5. Cytoskeletal regulation of dermal regeneration.

    PubMed

    Strudwick, Xanthe L; Cowin, Allison J

    2012-01-01

    Wound healing results in the repair of injured tissues however fibrosis and scar formation are, more often than not the unfortunate consequence of this process. The ability of lower order vertebrates and invertebrates to regenerate limbs and tissues has been all but lost in mammals; however, there are some instances where glimpses of mammalian regenerative capacity do exist. Here we describe the unlocked potential that exists in mammals that may help us understand the process of regeneration post-injury and highlight the potential role of the actin cytoskeleton in this process. The precise function and regulation of the cytoskeleton is critical to the success of the healing process and its manipulation may therefore facilitate regenerative healing. The gelsolin family of actin remodelling proteins in particular has been shown to have important functions in wound healing and family member Flightless I (Flii) is involved in both regeneration and repair. Understanding the interactions between different cytoskeletal proteins and their dynamic control of processes including cellular adhesion, contraction and motility may assist the development of therapeutics that will stimulate regeneration rather than repair. PMID:24710556

  6. Cryopump regeneration method and apparatus

    SciTech Connect

    Andeen, B.R.; Pandorf, R.C.

    1988-01-12

    A vacuum system is described comprising: a cryopump for evacuating a chamber; an ejector pump in direct communication with the cryopump through a valve for removing gas from the cryopump during regeneration; and a source of pressurized, substantially inert gas in a communication with the ejector pump for use as the actuating fluid in the ejector pump.

  7. Cytoskeletal Regulation of Dermal Regeneration

    PubMed Central

    Strudwick, Xanthe L.; Cowin, Allison J.

    2012-01-01

    Wound healing results in the repair of injured tissues however fibrosis and scar formation are, more often than not the unfortunate consequence of this process. The ability of lower order vertebrates and invertebrates to regenerate limbs and tissues has been all but lost in mammals; however, there are some instances where glimpses of mammalian regenerative capacity do exist. Here we describe the unlocked potential that exists in mammals that may help us understand the process of regeneration post-injury and highlight the potential role of the actin cytoskeleton in this process. The precise function and regulation of the cytoskeleton is critical to the success of the healing process and its manipulation may therefore facilitate regenerative healing. The gelsolin family of actin remodelling proteins in particular has been shown to have important functions in wound healing and family member Flightless I (Flii) is involved in both regeneration and repair. Understanding the interactions between different cytoskeletal proteins and their dynamic control of processes including cellular adhesion, contraction and motility may assist the development of therapeutics that will stimulate regeneration rather than repair. PMID:24710556

  8. Epithelial barrier and oral bacterial infection.

    PubMed

    Groeger, Sabine E; Meyle, Joerg

    2015-10-01

    The oral epithelial barrier separates the host from the environment and provides the first line of defense against pathogens, exogenous substances and mechanical stress. It consists of underlying connective tissue and a stratified keratinized epithelium with a basement membrane, whose cells undergo terminal differentiation resulting in the formation of a mechanically resistant surface. Gingival keratinocytes are connected by various transmembrane proteins, such as tight junctions, adherens junctions and gap junctions, each of which has a specialized structure and specific functions. Periodontal pathogens are able to induce inflammatory responses that lead to attachment loss and periodontal destruction. A number of studies have demonstrated that the characteristics of pathogenic oral bacteria influence the expression and structural integrity of different cell-cell junctions. Tissue destruction can be mediated by host cells following stimulation with cytokines and bacterial products. Keratinocytes, the main cell type in gingival epithelial tissues, express a variety of proinflammatory cytokines and chemokines, including interleukin-1alpha, interleukin-1beta, interleukin-6, interleukin-8 and tumor necrosis factor-alpha. Furthermore, the inflammatory mediators that may be secreted by oral keratinocytes are vascular endothelial growth factor, prostaglandin E2 , interleukin-1 receptor antagonist and chemokine (C-C motif) ligand 2. The protein family of matrix metalloproteinases is able to degrade all types of extracellular matrix protein, and can process a number of bioactive molecules. Matrix metalloproteinase activities under inflammatory conditions are mostly deregulated and often increased, and those mainly relevant in periodontal disease are matrix metalloproteinases 1, 2, 3, 8, 9, 13 and 24. Viral infection may also influence the epithelial barrier. Studies show that the expression of HIV proteins in the mucosal epithelium is correlated with the disruption of

  9. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

    NASA Technical Reports Server (NTRS)

    Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

    2002-01-01

    Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

  10. Frequent genomic alterations in epithelium measured by microsatellite instability following allogeneic hematopoietic cell transplantation in humans.

    PubMed

    Faber, Philipp; Fisch, Paul; Waterhouse, Miguel; Schmitt-Gräff, Annette; Bertz, Hartmut; Finke, Jürgen; Spyridonidis, Alexandros

    2006-04-15

    Although typically found in cancers, frameshift mutations in microsatellites have also been detected in chronically inflamed tissues. Allogeneic hematopoietic cell transplantation (HCT) may potentially produce chronic tissue stress through graft-versus-host reactions. We examined non-neoplastic epithelial tissues (colon, buccal) obtained 1 to 5061 days after human allogeneic HCT for the presence of genomic alterations at 3 tetranucleotide and 3 mononucleotide microsatellite loci. Novel bands indicative of microsatellite instability (MSI) at tetranucleotide repeats were detected in laser-microdissected colonic crypts and in buccal smears of 75% and 42% of patients who received an allograft, respectively. In contrast, no MSI was found in similar tissues from control subjects and from patients after intensive chemotherapy or in buccal cells from patients after autologous HCT. The MSI found in colon, which was often affected by graft-versus-host disease, was not due to loss of expression or nitrosylation of DNA repair proteins. MSI in clinically intact oral mucosa was more frequently found at later time points after HCT. MSI was also found in 3 posttransplant squamous cell cancers examined. Our data show that genomic alterations in epithelium regularly occur after allogeneic HCT and may be implicated in the evolution of posttransplantation diseases, including secondary cancer. PMID:16368884

  11. Pigment Epithelium Derived Factor Peptide Protects Murine Hepatocytes from Carbon Tetrachloride-Induced Injury

    PubMed Central

    Shih, Shou-Chuan; Ho, Tsung-Chuan; Chen, Show-Li; Tsao, Yeou-Ping

    2016-01-01

    Fibrogenesis is induced by repeated injury to the liver and reactive regeneration and leads eventually to liver cirrhosis. Pigment epithelium derived factor (PEDF) has been shown to prevent liver fibrosis induced by carbon tetrachloride (CCl4). A 44 amino acid domain of PEDF (44-mer) was found to have a protective effect against various insults to several cell types. In this study, we investigated the capability of synthetic 44-mer to protect against liver injury in mice and in primary cultured hepatocytes. Acute liver injury, induced by CCl4, was evident from histological changes, such as cell necrosis, inflammation and apoptosis, and a concomitant reduction of glutathione (GSH) and GSH redox enzyme activities in the liver. Intraperitoneal injection of the 44-mer into CCl4-treated mice abolished the induction of AST and ALT and markedly reduced histological signs of liver injury. The 44-mer treatment can reduce hepatic oxidative stress as evident from lower levels of lipid hydroperoxide, and higher levels of GSH. CCl4 caused a reduction of Bcl-xL, PEDF and PPARγ, which was markedly restored by the 44-mer treatment. Consequently, the 44-mer suppressed liver fibrosis induced by repeated CCl4 injury. Furthermore, our observations in primary culture of rat hepatocytes showed that PEDF and the 44-mer protected primary rat hepatocytes against apoptosis induced by serum deprivation and TGF-β1. PEDF/44-mer induced cell protective STAT3 phosphorylation. Pharmacological STAT3 inhibition prevented the antiapoptotic action of PEDF/44-mer. Among several PEDF receptor candidates that may be responsible for hepatocyte protection, we demonstrated that PNPLA2 was essential for PEDF/44-mer-mediated STAT3 phosphorylation and antiapoptotic activity by using siRNA to selectively knockdown PNPLA2. In conclusion, the PEDF 44-mer protects hepatocytes from single and repeated CCl4 injury. This protective effect may stem from strengthening the counter oxidative stress capacity and

  12. Sox2 and Pax6 Play Counteracting Roles in Regulating Neurogenesis within the Murine Olfactory Epithelium

    PubMed Central

    Packard, Adam I.; Lin, Brian; Schwob, James E.

    2016-01-01

    In the adult olfactory epithelium, the transcription factors Pax6 and Sox2 are co-expressed in sustentacular cells, horizontal basal cells (HBCs), and less-differentiated globose basal cells (GBCs)–both multipotent and transit amplifying categories—but are absent from immediate neuronal precursor GBCs and olfactory sensory neurons (OSNs). We used retroviral-vector transduction to over-express Pax6 and Sox2 individually and together during post-lesion recovery to determine how they regulate neuronal differentiation. Both Pax6 and Sox2, separately and together, can suppress the production of OSNs, as fewer clones contain neurons than with empty vector (EV), although this effect is not absolute. In this regard, Pax6 has the strongest effect when acting alone. In clones where neurons form, Pax6 reduces neuron numbers by comparison with EV, while Sox2 expands their numbers. Co-transduction with Pax6 and Sox2 produces an intermediate result. The increased production of OSNs driven by Sox2 is due to the expansion of neuronal progenitors, since proliferation and the numbers of Ascl1, Neurog1, and NeuroD1-expressing GBCs are increased. Conversely, Pax6 seems to accelerate neuronal differentiation, since Ascl1 labeling is reduced, while Neurog1- and NeuroD1-labeled GBCs are enriched. As a complement to the over-expression experiments, elimination of Sox2 in spared cells of floxed Sox2 mice, by retroviral Cre or by K5-driven CreERT2, reduces the production of OSNs and non-neuronal cells during OE regeneration. These data suggest that Pax6 and Sox2 have counteracting roles in regulating neurogenesis, in which Pax6 accelerates neuronal production, while Sox2 retards it and expands the pool of neuronal progenitors. PMID:27171428

  13. In vitro reconstruction of human junctional and sulcular epithelium

    PubMed Central

    Dabija-Wolter, G; Bakken, V; Cimpan, M R; Johannessen, A C; Costea, D E

    2013-01-01

    BACKGROUND The aim of this study was to develop and characterize standardized in vitro three-dimensional organotypic models of human junctional epithelium (JE) and sulcular epithelium (SE). METHODS Organotypic models were constructed by growing human normal gingival keratinocytes on top of collagen matrices populated with gingival fibroblasts (GF) or periodontal ligament fibroblasts (PLF). Tissues obtained were harvested at different time points and assessed for epithelial morphology, proliferation (Ki67), expression of JE-specific markers (ODAM and FDC-SP), cytokeratins (CK), transglutaminase, filaggrin, and basement membrane proteins (collagen IV and laminin1). RESULTS The epithelial component in 3- and 5-day organotypics showed limited differentiation and expressed Ki-67, ODAM, FDC-SP, CK 8, 13, 16, 19, and transglutaminase in a similar fashion to control JE samples. PLF supported better than GF expression of CK19 and suprabasal proliferation, although statistically significant only at day 5. Basement membrane proteins started to be deposited only from day 5. The rate of proliferating cells as well as the percentage of CK19-expressing cells decreased significantly in 7- and 9-day cultures. Day 7 organotypics presented higher number of epithelial cell layers, proliferating cells in suprabasal layers, and CK expression pattern similar to SE. CONCLUSION Both time in culture and fibroblast type had impact on epithelial phenotype. Five-day cultures with PLF are suggested as JE models, 7-day cultures with PLF or GF as SE models, while 9-day cultures with GF as gingival epithelium (GE) models. Such standard, reproducible models represent useful tools to study periodontal bacteria–host interactions in vitro. PMID:22947066

  14. Expression of Signaling Components in Embryonic Eyelid Epithelium

    PubMed Central

    Meng, Qinghang; Jin, Chang; Chen, Yinglei; Chen, Jing; Medvedovic, Mario; Xia, Ying

    2014-01-01

    Closure of an epithelium opening is a critical morphogenetic event for development. An excellent example for this process is the transient closure of embryonic eyelid. Eyelid closure requires shape change and migration of epithelial cells at the tip of the developing eyelids, and is dictated by numerous signaling pathways. Here we evaluated gene expression in epithelial cells isolated from the tip (leading edge, LE) and inner surface epithelium (IE) of the eyelid from E15.5 mouse fetuses by laser capture microdissection (LCM). We showed that the LE and IE cells are different at E15.5, such that IE had higher expression of muscle specific genes, while LE acquired epithelium identities. Despite their distinct destinies, these cells were overall similar in expression of signaling components for the “eyelid closure pathways”. However, while the LE cells had more abundant expression of Fgfr2, Erbb2, Shh, Ptch1 and 2, Smo and Gli2, and Jag1 and Notch1, the IE cells had more abundant expression of Bmp5 and Bmpr1a. In addition, the LE cells had more abundant expression of adenomatosis polyposis coli down-regulated 1 (Apcdd1), but the IE cells had high expression of Dkk2. Our results suggest that the functionally distinct LE and IE cells have also differential expression of signaling molecules that may contribute to the cell-specific responses to morphogenetic signals. The expression pattern suggests that the EGF, Shh and NOTCH pathways are preferentially active in LE cells, the BMP pathways are effective in IE cells, and the Wnt pathway may be repressed in LE and IE cells via different mechanisms. PMID:24498290

  15. Response of macaque bronchiolar epithelium to ambient concentrations of ozone

    SciTech Connect

    Harkema, J.R.; Plopper, C.G.; Hyde, D.M.; St. George, J.A.; Wilson, D.W.; Dungworth, D.L. )

    1993-09-01

    Recently, we reported that exposure to ambient concentrations of ozone, near the U.S. National Ambient Air Quality Standard (0.12 ppm), induced significant nasal epithelial lesions in a non-human primate, the bonnet monkey. The present study defines the effects of ambient concentrations of ozone on the surface epithelium lining respiratory bronchioles and on the underlying bronchiolar interstitium in these same monkeys. Bonnet monkeys were exposed to filtered air or to 0.15 or 0.30 ppm ozone 8 hours/day for 6 or 90 days. At the end of exposures, monkeys were anesthetized and killed by exsanguination. Microdissected bronchiolar airways of infusion-fixed lungs were evaluated morphometrically by light microscopy and quantitatively by scanning and transmission electron microscopy for ozone-induced epithelial changes. Hyperplasia of nonciliated, cuboidal epithelial cells and intraluminal accumulation of macrophages characterized ozone-induced lesions in respiratory bronchioles. There were no significant differences in epithelial thickness or cell numbers among ozone-exposed groups. Ozone-exposed epithelium was composed of 80% cuboidal and 20% squamous cells compared with 40% cuboidal and 60% squamous cells in filtered air controls. In addition, the arithmetic mean thickness of the surface epithelium, a measure of tissue mass per unit area of basal lamina, was significantly increased in all of the ozone-exposed groups. The number of cuboidal epithelial cells per surface area of basal lamina was increased above control values by 780% after 6 days exposure to 0.15 ppm, 777% after 90 days to 0.15 ppm, and 996% after 90 days exposure to 0.30 ppm. There was also a significant ozone-induced increase in the thickness of the bronchiolar interstitium that was due to an increase in both cellular and acellular components.

  16. Cell cycle of globose basal cells in rat olfactory epithelium.

    PubMed

    Huard, J M; Schwob, J E

    1995-05-01

    The olfactory epithelium of adult mammals has the unique property of generating olfactory sensory neurons throughout life. Cells of the basal compartment, which include horizontal and globose basal cells, are responsible for the ongoing process of neurogenesis in this system. We report here that the globose basal cells in olfactory epithelium of rats, as in mice, are the predominant type of proliferating cell, and account for 97.6% of the actively dividing cells in the basal compartment of the normal epithelium. Globose basal cells have not been fully characterized in terms of their proliferative properties, and the dynamic aspects of neurogenesis are not well understood. As a consequence, it is uncertain whether cell kinetic properties are under any regulation that could affect the rate of neurogenesis. To address this gap in our knowledge, we have determined the duration of both the synthesis phase (S-phase) and the full cell cycle of globose basal cells in adult rats. The duration of the S-phase was found to be 9 hr in experiments utilizing sequential injections of either IdU followed by BrdU or 3H-thy followed by BrdU. The duration of the cell cycle was determined by varying the time interval between the injections of 3H-thy and BrdU and tracking the set of cells that exit S shortly after the first injection. With this paradigm, the interval required for these cells to traverse G2, M, G1, and a second S-phase, is equivalent to the duration of one mitotic cycle and equals 17 hr. These observations serve as the foundation to assess whether the cell cycle duration is subject to regulation in response to experimental injury, and whether such regulation is partly responsible for changes in the rate of neurogenesis in such settings. PMID:7647371

  17. Expression of stanniocalcin in the epithelium of human choroid plexus.

    PubMed

    Franzén, A M; Zhang, K Z; Westberg, J A; Zhang, W M; Arola, J; Olsen, H S; Andersson, L C

    2000-12-29

    Stanniocalcin (STC) is a 28 kD glycoprotein hormone originally found in bony fish in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized mammalian STC shows about 70% homology with fish STC. The epithelial cells of proximal tubuli in human and rat kidney and brain neurons have been found to express STC. Here we show that the epithelium of the choroid plexus, already at 16 weeks of fetal age, and of plexus papillomas, synthesize and express STC. Our findings suggest that STC may be of importance for the distribution of calcium and phosphate between the cerebrospinal fluid and blood. PMID:11134638

  18. Microwave effect on camphor binding to rat olfactory epithelium

    SciTech Connect

    Philippova, T.M.; Novoselov, V.I.; Bystrova, M.F.; Alekseev, S.I.

    1988-01-01

    Microwave radiation decreased specific camphor binding to a membrane fraction of rat epithelium but not to a Triton X-100 extract of this fraction. Inhibition of the ligand binding did not depend on the modulation frequency of the microwave field in the region 1-100 Hz and was not a linear function of specific absorption rate (SAR). The decreased ligand binding was due to a shedding or release of the specific camphor-binding protein from the membrane into solution. It is highly probable that several other membrane proteins may be shed into solution during microwave exposure.

  19. Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium

    PubMed Central

    Pukkila-Worley, Read; Ausubel, Frederick M

    2013-01-01

    Intestinal epithelial cells provide an essential line of defense for Caenorhabditis elegans against ingested pathogens. Because nematodes consume microorganisms as their food source, there has presumably been selection pressure to evolve and maintain immune defense mechanisms within the intestinal epithelium. Here we review recent advances that further define the immune signaling network within these cells and suggest mechanisms used by the nematode to monitor for infection. In reviewing studies of pathogenesis that use this simple model system, we hope to illustrate some of the basic principles of epithelial immunity that may also be of relevance in higher order hosts. PMID:22236697

  20. Diet, Microbiome, and the Intestinal Epithelium: An Essential Triumvirate?

    PubMed Central

    Guzman, Javier Rivera; Conlin, Victoria Susan; Jobin, Christian

    2013-01-01

    The intestinal epithelium represents a critical barrier protecting the host against diverse luminal noxious agents, as well as preventing the uncontrolled uptake of bacteria that could activate an immune response in a susceptible host. The epithelial monolayer that constitutes this barrier is regulated by a meshwork of proteins that orchestrate complex biological function such as permeability, transepithelial electrical resistance, and movement of various macromolecules. Because of its key role in maintaining host homeostasis, factors regulating barrier function have attracted sustained attention from the research community. This paper will address the role of bacteria, bacterial-derived metabolism, and the interplay of dietary factors in controlling intestinal barrier function. PMID:23586037

  1. Histological changes in radial forearm skin flaps in the oral cavity.

    PubMed

    Sinclair, A; Johnston, E; Badran, D H; Neilson, M; Soutar, D S; Robertson, A G; McDonald, S W

    2004-04-01

    We reported previously that skin flaps transplanted to the oral cavity in reconstructive surgery for oral cancer frequently acquired the gross appearance of buccal mucosa. The changes were shown to be reactive in nature. The "changed" flaps generally had a heavier infiltration of leukocytes in the dermis and appeared to have thicker epithelium. The present study quantifies these parameters, as well as the numbers of intraepithelial leukocytes. The flaps that had acquired the gross appearance of oral mucosa had significantly thicker epithelium, larger numbers of dermal leukocytes, and more intraepidermal inflammatory cells per unit length than flaps that retained the gross appearance of thin skin. No correlation was found between these changes and radiotherapy. PMID:15042571

  2. Method And Apparatus For Regenerating Nox Adsorbers

    DOEpatents

    Driscoll, J. Joshua; Endicott, Dennis L.; Faulkner, Stephen A.; Verkiel, Maarten

    2006-03-28

    Methods and apparatuses for regenerating a NOx adsorber coupled with an exhaust of an engine. An actuator drives a throttle valve to a first position when regeneration of the NOx adsorber is desired. The first position is a position that causes the regeneration of the NOx adsorber. An actuator drives the throttle valve to a second position while regeneration of the NOx adsorber is still desired. The second position being a position that is more open than the first position and operable to regenerate a NOx adsorber.

  3. Role of topical drugs in treatment of oral mucosal diseases. A literature review.

    PubMed

    Sheikh, Soheyl; Gupta, Deepak; Pallagatti, Shambulingappa; Singla, Isha; Gupta, Rajesh; Goel, Varun

    2013-11-01

    Few topical formulations have been designed specifically to treat oral mucosal diseases. Local drug delivery may provide a more targeted and efficient option than systemic delivery for diseases of the oral mucosa. The permeability to the topical drugs differs according to the thickness of the epithelium and the extent of keratinization. The loss of the permeability barrier in the oral mucosa, due to ulceration or erosion, leads to rapid diffusion of the drug into tissues as compared to the intact areas of the mucosa. Oral mucosal delivery has the potential to treat many different conditions and diseases, such as oral cancer, mucositis, lichen planus, herpes simplex, candidiasis, recurrent aphthous stomatitis, vesiculo-bullous diseases, neuropathic pain and salivary dysfunction. Each therapy requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. In this paper, topical medications are discussed, as these are advantageous for the treatment of oral mucosal lesions with fewer side effects. PMID:24600767

  4. Laser treatment of an oral squamous papilloma in a pediatric patient: a case report.

    PubMed

    Misir, Ahmet Ferhat; Demiriz, Levent; Barut, Figen

    2013-01-01

    Oral squamous papilloma is a benign proliferation of the stratified squamous epithelium, which results in a papillary or verrucous exophytic mass induced by human papilloma virus (HPV). These oral mucosa lesions are most often asymptomatic and have small progression. Laser assisted surgery is common nowadays with several advantages including successful hemostasis, devoid of sutures, wound sterilization and minimal post-operative pain and edema. The aim of this report is to present the oral squamous papilloma in a pediatric patient and its treatment with soft tissue laser. The lesion was excised with diode laser and the healing was uneventful in follow-up visit after one year. Oral squamous papillomas can be found in child's oral cavity and laser dentistry can be used by dental clinicians to treat these kinds of oral lesions and should be considered as an alternative to conventional surgery. PMID:24262405

  5. Oral sex, oral health and orogenital infections.

    PubMed

    Saini, Rajiv; Saini, Santosh; Sharma, Sugandha

    2010-01-01

    Oral sex is commonly practiced by sexually active male-female and same-gender couples of various ages, including adolescents. The various type of oral sex practices are fellatio, cunnilingus and analingus. Oral sex is infrequently examined in research on adolescents; oral sex can transmit oral, respiratory, and genital pathogens. Oral health has a direct impact on the transmission of infection; a cut in your mouth, bleeding gums, lip sores or broken skin increases chances of infection. Although oral sex is considered a low risk activity, it is important to use protection and safer sex precautions. There are various methods of preventing infection during oral sex such as physical barriers, health and medical issues, ethical issues and oral hygiene and dental issues. The lesions or unhealthy periodontal status of oral cavity accelerates the phenomenon of transmission of infections into the circulation. Thus consequences of unhealthy or painful oral cavity are significant and oral health should be given paramount importance for the practice of oral sex. PMID:20300419

  6. Regeneration: Thomas Hunt Morgan's window into development.

    PubMed

    Sunderland, Mary Evelyn

    2010-01-01

    Early in his career Thomas Hunt Morgan was interested in embryology and dedicated his research to studying organisms that could regenerate. Widely regarded as a regeneration expert, Morgan was invited to deliver a series of lectures on the topic that he developed into a book, Regeneration (1901). In addition to presenting experimental work that he had conducted and supervised, Morgan also synthesized and critiqued a great deal of work by his peers and predecessors. This essay probes into the history of regeneration studies by looking in depth at Regeneration and evaluating Morgan's contribution. Although famous for his work with fruit fly genetics, studying Regeneration illuminates Morgan's earlier scientific approach which emphasized the importance of studying a diversity of organisms. Surveying a broad range of regenerative phenomena allowed Morgan to institute a standard scientific terminology that continues to inform regeneration studies today. Most importantly, Morgan argued that regeneration was a fundamental aspect of the growth process and therefore should be accounted for within developmental theory. Establishing important similarities between regeneration and development allowed Morgan to make the case that regeneration could act as a model of development. The nature of the relationship between embryogenesis and regeneration remains an active area of research. PMID:20665231

  7. Use of the carbon dioxide laser in guided tissue regeneration wound healing in the beagle dog

    NASA Astrophysics Data System (ADS)

    Rossmann, Jeffrey A.; Parlar, Ates; Abdel-Ghaffar, Khaled A.; El-Khouli, Amr M.; Israel, Michael

    1996-04-01

    The concept of guided tissue regeneration (GTR) allowing cells from the periodontal ligament and alveolar bone to repopulate the treated root surface has shown the ability to obtain periodontal new attachment. Healing studies have also shown that conventional GTR therapy still does not exclude all the epithelium. This epithelial proliferation apically interferes with the establishment of the new connective tissue attachment to the root surface. The objective of this research study was to examine whether controlled de-epithelialization with the carbon dioxide laser during the healing phase after periodontal surgery, would retard the apical migration of the epithelium and thereby enhance the results obtained through guided tissue regeneration. Eight beagle dogs were used, the experimental side received de-epithelialization with the CO2 laser in conjunction with flap reflection and surgically created buccal osseous defects. Selected defects on each side were treated with ePTFE periodontal membranes. The laser de-epithelialization was repeated every 10 days until removal of the membranes. The control side received the same surgical treatment without laser application. This experimental design allowed histologic study of the new attachment obtained in defects treated with flap debridement with or without laser de-epithelialization and with or without ePTFE membranes. A statistical analysis was performed on the histometric data from 48 teeth in the 8 dogs after 4 months of healing. The results showed significant amounts of new attachment obtained from all four treatment modalities with no statistically significant differences for any one treatment. However, the trend towards enhanced regeneration with the combined treatment of laser and membrane vs. membrane alone or debridement alone was evident. The histologic analysis revealed a significant amount of newly formed `fat cementum' seen only on the laser treated teeth. This feature was the most remarkable finding of the

  8. Acanthamoebae bind to glycolipids of rabbit corneal epithelium.

    PubMed Central

    Panjwani, N; Zhao, Z; Baum, J; Pereira, M; Zaidi, T

    1992-01-01

    By use of a thin-layer chromatogram (TLC) overlay procedure, 35S-labeled acanthamoebae were shown to bind to seven glycolipids of rabbit corneal epithelium. Corneal epithelial cells were grown in culture and were subjected to Folch extraction to isolate a chloroform-rich lower phase containing neutral glycosphingolipids (NGSL) and an aqueous upper phase containing gangliosides, i.e., sialic acid-containing glycolipids. Thin-layer chromatography of the upper phase revealed the presence of 10 ganglioside components. Acanthamoebae were shown to bind to four of these components, referred to as 2, 3, 6, and 7. On TLC plates, ganglioside components 2 and 3 migrated slightly ahead of the glycolipid standard GD1a, component 7 comigrated with standard GM3, and component 6 migrated a little more slowly than GM3. Likewise, of the 10 NGSL known to be present in the lower phase, acanthamoebae bound to components 1, 5, and 6. NGSL components 1, 5, and 6 migrated on TLC plates with relative mobilities similar to those of standards asialo GM1, asialo GM2, and ceramidetrihexoside, respectively. We propose that one or more of the Acanthamoeba-reactive glycolipids of corneal epithelium identified in this study may play a role in the pathogenesis of Acanthamoeba keratitis by mediating the adherence of the parasites to the cornea. Images PMID:1639517

  9. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity.

    PubMed

    Westphalen, Kristin; Gusarova, Galina A; Islam, Mohammad N; Subramanian, Manikandan; Cohen, Taylor S; Prince, Alice S; Bhattacharya, Jahar

    2014-02-27

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca(2+) waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca(2+)-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation. PMID:24463523

  10. An Apical-Membrane Chloride Channel in Human Tracheal Epithelium

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.

    1986-06-01

    The mechanism of chloride transport by airway epithelia has been of substantial interest because airway and sweat gland-duct epithelia are chloride-impermeable in cystic fibrosis. The decreased chloride permeability prevents normal secretion by the airway epithelium, thereby interfering with mucociliary clearance and contributing to the morbidity and mortality of the disease. Because chloride secretion depends on and is regulated by chloride conductance in the apical cell membrane, the patch-clamp technique was used to directly examine single-channel currents in primary cultures of human tracheal epithelium. The cells contained an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches. The channel was also blocked by analogs of carboxylic acid that decrease apical chloride conductance in intact epithelia. When attached to the cell, the channel was activated by isoproterenol, although the channel was also observed to open spontaneously. However, in some cases, the channel was only observed after the patch was excised from the cell. These results suggest that this channel is responsible for the apical chloride conductance in airway epithelia.

  11. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    NASA Astrophysics Data System (ADS)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  12. Electrodeposition of pronectin for titanium to augment gingival epithelium adhesion.

    PubMed

    Kawabata, Shingo; Asano, Kazunari; Miyazawa, Atsuko; Satoh, Tazuko; Tabata, Yasuhiko

    2013-05-01

    This paper is one trial of surface modification of titanium with pronectin F+ (PN) of an artificial protein to enhance gingival adhesion. Titanium plates were electrodeposited in the PN solution to prepare PN-electrodeposited titanium plates. When PN detachment from the PN-electrodeposited titanium plates was investigated, no detachment was observed, in contrast to the case of titanium plates simply coated with PN. A cell culture experiment demonstrated that electrodeposited PN had an inherent ability to enhance the initial attachment of gingival epithelial cells. The PN-electrodeposited titanium plates were implanted between the gingival epithelium and the underlying bone tissue of rabbits to evaluate epithelial growth on the plates and their gingival adhesion. Non-treated and PN-coated titanium plates were used as controls. PN electrodeposition enhanced epithelial growth and adhesion of titanium plates to a significantly great extent compared with PN-coated plates. These findings demonstrate that PN electrodeposition is a promising method to enhance epithelium adhesion onto a titanium surface. PMID:22294437

  13. Choline transport in the isolated rabbit corneal epithelium

    SciTech Connect

    Faust, R.L.

    1988-01-01

    In the present study, isolated epithelial sheets were obtained by performing two sequential anterior keratectomies, three weeks apart, on rabbit corneas. Light microscopy of the isolated sheets revealed a multilayered epithelium with an intact basal cell layer without contamination from other cell types. The accumulation of ({sup 3}H)choline into the epithelial sheets was studied at substrate concentrations varying from 1 to 100 {mu}Moles with and without the addition of specific metabolic and stereochemical inhibitors. Accumulation of ({sup 3}H)choline into these sheets was saturable. Kinetic analysis, performed by estimation from double-reciprocal plots, revealed a single component system with a K{sub m} of 24.9 {mu}M. The metabolic inhibitors potassium cyanide and ouabain showed no effect on the uptake of ({sup 3}H)choline; however, the stereochemical inhibitor hemicholinium-3 significantly reduced the accumulation of radiolabel at both high and low substrate concentrations. The results suggest a non-energy dependent yet a highly specific transport system for the accumulation of choline into the rabbit epithelium.

  14. Selective gene expression by rat gastric corpus epithelium

    PubMed Central

    Goebel, M.; Stengel, A.; Sachs, G.

    2011-01-01

    The gastrointestinal (GI) tract is divided into several segments that have distinct functional properties, largely absorptive. The gastric corpus is the only segment thought of as largely secretory. Microarray hybridization of the gastric corpus mucosal epithelial cells was used to compare gene expression with other segments of the columnar GI tract followed by statistical data subtraction to identify genes selectively expressed by the rat gastric corpus mucosa. This provides a means of identifying less obvious specific functions of the corpus in addition to its secretion-related genes. For example, important properties found by this GI tract comparative transcriptome reflect the energy demand of acid secretion, a role in lipid metabolism, the large variety of resident neuroendocrine cells, responses to damaging agents and transcription factors defining differentiation of its epithelium. In terms of overlap of gastric corpus genes with the rest of the GI tract, the distal small bowel appears to express many of the gastric corpus genes in contrast to proximal small and large bowel. This differential map of gene expression by the gastric corpus epithelium will allow a more detailed description of major properties of the gastric corpus and may lead to the discovery of gastric corpus cell differentiation genes and those mis-regulated in gastric carcinomas. PMID:21177383

  15. Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations.

    PubMed

    Morita, Ritsuko; Kihira, Miho; Nakatsu, Yousuke; Nomoto, Yohei; Ogawa, Miho; Ohashi, Kazumasa; Mizuno, Kensaku; Tachikawa, Tetsuhiko; Ishimoto, Yukitaka; Morishita, Yoshihiro; Tsuji, Takashi

    2016-01-01

    The morphologies of ectodermal organs are shaped by appropriate combinations of several deformation modes, such as invagination and anisotropic tissue elongation. However, how multicellular dynamics are coordinated during deformation processes remains to be elucidated. Here, we developed a four-dimensional (4D) analysis system for tracking cell movement and division at a single-cell resolution in developing tooth epithelium. The expression patterns of a Fucci probe clarified the region- and stage-specific cell cycle patterns within the tooth germ, which were in good agreement with the pattern of the volume growth rate estimated from tissue-level deformation analysis. Cellular motility was higher in the regions with higher growth rates, while the mitotic orientation was significantly biased along the direction of tissue elongation in the epithelium. Further, these spatio-temporal patterns of cellular dynamics and tissue-level deformation were highly correlated with that of the activity of cofilin, which is an actin depolymerization factor, suggesting that the coordination of cellular dynamics via actin remodeling plays an important role in tooth epithelial morphogenesis. Our system enhances the understanding of how cellular behaviors are coordinated during ectodermal organogenesis, which cannot be observed from histological analyses. PMID:27588418

  16. The skin of fish as a transport epithelium: a review.

    PubMed

    Glover, Chris N; Bucking, Carol; Wood, Chris M

    2013-10-01

    The primary function of fish skin is to act as a barrier. It provides protection against physical damage and assists with the maintenance of homoeostasis by minimising exchange between the animal and the environment. However in some fish, the skin may play a more active physiological role. This is particularly true in species that inhabit specialised environmental niches (e.g. amphibious and air-breathing fish such as the lungfish), those with physiological characteristics that may subvert the need for the integument as a barrier (e.g. the osmoconforming hagfish), and/or fish with anatomical modifications of the epidermis (e.g. reduced epithelial thickness). Using examples from different fish groups (e.g. hagfishes, elasmobranchs and teleosts), the importance of fish skin as a transport epithelium for gases, ions, nitrogenous waste products, and nutrients was reviewed. The role of the skin in larval fish was also examined, with early life stages often utilising the skin as a surrogate gill, prior to the development of a functional branchial epithelium. PMID:23660826

  17. Regulation of gene expression in the intestinal epithelium.

    PubMed

    Richmond, Camilla A; Breault, David T

    2010-01-01

    Regulation of gene expression within the intestinal epithelium is complex and controlled by various signaling pathways that regulate the balance between proliferation and differentiation. Proliferation is required both to grow and to replace cells lost through apoptosis and attrition, yet in all but a few cells, differentiation must take place to prevent uncontrolled growth (cancer) and to provide essential functions. In this chapter, we review the major signaling pathways underlying regulation of gene expression within the intestinal epithelium, based primarily on data from mouse models, as well as specific morphogens and transcription factor families that have a major role in regulating intestinal gene expression, including the Hedgehog family, Forkhead Box (FOX) factors, Homeobox (HOX) genes, ParaHox genes, GATA transcription factors, canonical Wnt/β-catenin signaling, EPH/Ephrins, Sox9, BMP signaling, PTEN/PI3K, LKB1, K-RAS, Notch pathway, HNF, and MATH1. We also briefly highlight important emerging areas of gene regulation, including microRNA (miRNA) and epigenetic regulation. PMID:21075346

  18. Nanotopography follows force in TGF-β1 stimulated epithelium

    NASA Astrophysics Data System (ADS)

    Thoelking, Gerold; Reiss, Bjoern; Wegener, Joachim; Oberleithner, Hans; Pavenstaedt, Hermann; Riethmuller, Christoph

    2010-07-01

    Inflammation and cellular fibrosis often imply an involvement of the cytokine TGF-β1. TGF-β1 induces epithelial-to-mesenchymal transdifferentiation (EMT), a term describing the loss of epithelium-specific function. Indicative for this process are an elongated cell shape parallel to stress fibre formation. Many signalling pathways of TGF-β1 have been discovered, but mechanical aspects have not yet been investigated. In this study, atomic force microscopy (AFM) was used to analyse surface topography and mechanical properties of EMT in proximal kidney tubule epithelium (NRK52E). Elongated cells, an increase of stress fibre formation and a loss of microvillus compatible structures were observed as characteristic signs of EMT. Furthermore, AFM could identify an increase in stiffness by 71% after six days of stimulation with TGF-β1. As a novel topographical phenomenon, nodular protrusions emerged at the cell-cell junctions. They occurred preferentially at sites where stress fibres cross the border. Since these nodular protrusions were sensitive to inhibitors of force generation, they can indicate intracellular tension. The results demonstrate a manifest impact of elevated tension on the cellular topography.

  19. The regeneration capacity of the flatworm Macrostomum lignano—on repeated regeneration, rejuvenation, and the minimal size needed for regeneration

    PubMed Central

    Ladurner, P.; Nimeth, K.; Gschwentner, R.; Rieger, R.

    2006-01-01

    The lion’s share of studies on regeneration in Plathelminthes (flatworms) has been so far carried out on a derived taxon of rhabditophorans, the freshwater planarians (Tricladida), and has shown this group’s outstanding regeneration capabilities in detail. Sharing a likely totipotent stem cell system, many other flatworm taxa are capable of regeneration as well. In this paper, we present the regeneration capacity of Macrostomum lignano, a representative of the Macrostomorpha, the basal-most taxon of rhabditophoran flatworms and one of the most basal extant bilaterian protostomes. Amputated or incised transversally, obliquely, and longitudinally at various cutting levels, M. lignano is able to regenerate the anterior-most body part (the rostrum) and any part posterior of the pharynx, but cannot regenerate a head. Repeated regeneration was observed for 29 successive amputations over a period of almost 12 months. Besides adults, also first-day hatchlings and older juveniles were shown to regenerate after transversal cutting. The minimum number of cells required for regeneration in adults (with a total of 25,000 cells) is 4,000, including 160 neoblasts. In hatchlings only 1,500 cells, including 50 neoblasts, are needed for regeneration. The life span of untreated M. lignano was determined to be about 10 months. PMID:16604349

  20. Epidermal growth factor attenuates tubular necrosis following mercuric chloride damage by regeneration of indigenous, not bone marrow-derived cells

    PubMed Central

    Yen, Tzung-Hai; Alison, Malcolm R; Goodlad, Robert A; Otto, William R; Jeffery, Rosemary; Cook, H Terence; Wright, Nicholas A; Poulsom, Richard

    2015-01-01

    To assess effects of epidermal growth factor (EGF) and pegylated granulocyte colony-stimulating factor (P-GCSF; pegfilgrastim) administration on the cellular origin of renal tubular epithelium regenerating after acute kidney injury initiated by mercuric chloride (HgCl2). Female mice were irradiated and male whole bone marrow (BM) was transplanted into them. Six weeks later recipient mice were assigned to one of eight groups: control, P-GCSF+, EGF+, P-GCSF+EGF+, HgCl2, HgCl2+P-GCSF+, HgCl2+EGF+ and HgCl2+P-GCSF+EGF+. Following HgCl2, injection tubular injury scores increased and serum urea nitrogen levels reached uraemia after 3 days, but EGF-treated groups were resistant to this acute kidney injury. A four-in-one analytical technique for identification of cellular origin, tubular phenotype, basement membrane and S-phase status revealed that BM contributed 1% of proximal tubular epithelium in undamaged kidneys and 3% after HgCl2 damage, with no effects of exogenous EGF or P-GCSF. Only 0.5% proximal tubular cells were seen in S-phase in the undamaged group kidneys; this increased to 7–8% after HgCl2 damage and to 15% after addition of EGF. Most of the regenerating tubular epithelium originated from the indigenous pool. BM contributed up to 6.6% of the proximal tubular cells in S-phase after HgCl2 damage, but only to 3.3% after additional EGF. EGF administration attenuated tubular necrosis following HgCl2 damage, and the major cause of this protective effect was division of indigenous cells, whereas BM-derived cells were less responsive. P-GCSF did not influence damage or regeneration. PMID:25389045

  1. microRNA-dependent Temporal Gene Expression in the Ureteric Bud Epithelium during Mammalian Kidney Development

    PubMed Central

    Nagalakshmi, Vidya K.; Lindner, Volkhard; Wessels, Andy; Yu, Jing

    2014-01-01

    Background Our previous study on mouse mutants with the ureteric bud (UB) epithelium-specific Dicer deletion (Dicer UB mutants) demonstrated the significance of UB epithelium-derived miRNAs in UB development. Results Our whole-genome transcriptional profiling showed that the Dicer mutant UB epithelium abnormally retained transcriptional features of the early UB epithelium and failed to express many genes associated with collecting duct differentiation. Further, we identified a temporal expression pattern of early UB genes during UB epithelium development in which gene expression was detected at early developmental stages and became undetectable by E14.5. In contrast, expression of early UB genes persisted at later stages in the Dicer mutant UB epithelium and increased at early stages. Our bioinformatics analysis of the abnormally persistently expressed early genes in the Dicer mutant UB epithelium showed significant enrichment of the let-7 family miRNA targets. We further identified a temporal expression pattern of let-7 miRNAs in the UB epithelium that is anti-parallel to that of some early UB genes during kidney development. Conclusions We propose a model in which the let-7 family miRNAs silence the expression of a subset of early genes in the UB epithelium at later developmental stages in order to promote collecting duct differentiation. PMID:25369991

  2. Islet cell plasticity and regeneration.

    PubMed

    Migliorini, Adriana; Bader, Erik; Lickert, Heiko

    2014-06-01

    Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of β-cells resulting in failure of metabolic control. Even though type 1 and 2 diabetes differ in their pathogenesis, restoring β-cell function is the overarching goal for improved therapy of both diseases. This could be achieved either by cell-replacement therapy or by triggering intrinsic regenerative mechanisms of the pancreas. For type 1 diabetes, a combination of β-cell replacement and immunosuppressive therapy could be a curative treatment, whereas for type 2 diabetes enhancing endogenous mechanisms of β-cell regeneration might optimize blood glucose control. This review will briefly summarize recent efforts to allow β-cell regeneration where the most promising approaches are currently (1) increasing β-cell self-replication or neogenesis from ductal progenitors and (2) conversion of α-cells into β-cells. PMID:24749056

  3. Diverse routes to liver regeneration.

    PubMed

    Alison, Malcolm R; Lin, Wey-Ran

    2016-02-01

    The liver's ability to regenerate is indisputable; for example, after a two-thirds partial hepatectomy in rats all residual hepatocytes can divide, questioning the need for a specific stem cell population. On the other hand, there is a potential stem cell compartment in the canals of Hering, giving rise to ductular reactions composed of hepatic progenitor cells (HPCs) when the liver's ability to regenerate is hindered by replicative senescence, but the functional relevance of this response has been questioned. Several papers have now clarified regenerative mechanisms operative in the mouse liver, suggesting that the liver is possibly unrivalled in its versatility to replace lost tissue. Under homeostatic conditions a perivenous population of clonogenic hepatocytes operates, whereas during chronic damage a minor population of periportal clonogenic hepatocytes come to the fore, while the ability of HPCs to completely replace the liver parenchyma has now been shown. PMID:26510495

  4. Approaches for Enhancing Oral Bioavailability of Peptides and Proteins

    PubMed Central

    Renukuntla, Jwala; Vadlapudi, Aswani Dutt; Patel, Ashaben; Boddu, Sai HS.; Mitra, Ashim K

    2013-01-01

    Oral delivery of peptide and protein drugs faces immense challenge partially due to the gastrointestinal (GI) environment. In spite of considerable efforts by industrial and academic laboratories, no major breakthrough in the effective oral delivery of polypeptides and proteins has been accomplished. Upon oral administration, gastrointestinal epithelium acts as a physical and biochemical barrier for absorption of proteins resulting in low bioavailability (typically less than 1–2%). An ideal oral drug delivery system should be capable of a) maintaining the integrity of protein molecules until it reaches the site of absorption, b) releasing the drug at the target absorption site, where the delivery system appends to that site by virtue of specific interaction, and c) retaining inside the gastrointestinal tract irrespective of its transitory constraints. Various technologies have been explored to overcome the problems associated with the oral delivery of macromolecules such as insulin, gonadotropin-releasing hormones, calcitonin, human growth factor, vaccines, enkephalins, and interferons, all of which met with limited success. This review article intends to summarize the physiological barriers to oral delivery of peptides and proteins and novel pharmaceutical approaches to circumvent these barriers and enhance oral bioavailability of these macromolecules. PMID:23428883

  5. Molecular mechanisms of epithelial regeneration and neovascularization during healing of gastric and esophageal ulcers.

    PubMed

    Tarnawski, A S; Ahluwalia, A

    2012-01-01

    In this paper we reviewed and updated current views on the cellular and molecular mechanisms of gastric and esophageal ulcer healing. Gastric ulcer healing encompasses inflammation, cell proliferation, epithelial regeneration, gland reconstruction, formation of granulation tissue, neovascularization (new blood vessel formation), interactions between various cells and the matrix and tissue remodeling, resulting in scar formation. All these events are controlled by the cytokines and growth factors, GI hormones including gastrin, CCK, and orexigenic peptides such as ghrelin, orexin-A and obestatin as well as Cox2 generated prostaglandins. These growth factors and hormones trigger cell proliferation, migration, and survival utilizing Ras, MAPK, PI-3K/AKT, PLC-γ and Rho/Rac/actin signaling pathways. Hypoxia triggers activation of some of these genes (e.g., VEGF) via hypoxia inducible factor (HIF). Growth factors: EGF, HGF, IGF-1, their receptors and Cox2 are important for epithelial cell proliferation, migration, re-epithelialization and regeneration of gastric glands during gastric ulcer healing. Serum response factor (SRF) is also essential for re-epithelialization and muscle restoration. VEGF, bFGF, angiopoietins, nitric oxide, endothelin, prostaglandins and metalloproteinases are important for angiogenesis, vascular remodeling and mucosal regeneration within gastric ulcer scar. SRF is critical limiting factor for VEGF-induced angiogenesis. Esophageal ulcer healing follows similar pattern to gastric ulcer, but KGF and its receptor are the key players in regeneration of the epithelium. In addition to local mucosal cells from viable mucosa bordering necrosis, circulating bone marrow derived stem and progenitor cells are potentially important for ulcer healing, contributing to the regeneration of epithelial and connective tissue components and neovascularization. PMID:22300072

  6. Clinical and biochemical studies support smokeless tobacco's carcinogenic potential in the human oral cavity.

    PubMed

    Mallery, Susan R; Tong, Meng; Michaels, Gregory C; Kiyani, Amber R; Hecht, Stephen S

    2014-01-01

    In 2007, the International Agency for Research on Cancer presented compelling evidence that linked smokeless tobacco use to the development of human oral cancer. Although these findings imply vigorous local carcinogen metabolism, little is known about levels and distribution of phase I, II, and III (drug egress) enzymes in human oral mucosa. In this study here, we integrated clinical data, and imaging and histopathologic analyses of an oral squamous cell carcinoma that arose at the site of smokeless tobacco quid placement in a patient. Immunoblot and immunohistochemical (IHC) analyses were used to identify tumor and normal human oral mucosal smokeless tobacco-associated metabolic activation and detoxification enzymes. Human oral epithelium contains every known phase I enzyme associated with nitrosamine oxidative bioactivation with approximately 2-fold interdonor differences in protein levels. Previous studies have confirmed approximately 3.5-fold interdonor variations in intraepithelial phase II enzymes. Unlike the superficially located enzymes in nonreplicating esophageal surface epithelium, IHC studies confirmed that oral mucosal nitrosamine metabolizing enzymes reside in the basilar and suprabasilar region, which notably is the site of ongoing keratinocyte DNA replication. Clearly, variations in product composition, nitrosamine metabolism, and exposure duration will modulate clinical outcomes. The data presented here form a coherent picture consistent with the abundant experimental data that link tobacco-specific nitrosamines to human oral cancer. PMID:24265177

  7. Cell migration during heart regeneration in zebrafish.

    PubMed

    Tahara, Naoyuki; Brush, Michael; Kawakami, Yasuhiko

    2016-07-01

    Zebrafish possess the remarkable ability to regenerate injured hearts as adults, which contrasts the very limited ability in mammals. Although very limited, mammalian hearts do in fact have measurable levels of cardiomyocyte regeneration. Therefore, elucidating mechanisms of zebrafish heart regeneration would provide information of naturally occurring regeneration to potentially apply to mammalian studies, in addition to addressing this biologically interesting phenomenon in itself. Studies over the past 13 years have identified processes and mechanisms of heart regeneration in zebrafish. After heart injury, pre-existing cardiomyocytes dedifferentiate, enter the cell cycle, and repair the injured myocardium. This process requires interaction with epicardial cells, endocardial cells, and vascular endothelial cells. Epicardial cells envelope the heart, while endocardial cells make up the inner lining of the heart. They provide paracrine signals to cardiomyocytes to regenerate the injured myocardium, which is vascularized during heart regeneration. In addition, accumulating results suggest that local migration of these major cardiac cell types have roles in heart regeneration. In this review, we summarize the characteristics of various heart injury methods used in the research community and regeneration of the major cardiac cell types. Then, we discuss local migration of these cardiac cell types and immune cells during heart regeneration. Developmental Dynamics 245:774-787, 2016. © 2016 Wiley Periodicals, Inc. PMID:27085002

  8. Response of macaque bronchiolar epithelium to ambient concentrations of ozone.

    PubMed Central

    Harkema, J. R.; Plopper, C. G.; Hyde, D. M.; St George, J. A.; Wilson, D. W.; Dungworth, D. L.

    1993-01-01

    Recently, we reported that exposure to ambient concentrations of ozone, near the U.S. National Ambient Air Quality Standard (0.12 ppm), induced significant nasal epithelial lesions in a non-human primate, the bonnet monkey. The present study defines the effects of ambient concentrations of ozone on the surface epithelium lining respiratory bronchioles and on the underlying bronchiolar interstitium in these same monkeys. Bonnet monkeys were exposed to filtered air or to 0.15 or 0.30 ppm ozone 8 hours/day for 6 or 90 days. At the end of exposures, monkeys were anesthetized and killed by exsanguination. Microdissected bronchiolar airways of infusion-fixed lungs were evaluated morphometrically by light microscopy and quantitatively by scanning and transmission electron microscopy for ozone-induced epithelial changes. Hyperplasia of nonciliated, cuboidal epithelial cells and intraluminal accumulation of macrophages characterized ozone-induced lesions in respiratory bronchioles. There were no significant differences in epithelial thickness or cell numbers among ozone-exposed groups. Ozone-exposed epithelium was composed of 80% cuboidal and 20% squamous cells compared with 40% cuboidal and 60% squamous cells in filtered air controls. In addition, the arithmetic mean thickness of the surface epithelium, a measure of tissue mass per unit area of basal lamina, was significantly increased in all of the ozone-exposed groups. The number of cuboidal epithelial cells per surface area of basal lamina was increased above control values by 780% after 6 days exposure to 0.15 ppm, 777% after 90 days to 0.15 ppm, and 996% after 90 days exposure to 0.30 ppm. There was also a significant ozone-induced increase in the thickness of the bronchiolar interstitium that was due to an increase in both cellular and acellular components. These results demonstrate that exposure to low ambient concentrations of ozone, near the current. National Ambient Air Quality Standard, induces pulmonary lesions

  9. ATP-sensitive K(+) channels in rat colonic epithelium.

    PubMed

    Pouokam, Ervice; Bader, Sandra; Brück, Brigitta; Schmidt, Bärbel; Diener, Martin

    2013-06-01

    ATP-sensitive K(+) (KATP) channels couple the metabolic state of a cell to its electrical activity. They consist of a hetero-octameric complex with pore-forming Kir6.x (Kir6.1, Kir6.2) and regulatory sulfonylurea receptor (SUR) subunits. Functional data indicate that KATP channels contribute to epithelial K(+) currents at colonic epithelia. However, their molecular identity and their properties are largely unknown. Therefore, changes in short-circuit current (I sc) induced by the KATP channel opener pinacidil (5 10(-4) mol l(-1)) were measured in Ussing chambers under control conditions and in the presence of different blockers of KATP channels. The channel subunits expressed by the colonic epithelium were identified by immunohistochemistry and by RT-PCR. The K(+) channel opener, when administered at the serosal side, induced an increase in I sc consistent with the induction of transepithelial Cl(-) secretion after activation of basolateral K(+) channels, whereas mucosal administration of pinacidil resulted in a negative I sc. The increase in I sc evoked by serosal pinacidil was inhibited by serosal administration of glibenclamide (5 10(-4) mol l(-1)) and gliclazide (10(-6) mol l(-1)), but was resistant even against a high concentration (10(-2) mol l(-1)) of tolbutamide. In contrast, none of these inhibitors (administered at the mucosal side) reduced significantly the negative I sc induced by mucosal pinacidil. Instead, pinacidil inhibited Cl(-) currents across apical Cl(-) channels in basolaterally depolarized epithelia indicating that the negative I sc induced by mucosal pinacidil is due to a transient inhibition of Cl(-) secretion. In mRNA prepared from isolated colonic crypts, messenger RNA for both pore-forming subunits, Kir6.1 and Kir6.2, and two regulatory subunits (SUR1 and SUR2B) was found. Expression within the colonic epithelium was confirmed for these subunits by immunohistochemistry. In consequence, KATP channels are present in the basolateral membrane

  10. Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice.

    PubMed

    Sahu, Bhubanananda; Sun, Wenyu; Perusek, Lindsay; Parmar, Vipulkumar; Le, Yun-Zheng; Griswold, Michael D; Palczewski, Krzysztof; Maeda, Akiko

    2015-11-01

    Regeneration of the visual chromophore, 11-cis-retinal, is a crucial step in the visual cycle required to sustain vision. This cycle consists of sequential biochemical reactions that occur in photoreceptor cells and the retinal pigmented epithelium (RPE). Oxidation of 11-cis-retinol to 11-cis-retinal is accomplished by a family of enzymes termed 11-cis-retinol dehydrogenases, including RDH5 and RDH11. Double deletion of Rdh5 and Rdh11 does not limit the production of 11-cis-retinal in mice. Here we describe a third retinol dehydrogenase in the RPE, RDH10, which can produce 11-cis-retinal. Mice with a conditional knock-out of Rdh10 in RPE cells (Rdh10 cKO) displayed delayed 11-cis-retinal regeneration and dark adaption after bright light illumination. Retinal function measured by electroretinogram after light exposure was also delayed in Rdh10 cKO mice as compared with controls. Double deletion of Rdh5 and Rdh10 (cDKO) in mice caused elevated 11/13-cis-retinyl ester content also seen in Rdh5(-/-)Rdh11(-/-) mice as compared with Rdh5(-/-) mice. Normal retinal morphology was observed in 6-month-old Rdh10 cKO and cDKO mice, suggesting that loss of Rdh10 in the RPE does not negatively affect the health of the retina. Compensatory expression of other retinol dehydrogenases was observed in both Rdh5(-/-) and Rdh10 cKO mice. These results indicate that RDH10 acts in cooperation with other RDH isoforms to produce the 11-cis-retinal chromophore needed for vision. PMID:26391396

  11. Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation

    NASA Astrophysics Data System (ADS)

    Li, Fengfu; Carlsson, David; Lohmann, Chris; Suuronen, Erik; Vascotto, Sandy; Kobuch, Karin; Sheardown, Heather; Munger, Rejean; Nakamura, Masatsugu; Griffith, May

    2003-12-01

    Our objective was to determine whether key properties of extracellular matrix (ECM) macromolecules can be replicated within tissue-engineered biosynthetic matrices to influence cellular properties and behavior. To achieve this, hydrated collagen and N-isopropylacrylamide copolymer-based ECMs were fabricated and tested on a corneal model. The structural and immunological simplicity of the cornea and importance of its extensive innervation for optimal functioning makes it an ideal test model. In addition, corneal failure is a clinically significant problem. Matrices were therefore designed to have the optical clarity and the proper dimensions, curvature, and biomechanical properties for use as corneal tissue replacements in transplantation. In vitro studies demonstrated that grafting of the laminin adhesion pentapeptide motif, YIGSR, to the hydrogels promoted epithelial stratification and neurite in-growth. Implants into pigs' corneas demonstrated successful in vivo regeneration of host corneal epithelium, stroma, and nerves. In particular, functional nerves were observed to rapidly regenerate in implants. By comparison, nerve regeneration in allograft controls was too slow to be observed during the experimental period, consistent with the behavior of human cornea transplants. Other corneal substitutes have been produced and tested, but here we report an implantable matrix that performs as a physiologically functional tissue substitute and not simply as a prosthetic device. These biosynthetic ECM replacements should have applicability to many areas of tissue engineering and regenerative medicine, especially where nerve function is required. regenerative medicine | tissue engineering | cornea | implantation | innervation

  12. A brief history of hair cell regeneration research and speculations on the future.

    PubMed

    Rubel, Edwin W; Furrer, Stephanie A; Stone, Jennifer S

    2013-03-01

    Millions of people worldwide suffer from hearing and balance disorders caused by loss of the sensory hair cells that convert sound vibrations and head movements into electrical signals that are conveyed to the brain. In mammals, the great majority of hair cells are produced during embryogenesis. Hair cells that are lost after birth are virtually irreplaceable, leading to permanent disability. Other vertebrates, such as fish and amphibians, produce hair cells throughout life. However, hair cell replacement after damage to the mature inner ear was either not investigated or assumed to be impossible until studies in the late 1980s proved this to be false. Adult birds were shown to regenerate lost hair cells in the auditory sensory epithelium after noise- and ototoxic drug-induced damage. Since then, the field of hair cell regeneration has continued to investigate the capacity of the auditory and vestibular epithelia in vertebrates (fishes, birds, reptiles, and mammals) to regenerate hair cells and to recover function, the molecular mechanisms governing these regenerative capabilities, and the prospect of designing biologically-based treatments for hearing loss and balance disorders. Here, we review the major findings of the field during the past 25 years and speculate how future inner ear repair may one day be achieved. PMID:23321648

  13. FSP1+ fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells

    PubMed Central

    Sun, Lina; Sun, Chenming; Liang, Zhanfeng; Li, Hongran; Chen, Lin; Luo, Haiying; Zhang, Hongmei; Ding, Pengbo; Sun, Xiaoning; Qin, Zhihai; Zhao, Yong

    2015-01-01

    Thymic epithelial cells (TECs) form a 3-dimentional network supporting thymocyte development and maturation. Besides epithelium and thymocytes, heterogeneous fibroblasts are essential components in maintaining thymic microenvironments. However, thymic fibroblast characteristics, development and function remain to be determined. We herein found that thymic non-hematopoietic CD45-FSP1+ cells represent a unique Fibroblast specific protein 1 (FSP1)—fibroblast-derived cell subset. Deletion of these cells in FSP1-TK transgenic mice caused thymus atrophy due to the loss of TECs, especially mature medullary TECs (MHCIIhigh, CD80+ and Aire+). In a cyclophosphamide-induced thymus injury and regeneration model, lack of non-hematopoietic CD45-FSP1+ fibroblast subpopulation significantly delayed thymus regeneration. In fact, thymic FSP1+ fibroblasts released more IL-6, FGF7 and FSP1 in the culture medium than their FSP1- counterparts. Further experiments showed that the FSP1 protein could directly enhance the proliferation and maturation of TECs in the in vitro culture systems. FSP1 knockout mice had significantly smaller thymus size and less TECs than their control. Collectively, our studies reveal that thymic CD45-FSP1+ cells are a subpopulation of fibroblasts, which is crucial for the maintenance and regeneration of TECs especially medullary TECs through providing IL-6, FGF7 and FSP1. PMID:26445893

  14. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

  15. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

    PubMed Central

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4–8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer’s patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

  16. Stem Cells and Lung Regeneration

    PubMed Central

    El-Badrawy, Mohammad K.; Shalabi, Nesrein M.; Mohamed, Mie A.; Ragab, Amany; Abdelwahab, Heba Wagih

    2016-01-01

    Background:Tissues such as the lung, liver, and pancreas that have a low steady-state cell turnover yet can respond robustly after injury to replace damaged cells. The airway epithelium is exposed to inhaled particles and pathogens that may lead to the development of a many infectious and inflammatory respiratory diseases. Lung transplantation is an accepted modality of treatment for end-stage lung diseases. Since the early 1990 s, more than 26,000 lung transplants have been performed at centers worldwide. However, the availability of donor tissues and organs is limited, which presents a serious limitation for widespread transplantation surgery. The appearance of bioengineered lung and tracheal tissue transplants is considered a promising alternative to the classical transplantation of donor organ/tissue. Stem cells therapy arises as a new therapeutic approach, with a wide application potential. PMID:27426083

  17. [Tear in retinal pigment epithelium under anti-VEGF therapy for exudative age-related macular degeneration : function recovery under intensive therapy].

    PubMed

    Bartels, S; Barrelmann, A; Book, B; Heimes, B; Gutfleisch, M; Spital, G; Pauleikhoff, D; Lommatzsch, A

    2014-05-01

    This article reports the case of a 72-year-old woman with pigment epithelial detachment with occult choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD) which developed under anti-vascular endothelial growth factor (VEGF) therapy of a tear in the retinal pigment epithelium (RPE). In the area of free RPE autofluorescence was completely absent and the microperimetry in this area showed an absolute scotoma. The visual acuity was 0.1. After continuation of anti-VEGF therapy because of persistent subretinal and intraretinal fluid over 3 years an increased autofluorescence was observed and the microperimetry showed an increase in central retinal sensitivity. The central visual acuity improved to 0.5 and in this area a whitish subretinal tissue formed morphologically. In the spectral domain optical coherence tomography (SD-OCT) image this structure was hyperreflective which might suggest a certain regeneration process of the RPE under anti-VEGF-therapy. PMID:24046170

  18. Retinal pigment epithelium engineering using synthetic biodegradable polymers.

    PubMed

    Lu, L; Yaszemski, M J; Mikos, A G

    2001-12-01

    Retinal pigment epithelium (RPE) plays a key role in the maintenance of the normal functions of the retina, especially photoreceptors. Alteration in RPE structure and function is implicated in a variety of ocular disorders. Tissue engineering strategies using synthetic biodegradable polymers as temporary substrates for RPE cell culture and subsequent transplantation may provide a promising new therapy. In this review article, the manufacture of thin biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) films and their degradation behavior in vitro are discussed. RPE cell proliferation and differentiation on these PLGA films are reviewed. The fabrication of model substrates with desired chemical micropatterns in the micrometer scale is discussed and the effects of surface patterning on RPE morphology and function are assessed. Finally. the preparation of biodegradable micropatterns with adhesive PLGA and non-adhesive poly(ethylene glycol)/PLA domains to modulate RPE cell adhesion is presented. PMID:11700807

  19. Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium

    PubMed Central

    Mabbott, Neil A.; Donaldson, David S.; Ohno, Hiroshi; Williams, Ifor R.; Mahajan, Arvind

    2013-01-01

    SUMMARY The transcytosis of antigens across the gut epithelium by microfold cells (M cells) is important for the induction of efficient immune responses to some mucosal antigens in Peyer’s patches. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells. This review highlights these important advances, with particular emphasis on: the host genes which control the functional maturation of M cells; how this knowledge has led to the rapid advance in our understanding of M-cell biology in the steady-state and during aging; molecules expressed on M cells which appear to be used as “immunosurveillance” receptors to sample pathogenic microorganisms in the gut; how certain pathogens appear to exploit M cells to infect the host; and finally how this knowledge has been used to specifically target antigens to M cells to attempt to improve the efficacy of mucosal vaccines. PMID:23695511

  20. Electroolfactogram (EOG) Recording in the Mouse Main Olfactory Epithelium

    PubMed Central

    Chen, Xuanmao; Xia, Zhengui; Storm, Daniel R.

    2016-01-01

    Olfactory sensory neurons in the main olfactory epithelium (MOE) are responsible for detecting odorants and EOG recording is a reliable approach to analyze the peripheral olfactory function. However, recently we revealed that rodent MOE can also detect the air pressure caused by airflow. The sensation of airflow pressure and odorants may function in synergy to facilitate odorant perception during sniffing. We have reported that the pressure-sensitive response in the MOE can also be assayed by EOG recording. Here we describe procedures for pressure-sensitive as well as odorant-stimulated EOG measurement in the mouse MOE. The major difference between the pressure-sensitive EOG response and the odorant-stimulated response was whether to use pure air puff or use an odorized air puff.

  1. X-ray microanalysis of hamster tracheal epithelium

    SciTech Connect

    Spencer, A.J.; Roomans, G.M. )

    1989-06-01

    Studies of ion transport across respiratory epithelia are of great interest if we are to understand the pathophysiology of diseases such as cystic fibrosis in which ion transport is abnormal. Concentrations of elements were determined in various subcellular regions of normal or isoproterenol-treated hamster tracheal epithelium, using X-ray microanalysis of freeze-dried cryosections. Samples of trachea were taken from animals under anesthesia and either frozen in situ or dissected and plunge frozen. Concentrations of Mg, P, S, Cl, K and Ca were higher in cytoplasm and nuclei of control epithelial cells in dissected samples than in cryoneedle samples. Following treatment with isoproterenol, a large decrease in the concentration of Cl was observed. The results confirm that cyclic AMP-regulated chloride secretion is unaffected by anesthesia.

  2. Intermediate Filaments and Polarization in the Intestinal Epithelium.

    PubMed

    Coch, Richard A; Leube, Rudolf E

    2016-01-01

    The cytoplasmic intermediate filament cytoskeleton provides a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. This is particularly apparent in the intestinal epithelium, in which the intermediate filament network is localized below the apical terminal web region and is anchored to the apical junction complex. This arrangement is conserved from the nematode Caenorhabditis elegans to humans. The review summarizes compositional, morphological and functional features of the polarized intermediate filament cytoskeleton in intestinal cells of nematodes and mammals. We emphasize the cross talk of intermediate filaments with the actin- and tubulin-based cytoskeleton. Possible links of the intermediate filament system to the distribution of apical membrane proteins and the cell polarity complex are highlighted. Finally, we discuss how these properties relate to the establishment and maintenance of polarity in the intestine. PMID:27429003

  3. Evaluation of different pig oral mucosa sites as permeability barrier models for drug permeation studies.

    PubMed

    Franz-Montan, Michelle; Serpe, Luciano; Martinelli, Claudia Cristina Maia; da Silva, Camila Batista; Santos, Cleiton Pita Dos; Novaes, Pedro Duarte; Volpato, Maria Cristina; de Paula, Eneida; Lopez, Renata Fonseca Vianna; Groppo, Francisco Carlos

    2016-01-01

    The objective of the present study was to investigate the influence of preparation and storage conditions on the histology and permeability of different parts of porcine oral mucosa used for in vitro studies of transbuccal formulations. Fresh and frozen (-20°C and -80°C, with or without cryoprotectant) epithelia of porcine palatal, gingival, dorsum of the tongue, and buccal mucosa were submitted for histological analyses to determine the effects of storage conditions on barrier integrity. Permeation of lidocaine hydrochloride (used as a hydrophilic model drug) across fresh and previously frozen oral epithelium was measured in order to evaluate the barrier function. Histological evaluation demonstrated that the oral epithelium was successfully separated from the connective tissue, except for gingival mucosa. After storage under different conditions, all tissues presented desquamation of superficial layers and spherical spaces induced by the freezing process. The permeability of lidocaine hydrochloride varied among the fresh oral mucosa and generally increased after freezing. In conclusion, fresh epithelium from the buccal and dorsum of the tongue mucosa should be used for in vitro studies investigating hydrophilic drug transport when these are the desired clinical application sites. However, when the palate is the target site, both fresh and frozen (for up to 4weeks, without addition of cryoprotectant) samples could be used. The addition of glycerol as a cryoprotectant should be avoided due to increased lidocaine hydrochloride permeability. PMID:26435216

  4. Alterations in phenotypic biochemical markers in bladder epithelium during tumorigenesis.

    PubMed

    Rao, J Y; Hemstreet, G P; Hurst, R E; Bonner, R B; Jones, P L; Min, K W; Fradet, Y

    1993-09-01

    Phenotypic biochemical markers of oncogenesis and differentiation were mapped in bladder biopsies to investigate changes that occur in bladder tumorigenesis and to identify markers for increased bladder cancer risk. Touch preparations from biopsy specimens from 30 patients were obtained from tumors, the adjacent bladder epithelium, and random distant bladder epithelium. Markers, including DNA ploidy, epidermal growth factor receptor (EGFR), and oncoproteins, were quantified in individual cells by using quantitative fluorescence image analysis. Cluster analysis revealed the markers fell into three independent groups: (i) G-actin and EGFR; (ii) ploidy, cytology, and p185 (HER-2/neu oncoprotein) (ERBB2); and (iii) p300, a low-grade tumor antigen. Each marker displayed a gradient of abnormality from distant field to adjacent field to tumor. Different patterns for each marker suggested a developmental sequence of bladder cancer oncogenesis; G-actin was altered in 58% of distant biopsies (vs. 0/6 normals, P < 0.001), ploidy and cytology were altered in < 20% of distant fields and approximately 80% of tumors, and the other markers were intermediate. Patterns of EGFR and p185 suggest low-and high-grade tracks diverge early (P < 0.05 by Mann-Whitney U test for EGFR and ANOVA for p185). In conclusion, this study shows that a sequence of phenotypic changes accompanies development and progression of bladder cancers. Biochemical alterations in cells of the bladder field are often detectable before abnormal pathology, and markers previously thought to be limited to tumors were found in the field. The hierarchy of expression may be useful in identifying high-risk patients, assessing completeness of response to therapy, and monitoring and predicting recurrence. PMID:8367495

  5. Mechanical strain inhibits repair of airway epithelium in vitro.

    PubMed

    Savla, U; Waters, C M

    1998-06-01

    The repair of airway epithelium after injury is crucial in restoring epithelial barrier integrity. Although the airway epithelium is stretched and compressed due to changes in both circumferential and longitudinal dimensions during respiration and may be overdistended during mechanical ventilation, the effect of cyclic strain on the repair of epithelial wounds is unknown. Human and cat airway epithelial cells were cultured on flexible membranes, wounded by scraping with a metal spatula, and subjected to cyclic strain using the Flexercell Strain Unit. Because the radial strain profile in the wells was nonuniform, we compared closure in regions of elongation and compression within the same well. Both cyclic elongation and cyclic compression significantly slowed repair, with compression having the greatest effect. This attenuation was dependent upon the time of relaxation (TR) during the cycle. When wells were stretched at 10 cycles/min (6 s/cycle) with TR = 5 s, wounds closed similarly to wounds in static wells, whereas in wells with TR = 1 s, significant inhibition was observed. As the TR during cycles increased (higher TR), wounds closed faster. We measured the effect of strain at various TRs on cell area and centroid-centroid distance (CD) as a measure of spreading and migration. While cell area and CD in static wells significantly increased over time, the area and CD of cells in the elongated regions did not change. Cells in compressed regions were significantly smaller, with significantly lower CD. Cell area and CD became progressively larger with increasing TR. These results suggest that mechanical strain inhibits epithelial repair. PMID:9609726

  6. A quantitative metabolomics peek into planarian regeneration.

    PubMed

    Natarajan, Nivedita; Ramakrishnan, Padma; Lakshmanan, Vairavan; Palakodeti, Dasaradhi; Rangiah, Kannan

    2015-05-21

    The fresh water planarian species Schmidtea mediterranea is an emerging stem cell model because of its capability to regenerate a whole animal from a small piece of tissue. It is one of the best model systems to address the basic mechanisms essential for regeneration. Here, we are interested in studying the roles of various amines, thiols and nucleotides in planarian regeneration, stem cell function and growth. We developed mass spectrometry based quantitative methods and validated the differential enrichment of 35 amines, 7 thiol metabolites and 4 nucleotides from both intact and regenerating planarians. Among the amines, alanine in sexual and asparagine in asexual are the highest (>1000 ng/mg) in the intact planarians. The levels of thiols such as cysteine and GSH are 651 and 1107 ng mg(-1) in planarians. Among the nucleotides, the level of cGMP is the lowest (0.03 ng mg(-1)) and the level of AMP is the highest (187 ng mg(-1)) in both of the planarian strains. We also noticed increasing levels of amines in both anterior and posterior regenerating planarians. The blastema from day 3 regenerating planarians also showed higher amounts of many amines. Interestingly, the thiol (cysteine and GSH) levels are well maintained during planarian regeneration. This suggests an inherent and effective mechanism to control induced oxidative stress because of the robust regeneration and stem cell proliferation. Like in intact planarians, the level of cGMP is also very low in regenerating planarians. Surprisingly, the levels of amines and thiols in head regenerating blastemas are ∼3 times higher compared to those for tail regenerating blastemas. Thus our results strongly indicate the potential roles of amines, thiols and nucleotides in planarian regeneration. PMID:25815385

  7. [Prevention of oral cancer].

    PubMed

    Roodenburg, J L; Vermey, A; Nauta, J M

    1994-05-01

    Etiology control is the most important primary prevention of oral cancer. The use of tobacco and alcohol increases the risk of a squamous cell carcinoma of the oral mucosa. The dentist can play an important role in the secondary prevention or screening for premalignant lesions, asymptomatic malignancies and second primary tumours of the oral cavity. Because of their age, edentulous patients run a high risk of oral cancer. Therefore, a regular oral check-up of these patients should be recommended. PMID:11830977

  8. Oral Health in Pregnancy.

    PubMed

    Hartnett, Erin; Haber, Judith; Krainovich-Miller, Barbara; Bella, Abigail; Vasilyeva, Anna; Lange Kessler, Julia

    2016-01-01

    Oral health is crucial to overall health. Because of normal physiologic changes, pregnancy is a time of particular vulnerability in terms of oral health. Pregnant women and their providers need more knowledge about the many changes that occur in the oral cavity during pregnancy. In this article we describe the importance of the recognition, prevention, and treatment of oral health problems in pregnant women. We offer educational strategies that integrate interprofessional oral health competencies. PMID:27281467

  9. NORMAL GENE EXPRESSION IN MALE F344 RAT NASAL TRANSITIONAL/RESPIRATORY EPITHELIUM

    EPA Science Inventory

    Abstract

    The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity in rodents. Gene expression profiles were determined in order to provide normal baseline data for nasal transitional/respiratory epithelium from healthy rats. Ce...

  10. STUDIES OF NORMAL GENE EXPRESSION IN THE RAT NASAL EPITHELIUM USNG CDNA ARRAY TECHNOLOGY

    EPA Science Inventory


    Studies of Normal Gene Expression in the Rat Nasal Epithelium Using cDNA Array

    The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity .Gene expression data are being used increasingly for studies of such conditions. In or...

  11. Respiratory epithelium lined cysts presenting in the orbit without associated mucocele formation.

    PubMed

    James, C R; Lyness, R; Wright, J E

    1986-05-01

    Three patients presented with orbital cysts lined with upper respiratory tract epithelium. In each case there was no evidence of an associated mucocele. Two patients had a past history of orbital trauma, and the third had had preceding sinus surgery. It is postulated that these cysts were caused by traumatic herniation of nasal sinus epithelium cells into the orbit. PMID:3964639

  12. Scattering attenuation microscopy of oral epithelial dysplasia

    NASA Astrophysics Data System (ADS)

    Tomlins, Pete H.; Adegun, Oluyori; Hagi-Pavli, Eleni; Piper, Kim; Bader, Dan; Fortune, Farida

    2010-11-01

    We present a new method for quantitative visualization of premalignant oral epithelium called scattering attenuation microscopy (SAM). Using low-coherence interferometry, SAM projects measurements of epithelial optical attenuation onto an image of the tissue surface as a color map. The measured attenuation is dominated by optical scattering that provides a metric of the severity of oral epithelial dysplasia (OED). Scattering is sensitive to the changes in size and distribution of nuclear material that are characteristic of OED, a condition recognized by the occurrence of basal-cell-like features throughout the epithelial depth. SAM measures the axial intensity change of light backscattered from epithelial tissue. Scattering measurements are obtained from sequential axial scans of a 3-D tissue volume and displayed as a 2-D SAM image. A novel segmentation method is used to confine scattering measurement to epithelial tissue. This is applied to oral biopsy samples obtained from 19 patients. Our results show that imaging of tissue scattering can be used to discriminate between different dysplastic severities and furthermore presents a powerful tool for identifying the most representative tissue site for biopsy.

  13. Assembly Methods for Etched Foil Regenerators

    NASA Astrophysics Data System (ADS)

    Mitchell, Matthew P.

    2004-06-01

    Etched foil appears to offer substantial advantages over other regenerator materials, especially for annular regenerators. However, assembly of etched foil regenerators has been difficult because etching regenerator patterns in foil is most satisfactorily accomplished using pieces too small for a complete, spiral-wrapped regenerator. Two techniques have been developed to deal with that problem: For spiral-wrapped regenerators, a new technique for joining pieces of foil using tabs has been successfully employed. The joints are no thicker than the parent material. The tabs substantially fill the holes into which they are locked, virtually eliminating any undesired leak path through the regenerator. The holes constitute breaks in the conductive path through the regenerator. A patent is pending. An alternate method is to insert pieces of foil in a cylindrical housing one at a time. An inflatable bladder presses each newly-inserted piece of foil against the previous layer until both edges slip past each other and contact the previously-installed piece. When the bladder is deflated, the natural springiness of the foil causes the cut edges to seek the wall and meet each other in a butt joint. A patent on the method has been issued; a patent on the resulting regenerator is pending.

  14. Unraveling tissue regeneration pathways using chemical genetics.

    PubMed

    Mathew, Lijoy K; Sengupta, Sumitra; Kawakami, Atsushi; Andreasen, Eric A; Löhr, Christiane V; Loynes, Catherine A; Renshaw, Stephen A; Peterson, Randall T; Tanguay, Robert L

    2007-11-30

    Identifying the molecular pathways that are required for regeneration remains one of the great challenges of regenerative medicine. Although genetic mutations have been useful for identifying some molecular pathways, small molecule probes of regenerative pathways might offer some advantages, including the ability to disrupt pathway function with precise temporal control. However, a vertebrate regeneration model amenable to rapid throughput small molecule screening is not currently available. We report here the development of a zebrafish early life stage fin regeneration model and its use in screening for small molecules that modulate tissue regeneration. By screening 2000 biologically active small molecules, we identified 17 that specifically inhibited regeneration. These compounds include a cluster of glucocorticoids, and we demonstrate that transient activation of the glucocorticoid receptor is sufficient to block regeneration, but only if activation occurs during wound healing/blastema formation. In addition, knockdown of the glucocorticoid receptor restores regenerative capability to nonregenerative, glucocorticoid-exposed zebrafish. To test whether the classical anti-inflammatory action of glucocorticoids is responsible for blocking regeneration, we prevented acute inflammation following amputation by antisense repression of the Pu.1 gene. Although loss of Pu.1 prevents the inflammatory response, regeneration is not affected. Collectively, these results indicate that signaling from exogenous glucocorticoids impairs blastema formation and limits regenerative capacity through an acute inflammation-independent mechanism. These studies also demonstrate the feasibility of exploiting chemical genetics to define the pathways that govern vertebrate regeneration. PMID:17848559

  15. Plant regeneration: cellular origins and molecular mechanisms.

    PubMed

    Ikeuchi, Momoko; Ogawa, Yoichi; Iwase, Akira; Sugimoto, Keiko

    2016-05-01

    Compared with animals, plants generally possess a high degree of developmental plasticity and display various types of tissue or organ regeneration. This regenerative capacity can be enhanced by exogenously supplied plant hormones in vitro, wherein the balance between auxin and cytokinin determines the developmental fate of regenerating organs. Accumulating evidence suggests that some forms of plant regeneration involve reprogramming of differentiated somatic cells, whereas others are induced through the activation of relatively undifferentiated cells in somatic tissues. We summarize the current understanding of how plants control various types of regeneration and discuss how developmental and environmental constraints influence these regulatory mechanisms. PMID:27143753

  16. Angiogenesis is inhibitory for mammalian digit regeneration

    PubMed Central

    Yu, Ling; Yan, Mingquan; Simkin, Jennifer; Ketcham, Paulina D.; Leininger, Eric; Han, Manjong

    2014-01-01

    Abstract The regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti‐angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka, K. (2010). BMP signaling induces digit regeneration in neonatal mice. Development, 137, 551–559). Here we show that during regeneration Vegfa transcripts are not detected in the blastema but are expressed at the onset of differentiation. Treating the amputation wound with vascular endothelial growth factor enhances angiogenesis but inhibits regeneration. We next tested bone morphogenetic protein 9 (BMP9), another known mediator of angiogenesis, and found that BMP9 is also a potent inhibitor of digit tip regeneration. BMP9 induces Vegfa expression in the digit stump suggesting that regenerative failure is mediated by enhanced angiogenesis. Finally, we show that BMP9 inhibition of regeneration is completely rescued by treatment with pigment epithelium‐derived factor. These studies show that precocious angiogenesis is inhibitory for regeneration, and provide compelling evidence that the regulation of angiogenesis is a critical factor in designing therapies aimed at stimulating mammalian regeneration.

  17. The cellular basis for animal regeneration

    PubMed Central

    Tanaka, Elly; Reddien, Peter W.

    2011-01-01

    The ability of animals to regenerate missing parts is a dramatic and poorly understood aspect of biology. The sources of new cells for these regenerative phenomena have been sought for decades. Recent advances involving cell fate tracking in complex tissues have shed new light on the cellular underpinnings of regeneration in Hydra, planarians, zebrafish, Xenopus, and Axolotl. Planarians accomplish regeneration with use of adult pluripotent stem cells, whereas several vertebrates utilize a collection of lineage-restricted progenitors from different tissues. Together, an array of cellular strategies—from pluripotent stem cells to tissue-specific stem cells and dedifferentiation—are utilized for regeneration. PMID:21763617

  18. Odontogenic Ameloblast-associated Protein (ODAM) Mediates Junctional Epithelium Attachment to Teeth via Integrin-ODAM-Rho Guanine Nucleotide Exchange Factor 5 (ARHGEF5)-RhoA Signaling.

    PubMed

    Lee, Hye-Kyung; Ji, Suk; Park, Su-Jin; Choung, Han-Wool; Choi, Youngnim; Lee, Hyo-Jung; Park, Shin-Young; Park, Joo-Cheol

    2015-06-01

    Adhesion of the junctional epithelium (JE) to the tooth surface is crucial for maintaining periodontal health. Although odontogenic ameloblast-associated protein (ODAM) is expressed in the JE, its molecular functions remain unknown. We investigated ODAM function during JE development and regeneration and its functional significance in the initiation and progression of periodontitis and peri-implantitis. ODAM was expressed in the normal JE of healthy teeth but absent in the pathologic pocket epithelium of diseased periodontium. In periodontitis and peri-implantitis, ODAM was extruded from the JE following onset with JE attachment loss and detected in gingival crevicular fluid. ODAM induced RhoA activity and the expression of downstream factors, including ROCK (Rho-associated kinase), by interacting with Rho guanine nucleotide exchange factor 5 (ARHGEF5). ODAM-mediated RhoA signaling resulted in actin filament rearrangement. Reduced ODAM and RhoA expression in integrin β3- and β6-knockout mice revealed that cytoskeleton reorganization in the JE occurred via integrin-ODAM-ARHGEF5-RhoA signaling. Fibronectin and laminin activated RhoA signaling via the integrin-ODAM pathway. Finally, ODAM was re-expressed with RhoA in regenerating JE after gingivectomy in vivo. These results suggest that ODAM expression in the JE reflects a healthy periodontium and that JE adhesion to the tooth surface is regulated via fibronectin/laminin-integrin-ODAM-ARHGEF5-RhoA signaling. We also propose that ODAM could be used as a biomarker of periodontitis and peri-implantitis. PMID:25911094

  19. Odontogenic Ameloblast-associated Protein (ODAM) Mediates Junctional Epithelium Attachment to Teeth via Integrin-ODAM-Rho Guanine Nucleotide Exchange Factor 5 (ARHGEF5)-RhoA Signaling*

    PubMed Central

    Lee, Hye-Kyung; Ji, Suk; Park, Su-Jin; Choung, Han-Wool; Choi, Youngnim; Lee, Hyo-Jung; Park, Shin-Young; Park, Joo-Cheol

    2015-01-01

    Adhesion of the junctional epithelium (JE) to the tooth surface is crucial for maintaining periodontal health. Although odontogenic ameloblast-associated protein (ODAM) is expressed in the JE, its molecular functions remain unknown. We investigated ODAM function during JE development and regeneration and its functional significance in the initiation and progression of periodontitis and peri-implantitis. ODAM was expressed in the normal JE of healthy teeth but absent in the pathologic pocket epithelium of diseased periodontium. In periodontitis and peri-implantitis, ODAM was extruded from the JE following onset with JE attachment loss and detected in gingival crevicular fluid. ODAM induced RhoA activity and the expression of downstream factors, including ROCK (Rho-associated kinase), by interacting with Rho guanine nucleotide exchange factor 5 (ARHGEF5). ODAM-mediated RhoA signaling resulted in actin filament rearrangement. Reduced ODAM and RhoA expression in integrin β3- and β6-knockout mice revealed that cytoskeleton reorganization in the JE occurred via integrin-ODAM-ARHGEF5-RhoA signaling. Fibronectin and laminin activated RhoA signaling via the integrin-ODAM pathway. Finally, ODAM was re-expressed with RhoA in regenerating JE after gingivectomy in vivo. These results suggest that ODAM expression in the JE reflects a healthy periodontium and that JE adhesion to the tooth surface is regulated via fibronectin/laminin-integrin-ODAM-ARHGEF5-RhoA signaling. We also propose that ODAM could be used as a biomarker of periodontitis and peri-implantitis. PMID:25911094

  20. Plant lectins as carriers for oral drugs: is wheat germ agglutinin a suitable candidate?

    PubMed

    Dalla Pellegrina, Chiara; Rizzi, Corrado; Mosconi, Silvia; Zoccatelli, Gianni; Peruffo, Angelo; Chignola, Roberto

    2005-09-01

    Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed also by gastrointestinal epithelial cells. WGA is currently investigated as an anti-tumor drug and as a carrier for oral drugs. Information on whether it can cross the gastrointestinal epithelium and on its possible effects on the integrity of the epithelial layer is however scanty or lacking, and herein we address these issues. Differentiated Caco2 cells have been used as a model of polarized intestinal epithelium. WGA concentration at both the apical and the basolateral side of the epithelium has been quantified using a sensitive ELISA assay (sensitivity threshold 0.84 nM). Trans epithelial electrical resistance (TEER) has been measured to evaluate the integrity of the epithelium upon treatments with WGA. (3)H-Mannitol (182.2 Da) and FITC-dextran (3000 Da) have been used to measure the permeability of the epithelium. Cell viability has been measured by the MTT, by 7-AAD uptake, and Annexin-V binding assays. Up to a concentration of 5.6 microM, approximately 0.1% of intact WGA molecules only could cross the epithelial layer. WGA perturbed the integrity of the epithelium and increased the permeability of the tissue in a dose- and time-dependent manner. WGA did not induce cell death but increased the permeability of individual cells to 7-AAD which is normally not uptaken by viable cells. These data allowed us to define a toxicity threshold for WGA on epithelial cells. WGA suitability as a carrier for oral drugs can therefore be evaluated on a rational basis. PMID:16102568

  1. [Regeneration of planarians: experimental object].

    PubMed

    Sheĭman, I M; Kreshchenko, I D

    2015-01-01

    We discuss the expediency of using invertebrates, such as flatworms and planarians, as experimental objects. Free-living planarian flatworms (phylum Platyhelminthes, class Turbellaria) are invertebrate animals in which a bilateral symmetry appears for the first time in evolution and organs and tissues form. As the highest ecological link of the food chain--predators--these animals are characterized by a set of behavioral reactions controlled by a differentiated central nervous system. Planarians have unsurpassed ability to regenerate lost or damaged body parts. Owing to the ease of their breeding and their convenience for manipulations, these animals are used to study the influence of chemical and physical factors on the processes of life, growth, and reproduction. Currently, planarians are recognized as a model for biological research in the field of regeneration, stem cell biology, study of their proliferation and differentiation, as well as the regulatory mechanisms of morphogenetic processes. The genome of the planarian Schmidtea mediterranea was fully sequenced, which opened up the opportunity to work with this object at the molecular biological level. Furthermore, planarians are used in neurobiological and toxicological studies, in studying the evolutionary aspects of centralization of the nervous system, mechanisms of muscle contraction, and in the development of new antiparasitic drugs. This review aims to demonstrate the relevance and diversity of research conducted on simple biological objects--planarians--to awider audience to show the historical continuity of these studies and their wide geographical distribution and to focus on the studies carried out in Russia, which, as a rule, are not included in the foreign reviews on planarian regeneration. PMID:25898529

  2. Towards Regeneration of Articular Cartilage

    PubMed Central

    Iwamoto, Masahiro; Ohta, Yoichi; Larmour, Colleen; Enomoto-Iwamoto, Motomi

    2014-01-01

    Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site. PMID:24078496

  3. Epstein-Barr Virus and Its Association with Oral Hairy Leukoplakia: A Short Review.

    PubMed

    Khammissa, Razia Abdool Gafaar; Fourie, Jeanine; Chandran, Rakesh; Lemmer, Johan; Feller, Liviu

    2016-01-01

    In immunocompromised subjects, Epstein-Barr virus (EBV) infection of terminally differentiated oral keratinocytes may result in subclinical productive infection of the virus in the stratum spinosum and in the stratum granulosum with shedding of infectious virions into the oral fluid in the desquamating cells. In a minority of cases this productive infection with dysregulation of the cell cycle of terminally differentiated epithelial cells may manifest as oral hairy leukoplakia. This is a white, hyperkeratotic, benign lesion of low morbidity, affecting primarily the lateral border of the tongue. Factors that determine whether productive EBV replication within the oral epithelium will cause oral hairy leukoplakia include the fitness of local immune responses, the profile of EBV gene expression, and local environmental factors. PMID:27047546

  4. Epstein-Barr Virus and Its Association with Oral Hairy Leukoplakia: A Short Review

    PubMed Central

    Khammissa, Razia Abdool Gafaar; Fourie, Jeanine; Chandran, Rakesh; Lemmer, Johan

    2016-01-01

    In immunocompromised subjects, Epstein-Barr virus (EBV) infection of terminally differentiated oral keratinocytes may result in subclinical productive infection of the virus in the stratum spinosum and in the stratum granulosum with shedding of infectious virions into the oral fluid in the desquamating cells. In a minority of cases this productive infection with dysregulation of the cell cycle of terminally differentiated epithelial cells may manifest as oral hairy leukoplakia. This is a white, hyperkeratotic, benign lesion of low morbidity, affecting primarily the lateral border of the tongue. Factors that determine whether productive EBV replication within the oral epithelium will cause oral hairy leukoplakia include the fitness of local immune responses, the profile of EBV gene expression, and local environmental factors. PMID:27047546

  5. Bone regeneration and stem cells

    PubMed Central

    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  6. Regenerator matrix physical property data

    NASA Technical Reports Server (NTRS)

    Fucinari, C. A.

    1980-01-01

    Among several cellular ceramic structures manufactured by various suppliers for regenerator application in a gas turbine engine, three have the best potential for achieving durability and performance objectives for use in gas turbines, Stirling engines, and waste heat recovery systems: (1) an aluminum-silicate sinusoidal flow passage made from a corrugated wate paper process; (2) an extruded isosceles triangle flow passage; and (3) a second generation matrix incorporating a square flow passage formed by an embossing process. Key physical and thermal property data for these configurations presented include: heat transfer and pressure drop characteristics, compressive strength, tensile strength and elasticity, thermal expansion characteristics, chanical attack, and thermal stability.

  7. Raman mapping of oral buccal mucosa: a spectral histopathology approach

    NASA Astrophysics Data System (ADS)

    Behl, Isha; Kukreja, Lekha; Deshmukh, Atul; Singh, S. P.; Mamgain, Hitesh; Hole, Arti R.; Krishna, C. Murali

    2014-12-01

    Oral cancer is one of the most common cancers worldwide. One-fifth of the world's oral cancer subjects are from India and other South Asian countries. The present Raman mapping study was carried out to understand biochemical variations in normal and malignant oral buccal mucosa. Data were acquired using WITec alpha 300R instrument from 10 normal and 10 tumors unstained tissue sections. Raman maps of normal sections could resolve the layers of epithelium, i.e. basal, intermediate, and superficial. Inflammatory, tumor, and stromal regions are distinctly depicted on Raman maps of tumor sections. Mean and difference spectra of basal and inflammatory cells suggest abundance of DNA and carotenoids features. Strong cytochrome bands are observed in intermediate layers of normal and stromal regions of tumor. Epithelium and stromal regions of normal cells are classified by principal component analysis. Classification among cellular components of normal and tumor sections is also observed. Thus, the findings of the study further support the applicability of Raman mapping for providing molecular level insights in normal and malignant conditions.

  8. Langerhans Cell Expression in Oral Submucous Fibrosis: An Immunohistochemical Analysis

    PubMed Central

    Narasimhan, Malathi

    2015-01-01

    Introduction Langerhans cells (LCs), are dendritic cells of the epithelium which play a role in an array of oral lesions from gingivitis to oral cancer. Oral Submucous Fibrosis (OSMF), a potentially malignant disorder (PMD), is an insidious chronic disease with juxta-epithelial inflammatory changes leading to fibrosis. Langerhans cells (LCs) may play a part in the ongoing inflammatory dysregulation of OSMF. Objective The study was aimed at elucidating the distribution of LCs in varying grades of OSMF. Materials and Methods A retrospective study using 39 cases of OSMF, graded using Haematoxylin and Eosin (H&E) stained section. Immunohistochemistry was performed using polyclonal anti- CD1a antibodies to identify LCs in 5 cases of normal tissue and 39 samples of OSMF. The distribution of LCs among the various grades and normal mucosa analysed using Mann-Whitney U test. Results LC population in the OSMF was significantly higher when compared to the normal epithelium (p<0.001). Within the grades the advanced stage had more LCs than the other stages. Conclusion The increase in LCs might indicate the role of antigenic exposure in turn leading to cell mediated immunity in OSMF. Thus the fibrosis in OSMF might have a direct link to LCs. PMID:26393203

  9. A review of biodegradable polymeric systems for oral insulin delivery.

    PubMed

    Luo, Yue Yuan; Xiong, Xiang Yuan; Tian, Yuan; Li, Zi Ling; Gong, Yan Chun; Li, Yu Ping

    2016-07-01

    Currently, repeated routine subcutaneous injections of insulin are the standard treatment for insulin-dependent diabetic patients. However, patients' poor compliance for injections often fails to achieve the stable concentration of blood glucose. As a protein drug, the oral bioavailability of insulin is low due to many physiological reasons. Several carriers, such as macromolecules and liposomes have been used to deliver drugs in vivo. In this review article, the gastrointestinal barriers of oral insulin administration are described. Strategies for increasing the bioavailability of oral insulin, such absorption enhancers, enzyme inhibitors, enteric coatings are also introduced. The potential absorption mechanisms of insulin-loaded nanoparticles across the intestinal epithelium, including intestinal lymphatic route, transcellular route and paracellular route are discussed in this review. Natural polymers, such as chitosan and its derivates, alginate derivatives, γ-PGA-based materials and starch-based nanoparticles have been exploited for oral insulin delivery; synthetic polymers, such as PLGA, PLA, PCL and PEA have also been developed for oral administration of insulin. This review focuses on recent advances in using biodegradable natural and synthetic polymers for oral insulin delivery along with their future prospects. PMID:26066036

  10. Microphthalmia-associated transcription factor regulates the visual cycle genes Rlbp1 and Rdh5 in the retinal pigment epithelium

    PubMed Central

    Wen, Bin; Li, Shuang; Li, Huirong; Chen, Yu; Ma, Xiaoyin; Wang, Jing; Lu, Fan; Qu, Jia; Hou, Ling

    2016-01-01

    Regeneration of the visual pigment by cells of the retinal pigment epithelium (RPE) is fundamental to vision. Here we show that the microphthalmia-associated transcription factor, MITF, which plays a central role in the development and function of RPE cells, regulates the expression of two visual cycle genes, Rlbp1 which encodes retinaldehyde binding protein-1 (RLBP1), and Rdh5, which encodes retinol dehydrogenase-5 (RDH5). First, we found that Rlbp1 and Rdh5 are downregulated in optic cups and presumptive RPEs of Mitf-deficient mouse embryos. Second, experimental manipulation of MITF levels in human RPE cells in culture leads to corresponding modulations of the endogenous levels of RLBP1 and RDH5. Third, the retinal degeneration associated with the disruption of the visual cycle in Mitf-deficient mice can be partially corrected both structurally and functionally by an exogenous supply of 9-cis-retinal. We conclude that the expression of Rlbp1 and Rdh5 critically depends on functional Mitf in the RPE and suggest that MITF has an important role in controlling retinoid processing in the RPE. PMID:26876013

  11. Tooth Germ-Like Construct Transplantation for Whole-Tooth Regeneration: An In Vivo Study in the Miniature Pig.

    PubMed

    Yang, Kai-Chiang; Kitamura, Yutaka; Wu, Chang-Chin; Chang, Hao-Hueng; Ling, Thai-Yen; Kuo, Tzong-Fu

    2016-04-01

    The purpose of this study was to demonstrate the feasibility of whole-tooth regeneration using a tooth germ-like construct. Dental pulp from upper incisors, canines, premolars, and molars were extracted from sexually mature miniature pigs. Pulp tissues were cultured and expanded in vitro to obtain dental pulp stem cells (DPSCs), and cells were differentiated into odontoblasts and osteoblasts. Epithelial cells were isolated from gingival epithelium. The epithelial cells, odontoblasts, and osteoblasts were seeded onto the surface, upper, and lower layers, respectively, of a bioactive scaffold. The lower first and second molar tooth germs were removed bilaterally and the layered cell/scaffold constructs were transplanted to the mandibular alveolar socket of a pig. At 13.5 months postimplantation, seven of eight pigs developed two teeth with crown, root, and pulp structures. Enamel-like tissues, dentin, cementum, odontoblasts, and periodontal tissues were found upon histological inspection. The regenerated tooth expressed dentin matrix protein-1 and osteopontin. All pigs had regenerated molar teeth regardless of the original tooth used to procure the DPSCs. Pigs that had tooth germs removed or who received empty scaffolds did not develop teeth. Although periodontal ligaments were generated, ankylosis was found in some animals. This study revealed that implantation of a tooth germ-like structure generated a complete tooth with a high success rate. The implant location may influence the morphology of the regenerated tooth. PMID:26582651

  12. Partial CO combustion with staged regeneration of catalyst

    SciTech Connect

    Cabrera, C.A.; Myers, D.N.; Hammershaimb, H.V.

    1989-07-18

    This paper describes a process for the regeneration of spent hydrocarbon conversion catalyst withdrawn from a fluidized reaction zone. The process comprises the steps of: passing to a lower locus of a combustion zone of a riser-type fluidized regeneration zone; spent catalyst from the reaction zone, a stream comprising regenerated catalyst from a hereinafter described dense bed regeneration zone, and a first oxygen containing regeneration gas stream in an amount sufficient to maintain fast fluidized conditions; oxidizing coke and coke combustion by-products in the combustion zone while transporting the spent and regenerated catalyst upward in cocurrent flow with rising regeneration gas; passing catalyst and regeneration gas upward in cocurrent flow and therein oxidizing coke and coke combustion by-products to produce partially regenerated catalyst and a spent first generation gas; discharging partially regenerated and regenerated catalyst and the spent first regeneration gas from an upper locus of the riser regeneration zone into a catalyst disengagement zone through an outlet means that effects at least a partial separation of catalyst and regeneration gas. Thereby causing an initial separation of catalyst and the spend first regeneration gas; allowing partially regenerated and regenerated catalyst discharged through the outlet means to settle downward through a dilute phase above a dense fluidized bed and introducing into the dense fluidized bed a second oxygen containing regeneration gas stream in a quantity at least sufficient to produce regenerated catalyst having less than 0.1 wt% coke and to oxidize essentially all of the carbon monoxide produced.

  13. [Stem cells and cardiac regeneration].

    PubMed

    Perez Millan, Maria Ines; Lorenti, Alicia

    2006-01-01

    Stem cells are defined by virtue of their functional attributes: absence of tissue specific differentitated markers, capable of proliferation, able to self-maintain the population, able to produce a large number of differentiated, functional progeny, able to regenerate the tissue after injury. Cell therapy is an alternative for the treatment of several diseases, like cardiac diseases (cell cardiomyoplasty). A variety of stem cells could be used for cardiac repair: from cardiac and extracardiac sources. Each cell type has its own profile of advantages, limitations, and practicability issues in specific clinical settings. Differentiation of bone marrow stem cells to cardiomyocyte-like cells have been observed under different culture conditions. The presence of resident cardiac stem cell population capable of differentiation into cardiomyocyte or vascular lineage suggests that these cells could be used for cardiac tissue repair, and represent a great promise for clinical application. Stem cells mobilization by cytokines may also offer a strategy for cardiac regeneration. The use of stem cells (embryonic and adult) may hold the key to replacing cells lost in many devastating diseases. This potential benefit is a major focus for stem cell research. PMID:17240634

  14. Microwave Regenerable Air Purification Device

    NASA Technical Reports Server (NTRS)

    Atwater, James E.; Holtsnider, John T.; Wheeler, Richard R., Jr.

    1996-01-01

    The feasibility of using microwave power to thermally regenerate sorbents loaded with water vapor, CO2, and organic contaminants has been rigorously demonstrated. Sorbents challenged with air containing 0.5% CO2, 300 ppm acetone, 50 ppm trichloroethylene, and saturated with water vapor have been regenerated, singly and in combination. Microwave transmission, reflection, and phase shift has also been determined for a variety of sorbents over the frequency range between 1.3-2.7 GHz. This innovative technology offers the potential for significant energy savings in comparison to current resistive heating methods because energy is absorbed directly by the material to be heated. Conductive, convective and radiative losses are minimized. Extremely rapid heating is also possible, i.e., 1400 C in less than 60 seconds. Microwave powered thermal desorption is directly applicable to the needs of Advance Life Support in general, and of EVA in particular. Additionally, the applicability of two specific commercial applications arising from this technology have been demonstrated: the recovery for re-use of acetone (and similar solvents) from industrial waste streams using a carbon based molecular sieve; and the separation and destruction of trichloroethylene using ZSM-5 synthetic zeolite catalyst, a predominant halocarbon environmental contaminant. Based upon these results, Phase II development is strongly recommended.

  15. Infection, Inflammation, and Bone Regeneration

    PubMed Central

    Thomas, M.V.; Puleo, D.A.

    2011-01-01

    Various strategies have been developed to promote bone regeneration in the craniofacial region. Most of these interventions utilize implantable materials or devices. Infections resulting from colonization of these implants may result in local tissue destruction in a manner analogous to periodontitis. This destruction is mediated via the expression of various inflammatory mediators and tissue-destructive enzymes. Given the well-documented association among microbial biofilms, inflammatory mediators, and tissue destruction, it seems reasonable to assume that inflammation may interfere with bone healing and regeneration. Paradoxically, recent evidence also suggests that the presence of certain pro-inflammatory mediators is actually required for bone healing. Bone injury (e.g., subsequent to a fracture or surgical intervention) is followed by a choreographed cascade of events, some of which are dependent upon the presence of pro-inflammatory mediators. If inflammation resolves promptly, then proper bone healing may occur. However, if inflammation persists (which might occur in the presence of an infected implant or graft material), then the continued inflammatory response may result in suboptimal bone formation. Thus, the effect of a given mediator is dependent upon the temporal context in which it is expressed. Better understanding of this temporal sequence may be used to optimize regenerative outcomes. PMID:21248364

  16. Extracellular Control of Limb Regeneration

    NASA Astrophysics Data System (ADS)

    Calve, S.; Simon, H.-G.

    Adult newts possess the ability to completely regenerate organs and appendages. Immediately after limb loss, the extracellular matrix (ECM) undergoes dramatic changes that may provide mechanical and biochemical cues to guide the formation of the blastema, which is comprised of uncommitted stem-like cells that proliferate to replace the lost structure. Skeletal muscle is a known reservoir for blastema cells but the mechanism by which it contributes progenitor cells is still unclear. To create physiologically relevant culture conditions for the testing of primary newt muscle cells in vitro, the spatio-temporal distribution of ECM components and the mechanical properties of newt muscle were analyzed. Tenascin-C and hyaluronic acid (HA) were found to be dramatically upregulated in the amputated limb and were co-expressed around regenerating skeletal muscle. The transverse stiffness of muscle measured in situ was used as a guide to generate silicone-based substrates of physiological stiffness. Culturing newt muscle cells under different conditions revealed that the cells are sensitive to both matrix coating and substrate stiffness: Myoblasts on HA-coated soft substrates display a rounded morphology and become more elongated as the stiffness of the substrate increases. Coating of soft substrates with matrigel or fibronectin enhanced cell spreading and eventual cell fusion.

  17. Progenitor Cells and Podocyte Regeneration

    PubMed Central

    Shankland, Stuart J.; Pippin, Jeffrey W.; Duffield, Jeremy S.

    2014-01-01

    The very limited ability of adult podocytes to proliferate in vivo is clinically significant because: podocytes form a vascular barrier which is functionally critical to the nephron; podocyte hypoplasia is a characteristic of disease; and inadequate regeneration of podocytes is a major cause of persistent podocyte hypoplasia. Excessive podocyte loss or inadequate replacement leads to glomerulosclerosis in many progressive kidney diseases. Thus, restoration of podocyte cell density is almost certainly reliant on regeneration by podocyte progenitors. However such putative progenitors have remained elusive until recently. In this review we describe the developmental processes leading to podocyte and parietal epithelial cell (PEC) formation during glomerulogenesis. We compare evidence that in normal human kidneys PECs expressing ‘progenitor’ markers CD133 and CD24 can differentiate into podocytes in vitro and in vivo with evidence from animal models suggesting a more limited role of PEC-capacity to serve as podocyte progenitors in adults. We will highlight tantalizing new evidence that specialized vascular wall cells of afferent arterioles including those which produce renin in healthy kidney, provide a novel local progenitor source of new PECs and podocytes in response to podocyte hypoplasia in the adult, and draw comparisons with glomerulogenesis. PMID:25217270

  18. Nonventing, Regenerable, Lightweight Heat Absorber

    NASA Technical Reports Server (NTRS)

    Izenson, Michael G.; Chen, Weibo

    2008-01-01

    A lightweight, regenerable heat absorber (RHA), developed for rejecting metabolic heat from a space suit, may also be useful on Earth for short-term cooling of heavy protective garments. Unlike prior space-suit-cooling systems, a system that includes this RHA does not vent water. The closed system contains water reservoirs, tubes through which water is circulated to absorb heat, an evaporator, and an absorber/radiator. The radiator includes a solution of LiCl contained in a porous material in titanium tubes. The evaporator cools water that circulates through a liquid-cooled garment. Water vapor produced in the evaporator enters the radiator tubes where it is absorbed into the LiCl solution, releasing heat. Much of the heat of absorption is rejected to the environment via the radiator. After use, the RHA is regenerated by heating it to a temperature of 100 C for about 2 hours to drive the absorbed water back to the evaporator. A system including a prototype of the RHA was found to be capable of maintaining a temperature of 20 C while removing heat at a rate of 200 W for 6 hours.

  19. Stem cell therapy in oral and maxillofacial region: An overview

    PubMed Central

    Sunil, PM; Manikandhan, R; Muthu, MS; Abraham, S

    2012-01-01

    Cells with unique capacity for self-renewal and potency are called stem cells. With appropriate biochemical signals stem cells can be transformed into desirable cells. The idea behind this article is to shortly review the obtained literature on stem cell with respect to their properties, types and advantages of dental stem cells. Emphasis has been given to the possibilities of stem cell therapy in the oral and maxillofacial region including regeneration of tooth and craniofacial defects. PMID:22434942

  20. Comparative study of nanoparticle-mediated transfection in different GI epithelium co-culture models.

    PubMed

    Loo, Yihua; Grigsby, Christopher L; Yamanaka, Yvonne J; Chellappan, Malathi K; Jiang, Xuan; Mao, Hai-Quan; Leong, Kam W

    2012-05-30

    Oral nonviral gene delivery is the most attractive and arguably the most challenging route of administration. To identify a suitable carrier, we studied the transport of different classes (natural polymer, synthetic polymer and synthetic lipid-polymer) of DNA nanoparticles through three well-characterized cellular models of intestinal epithelium (Caco2, Caco2-HT29MTX and Caco2-Raji). Poly(phosphoramidate-dipropylamine) (PPA) and Lipid-Protamine-DNA (LPD) nanoparticles consistently showed the highest level of human insulin mRNA expression and luciferase protein expression in these models, typically at least three orders of magnitude above background. All of the nanoparticles increased tight junction permeability, with PPA and PEI having the most dramatic transepithelial electrical resistance (TEER) decreases of (35.3±8.5%) and (37.5±1.5%) respectively in the first hour. The magnitude of TEER decrease correlated with nanoparticle surface charge, implicating electrostatic interactions with the tight junction proteins. However, confocal microscopy revealed that the nanoparticles were mostly uptaken by the enterocytes. Quantitative uptake and transport experiments showed that the endocytosed, quantum dot (QD)-labeled PPA-DNA nanoparticles remained in the intestinal cells even after 24h. Negligible amount of quantum dot labeled DNA was detected in the basolateral chamber, with the exception of the Caco2-Raji co-cultures, which internalized nanoparticles 2 to 3 times more readily compared to Caco2 and Caco2-HT29MTX cultures. PEGylation decreased the transfection efficacy by at least an order of magnitude, lowered the magnitude of TEER decrease and halved the uptake of PPA-DNA nanoparticles. A key finding was insulin mRNA being detected in the underlying HepG2 cells, signifying that some of the plasmid was transported across the intestinal epithelial layer while retaining at least partial bioactivity. However, the inefficient transport suggests that transcytosis alone

  1. [Oral viral infections].

    PubMed

    Parent, Dominique

    2016-02-01

    Exclude herpes infection in the presence of acute oral ulcers of unknown origin, particularly in patients in poor general condition. Remember that asymptomatic HSV-1 shedding in saliva may result in an oral-genital transmission. Perform an anogenital examination and a screening for other sexually transmitted diseases when oral warts are diagnosed. Search for immunosuppression and monitor the patient (screening for a potential associated carcinoma) when there is rapid growth of oral warts. Consider all the clinical signs (systemic, skin, other mucosa, immunity...) when a patient has an enanthem or oral ulcerations. Ask for a HIV test when an oral Kaposi's sarcoma, a hairy leukoplakia or major aphthae are diagnosed. PMID:26854091

  2. Cells of origin of squamous epithelium, dysplasia and cancer in the head and neck region after bone marrow transplantation.

    PubMed

    Kano, Yoshihiro; Ishii, Hideshi; Konno, Masamitsu; Yamasaki, Makoto; Miyata, Hiroshi; Nishikawa, Shimpei; Hamabe, Atsushi; Ogawa, Hisataka; Takahashi, Hidekazu; Ohta, Katsuya; Hasegawa, Shinichiro; Tanaka, Kouji; Fukusumi, Takahito; Otsuka, Masahisa; Kawamoto, Koichi; Haraguchi, Naotsugu; Fujimoto, Rika; Isobe, Masaharu; Tomita, Yasuhiko; Matsuura, Nariaki; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2014-02-01

    Secondary solid tumors that occur after hematopoietic stem cell transplantation (HSCT) are late complications of HSCT. Previously, secondary solid tumors were considered to be recipient-derived cells because transplanted cells do not contain epithelial cells. Recently, however, not only donor‑derived epithelial cells but also donor-derived secondary solid tumors have also been reported in mice and humans. It means that circulating bone marrow-derived stem cells (BMDCs) including hematopoietic stem cells include the stem cells of many tissue types and the precancerous cells of many solid tumors. In most reports of donor-derived secondary solid tumors, however, tumors contained a low proportion of BMDC-derived epithelial cells in mixed solid tumor tissues. To our knowledge, there are only five known cases of completely donor-derived tumor tissues, i.e., four oral SCCs and a pharyngeal SCC. In this study, we analyzed five human clinical samples of solid tumors, i.e., two esophageal squamous cell carcinomas (SCCs), two oral SCCs and a tongue carcinoma. In the oral and tongue, completely donor-derived tissues were not observed, but in esophagus a completely donor-derived esophageal epidermis and SCC were observed for the first time. In addition, in another esophageal SCC patient, a completely donor-derived dysplasia region of esophageal epidermis was observed near recipient-derived SCC. This study suggests that BMDC-derived cells include the stem cells of esophageal epidermis and the precancerous cells of esophageal SCC and can differentiate into esophageal epithelium and esophageal SCC. PMID:24317739

  3. Scaffolds in vascular regeneration: current status

    PubMed Central

    Thottappillil, Neelima; Nair, Prabha D

    2015-01-01

    An ideal vascular substitute, especially in <6 mm diameter applications, is a major clinical essentiality in blood vessel replacement surgery. Blood vessels are structurally complex and functionally dynamic tissue, with minimal regeneration potential. These have composite extracellular matrix (ECM) and arrangement. The interplay between ECM components and tissue specific cells gives blood vessels their specialized functional attributes. The core of vascular tissue engineering and regeneration relies on the challenges in creating vascular conduits that match native vessels and adequately regenerate in vivo. Out of numerous vascular regeneration concerns, the relevance of ECM emphasizes much attention toward appropriate choice of scaffold material and further scaffold development strategies. The review is intended to be focused on the various approaches of scaffold materials currently in use in vascular regeneration and current state of the art. Scaffold of choice in vascular tissue engineering ranges from natural to synthetic, decellularized, and even scaffold free approach. The applicability of tubular scaffold for in vivo vascular regeneration is under active investigation. A patent conduit with an ample endothelial luminal layer that can regenerate in vivo remains an unanswered query in the field of small diameter vascular tissue engineering. Besides, scaffolds developed for vascular regeneration, should aim at providing functional substitutes for use in a regenerative approach from the laboratory bench to patient bedside. PMID:25632236

  4. Enzymatic regeneration of adenosine triphosphate cofactor

    NASA Technical Reports Server (NTRS)

    Marshall, D. L.

    1974-01-01

    Regenerating adenosine triphosphate (ATP) from adenosine diphosphate (ADP) by enzymatic process which utilizes carbamyl phosphate as phosphoryl donor is technique used to regenerate expensive cofactors. Process allows complex enzymatic reactions to be considered as candidates for large-scale continuous processes.

  5. Expression of CD1a by Langerhan’s Cells in Oral Lichen Planus - A Retrospective Analysis

    PubMed Central

    Sakki, Esther Priyadarshini; Kumar, Yennavaram Vijay; Kolimi, Sadananda; Perika, Ravi; Karthik, Kalepu Venkata; Kumar, Kandukuri Mahesh; Kalyan, Venumbaka Siva

    2016-01-01

    Introduction Langerhan’s Cells (LCs) are dendritic cells of the oral epithelium which play a role in a series of oral lesions from gingivitis to oral cancer. Oral Lichen Planus (OLP) is an oral mucosal T-lymphocyte mediated immunologic reaction to an unidentified putative antigen or allergen. Aim The aim of this study was to quantify the presence of immature LCs in OLP comparing them with normal epithelium. Materials and Methods A retrospective study using 30 of OLP cases were conducted. Immunohistochemistry was performed using polyclonal anti-CD1a antibodies to identify LCs in 10 cases of normal tissue and 30 samples of OLP. The distribution of LCs among lesional tissue and normal mucosa was analysed using Mann-Whitney U test. Results LC population in OLP was significantly higher when compared to the normal epithelium (p<0.001). Conclusion The increase in LCs indicates the active role played during the antigen detection in OLP and subsequent presentation to T-lymphocytes. PMID:27504405

  6. Whole Tooth Regeneration as a Future Dental Treatment.

    PubMed

    Oshima, Masamitsu; Tsuji, Takashi

    2015-01-01

    Dental problems caused by dental caries, periodontal disease and tooth injury compromise the oral and general health issues. Current advances for the development of regenerative therapy have been influenced by our understanding of embryonic development, stem cell biology, and tissue engineering technology. Tooth regenerative therapy for tooth tissue repair and whole tooth replacement is currently expected a novel therapeutic concept with the full recovery of tooth physiological functions. Dental stem cells and cell-activating cytokines are thought to be candidate approach for tooth tissue regeneration because they have the potential to differentiate into tooth tissues in vitro and in vivo. Whole tooth replacement therapy is considered to be an attractive concept for next generation regenerative therapy as a form of bioengineered organ replacement. For realization of whole tooth regeneration, we have developed a novel three-dimensional cell manipulation method designated the "organ germ method". This method involves compartmentalisation of epithelial and mesenchymal cells at a high cell density to mimic multicellular assembly conditions and epithelial-mesenchymal interactions in organogenesis. The bioengineered tooth germ generates a structurally correct tooth in vitro, and erupted successfully with correct tooth structure when transplanted into the oral cavity. We have ectopically generated a bioengineered tooth unit composed of a mature tooth, periodontal ligament and alveolar bone, and that tooth unit was engrafted into an adult jawbone through bone integration. Bioengineered teeth were also able to perform physiological tooth functions such as mastication, periodontal ligament function and response to noxious stimuli. In this review, we describe recent findings and technologies underpinning whole tooth regenerative therapy. PMID:26545754

  7. Can pancreatic duct-derived progenitors be a source of islet regeneration?

    SciTech Connect

    Xia, Bing; Zhan, Xiao-Rong; Yi, Ran; Yang, Baofeng

    2009-06-12

    The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing {beta}-cells. The functional mass of {beta}-cells is decreased in type 1 diabetes, so replacing missing {beta}-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the {beta}-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding {beta}-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet {beta}-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal cells as

  8. Spatially organized response zones in rat olfactory epithelium.

    PubMed

    Scott, J W; Shannon, D E; Charpentier, J; Davis, L M; Kaplan, C

    1997-04-01

    Electroolfactogram recordings were made with a four-electrode assembly from the olfactory epithelium overlying the endoturbinate bones facing the nasal septum. In this study we tested whether odors of different chemical structures produce maximal responses along longitudinally oriented regions following the olfactory receptor gene expression zones described in the literature. The distribution of responses along the dorsal-to-ventral direction of this epithelium (i.e., across the expression zones) was tested in two types of experiments. In one, four electrodes were fixed along the dorsal-to-ventral axis of one turbinate bone. In the other, four electrodes were placed in corresponding positions on four turbinate bones and moved together up toward the top of the bone. These experiments compared the odorants limonene and alpha-terpinene, which are simple hydrocarbons, with carvone and menthone, which differ from the hydrocarbons by the presence of ketone groups. All responses were standardized to an amyl acetate or ethyl butyrate standard. The responses to limonene and alpha-terpinene were often larger for the ventral electrodes. The responses to carvone and menthone were largest for the dorsal electrodes. Intermediate electrodes gave responses that were intermediate in amplitude for these odors. The possibility that direction of air flow caused the observed response distributions was directly tested in experiments with odor nozzles placed in two positions. The relatively larger dorsal responses to carvone and relatively larger ventral responses to limonene were present despite odor nozzle position. We conclude that the responses to this set of odors vary systematically in a fashion parallel to the four gene expression zones. The odorant property that governs this response distribution may be related to the presence of oxygen-containing functional groups. Certain odors evoked larger responses at the intermediate electrode sites than at other sites. Cineole was the best

  9. Interactions between trophoblast and uterine epithelium: monitoring of adhesive forces.

    PubMed

    Thie, M; Röspel, R; Dettmann, W; Benoit, M; Ludwig, M; Gaub, H E; Denker, H W

    1998-11-01

    At embryo implantation, it is postulated that the initial contact between blastocyst and maternal tissues is by adhesion of the trophoblast to the uterine epithelium. This cell-to-cell interaction is thought to be critical for implantation, although the actual adhesive forces have never been determined. In the present study, the atomic force microscope (AFM) was used to study the adhesion between human uterine epithelial cell lines (HEC-1-A; RL95-2) and human trophoblast-type cells (JAR). Specific interaction forces of these epithelia via their apical cell poles were determined on the basis of approach-and-separation cycles. For this purpose, the AFM tip was functionalized with JAR cells, then brought to the surface of uterine epithelial monolayers and was kept in contact for different periods of time (ms, 1, 10, 20, 40 min). The approach force curves displayed repulsive interactions for both HEC-1-A and RL95-2 cells. However, RL95-2 cells (with a smooth surface structure and a thin glycocalyx) showed lower values of the repulsive regime than HEC-1-A cells (with a rough surface structure and a thick glycocalyx). After having overcome repulsive interactions, the initial contact was followed by adhesive interactions. For contact times of 20 and 40 min, RL95-2 cells, but not HEC-1-A cells, showed specific JAR binding, i.e. the separation force curves displayed repeated rupture events in the range of 1-3 nN with a distance between 7-15 microm and, thereafter, a final rupture event at a distance of up to 45 microm. These features point to the formation of strong cell-to-cell bonds. Collectively, these studies provide the first definition of interaction forces between the trophoblast and the uterine epithelium, and are consistent with the hypothesis that an RL95-2-like architecture of uterine epithelial cells, i.e. an non-polarized phenotype, is essential for apical adhesiveness for the human trophoblast. PMID:9853883

  10. Complement components of nerve regeneration conditioned fluid influence the microenvironment of nerve regeneration

    PubMed Central

    Li, Guang-shuai; Li, Qing-feng; Dong, Ming-min; Zan, Tao; Ding, Shuang; Liu, Lin-bo

    2016-01-01

    Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber. A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration. In this study, we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve. Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis confirmed that there were more than 10 complement components (complement factor I, C1q-A, C1q-B, C2, C3, C4, C5, C7, C8β and complement factor D) in the nerve regeneration conditioned fluid and each varied at different time points. These findings suggest that all these complement components have a functional role in nerve regeneration. PMID:27212935

  11. Tityus: a forgotten myth of liver regeneration.

    PubMed

    Tiniakos, Dina G; Kandilis, Apostolos; Geller, Stephen A

    2010-08-01

    The ancient Greek myth of Tityus is related to liver regeneration in the same way as the well known myth of Prometheus is. Depictions of the punishment of Prometheus are frequently used by lecturers on liver regeneration; however, Tityus remains unknown despite the fact that he received the same punishment and his myth could also be used as a paradigm for the organ's extraordinary ability to regenerate. Nevertheless, there is no convincing evidence that ancient Greeks had any specific knowledge about liver regeneration, a concept introduced in the early 19th century. We describe and analyze the myth of Tityus and compare it to the myth of Prometheus. We also explore artistic and literary links and summarize recent scientific data on the mechanisms of liver regeneration. Finally, we highlight links of the legend of Tityus with other sciences. PMID:20472318

  12. Protoplast formation and regeneration in Lactobacillus delbrueckii.

    PubMed

    Singhvi, Mamta; Joshi, Dipti; Gaikaiwari, Shalaka; Gokhale, Digambar V

    2010-03-01

    Method for production and regeneration of Lactobacillus delbrueckii protoplasts are described. The protoplasts were obtained by treatment with a mixture of lysozyme and mutanolysin in protoplast buffer at pH 6.5 with different osmotic stabilizers. The protoplasts were regenerated on deMan, Rogosa and Sharpe (MRS) with various osmotic stabilizers. Maximum protoplast formation was obtained in protoplast buffer with sucrose as an osmotic stabilizer using a combination of lysozyme (1 mg/ml) and mutanolysin (10 μg/ml). Maximum protoplast regeneration was obtained on MRS medium with sucrose (0.5 M) as an osmotic stabilizer. The regeneration medium was also applicable to other species of lactobacilli as well. This is, to our knowledge, the first report on protoplast formation and efficient regeneration in case of L. delbrueckii. PMID:23100814

  13. NOx adsorber and method of regenerating same

    SciTech Connect

    Endicott, Dennis L.; Verkiel, Maarten; Driscoll, James J.

    2007-01-30

    New technologies, such as NOx adsorber catalytic converters, are being used to meet increasingly stringent regulations on undesirable emissions, including NOx emissions. NOx adsorbers must be periodically regenerated, which requires an increased fuel consumption. The present disclosure includes a method of regenerating a NOx adsorber within a NOx adsorber catalytic converter. At least one sensor positioned downstream from the NOx adsorber senses, in the downstream exhaust, at least one of NOx, nitrous oxide and ammonia concentrations a plurality of times during a regeneration phase. The sensor is in communication with an electronic control module that includes a regeneration monitoring algorithm operable to end the regeneration phase when a time rate of change of the at least one of NOx, nitrous oxide and ammonia concentrations is after an expected plateau region begins.

  14. Transmigration of macrophages across the choroid plexus epithelium in response to the feline immunodeficiency virus

    PubMed Central

    Meeker, Rick B.; Bragg, D. C.; Poulton, Winona; Hudson, Lola

    2013-01-01

    Although lentiviruses such as human, feline and simian immunodeficiency viruses (HIV, FIV, SIV) rapidly gain access to cerebrospinal fluid (CSF), the mechanisms that control this entry are not well understood. One possibility is that the virus may be carried into the brain by immune cells that traffic across the blood–CSF barrier in the choroid plexus. Since few studies have directly examined macrophage trafficking across the blood–CSF barrier, we established transwell and explant cultures of feline choroid plexus epithelium and measured trafficking in the presence or absence of FIV. Macrophages in co-culture with the epithelium showed significant proliferation and robust trafficking that was dependent on the presence of epithelium. Macrophage migration to the apical surface of the epithelium was particularly robust in the choroid plexus explants where 3-fold increases were seen over the first 24 h. Addition of FIV to the cultures greatly increased the number of surface macrophages without influencing replication. The epithelium in the transwell cultures was also permissive to PBMC trafficking, which increased from 17 to 26% of total cells after exposure to FIV. Thus, the choroid plexus epithelium supports trafficking of both macrophages and PBMCs. FIV significantly enhanced translocation of macrophages and T cells indicating that the choroid plexus epithelium is likely to be an active site of immune cell trafficking in response to infection. PMID:22281685

  15. Identification of GATA-4 as a novel transcriptional regulatory component of regenerating islet-derived family members.

    PubMed

    Lepage, David; Bruneau, Joannie; Brouillard, Geneviève; Jones, Christine; Lussier, Carine R; Rémillard, Anthony; Lemieux, Étienne; Asselin, Claude; Boudreau, François

    2015-12-01

    Intestinal epithelial cells are exposed to luminal bacterial threat and require adequate defense mechanisms to ensure host protection and epithelium regeneration against possible deleterious damage. Differentiated intestinal epithelial cells produce antimicrobial and regenerative components that protect against such challenges. Few intestinal specific transcription factors have been identified to control the switching from repression to activation of this class of gene. Herein, we show that gene transcription of some regenerating islet-derived (REG) family members is dependent on the transcription factor GATA-4. Silencing of GATA-4 expression in cultured intestinal epithelial cells identified Reg3β as a target gene using an unbiased approach of gene expression profiling. Co-transfection and RNA interference assays identified complex GATA-4-interactive transcriptional components required for the activation or repression of Reg3β gene activity. Conditional deletion of Gata4 in the mouse intestinal epithelium supported its regulatory role for Reg1, Reg3α, Reg3β and Reg3γ genes. Reg1 dramatic down-modulation of expression in Gata4 conditional null mice was associated with a significant decrease in intestinal epithelial cell migration. Altogether, these results identify a novel and complex role for GATA-4 in the regulation of REG family members gene expression. PMID:26477491

  16. Specific responses in rat small intestinal epithelial mRNA expression and protein levels during chemotherapeutic damage and regeneration.

    PubMed

    Verburg, Melissa; Renes, Ingrid B; Van Nispen, Danielle J P M; Ferdinandusse, Sacha; Jorritsma, Marieke; Büller, Hans A; Einerhand, Alexandra W C; Dekker, Jan

    2002-11-01

    The rapidly dividing small intestinal epithelium is very sensitive to the cytostatic drug methotrexate. We investigated the regulation of epithelial gene expression in rat jejunum during methotrexate-induced damage and regeneration. Ten differentiation markers were localized on tissue sections and quantified at mRNA and protein levels relative to control levels. We analyzed correlations in temporal expression patterns between markers. mRNA expression of enterocyte and goblet cell markers decreased significantly during damage for a specific period. Of these, sucrase-isomaltase (-62%) and CPS (-82%) were correlated. Correlations were also found between lactase (-76%) and SGLT1 (-77%) and between I-FABP (-52%) and L-FABP (-45%). Decreases in GLUT5 (-53%), MUC2 (-43%), and TFF3 (-54%) mRNAs occurred independently of any of the other markers. In contrast, lysozyme mRNA present in Paneth cells increased (+76%). At the protein level, qualitative and quantitative changes were in agreement with mRNA expression, except for Muc2 (+115%) and TFF3 (+81%), which increased significantly during damage, following independent patterns. During regeneration, expression of each marker returned to control levels. The enhanced expression of cytoprotective molecules (Muc2, TFF3, lysozyme) during damage represents maintenance of goblet cell and Paneth cell functions, most likely to protect the epithelium. Decreased expression of enterocyte-specific markers represents decreased enterocyte function, of which fatty acid transporters were least affected. PMID:12417619

  17. Embryonic myogenesis pathways in muscle regeneration.

    PubMed

    Zhao, Po; Hoffman, Eric P

    2004-02-01

    Embryonic myogenesis involves the staged induction of myogenic regulatory factors and positional cues that dictate cell determination, proliferation, and differentiation into adult muscle. Muscle is able to regenerate after damage, and muscle regeneration is generally thought to recapitulate myogenesis during embryogenesis. There has been considerable progress in the delineation of myogenesis pathways during embryogenesis, but it is not known whether the same signaling pathways are relevant to muscle regeneration in adults. Here, we defined the subset of embryogenesis pathways induced in muscle regeneration using a 27 time-point in vivo muscle regeneration series. The embryonic Wnt (Wnt1, 3a, 7a, 11), Shh pathway, and the BMP (BMP2, 4, 7) pathway were not induced during muscle regeneration. Moreover, antagonists of Wnt signaling, sFRP1, sFRP2, and sFRP4 (secreted frizzled-related proteins) were significantly up-regulated, suggesting active inhibition of the Wnt pathway. The pro-differentiation FGFR4 pathway was transiently expressed at day 3, commensurate with expression of MyoD, Myogenin, Myf5, and Pax7. Protein verification studies showed fibroblast growth factor receptor 4 (FGFR4) protein to be strongly expressed in differentiating myoblasts and newly formed myotubes. We present evidence that FGF6 is likely the key ligand for FGFR4 during muscle regeneration, and further suggest that FGF6 is released from necrotic myofibers where it is then sequestered by basal laminae. We also confirmed activation of Notch1 in the regenerating muscle. Finally, known MyoD coactivators (MEF2A, p/CIP, TCF12) and repressors (Twist, Id2) were strongly induced at appropriate time points. Taken together, our results suggest that embryonic positional signals (Wnt, Shh, and BMP) are not induced in postnatal muscle regeneration, whereas cell-autonomous factors (Pax7, MRFs, FGFR4) involving muscle precursor proliferation and differentiation are recapitulated by muscle regeneration. PMID

  18. Oral Cancer Foundation

    MedlinePlus

    ... Famous People Famous historical Arts & Entertainment Sports figures ... The Oral Cancer Foundation The Oral Cancer Foundation is a national public service, non-profit entity designed to reduce suffering ...

  19. Kinetics of Lipofuscin Formation in Aging Retinal Pigment Epithelium Cells

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, Hans E.

    2010-03-01

    Lipofuscin is a deposit that is formed over time by aggregation and clustering of incompletely degraded membrane material in various types of cells. Lipofuscin is made of free-radical-damaged protein and fat and is known to be present in age- related macular dgeneration (AMD), Alzheimer disease, and Parkinson disease. AMD is the leading cause of blindness in adults. The degradation of retinal pigment epithelium cells (RPE) through accumulation of lipsofuscin is considered a significant pathogenic factor in the development of AMD. We will present the results of a study of the kinetics of lipofuscin growth in RPE cells using Kinetic Monte Carlo simulations and scaling theory on a cluster aggregation model. The model captures the essential physics of lipofuscin growth in the cells. A remarkable feature is that small particles may be removed from the cells while the larger ones become fixed and grow by aggregation. We compare our results with the number of lipofuscin granules in eyes with early age-related degeneration.

  20. Pathways of ion movement in the canine tracheal epithelium.

    PubMed

    Welsh, M J; Widdicombe, J H

    1980-09-01

    The pathways of ion movement across canine tracheal epithelium, a Cl-secreting tissue, were examined by three techniques. First, the measurement of simultaneous, unidirectional fluxes of Na or Cl and mannitol, a large hydrophilic molecule that serves as a marker of the paracellular pathway, indicated that a significant fraction of both the Na flux from submucosa to mucosa (J Na sm) and the flux of Cl from mucosa to submucosa (J Cl ms) traverse the cellular pathway. The ratio of the Na-to-Cl diffusion coefficients through the paracellular pathway was 0.23, in contrast to the free solution ratio of 0.63. Second, in voltage-clamp experiments we examined the effect of transepithelial voltage differences on the unidirectional fluxes of Na and Cl. The results agree with the previous findings, suggesting that there are voltage-independent, or transcellular, backfluxes of Na and Cl, and that the relative permeability of Na to Cl through the voltage-dependent (presumably paracellular) pathway was 0.28. Third, measurement of transepithelial diffusion potentials gave a Na-to-Cl permeability ratio of 0.31 +/- 0.02 (mean +/- SE). These results suggest that there are significant transcellular backfluxes of Na and Cl and that the paracellular pathway in the canine trachea is anion selective. An anion-selective pathway would tend to shunt the secreted Cl back through the paracellular pathway, thus minimizing the net ion and fluid movement across the tissue in the open-circuit condition. PMID:7435560

  1. Characterization of nucleoside transport systems in cultured rat epididymal epithelium.

    PubMed

    Leung, G P; Ward, J L; Wong, P Y; Tse, C M

    2001-05-01

    The nucleoside transport systems in cultured epididymal epithelium were characterized and found to be similar between the proximal (caput and corpus) and distal (cauda) regions of the epididymis. Functional studies revealed that 70% of the total nucleoside uptake was Na(+) dependent, while 30% was Na(+) independent. The Na(+)-independent nucleoside transport was mediated by both the equilibrative nitrobenzylthioinosine (NBMPR)-sensitive system (40%) and the NBMPR-insensitive system (60%), which was supported by a biphasic dose response to NBMPR inhibition. The Na(+)-dependent [(3)H]uridine uptake was selectively inhibited 80% by purine nucleosides, indicating that the purine nucleoside-selective N1 system is predominant. Since Na(+)-dependent [(3)H]guanosine uptake was inhibited by thymidine by 20% and Na(+)-dependent [(3)H]thymidine uptake was broadly inhibited by purine and pyrimidine nucleosides, this suggested the presence of the broadly selective N3 system accounting for 20% of Na(+)-dependent nucleoside uptake. Results of RT-PCR confirmed the presence of mRNA for equilibrative nucleoside transporter (ENT) 1, ENT2, and concentrative nucleoside transporter (CNT) 2 and the absence of CNT1. It is suggested that the nucleoside transporters in epididymis may be important for sperm maturation by regulating the extracellular concentration of adenosine in epididymal plasma. PMID:11287319

  2. The intestinal epithelium as guardian of gut barrier integrity.

    PubMed

    Zhang, Kaiyi; Hornef, Mathias W; Dupont, Aline

    2015-11-01

    A single layer of epithelial cells separates the intestinal lumen from the underlying sterile tissue. It is exposed to a multitude of nutrients and a large number of commensal bacteria. Although the presence of commensal bacteria significantly contributes to nutrient digestion, vitamin synthesis and tissue maturation, their high number represents a permanent challenge to the integrity of the epithelial surface keeping the local immune system constantly on alert. In addition, the intestinal mucosa is challenged by a variety of enteropathogenic microorganisms. In both circumstances, the epithelium actively contributes to maintaining host-microbial homeostasis and antimicrobial host defence. It deploys a variety of mechanisms to restrict the presence of commensal bacteria to the intestinal lumen and to prevent translocation of commensal and pathogenic microorganisms to the underlying tissue. Enteropathogenic microorganisms in turn have learnt to evade the host's immune system and circumvent the antimicrobial host response. In the present article, we review recent advances that illustrate the intense and intimate host-microbial interaction at the epithelial level and improve our understanding of the mechanisms that maintain the integrity of the intestinal epithelial barrier. PMID:26294173

  3. [Morphology of the reproductive age women cervical epithelium under hypothyreosis].

    PubMed

    Beruchashvili, M; Gogiashvili, L; Tsagareli, Z; Topuriya, Z

    2013-01-01

    The purpose of the investigation was to examine the morphological manifestations of hypothyreosis in the reproductive age women cervical mucosa. With clinically verified hypothyreosis in 1524 cases, 538 patients had a different variants of endocervical pathology, accounting for two major research groups: I - (n=259) operated by colloidal goiter treated by L-thyroxin during last 3 years, II - (n=279) with similar diagnosis, without replacement therapy within last 3 years. Therapeutic and diagnostic scrapings from cervix, as well as parallel samples of the operative removal thyroid gland (TG), after staining with hematoxylin and eosin and picrofuchsin by van Gieson were studied morphologically. The different variants of the cervical mucosa reaction from simple hyperplasia in treated group to adenomyosis with stratification of epithelium, and the tendency of sclerosis and atrophy in the group not receiving L-thyroxin were revealed. In all compared cases Spearmen correlation coefficient had high level of relevance (0,00003). We believe that the cervix changes are the consequence of the decrease of sensitivity to estrogen under the low level of T3 and T4 and increase TSH in plasma. Molecular atypia of endocervical cells clearly demon-strates cross-combination of two leading hormonal systems. PMID:23388537

  4. Cytokeratin expression and acetowhite change in cervical epithelium.

    PubMed Central

    Maddox, P; Szarewski, A; Dyson, J; Cuzick, J

    1994-01-01

    AIM--To investigate the distribution of cytokeratins 10, 13, 14 and 19 in biopsy specimens taken from acetowhite and non-acetowhite areas of the cervix. METHOD--Cervical biopsy specimens were taken from both acetowhite and non-acetowhite areas from 44 patients who presented with abnormal cervical cytology. The specimens were snap frozen in liquid nitrogen and multiple sections taken from each specimen. Staining was performed for cytokeratins 10, 13, 14, 19 and NADPH diaphorase enzyme. The areas of each section positive for the various markers were measured. RESULTS--Cytokeratin 10 positive cells were greatly increased in number in acetowhite biopsy specimens compared with non-acetowhite samples (45.1% v 2.8%; p < 0.0001). Cytokeratin 19 was also increased, but to a lesser extent (17.8% v 5.5%; p < 0.0001). In contrast, the almost universal expression of cytokeratin 13 was reduced in acetowhite biopsy specimens (86.2% v 96.9%; p < 0.0001). Cytokeratin 14 was found diffusely in the basal region of the stratified squamous epithelium and was marginally more apparent in the acetowhite biopsy specimens (p = 0.04). CONCLUSION--It is suggested that the presence of cytokeratin 10 may be an essential requirement for the formation of acetowhite change in association with the cellular swelling caused by acetic acid. Images PMID:7510721

  5. Role of Epithelium Sodium Channel in Bone Formation

    PubMed Central

    Wang, Ruo-Yu; Yang, Shu-Hua; Xu, Wei-Hua

    2016-01-01

    Objective: To review the recent developments in the mechanisms of epithelium sodium channels (ENaCs) induced bone formation and regulation. Data Sources: Studies written in English or Chinese were searched using Medline, PubMed and the index of Chinese-language literature with time restriction from 2005 to 2014. Keywords included ENaC, bone, bone formation, osteonecrosis, estrogen, and osteoporosis. Data from published articles about the structure of ENaC, mechanism of ENaC in bone formation in recent domestic and foreign literature were selected. Study Selection: Abstract and full text of all studies were required to obtain. Studies those were not accessible and those did not focus on the keywords were excluded. Results: ENaCs are tripolymer ion channels which are assembled from homologous α, β, and γ subunits. Crystal structure of ENaCs suggests that ENaC has a central ion-channel located in the central symmetry axis of the three subunits. ENaCs are protease sensitive channels whose iron-channel activity is regulated by the proteolytic reaction. Channel opening probability of ENaCs is regulated by proteinases, mechanical force, and shear stress. Several molecules are involved in regulation of ENaCs in bone formation, including nitride oxide synthases, voltage-sensitive calcium channels, and cyclooxygenase-2. Conclusion: The pathway of ENaC involved in shear stress has an effect on stimulating osteoblasts even bone formation by estrogen interference. PMID:26904995

  6. Sulfate transport in apical membrane vesicles isolated from tracheal epithelium

    SciTech Connect

    Elgavish, A.; DiBona, D.R.; Norton, P.; Meezan, E.

    1987-09-01

    Sulfate uptake in apical membrane vesicles isolated from bovine tracheal epithelium is shown to occur into an osmotically sensitive intravesicular space, via a carrier-mediated system. This conclusion is based on three lines of evidence: 1) saturation kinetics: 2) substrate specificity; and 3) inhibition by the anion transport inhibitors SITS and DIDS. The affinity of the transport system is highest in low ionic strength media and decreases in the presence of gluconate. Chloride appears to cis-inhibit sulfate uptake and to trans-stimulate sulfate efflux. Cis-inhibition and trans-stimulation studies with a variety of anions indicate that this exchange system may be shared by HCO/sub 3//sup -/, S/sub 2/O/sub 3//sup 2 -/, SeO/sub 4//sup 2 -/, and MoO/sub 4//sup 2 -/ but not by H/sub 2/PO/sub 4//sup -/ or HAsO/sub 4//sup 2/. Studies indicate that protons may play two distinct roles in sulfate transport in this system. These studies show that the carrier-mediated system can function in the absence of chloride. The overshoot observed in the presence of a proton gradient indicates that under those conditions the mechanism of transport may be a SO/sub 4//sup 2 -/-OH/sup -/ exchange.

  7. Desmosomes in the uterine epithelium of noninvasive skink placentae.

    PubMed

    Biazik, Joanna M; Thompson, Michael B; Murphy, Christopher R

    2010-03-01

    Australian species of viviparous skinks have noninvasive epitheliochorial placentation where there is no breeching or interruption of the uterine epithelial cell barrier. This is contrary to some African and South American species of skinks which exhibit invading chorionic cells and a localized endotheliochorial placenta. The desmosomes, which maintain the adhesive properties of the junctional complex between uterine epithelial cells, were found to decrease as gestation progressed in the uterus of two highly placentotrophic Australian skinks, but no changes in desmosomal numbers were present in the uterus of two Australian oviparous skinks or viviparous skinks with a simple placenta. In mammals, desmosomes decrease in the uterine epithelium of species with invasive hemochorial placentation, where less chemical and mechanical adhesion between cells assists the invading trophoblast at the time of implantation. However, Australian viviparous skinks do not have an invasive trophoblast; yet, similarities in decreasing lateral cellular adhesion exist in the uterus of both invasive and noninvasive placental types. This similarity in cellular mechanisms suggests a conservation of plasma membrane changes across placentation irrespective of reptilian or mammalian origin. PMID:20169564

  8. Lectin reactivities as intermediate biomarkers in premalignant colorectal epithelium.

    PubMed

    Boland, C R; Martin, M A; Goldstein, I J

    1992-01-01

    Normal colonic epithelial cells undergo maturation as they traverse the crypt to the lumenal surface. The binding of lectins to goblet cell mucins and other glycoconjugates changes as the cells migrate and differentiate. Additional stepwise modifications in glycoconjugate expression occur in premalignant and malignant neoplasms that may be detected by lectin binding studies. The lectins Dolichos biflorus agglutinin (DBA) and soybean agglutinin (SBA) have been developed as markers of differentiation in normal-appearing colonic epithelium. Using a quantitative biometric system to score tissues, reduced levels of lectin binding have been found in rectal tissue from patients with familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer. The lectin Amaranthus caudatus agglutinin (ACA) binds to a cytoplasmic glycoconjugate expressed at the base of the colonic crypt and serves as a possible proliferation marker in the distal, but not proximal, colon. ACA binding increases in tandem with increased levels of proliferation (using BrdU incorporation) in neoplastic tissues. Binding by the peanut lectin (PNA) occurs late in the adenoma-to-carcinoma sequence--in larger adenomas and in cancers--and serves as a marker of advancing neoplasia. Lectins identify the stepwise changes that occur during normal differentiation, proliferation and in advancing neoplasia. By selecting the appropriate probe, biomarkers may be developed for early, intermediate, and late events in colorectal cancer. PMID:1469891

  9. Retinal pigment epithelium transplantation: concepts, challenges, and future prospects

    PubMed Central

    Alexander, P; Thomson, H A J; Luff, A J; Lotery, A J

    2015-01-01

    The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD. PMID:26043704

  10. Retinal pigment epithelium transplantation: concepts, challenges, and future prospects.

    PubMed

    Alexander, P; Thomson, H A J; Luff, A J; Lotery, A J

    2015-08-01

    The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD. PMID:26043704

  11. Surface characteristics of isopod digestive gland epithelium studied by SEM.

    PubMed

    Millaku, Agron; Leser, Vladka; Drobne, Damjana; Godec, Matjaz; Torkar, Matjaz; Jenko, Monika; Milani, Marziale; Tatti, Francesco

    2010-05-01

    The structure of the digestive gland epithelium of a terrestrial isopod Porcellio scaber has been investigated by conventional scanning electron microscopy (SEM), focused ion beam-scanning electron microscopy (FIB/SEM), and light microscopy in order to provide evidence on morphology of the gland epithelial surface in animals from a stock culture. We investigated the shape of cells, extrusion of lipid droplets, shape and distribution of microvilli, and the presence of bacteria on the cell surface. A total of 22 animals were investigated and we found some variability in the appearance of the gland epithelial surface. Seventeen of the animals had dome-shaped digestive gland "normal" epithelial cells, which were densely and homogeneously covered by microvilli and varying proportions of which extruded lipid droplets. On the surface of microvilli we routinely observed sparsely distributed bacteria of different shapes. Five of the 22 animals had "abnormal" epithelial cells with a significantly altered shape. In three of these animals, the cells were much smaller, partly or completely flat or sometimes pyramid-like. A thick layer of bacteria was detected on the microvillous border, and in places, the shape and size of microvilli were altered. In two animals, hypertrophic cells containing large vacuoles were observed indicating a characteristic intracellular infection. The potential of SEM in morphological investigations of epithelial surfaces is discussed. PMID:20155290

  12. Expression of homeobox genes in the mouse olfactory epithelium.

    PubMed

    Parrilla, Marta; Chang, Isabelle; Degl'Innocenti, Andrea; Omura, Masayo

    2016-10-01

    Homeobox genes constitute a large family of genes widely studied because of their role in the establishment of the body pattern. However, they are also involved in many other events during development and adulthood. The main olfactory epithelium (MOE) is an excellent model to study neurogenesis in the adult nervous system. Analyses of homeobox genes during development show that some of these genes are involved in the formation and establishment of cell diversity in the MOE. Moreover, the mechanisms of expression of odorant receptors (ORs) constitute one of the biggest enigmas in the field. Analyses of OR promoters revealed the presence of homeodomain binding sites in their sequences. Here we characterize the expression patterns of a set of 49 homeobox genes in the MOE with in situ hybridization. We found that seven of them (Dlx3, Dlx5, Dlx6, Msx1, Meis1, Isl1, and Pitx1) are zonally expressed. The homeobox gene Emx1 is expressed in three guanylate cyclase(+) populations, two located in the MOE and the third one in an olfactory subsystem known as Grüneberg ganglion located at the entrance of the nasal cavity. The homeobox gene Tshz1 is expressed in a unique patchy pattern across the MOE. Our findings provide new insights to guide functional studies that aim to understand the complexity of transcription factor expression and gene regulation in the MOE. J. Comp. Neurol. 524:2713-2739, 2016. © 2016 Wiley Periodicals, Inc. PMID:27243442

  13. Effect of ammonium on bacterial adherence to bladder transitional epithelium.

    PubMed

    Parsons, C L; Stauffer, C; Mulholland, S G; Griffith, D P

    1984-08-01

    The virulence of urease-producing bacteria depends on the ability of urease to degrade urea into ammonia and thereby to alkalinize the urine. Infections caused by urease-producing organisms such as Proteus mirabilis are particularly difficult to manage clinically. We have shown that the layer of glycosaminoglycans at the bladder surface protects against infection by blocking the adherence of bacteria to the epithelium. To determine whether urease-producing urinary pathogens owe their virulence in part to an ability to inactivate the protective effect of the glycosaminoglycan layer, we tested the ability of ammonium chloride to alter bacterial adherence to the normal vesical mucosa. We used an in vivo adherence assay that we have described previously in rabbits. Control animals received sodium chloride adjusted to the same pH as the ammonium chloride. We found that 0.25 M ammonium chloride significantly increases bacterial adherence to normal vesical mucosa as compared to adherence in controls receiving 0.25 M sodium chloride (p less than 0.05). These data suggest that urease plays a hitherto undescribed role in bacterial virulence by altering the antiadherence activity of the glycosaminoglycan layer present at the transitional cell surface. PMID:6376829

  14. Morphological integrity of the bronchial epithelium in mild asthma.

    PubMed Central

    Lozewicz, S; Wells, C; Gomez, E; Ferguson, H; Richman, P; Devalia, J; Davies, R J

    1990-01-01

    In severe asthma bronchial epithelial cells are damaged and detached, and it has been proposed that such damage might lead to the bronchial hyperresponsiveness that characterises asthma. To investigate the relation between airway hyperresponsiveness and epithelial damage, biopsy specimens of the bronchial mucus membrane were obtained at fibreoptic bronchoscopy from 11 patients with mild atopic asthma and airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) less than 1.0 mg/ml), and from 17 healthy non-atopic subjects who did not have airway hyperresponsiveness (PC20 methacholine greater than 8.0 mg/ml). Observers who were blind to the presence or absence of asthma examined the biopsy specimens by light and electron microscopy. Epithelial cells, intercellular spaces, and goblet cells were counted. Intercellular junctional complexes were examined, and a semiquantitative assessment was made of ciliary loss, non-parallel central ciliary filaments, and vacuoles in ciliated cells. There were no differences between the asthmatic and healthy groups in any of these measurements. These findings indicate that airway hyperresponsiveness may be present when there is no apparent change in the structure of the bronchial epithelium. PMID:2321171

  15. Cellular and shunt conductances of toad bladder epithelium.

    PubMed

    Gordon, L G

    1978-12-29

    Toad urinary bladders were mounted in Ussing-type chambers and volt-age-clamped. At nonzero voltages only, small fluctuations in current, delta I, and therefore in tissue conductance, delta Gt, were detected. These fluctuations were caused by the smooth muscle of the underlying tissue which could be monitored continuously and simultaneously with the current, I. Inhibition of the smooth muscle contraction with verapamil (2 X 10(-5) M) abolished the fluctuations in I and Gt. Amiloride (10(-4) M) had no significant effect on the magnitude of delta Gt, oxytocin increased Gt without affecting delta Gt, and mucosal hypertonicity produced by mannitol increased delta Gt. These results are consistent with the hypothesis that two parallel pathways exist for passive current flow across the toad urinary bladder: one, the cellular pathway, was not affected by smooth muscle activity; the other, the paracellular pathway, was the route whose conductance was altered by the action of the smooth muscle. Thus the relationship between the cellular and shunt conductances of the epithelium of the toad urinary bladder, under a variety of conditions, can be investigated by utilizing the effects of the movement of the smooth muscle. PMID:110941

  16. Electrically assisted delivery of macromolecules into the corneal epithelium

    PubMed Central

    Hao, Jinsong; Li, S. Kevin; Liu, Chia-Yang; Kao, Winston W.Y.

    2009-01-01

    Electrically assisted delivery is noninvasive and has been investigated in a number of ocular drug delivery studies. The objectives of this study were to examine the feasibility of electrically assisted delivery of macromolecules such as small interfering RNA (siRNA) into the corneal epithelium, to optimize the iontophoresis and electroporation methods, and to study the mechanisms of corneal iontophoresis for macromolecules. Anodal and cathodal iontophoresis, electroporation and their combinations were the methods examined with mice in vivo. Cyanine 3 (Cy3) glyceraldehyde 3-phosphate dehydrogenease (GAPDH) siRNA and fluorescein isothiocyanate (FITC)-dextran of different molecular weights (4 to 70 kDa) were the macromolecules studied. Microscopy and histology after cryostat sectioning were used to analyze and compare the delivery of the macromolecules to the cornea. Iontophoresis was effective in delivering siRNA and dextran up to 70 kDa into the cornea. The electroporation method studied was less effective than that of iontophoresis. Although both iontophoresis and electroporation alone can deliver the macromolecules into the cornea, these methods alone were not as effective as the combination of iontophoresis and electroporation (iontophoresis followed by electroporation). The significant enhancement of dextran delivery in anodal iontophoresis suggests that electroosmosis can be a significant flux enhancing mechanism during corneal iontophoresis. These results illustrate the feasibility of electrically assisted delivery of macromolecules such as siRNA into the cornea. PMID:19682448

  17. Chronic alcohol ingestion changes the landscape of the alveolar epithelium.

    PubMed

    Downs, Charles A; Trac, David; Brewer, Elizabeth M; Brown, Lou Ann; Helms, My N

    2013-01-01

    Similar to effects of alcohol on the heart, liver, and brain, the effects of ethanol (EtOH) on lung injury are preventable. Unlike other vital organ systems, however, the lethal effects of alcohol on the lung are underappreciated, perhaps because there are no signs of overt pulmonary disorder until a secondary insult, such as a bacterial infection or injury, occurs in the lung. This paper provides overview of the complex changes in the alveolar environment known to occur following both chronic and acute alcohol exposures. Contemporary animal and cell culture models for alcohol-induced lung dysfunction are discussed, with emphasis on the effect of alcohol on transepithelial transport processes, namely, epithelial sodium channel activity (ENaC). The cascading effect of tissue and phagocytic Nadph oxidase (Nox) may be triggered by ethanol exposure, and as such, alcohol ingestion and exposure lead to a prooxidative environment; thus impacting alveolar macrophage (AM) function and oxidative stress. A better understanding of how alcohol changes the landscape of the alveolar epithelium can lead to improvements in treating acute respiratory distress syndrome (ARDS) for which hospitalized alcoholics are at an increased risk. PMID:23509726

  18. Identification of transcripts overexpressed during airway epithelium differentiation.

    PubMed

    Chhin, B; Pham, J T; El Zein, L; Kaiser, K; Merrot, O; Bouvagnet, P

    2008-07-01

    Human airway epithelium, the defence at the forefront of protecting the respiratory tract, evacuates inhaled particles by a permanent beating of epithelial cell cilia. When deficient, this organelle causes primary ciliary dyskinesia, and, despite numerous studies, data regarding ciliated cell gene expression remain incomplete. The aim of the present study was to identify genes specifically expressed in human ciliated respiratory cells via transcriptional analysis. The transcriptome of dedifferentiated epithelial cells was subtracted from that of fully redifferentiated cells using complementary DNA representational difference analysis. In order to validate the results, gene overexpression in ciliated cells was confirmed by real-time PCR, and by comparing the present list of genes overexpressed in ciliated cells to lists obtained in previous studies. A total of 53 known and 12 unknown genes overexpressed in ciliated cells were identified. The majority (66%) of known genes had never previously been reported as being involved in ciliogenesis, and the unknown genes represent hypothetical novel transcript isoforms or new genes not yet reported in databases. Finally, several genes identified here were located in genomic regions involved in primary ciliary dyskinesia by linkage analysis. In conclusion, the present study revealed sequences of new cilia-related genes, new transcript isoforms and novel genes which should be further characterised to aid understanding of their function(s) and their probable disorder-related involvement. PMID:18321927

  19. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia.

    PubMed

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E; Ablonczy, Zsolt

    2016-01-01

    In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA), suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro) and fluid transport (in vivo). Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina. PMID:27617745

  20. Keratinization of the esophageal epithelium of domesticated mammals.

    PubMed

    Meyer, Wilfried; Schoennagel, Britta; Kacza, Johannes; Busche, Roger; Hornickel, Isabelle Nina; Hewicker-Trautwein, Marion; Schnapper, Anke

    2014-01-01

    We studied the esophageal epithelium for keratinization characteristics from samples of domesticated mammals of three nutrition groups (herbivores: horse, cattle, sheep; omnivores: pig, dog, rat; carnivores: cat) using histochemistry (keratins, disulfides), sulfur measurements, and cryo-SEM. Keratins were found in all esophageal layers of all species, except for the equine Stratum corneum. The positive reaction staining of Pan-keratin was remarkable, but decreased in intensity toward the outer layers, whereas in the pig and cat, staining was confined to the corneal layer. The herbivores revealed positive staining reactions in the upper Stratum spinosum, particularly in the sheep. Regarding single keratins, CK6 immunostating was found in most esophageal layers, but only weakly or negatively in the porcine and equine Stratum corneum. CK13 staining was restricted to the sheep and here was found in all layers. CK14 could be detected in the equine and feline Stratum basale, and upper vital layers of the dog and rat. CK17 appeared only in the Stratum spinosum and Stratum granulosum, but in all layers of the dog and cat. Disulfides reacted strongest in the Stratum corneum of the herbivores, as corroborated by the sulfur concentrations in the esophagus. Our study emphasized that keratins are very important for the mechanical stability of the epithelial cells and cell layers of the mammalian esophagus. The role of these keratins in the esophageal epithelia is of specific interest owing to the varying feed qualities and mechanical loads of different nutrition groups, which have to be countered. PMID:23948668

  1. HAD Oral History Project

    NASA Astrophysics Data System (ADS)

    Holbrook, Jarita

    2014-01-01

    The Historical Astronomy Division is the recipient of an American Institute of Physics Neils Bohr Library Grant for Oral History. HAD has assembled a team of volunteers to conduct oral history interviews since May 2013. Each oral history interview varies in length between two and six hours. This presentation is an introduction to the HAD Oral History Project and the activities of the team during the first six months of the grant.

  2. Oral Steroids for Dermatitis.

    PubMed

    Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K

    2015-01-01

    Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment. PMID:26125159

  3. RTF glovebox stripper regeneration development

    SciTech Connect

    Birchenall, A.K.

    1992-10-31

    Currently, the Replacement Tritium Facility (RTF) glovebox stripper system consists of a catalytic oxidation front end where trace tritium which may escape from the primary tritium process into the glovebox nitrogen system is oxidized to tritiated water. The tritiated water, along with normal water which may leak into the glovebox from the surrounding atmosphere, is then captured on a zeolite bed. Eventually, the zeolite bed becomes saturated with water and must be regenerated to remain effective as a stripper. This is accomplished by heating the zeolite and evolving the trapped water which is then passed over an elevated temperature uranium bed. A waste minimization program was instituted to address this issue. The program has two parallel paths. One path investigates replacing the entire glovebox stripper system with a system of getters to scavenge trace tritium. This report concentrates on the second path, retaining the catalytic oxidation front end but replacing the uranium bed water cracking with alternative technologies.

  4. Solar-regenerated desiccant dehumidification

    NASA Astrophysics Data System (ADS)

    Haves, P.

    1982-02-01

    The dehumidification requirements of buildings are discussed, and the most suitable desiccant material is identified as silica gel. Several conceptual designs for solar regenerated desiccant dehumidifiers using a solid desiccant are described. The construction and operation of a laboratory experiment to determine the performance of a packed bed of silica gel at low flow rate is described. The experimental results are presented and compared to the predictions of a simple computer model which assumes local equilibrium between the desiccant and the airstream. The simulations used to predict desiccant bed performance and the integration of the desiccant bed simulation with a simulation of the thermal performance of a passively cooled residence are described. Results for an average July day are presented. Sizing relationships derived from the simulation are described, and an economic analysis and recommendations for further work are presented.

  5. Regenerator for gas turbine engine

    DOEpatents

    Lewakowski, John J.

    1979-01-01

    A rotary disc-type counterflow regenerator for a gas turbine engine includes a disc-shaped ceramic core surrounded by a metal rim which carries a coaxial annular ring gear. Bonding of the metal rim to the ceramic core is accomplished by constructing the metal rim in three integral portions: a driving portion disposed adjacent the ceramic core which carries the ring gear, a bonding portion disposed further away from the ceramic core and which is bonded thereto by elastomeric pads, and a connecting portion connecting the bonding portion to the driving portion. The elastomeric pads are bonded to radially flexible mounts formed as part of the metal rim by circumferential slots in the transition portion and lateral slots extending from one end of the circumferential slots across the bonding portion of the rim.

  6. Developing Oral Communication Skills.

    ERIC Educational Resources Information Center

    Washington Office of the State Superintendent of Public Instruction, Olympia.

    Intended for use by both elementary and secondary school teachers, the two papers in this report stress the importance of developing students' oral and written communication skills. The first paper, "Relationship of Oral Communication to Reading," by Phil Backlund and John Johnson, argues that ability in oral communication is a prerequisite to the…

  7. Understanding Oral Learners

    ERIC Educational Resources Information Center

    Moon, W. Jay

    2012-01-01

    A five-year research project of seminary students from various cultural backgrounds revealed that the slight majority of contemporary seminary students studied are oral learners. Oral learners learn best and have their lives most transformed when professors utilize oral teaching and assessment methods. After explaining several preferences of oral…

  8. Oral Contraceptives and Cancer Risk

    MedlinePlus

    ... oral contraceptives are available in the United States today? How could oral contraceptives influence cancer risk? How ... oral contraceptives are available in the United States today? Two types of oral contraceptives (birth control pills) ...

  9. Head, Neck, and Oral Cancer

    MedlinePlus

    ... Neck and Oral Pathology Head, Neck and Oral Pathology Close to 42,000 Americans will be diagnosed ... Neck and Oral Pathology Head, Neck and Oral Pathology Close to 42,000 Americans will be diagnosed ...

  10. MHD seed recovery and regeneration

    NASA Astrophysics Data System (ADS)

    1988-10-01

    The TRW Econoseed MHD Seed Regeneration Process is based on the reaction of calcium formate with potassium sulfate spent seed from an MHD electric power generation plant. The process was tested at bench scale, design a proof of concept (POC) test plant, plan and cost a Phase 2 project for a POC plant evaluation and prepare a conceptual design of a 300 MW (t) commercial plant. The results of the project are as follows: (1) each of the unit operations is demonstrated, and (2) the data are incorporated into a POC plant design and project cost, as well as a 300 MW (t) commercial retrofit plant design and cost estimate. Specific results are as follows: (1) calcium formate can be produced at 100 percent yield in a total retention time of less than 5 minutes, (2) utilizing the calcium formate, spent seed can quantitatively be converted to potassium formate, potassium carbonate or mixtures of these with potassium sulfate as per the commercial design without measurable loss of potassium to insolubles at a total retention time under 20 minutes and ambient pressure, (3) the solid rejects form the process meet RCRA EP Toxicity requirements for safe disposal, and (4) filtration and evaporation data, as well as reaction data cited above, show that the Econoseed technology is ready for scale up to POC plant scale. Economics forecast studies show that the total cost per unit of potassium for seed regeneration by the Econoseed Process is in the range of $0.23 to $0.27/lb, a cost which is less than half the potassium cost of $0.63/lb for purchasing new potassium carbonate.

  11. Olfactory marker protein: turnover and transport in normal and regenerating neurons

    SciTech Connect

    Kream, R.M.; Margolis, F.L.

    1984-03-01

    A 19,000-dalton acidic protein designated olfactory marker protein (OMP) is a cell-specific marker of mature olfactory chemosensory neurons. Intranasal irrigation of mouse olfactory epithelium with (/sup 35/S)methionine labeled OMP to high specific activity. Turnover and transport characteristics of /sup 35/S-labeled OMP were compared to those of /sup 35/S-labeled global cytosol protein in groups of young, adult, and Triton-treated adult mice. The latter contained primarily large numbers of regenerating olfactory neurons. In olfactory epithelium of young and Triton-treated mice, the specific activity of OMP was three times that of global cytosol protein, whereas in adults the two measures were equal. In all three groups, however, the rate of degradation of OMP was roughly equal to that of cytosol protein (T1/2 . 5 to 6 days). By contrast, differences in T1/2 for OMP decline in the bulb of adult, young, and Triton-treated adult mice were highly significant (T1/2's of 9.3, 6.1, and 4 to 5 days, respectively; p . 0.001). The specific activity of (35S)methionine incorporated in OMP exceeded that of the free amino acid 5-fold, indicating minimal precursor reutilization during the course of our experiments. Turnover data indicate that increased isotope incorporation into OMP in the epithelium is matched by an accelerated rate of degradation in the bulb. This may be correlated with the physiological state or developmental age of the primary neurons since in young and Triton-treated adult mice, rapidly maturing ''young'' olfactory neurons represent a larger proportion of the total population than in adults. Thus, OMP behaves as a typical, relatively slowly transported soluble protein (v . 2 to 4 mm/day, slow component b).

  12. Rod Photopigment Kinetics After Photodisruption of the Retinal Pigment Epithelium

    PubMed Central

    Masella, Benjamin D.; Hunter, Jennifer J.; Williams, David R.

    2014-01-01

    Purpose. Advances in retinal imaging have led to the discovery of long-lasting retinal changes caused by light exposures below published safety limits, including disruption of the RPE. To investigate the functional consequences of RPE disruption, we combined adaptive optics ophthalmoscopy with retinal densitometry. Methods. A modified adaptive optics scanning light ophthalmoscope (AOSLO) measured the apparent density and regeneration rate of rhodopsin in two macaques before and after four different 568-nm retinal radiant exposures (RREs; 400–3200 J/cm2). Optical coherence tomography (OCT) was used to measure the optical path length through the photoreceptor outer segments before and after RPE disruption. Results. All tested RREs caused visible RPE disruption. Apparent rhodopsin density was significantly reduced following 1600 (P = 0.01) and 3200 J/cm2 (P = 0.007) exposures. No significant change in apparent density was observed in response to 800 J/cm2. Surprisingly, exposure to 400 J/cm2 showed a significant increase in apparent density (P = 0.047). Rhodopsin recovery rate was not significantly affected by these RREs. Optical coherence tomography measurements showed a significant decrease in the optical path length through the photoreceptor outer segments for RREs above 800 J/cm2 (P < 0.001). Conclusions. At higher RREs, optical path length through the outer segments was reduced. However, the rate of photopigment regeneration was unchanged. While some ambiguity remains as to the correlation between measured reflectivity and absolute rhodopsin density; at the lowest RREs, RPE disruption appears not to be accompanied by a loss of apparent rhodopsin density, which would have been indicative of functional loss. PMID:25316724

  13. Remodeling of Endogenous Mammary Epithelium by Breast Cancer Stem Cells

    PubMed Central

    Parashurama, Natesh; Lobo, Neethan A.; Ito, Ken; Mosley, Adriane R.; Habte, Frezghi G.; Zabala, Maider; Smith, Bryan R.; Lam, Jessica; Weissman, Irving L.; Clarke, Michael F.; Gambhir, Sanjiv S.

    2014-01-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  14. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    PubMed

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  15. Lhx8 Mediated Wnt and TGFβ Pathways in Tooth Development and Regeneration

    PubMed Central

    Zhou, Chen; Yang, Guodong; Chen, Mo; Wang, Chenglin; He, Ling; Xiang, Lusai; Chen, Danying; Ling, Junqi; Mao, Jeremy J.

    2015-01-01

    LIM homeobox 8 (Lhx8) is a highly conserved transcriptional factor with recently illustrated roles in cholinergic and GABAergic differentiation, and is expressed in neural crest derived craniofacial tissues during development. However, Lhx8 functions and signaling pathways are largely elusive. Here we showed that Lhx8 regulates dental mesenchyme differentiation and function via Wnt and TGFβ pathways. Lhx8 expression was restricted to dental mesenchyme from E11.5 to a peak at E14.5, and absent in dental epithelium. By reconstituting dental epithelium and mesenchyme in an E16.5 tooth organ, Lhx8 knockdown accelerated dental mesenchyme differentiation; conversely, Lhx8 overexpression attenuated dentin formation. Lhx8 overexpressed adult human dental pulp stem/progenitor cells in β-tricalcium phosphate cubes attenuated mineralized matrix production in vivo. Gene profiling revealed that postnatal dental pulp stem/progenitor cells upon Lhx8 overexpression modified several matrix related gene expression including Dspp, Cola1 and osteocalcin. Lhx8 transcriptionally activates Wnt and TGFβ pathways, and its attenuation upregulates multiple dentinogenesis genes. Together, Lhx8 regulates dentin development and regeneration by fine-turning Wnt and TGFβ signaling. PMID:26081866

  16. How much can the tubule regenerate and who does it? An open question

    PubMed Central

    Lombardi, Duccio; Becherucci, Francesca; Romagnani, Paola

    2016-01-01

    The tubular compartment of the kidney is the primary site of a wide range of insults that can result in acute kidney injury (AKI), a condition associated with high mortality and an increased risk to develop end-stage renal disease. Nevertheless, kidney function is often quickly recovered after tubular injury. How this happens has only partially been unveiled. Indeed, although it has clearly been demonstrated that regenerated epithelial cells arise from survived intratubular cells, the true entity, as well as the cellular source of this regenerative process, remains mostly unknown. Is whichever proximal tubular epithelial cell able to dedifferentiate and divide to replace neighboring lost tubular cells, thus suggesting an extreme regenerative ability of residual tubular epithelium, or is the regenerative potential of tubular epithelium limited, and mostly related to a preexisting population of intratubular scattered progenitor cells which are more resistant to death? Gaining insights on how this process takes place is essential for developing new therapeutic strategies to prevent AKI, as well as AKI-related chronic kidney disease. The aim of this review is to discuss why the answers to these questions are still open, and how further investigations are needed to understand which is the true regenerative potential of the tubule and who are the players that allow functional recovery after AKI. PMID:26175143

  17. Lhx8 mediated Wnt and TGFβ pathways in tooth development and regeneration.

    PubMed

    Zhou, Chen; Yang, Guodong; Chen, Mo; Wang, Chenglin; He, Ling; Xiang, Lusai; Chen, Danying; Ling, Junqi; Mao, Jeremy J

    2015-09-01

    LIM homeobox 8 (Lhx8) is a highly conserved transcriptional factor with recently illustrated roles in cholinergic and GABAergic differentiation, and is expressed in neural crest derived craniofacial tissues during development. However, Lhx8 functions and signaling pathways are largely elusive. Here we showed that Lhx8 regulates dental mesenchyme differentiation and function via Wnt and TGFβ pathways. Lhx8 expression was restricted to dental mesenchyme from E11.5 to a peak at E14.5, and absent in dental epithelium. By reconstituting dental epithelium and mesenchyme in an E16.5 tooth organ, Lhx8 knockdown accelerated dental mesenchyme differentiation; conversely, Lhx8 overexpression attenuated dentin formation. Lhx8 overexpressed adult human dental pulp stem/progenitor cells in β-tricalcium phosphate cubes attenuated mineralized matrix production in vivo. Gene profiling revealed that postnatal dental pulp stem/progenitor cells upon Lhx8 overexpression modified matrix related gene expression including Dspp, Cola1 and osteocalcin. Lhx8 transcriptionally activated Wnt and TGFβ pathways, and its attenuation upregulated multiple dentinogenesis genes. Together, Lhx8 regulates dentin development and regeneration by fine-turning Wnt and TGFβ signaling. PMID:26081866

  18. Weak Evidence of Regeneration Habitat but Strong Evidence of Regeneration Niche for a Leguminous Shrub

    PubMed Central

    Delerue, Florian; Gonzalez, Maya; Michalet, Richard; Pellerin, Sylvain; Augusto, Laurent

    2015-01-01

    The identification of an ecological niche specific to the regeneration phase has mobilised significant attention. However, the importance of the regeneration niche concept remains unclear. Our main objective was to study the existence of such a regeneration niche for a leguminous shrub, Ulex europaeus. This study was carried out in southwest France in the context of water and nutrient stresses (mainly phosphorus limitation) due to the presence of nutrient-poor sandy soils. We analysed the regeneration of the species from the germination of seeds and emergence of new seedlings until the seedlings reached young shrub size. Our design included a P fertilisation treatment. We also investigated microsite characteristics (micro-topography and vegetation development) as they can interact with meteorological conditions and determine water availability for seeds and seedlings. We found that P availability controlled seedling growth and the time necessary to reach young shrub size. Water availability appeared to impact the species germination and seedlings survival. We also found that P and water availability depended on the interactions between microsite characteristics and climatic variations. Finally we found evidence that P and water availability are important ecological factors shaping the regeneration niche of the species, but we found weak evidence that any microsite would be appropriate for the regeneration of the species in the long term. Future studies regarding regeneration niches need to distinguish more clearly the ecological factors important for regeneration (the regeneration niche per se) and the physical world where the seedlings appear and develop (the regeneration habitat). PMID:26098877

  19. Weak Evidence of Regeneration Habitat but Strong Evidence of Regeneration Niche for a Leguminous Shrub.

    PubMed

    Delerue, Florian; Gonzalez, Maya; Michalet, Richard; Pellerin, Sylvain; Augusto, Laurent

    2015-01-01

    The identification of an ecological niche specific to the regeneration phase has mobilised significant attention. However, the importance of the regeneration niche concept remains unclear. Our main objective was to study the existence of such a regeneration niche for a leguminous shrub, Ulex europaeus. This study was carried out in southwest France in the context of water and nutrient stresses (mainly phosphorus limitation) due to the presence of nutrient-poor sandy soils. We analysed the regeneration of the species from the germination of seeds and emergence of new seedlings until the seedlings reached young shrub size. Our design included a P fertilisation treatment. We also investigated microsite characteristics (micro-topography and vegetation development) as they can interact with meteorological conditions and determine water availability for seeds and seedlings. We found that P availability controlled seedling growth and the time necessary to reach young shrub size. Water availability appeared to impact the species germination and seedlings survival. We also found that P and water availability depended on the interactions between microsite characteristics and climatic variations. Finally we found evidence that P and water availability are important ecological factors shaping the regeneration niche of the species, but we found weak evidence that any microsite would be appropriate for the regeneration of the species in the long term. Future studies regarding regeneration niches need to distinguish more clearly the ecological factors important for regeneration (the regeneration niche per se) and the physical world where the seedlings appear and develop (the regeneration habitat). PMID:26098877

  20. Reintegration of the regenerated and the remaining tissues during joint regeneration in the newt Cynops pyrrhogaster

    PubMed Central

    Inoue, Takeshi; Yamada, Shigehito

    2015-01-01

    Abstract Urodele amphibians, such as newts, can regenerate a functional limb, including joints, after amputation at any level along the proximal−distal axis of the limb. The blastema can regenerate the limb morphology largely independently of the stump after proximal−distal identity has been established, but the remaining and regenerated tissues must be structurally reintegrated (matched in size and shape). Here we used newt joint regeneration as a model to investigate reintegration, because a functionally interlocking joint requires structural integration between its opposing skeletal elements. After forelimbs were amputated at the elbow joint, the joint was regenerated between the remaining and regenerated skeletal elements. The regenerated cartilage was thick around the amputated joint to make a reciprocally interlocking joint structure with the remaining bone. Furthermore, during regeneration, the extracellular matrix of the remaining tissues was lost, suggesting that the remaining tissues might contribute to the morphogenesis of regenerating cartilage. Our results showed that the area of the regenerated cartilage matched the area of the apposed remaining cartilage, thus contributing to formation of a functional structure.