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Sample records for laser epithelial keratomileusis

  1. Extensive corneal epithelial defect associated with internal hordeolum after uneventful laser in situ keratomileusis.

    PubMed

    Maldonado, Miguel J; Juberías, José R; Moreno-Montañés, Javier

    2002-09-01

    This report illustrates a retrospective case review in which extensive corneal epithelial ulceration occurred concomitantly with an internal hordeolum in the inferior forniceal conjunctiva 24 hours after an uneventful laser in situ keratomileusis. The internal hordeolum and epithelial defect were successfully managed using a bandage soft contact lens, a course of topical dexamethasone and tobramycin, and generous lubrication. PMID:12231335

  2. Long term results of no-alcohol laser epithelial keratomileusis and photorefractive keratectomy for myopia

    PubMed Central

    Spadea, Leopoldo; Verboschi, Francesca; De Rosa, Vittoria; Salomone, Mariella; Vingolo, Enzo Maria

    2015-01-01

    AIM To evaluate the long term clinical results of mechanical no-alcohol-assisted laser epithelial keratomileusis (LASEK) versus standard photorefractive keratectomy (PRK) for low-moderate myopia. METHODS Twenty-five eyes treated with LASEK and twenty-five eyes treated with PRK were evaluated with a mean follow-up duration of 60mo. Mechanical separation of the epithelium was performed with blunt spatula and without application of alcohol. Laser ablation was performed with the MEL-70 excimer laser. All patients were examined daily until epithelial closure; at 1, 3, 6, and 12mo, and every year subsequently. Main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, haze, efficacy and safety indexes. RESULTS Twenty-one eyes and 22 eyes completed follow-up of 60mo in LASEK and PRK group respectively. Manifest refraction at 60mo follow-up was -0.01 and 0.26 in LASEK and PRK group respectively. In the LASEK group mean UDVA and mean CDVA after 60mo were 20/22 and 20/20 respectively (P>0.01). In the PRK group mean UDVA and mean CDVA at 60mo follow-up were 20/20 and 20/20 after 60mo (P>0.01). The efficacy indexes were 0.87 and 0.95, and the safety indexes were 1.25 and 1.4 respectively for LASEK group and PRK group. CONCLUSION Both standard PRK and no-alcohol LASEK offer safe and effective correction of low-moderate myopia in the long term without any statistically significant difference between the two groups. PMID:26086011

  3. Fibrinous anterior uveitis following laser in situ keratomileusis.

    PubMed

    Parmar, Pragya; Salman, Amjad; Rajmohan, M; Jesudasan, Nelson C A

    2009-01-01

    A 29-year-old woman who underwent laser in situ keratomileusis (LASIK) for myopic astigmatism in both eyes presented with severe pain, photophobia and decreased visual acuity in the left eye eight days after surgery. Examination revealed severe anterior uveitis with fibrinous exudates in the anterior chamber, flap edema and epithelial bullae. Laboratory investigations for uveitis were negative and the patient required systemic and intensive topical steroids with cycloplegics to control the inflammation. This case demonstrates that severe anterior uveitis may develop after LASIK and needs prompt and vigorous management for resolution. PMID:19574707

  4. Cataractogenesis after Repeat Laser in situ Keratomileusis

    PubMed Central

    Mansour, Ahmad M.; Ghabra, Marwan

    2012-01-01

    There has been the unsubstantiated clinical impression that laser refractive surgery accelerates cataract development along with solid experimental data about the cataractogenic effects of excimer laser treatment. We present the first documented case of significant cataract formation in a young myope after repeat excimer laser ablation necessitating phacoemulsification with a posterior chamber implant. Proposed explanations include focusing of the ablation wave on the posterior capsule (acoustic wave lens epithelial damage), photooxidative stress of the lens (ultraviolet and inflammatory oxidative stress), and corticosteroid-induced cataract (lens toxicity). PMID:22949915

  5. Erlotinib-related keratopathy in a patient underwent laser in situ keratomileusis.

    PubMed

    Kau, Hui-Chuan; Tsai, Chieh-Chih

    2016-09-01

    Erlotinib is a tyrosine kinase inhibitor of the epidermal growth factor receptor. Since there is a wide expression of the epidermal growth factor receptors in the epithelial tissues of ocular surface and adnexa, ocular adverse reactions may happen during systemic administration of erlotinib. Previously reported ocular adverse reactions of erlotinib include trichomegaly, periorbital rash, ectropion, blepharitis, persistent corneal epithelial defect, corneal ulcer and perforation. We report the first case of erlotinib-related keratopathy in a patient who had received laser in situ keratomileusis. The patient presented a special picture of flap striae related to erlotinib. Improvement of keratopathy after cessation of erlotinib was demonstrated. PMID:26340340

  6. Peripheral Ulcerative Keratitis following Laser in situ Keratomileusis

    PubMed Central

    Burkholder, Bryn M.; Kuo, Irene C.

    2016-01-01

    Purpose We report a case of a patient with a history of glomerulonephropathy, not disclosed prior to laser in situ keratomileusis (LASIK), who developed severe postoperative peripheral ulcerative keratitis (PUK) soon after surgery. Method Case report. Results Within a week of surgery, the patient, who had no blepharitis or ocular surface disease, also developed diffuse lamellar keratitis (DLK) that was not contiguous with the PUK. Microbiologic evaluation of the flap interface disclosed no organisms, and no epithelial ingrowth was found. Both PUK and DLK resolved with topical and oral steroid therapy, and the patient's induced refractive error improved over the 12 months following LASIK. Conclusions Necrotizing keratitis has been described after LASIK surgery in patients with or without autoimmune disease. However, to our knowledge, there has been no case of PUK following LASIK. As shown by our patient's clinical course and the typical association of PUK with systemic conditions, patients with a history of atypical postinfectious sequelae may require additional preoperative counseling, vigilant postoperative monitoring, and possibly additional intervention. Because patients do not always divulge medical details, especially if an extraocular site was involved or illness occurred many years prior, this case demonstrates the importance of performing a diligent history that excludes autoimmune disorders or atypical postinfectious sequelae prior to proceeding with keratorefractive intervention. PMID:26889153

  7. Unexpected flap thickness in laser in situ keratomileusis.

    PubMed

    Giledi, Osama; Daya, Sheraz M

    2003-09-01

    We report a case of an unexpected thick flap during laser in situ keratomileusis (LASIK) that led to abandonment of surgery. This report illustrates the importance of stromal bed measurements after flap creation in LASIK. A thicker-than-expected flap can lead to a thinner-than-anticipated residual cornea and subsequent ectasia or even perforation during laser ablation. It is possible that reports of ectasia in normal thickness corneas reflect thicker-than-anticipated flaps. PMID:14522308

  8. All-femtosecond laser-assisted in situ keratomileusis

    NASA Astrophysics Data System (ADS)

    Gabryte, Egle; Danieliene, Egle; Vaiceliunaite, Agne; Ruksenas, Osvaldas; Vengris, Mikas; Danielius, Romualdas

    2013-03-01

    We present a femtosecond solid-state Yb:KGW laser system capable of performing the complete laser-assisted in situ keratomileusis (LASIK) ophthalmic procedure. The fundamental infrared radiation (IR) is used to create the corneal flap, and subsequently the corneal stromal ablation is performed using the ultraviolet (UV) pulses of the fifth harmonic. The heating of cornea, ablated surface quality, and healing outcomes of the surgeries performed using the femtosecond laser system are investigated by both ex vivo and in vivo experiments and compared to the results of conventional clinical ArF excimer laser application. The results of this research indicate the feasibility of clinical application of femtosecond UV lasers for LASIK procedure.

  9. Bilateral Simultaneous Rhegmatogenous Retinal Detachment following Laser in situ Keratomileusis

    PubMed Central

    Yumusak, Erhan; Ornek, Kemal; Ozkal, Fatma

    2016-01-01

    A 21-year-old woman developed simultaneous rhegmatogenous retinal detachment after laser in situ keratomileusis (LASIK) in both eyes. She underwent pars plana vitrectomy surgery combined with endolaser photocoagulation and silicone oil tamponade in the right eye. A week later, pneumatic retinopexy was done in the left eye. As the retinal tear did not seal, 360° scleral buckling surgery was performed and retina was attached. Bilateral simultaneous rhegmatogenous retinal detachment after LASIK for correction of myopia can be a serious complication. Patients should be informed about the possibility of this complication. PMID:27462264

  10. Bilateral Simultaneous Rhegmatogenous Retinal Detachment following Laser in situ Keratomileusis.

    PubMed

    Yumusak, Erhan; Ornek, Kemal; Ozkal, Fatma

    2016-01-01

    A 21-year-old woman developed simultaneous rhegmatogenous retinal detachment after laser in situ keratomileusis (LASIK) in both eyes. She underwent pars plana vitrectomy surgery combined with endolaser photocoagulation and silicone oil tamponade in the right eye. A week later, pneumatic retinopexy was done in the left eye. As the retinal tear did not seal, 360° scleral buckling surgery was performed and retina was attached. Bilateral simultaneous rhegmatogenous retinal detachment after LASIK for correction of myopia can be a serious complication. Patients should be informed about the possibility of this complication. PMID:27462264

  11. Bilateral Achromobacter xylosoxidans keratitis after laser in situ keratomileusis.

    PubMed

    Linke, Stephan J; Skevas, Christos; Richard, Gisbert; Katz, Toam

    2010-06-01

    A 31-year-old man was referred to us 2 months after bilateral laser in situ keratomileusis (LASIK). On presentation, the corrected distance visual acuity was hand motion in the right eye and 20/25 in the left eye. Slitlamp examination showed a diffuse central stromal infiltrate, flap melting, and hypopyon in the right eye and marked interface opacities with crystal-like edges in the left eye. Flap lift and irrigation were performed. Because of the progressive keratitis, penetrating keratoplasty (PKP) was done in both eyes. Achromobacter xylosoxidans was isolated from both corneal buttons, and therapy was changed to chloramphenicol prednisolone eyedrops 8 times a day and intravenous meropenem 500 mg 3 times a day according to sensitivity testing. Two months after surgery, both transplants remained clear. PMID:20494781

  12. Histopathological study of corneal flap striae following laser in situ keratomileusis in rabbits

    PubMed Central

    LIU, LI; SONG, FANG-ZHOU; BAO, LIAN-YUN

    2015-01-01

    The aim of the present study was to investigate the histopathological changes and wound healing process of rabbit corneas following conventional laser in situ keratomileusis (LASIK) with and without the complication of flap macrostriae. The right eyes of 14 rabbits underwent LASIK with the formation of flap striae (macrostriae group) and the left underwent LASIK alone (control group). Two rabbits were selected at random for sacrifice on days 1, 3, 7 and 14, and at 1, 3 and 6 months postoperatively. The histopathological characters of the corneas were compared by hematoxylin and eosin (H&E), periodic acid-Schiff (PAS) and Masson staining. In the control group, the epithelial basement membrane of the cornea exhibited microstriae and the arrangement of stromal collagen fibers was regular. The width of the microstriae in the flap was 20–40 μm one week after surgery and the microstriae were no longer visible two weeks postoperatively. In the macrostriae group, infiltration of polymorphonuclear cells occurred around the incision and irregular hyperplasia of the epithelium was observed due to undulation of the epithelial basement membrane on the first postoperative day. The collagen fibers and striae of the corneal stroma exhibited irregular undulation one month postoperatively. The area between the corneal flap and stromal bed was distinctly stained by PAS and Masson stains. Macrostriae with a width of 80–120 μm affecting two-thirds of the entire cornea remained visible six months postoperatively. In conclusion, the inflammatory reactions and clinical impact of flap macrostriae were severe. Macrostriae involving two-thirds of the entire cornea remained visible six months postoperatively. Longer-term studies are required to further elucidate the issues associated with corneal flap striae. PMID:25667649

  13. Femtosecond lasers for laser in situ keratomileusis: a systematic review and meta-analysis

    PubMed Central

    Huhtala, Anne; Pietilä, Juhani; Mäkinen, Petri; Uusitalo, Hannu

    2016-01-01

    Purpose The aim of this study was to review and meta-analyze whether there are differences between reported femtosecond (FS) lasers for laser-assisted in situ keratomileusis (LASIK) in terms of efficacy, predictability, and safety as primary outcomes and corneal flap thickness measurements and pre- and postoperative complications as secondary outcomes. Methods A comprehensive literature search of PubMed, Science Direct, Scopus, and Cochrane CENTRAL Trials Library databases was conducted to identify the relevant prospective randomized controlled trials of FS lasers for LASIK. Thirty-one articles describing a total of 5,404 eyes were included. Results Based on efficacy, IntraLase FS 10 and 30 kHz gave the best results. Based on predictability and safety, there were no differences between various FS lasers. FEMTO LDV and IntraLase FS 60 kHz produced the most accurate flap thicknesses. IntraLase and Wavelight SF200 had the fewest intraoperative complications. IntraLase, Visumax, and Wavelight FS200 had the most seldom postoperative complications. Conclusion There were dissimilarities between different FS lasers based on efficacy and intraoperative and postoperative complications. All FS lasers were predictable and safe for making corneal flaps in LASIK. PMID:27022236

  14. Comparison of efficacy, safety, and predictability of laser in situ keratomileusis using two laser suites

    PubMed Central

    Meidani, Alexandra; Tzavara, Chara

    2016-01-01

    Purpose The main aim of this study was to compare the efficacy, safety, and predictability of femtosecond laser-assisted in situ keratomileusis performed by two different laser suites in the treatment of myopia for up to 6 months. Methods In this two-site retrospective nonrandomized study, myopic eyes that underwent laser-assisted in situ keratomileusis using IntraLase FS 60 kHz formed group 1 and those using WaveLight FS200 femtosecond laser system formed group 2. Ablation was performed with Visx Star S4 IR and WaveLight EX500 Excimer lasers, respectively, in groups 1 and 2. Both groups were well matched for age, sex, and mean level of preoperative refractive spherical equivalent (MRSE). Uncorrected distance visual acuity, corrected distance visual acuity, and MRSE were evaluated preoperatively and at 1 week, 1 month, and 6 months after treatment. Results Fifty-six eyes of 28 patients were included in the study. At 6-month follow-up postop, 78.6% of eyes in group 1 and 92.8% of eyes in group 2 achieved an uncorrected distance visual acuity of 20/20 or better (P=0.252). 35.7% and 50% in group 1 and group 2, respectively, gained one line (P=0.179). No eye lost lines of corrected distance visual acuity. Twenty-five eyes in group 1 (92.7%) and 27 eyes in group 2 (96.3%) had MRSE within ±0.5 D in the 6-month follow-up (P>0.999). The mean efficacy index at 6 months was similar in group 1 and group 2 (mean 1.10±0.12 [standard deviation] vs 1.10±0.1) (P=0.799). The mean safety index was similar in group 1 and group 2 (mean 1.10±0.10 [standard deviation] vs 1.10±0.09) (P=0.407). Conclusion: The outcomes were excellent between the two laser suites. There were no significant differences at 6-month follow-up postop between the two laser systems. PMID:27601880

  15. Recent advances in laser in situ keratomileusis-associated dry eye.

    PubMed

    Xie, Wenjia

    2016-03-01

    Dry eye is the most common complication after laser in situ keratomileusis (LASIK). The major cause of LASIK-associated dry eye is corneal nerve damage. Early identification and treatment of post-operative dry eye are essential to prevent further ocular surface damage. This article reviews the recent studies of LASIK-associated dry eye, including clinical features, aetiology, risk factors, evaluations and treatment. The applications of novel technologies in LASIK-associated dry eye evaluation like anterior segment spectral-domain optical coherence tomography (SD-OCT) and corneal confocal microscopy are also introduced in this review. PMID:27012690

  16. Pneumococcal keratitis at the flap interface after laser in situ keratomileusis.

    PubMed

    Ramírez, Manuel; Hernández-Quintela, Everardo; Beltrán, Francisco; Naranjo-Tackman, Ramón

    2002-03-01

    A 28-year-old woman had uneventful laser in situ keratomileusis in the right eye. Six days postoperatively, she reported ocular pain and a large corneal stromal infiltrate was observed at the flap interface. A second surgery including lifting and excising the flap and scraping the stromal bed was performed. Topical antibiotics were prescribed. A bacterial culture revealed Streptococcus pneumoniae. The keratitis responded well to topical vancomycin. Twelve days after the second surgery, the stromal infiltrate had regressed, the hypopyon had resolved, and visual acuity was hand movements at 0.5 m. PMID:11973108

  17. Dry eye associated with laser in situ keratomileusis: Mechanical microkeratome versus femtosecond laser

    PubMed Central

    Salomão, Marcella Q.; Ambrósio, Renato; Wilson, Steven E.

    2014-01-01

    Purpose To compare the incidence of laser in situ keratomileusis (LASIK)–associated dry eye and the need for postoperative cyclosporine A treatment after flap creation with a femtosecond laser or a mechanical microkeratome. Setting Cole Eye Institute, Cleveland, Ohio, USA. Methods Eyes were randomized to flap creation with an IntraLase femtosecond laser (30 or 60 kHz) or a Hansatome microkeratome. No patient had signs, symptoms, or treatment of dry eye preoperatively. Flap thickness was determined by intraoperative ultrasonic pachymetry. Slitlamp assessments of the cornea and need for postoperative dry-eye treatment were evaluated preoperatively and 1 month postoperatively. Results The flap was created with the femtosecond laser in 113 eyes and with the microkeratome in 70 eyes. The difference in mean central flap thickness between the femtosecond group (111 μm ± 14 [SD]) and the microkeratome group (131 ± 25 μm) was statistically significant (P<.001). The incidence of LASIK-associated dry eye was statistically significantly higher in the microkeratome group (46%) than in the femtosecond group (8%) (P<.0001), as was the need for postoperative cyclosporine A treatment (24% and 7%, respectively) (P<.01). In the microkeratome group, there was no correlation between thick flaps and a higher incidence of LASIK-induced dry eye. Conclusions Eyes with femtosecond flaps had a lower incidence of LASIK-associated dry eye and required less treatment for the disorder. In addition to neurotrophic effects from corneal nerve cutting, other factors may be important because no correlation was found between flap thickness (or ablation depth) and the incidence of LASIK-induced dry eye. PMID:19781472

  18. Intraoperative and early postoperative flap-related complications of laser in situ keratomileusis using two types of Moria microkeratomes.

    PubMed

    Karabela, Yunus; Muftuoglu, Orkun; Gulkilik, Ibrahim Gokhan; Kocabora, Mehmet Selim; Ozsutcu, Mustafa

    2014-10-01

    The purpose of this study is to describe the incidence, management, and visual outcomes of intraoperative and early postoperative flap-related complications of laser in situ keratomileusis (LASIK) surgery using two types of Moria M2 microkeratomes. This retrospective analysis was performed on 806 primary LASIK cases. The intraoperative and early postoperative flap-related complications were identified and categorized according to type of Moria microkeratome. There were 52 intraoperative and early postoperative complications--one case of partial flap (0.124 %), one case of free flap (0.124 %), one case of small flap (0.124 %), 13 cases of epithelial defect (1.61 %), 12 cases of flap striae (1.49 %), 10 cases of diffuse lamellar keratitis (1.24 %), 10 cases of interface debris (1.24 %), three cases of epithelial ingrowth (0.37 %), and one case of microbial infection (0.124 %). The overall incidence of flap complications was 6.45 %. There were 27 right eye (6.73 %) and 25 left eye (6.17 %) complications. The incidence of complications with the Moria automated metallic head 130 microkeratome was 4.22 % and with the Moria single-use head 90 microkeratome was 2.23 %. We observed one culture-negative interface abscess which was cured with surgical cleaning and intensive medical treatment. The most common complication encountered was epithelial defects, followed by flap striae. Our study showed that LASIK with a microkeratome has a relatively low incidence of intraoperative and early postoperative flap complications. The authors have no financial interest in any of the issues contained in this article and have no proprietary interest in the development of marketing of or materials used in this study. PMID:24531872

  19. Laser in situ keratomileusis in patients with collagen vascular disease: a review of the literature

    PubMed Central

    Simpson, Rachel G; Moshirfar, Majid; Edmonds, Jason N; Christiansen, Steven M; Behunin, Nicholas

    2012-01-01

    Purpose To evaluate the current United States Food and Drug Administration (FDA) recommendations regarding laser in situ keratomileusis (LASIK) surgery in patients with collagen vascular diseases (CVD) and assess whether these patients make appropriate candidates for laser vision correction, and offer treatment recommendations based on identified clinical data. Methods A literature search was conducted using PubMed, Medline, and Ovid to identify all existing studies of LASIK in patients with collagen vascular diseases. The search was conducted without date limitations. Keywords used for the search included MeSH terms: laser in situ keratomileusis, LASIK, refractive surgery, ocular surgery, and cataract surgery connected by “and” with the following MeSH and natural-language terms: collagen vascular disease, rheumatic disease, systemic disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, seronegative spondyloarthropathy, HLA B27, ankylosing spondylitis, reactive arthritis, psoriatic arthritis. The abstracts for all studies meeting initial search criteria were reviewed; relevant studies were included. No prospective studies were found; however, four retrospective case studies were identified that examined LASIK surgery in patients with CVD. Several case reports were also identified in similar fashion. Results The FDA considers CVD a relative contraindication to LASIK surgery, due largely to the ocular complications associated with disease in the CVD spectrum. However, recent studies of LASIK in patients with CVD indicate LASIK may be safe for patients with very well-controlled systemic disease, minimal ocular manifestations, and no clinical signs or history of dry-eye symptoms. Conclusion LASIK surgery may be safe in patients with rheumatoid arthritis or systemic lupus erythematosus and the seronegative spondyloarthropathies if stringent preoperative criteria are met. Evidence suggests patients with Sjögren’s syndrome are not

  20. Traumatic flap displacement and subsequent diffuse lamellar keratitis after laser in situ keratomileusis.

    PubMed

    Schwartz, G S; Park, D H; Schloff, S; Lane, S S

    2001-05-01

    A 45-year-old man was struck in the left eye by the edge of a paper shopping bag 3 weeks after having laser in situ keratomileusis (LASIK). The injury resulted in partial displacement of the LASIK flap. The patient developed diffuse lamellar keratitis (DLK) the day after the flap was repositioned. By day 4, visual acuity diminished to 20/60. By day 9, the clinical evidence of the DLK had resolved, and by day 15, uncorrected visual acuity was 20/20. Eye trauma 3 weeks after LASIK can result in displacement of the LASIK flap, and DLK can develop following flap replacement. Long-term anatomic and visual results are usually good. PMID:11377912

  1. Cyanoacrylate repair of laser in situ keratomileusis corneal flap perforation by a snake bite.

    PubMed

    Korn, Bobby S; Korn, Tommy S

    2005-11-01

    A 30-year-old man who had laser in situ keratomileusis (LASIK) for myopia 1 year earlier developed a corneal perforation in the left eye from a boa constrictor. The patient presented to the emergency room, and a small corneal perforation just outside the visual axis was diagnosed within the LASIK flap. Cyanoacrylate adhesive was used to close the corneal perforation. The patient went on to full visual recovery with an uncorrected visual acuity of 20/20. This is the first reported case of a penetrating corneal injury from a serpent in an eye that had LASIK. Cyanoacrylate may be used to repair small traumatic corneal perforations with a favorable visual outcome in eyes that have had LASIK. PMID:16412943

  2. Epipolis-laser in situ keratomileusis versus photorefractive keratectomy for the correction of myopia: a meta-analysis.

    PubMed

    Wu, Wenjing; Wang, Yan; Xu, Lulu

    2015-10-01

    It is unclear whether epipolis-laser in situ keratomileusis (Epi-LASIK) has any significant advantage over photorefractive keratectomy (PRK) for correcting myopia. We undertook this meta-analysis of randomized controlled trials and cohort studies to examine possible differences in efficacy, predictability, and side effects between Epi-LASIK and PRK for correcting myopia. A system literature review was conducted in the PubMed, Cochrane Library EMBASE. The statistical analysis was performed by RevMan 5.0 software. The results included efficacy outcomes (percentage of eyes with 20/20 uncorrected visual acuity post-treatment), predictability (proportion of eyes within ±0.5 D of the target refraction), epithelial healing time, and the incidence of significant haze and pain scores after surgery. There are seven articles with total 987 eyes suitable for the meta-analysis. There is no statistical significance in the predictability between Epi-LASIK and PRK, the risk ratio (RR) is 1.03, 95% confidence interval (CI) [0.92, 1.16], p = 0.18; with respect to efficacy, the odds ratio is 1.43, 95% CI = [0.85, 2.40], p = 0.56 between Epi-LASIK and PRK, there is no statistical significance either. The epithelial cell layer healing time and the pain scores and the incidence of significant haze showed no significance between these two techniques although more pains can be found in Epi-LASIK than PRK at the early-stage post-operation. According to the above analysis, Epi-LASIK has good efficacy and predictability as PRK. In addition, both techniques have low pain scores and low incidence of significant haze. PMID:26253460

  3. Comparison of visual acuity of the patients on the first day after sub-Bowman keratomileusis or laser in situ keratomileusis

    PubMed Central

    Zhao, Wei; Wu, Ting; Dong, Ze-Hong; Feng, Jie; Ren, Yu-Feng; Wang, Yu-Sheng

    2016-01-01

    AIM To compare recovery of the visual acuity in patients one day after sub-Bowman keratomileusis (SBK) or laser in situ keratomileusis (LASIK). METHODS Data from 5923 eyes in 2968 patients that received LASIK (2755 eyes) or SBK (3168 eyes) were retrospectively analyzed. The eyes were divided into 4 groups according to preoperative spherical equivalent: between -12.00 to -9.00 D, extremely high myopia (n=396, including 192 and 204 in SBK and LASIK groups, respectively); -9.00 to -6.00 D, high myopia (n=1822, including 991 and 831 in SBK and LASIK groups, respectively), -6.00 to -3.00 D, moderate myopia (n=3071, including 1658 and 1413 in SBK and LASIK groups, respectively), and -3.00 to 0.00 D, low myopia (n=634, including 327 and 307 in SBK and LASIK groups, respectively). Uncorrected logMAR visual acuity values of patients were assessed under standard natural light. Analysis of variance was used for comparisons among different groups. RESULTS Uncorrected visual acuity values were 0.0115±0.1051 and 0.0466±0.1477 at day 1 after operation for patients receiving SBK and LASIK, respectively (P<0.01); visual acuity values of 0.1854±0.1842, 0.0615±0.1326, -0.0033±0.0978, and -0.0164±0.0972 were obtained for patients in the extremely high, high, moderate, and low myopia groups, respectively (P<0.01). In addition, significant differences in visual acuity at day 1 after operation were found between patients receiving SBK and LASIK in each myopia subgroup. CONCLUSION Compared with LASIK, SBK is safer and more effective, with faster recovery. Therefore, SBK is more likely to be accepted by patients than LASIK for better uncorrected visual acuity the day following operation. PMID:27158619

  4. Comparison of retina damage thresholds simulating the femtosecond-laser in situ keratomileusis (fs-LASIK) process with two laser systems in the CW- and fs-regime

    NASA Astrophysics Data System (ADS)

    Sander, M.; Minet, O.; Zabarylo, U.; Müller, M.; Tetz, M. R.

    2012-04-01

    The femtosecond-laser in situ keratomileusis procedure affords the opportunity to correct ametropia by cutting transparent corneal tissue with ultra-short laser pulses. Thereby the tissue cut is generated by a laser-induced optical breakdown in the cornea with ultra-short laser pulses in the near-infrared range. Compared to standard procedures such as photorefractive keratectomy and laser in-situ keratomileusis with the excimer laser, where the risk potential for the eye is low due to the complete absorption of ultraviolet irradiation from corneal tissue, only a certain amount of the pulse energy is deposited in the cornea during the fs-LASIK process. The remaining energy propagates through the eye and interacts with the retina and the strong absorbing tissue layers behind. The objective of the presented study was to determine and compare the retina damage thresholds during the fs-LASIK process simulated with two various laser systems in the CW- and fs-regime.

  5. Confocal Comparison of Corneal Reinnervation after Small Incision Lenticule Extraction (SMILE) and Femtosecond Laser In Situ Keratomileusis (FS-LASIK)

    PubMed Central

    Qin, Bing; Zhou, Zimei; Ni, Katherine; Le, Qihua; Xiang, Jun; Wei, Anji; Ma, Weiping; Zhou, Xingtao

    2013-01-01

    Purpose To evaluate corneal reinnervation, and the corresponding corneal sensitivity and keratocyte density after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). Methods In this prospective, non-randomized observational study, 18 patients (32 eyes) received SMILE surgery, and 22 patients (42 eyes) received FS-LASIK surgery to correct myopia. The corneal subbasal nerve density and microscopic morphological changes in corneal architecture were evaluated by confocal microscopy prior to surgery and at 1 week, 1 month, 3 months, and 6 months after surgery. A correlation analysis was performed between subbasal corneal nerve density and the corresponding keratocyte density and corneal sensitivity. Results The decrease in subbasal nerve density was less severe in SMILE-treated eyes than in FS-LASIK-treated eyes at 1 week (P = 0.0147), 1 month (P = 0.0243), and 3 months (P = 0.0498), but no difference was detected at the 6-month visit (P = 0.5277). The subbasal nerve density correlated positively with central corneal sensitivity in both groups (r = 0.416, P<0.0001, and r = 0.2567, P = 0.0038 for SMILE group and FS-LASIK group, respectively). The SMILE-treated eyes have a lower risk of developing peripheral empty space with epithelial cells filling in (P = 0.0005). Conclusions The decrease in subbasal nerve fiber density was less severe in the SMILE group than the FS-LASIK group in the first 3 months following the surgeries. The subbasal nerve density was correlated with central corneal sensitivity. PMID:24349069

  6. Assessment of ocular hemodynamics after laser in situ keratomileusis using color Doppler imaging.

    PubMed

    Abou Samra, Waleed; Samera, Waleed Abu; Shahin, Maha; El-Awady, Hatem; El-Rahman, Ashraf Abd; El-Toukhy, Nahed

    2014-04-01

    To investigate ocular blood flow changes in healthy myopic patients following laser in situ keratomileusis (LASIK) using color Doppler imaging. Sixteen eyes of 16 myopic patients were studied. LASIK was performed and intraocular pressure was raised to levels ≥65 mmHg. Color Doppler images were obtained to study the ophthalmic and central retinal arteries preoperatively and postoperatively at 1 day, 1 week, and 1 month. There was no significant correlation between patient age and preoperative ocular blood flow parameters. A significant positive correlation between the degree of myopia and the peak systolic volume of the ophthalmic artery (r = 0.6, P = 0.01) was found. A highly significant decrease in the peak systolic volume and end-diastolic volume with an increase in the resistive index of both arteries (P < 0.005) was seen at 1 day and 1 week postoperatively. There was no significant difference between the preoperative and postoperative data 1 month after the procedure. The findings of this study show temporary alterations in ocular blood flow parameters after LASIK. LASIK is an increasingly common lifestyle procedure and further studies on larger groups are still recommended. PMID:23743872

  7. Blade source effect on laser in situ keratomileusis flap thickness with the Amadeus I microkeratome

    PubMed Central

    Ruth, Adrienne L.; Lynn, Michael J.; Randleman, J. Bradley; Stulting, R. Doyle

    2013-01-01

    PURPOSE To determine the effect of different blades on laser in situ keratomileusis (LASIK) flap thickness created with the Amadeus I microkeratome (Ziemer Ophthalmic Systems). SETTING: METHODS This retrospective nonrandomized comparative case study from January 2005 through June 2006 compared LASIK flap thickness created with blades from 2 manufacturers: the Surepass from Surgical Instrument Systems and distributed by AMO and the ML7090 CLB distributed by Med-Logics, Inc. Sex, preoperative corneal thickness, surgical-eye sequence, flap thickness and variance, and residual stromal bed were evaluated in each group. RESULTS This study evaluated 424 eyes of 226 patients. Surepass blades were used in 238 eyes and ML7090 CLB blades in 186 eyes. There were no significant differences between the 2 blade groups in preoperative corneal thickness, sex, or cases with corneal thickness greater than 550 µm. Mean flap thickness and variance were significantly lower in the ML7090 CLB group than in the Surepass group (P<.0001). There were no significant differences in flap thickness in either group based on sex; however, in both groups, flap thickness was significantly lower in second eyes and in eyes with a preoperative thickness less than 550 µm (P<.001). CONCLUSIONS The Amadeus I microkeratome created thinner, more consistent LASIK flaps with the ML7090 CLB blade than with the Surepass blade. Preoperative corneal thickness and eye sequence affected flap thickness, while sex did not. PMID:18299064

  8. Factors Influencing Intraocular Pressure Changes after Laser In Situ Keratomileusis with Flaps Created by Femtosecond Laser or Mechanical Microkeratome.

    PubMed

    Lin, Meng-Yin; Chang, David C K; Shen, Yun-Dun; Lin, Yen-Kuang; Lin, Chang-Ping; Wang, I-Jong

    2016-01-01

    The aim of this study is to describe factors that influence the measured intraocular pressure (IOP) change and to develop a predictive model after myopic laser in situ keratomileusis (LASIK) with a femtosecond (FS) laser or a microkeratome (MK). We retrospectively reviewed preoperative, intraoperative, and 12-month postoperative medical records in 2485 eyes of 1309 patients who underwent LASIK with an FS laser or an MK for myopia and myopic astigmatism. Data were extracted, such as preoperative age, sex, IOP, manifest spherical equivalent (MSE), central corneal keratometry (CCK), central corneal thickness (CCT), and intended flap thickness and postoperative IOP (postIOP) at 1, 6 and 12 months. Linear mixed model (LMM) and multivariate linear regression (MLR) method were used for data analysis. In both models, the preoperative CCT and ablation depth had significant effects on predicting IOP changes in the FS and MK groups. The intended flap thickness was a significant predictor only in the FS laser group (P < .0001 in both models). In the FS group, LMM and MLR could respectively explain 47.00% and 18.91% of the variation of postoperative IOP underestimation (R2 = 0.47 and R(2) = 0.1891). In the MK group, LMM and MLR could explain 37.79% and 19.13% of the variation of IOP underestimation (R(2) = 0.3779 and 0.1913 respectively). The best-fit model for prediction of IOP changes was the LMM in LASIK with an FS laser. PMID:26824754

  9. Factors Influencing Intraocular Pressure Changes after Laser In Situ Keratomileusis with Flaps Created by Femtosecond Laser or Mechanical Microkeratome

    PubMed Central

    Lin, Meng-Yin; Chang, David C. K.; Shen, Yun-Dun; Lin, Yen-Kuang; Lin, Chang-Ping; Wang, I-Jong

    2016-01-01

    The aim of this study is to describe factors that influence the measured intraocular pressure (IOP) change and to develop a predictive model after myopic laser in situ keratomileusis (LASIK) with a femtosecond (FS) laser or a microkeratome (MK). We retrospectively reviewed preoperative, intraoperative, and 12-month postoperative medical records in 2485 eyes of 1309 patients who underwent LASIK with an FS laser or an MK for myopia and myopic astigmatism. Data were extracted, such as preoperative age, sex, IOP, manifest spherical equivalent (MSE), central corneal keratometry (CCK), central corneal thickness (CCT), and intended flap thickness and postoperative IOP (postIOP) at 1, 6 and 12 months. Linear mixed model (LMM) and multivariate linear regression (MLR) method were used for data analysis. In both models, the preoperative CCT and ablation depth had significant effects on predicting IOP changes in the FS and MK groups. The intended flap thickness was a significant predictor only in the FS laser group (P < .0001 in both models). In the FS group, LMM and MLR could respectively explain 47.00% and 18.91% of the variation of postoperative IOP underestimation (R2 = 0.47 and R2 = 0.1891). In the MK group, LMM and MLR could explain 37.79% and 19.13% of the variation of IOP underestimation (R2 = 0.3779 and 0.1913 respectively). The best-fit model for prediction of IOP changes was the LMM in LASIK with an FS laser. PMID:26824754

  10. Fulminant herpetic keratouveitis with flap necrosis following laser in situ keratomileusis: Case report and review of literature.

    PubMed

    Arora, Tarun; Sharma, Namrata; Arora, Supriya; Titiyal, Jeewan S

    2014-12-01

    A 25-year-old woman presented with redness, pain, and diminution of vision that occurred 2 weeks after microkeratome-assisted laser in situ keratomileusis (LASIK). On presentation, corneal edema, Descemet membrane folds, keratic precipitates, stromal infiltrates, and flap necrosis were observed. Delayed post-LASIK microbial keratitis was diagnosed. The patient had no history of ocular herpes. Culture and scraping showed no organisms. Immunofluorescence stain was positive for the herpes simplex virus antigen. The patient was started on oral valacyclovir, and progress was monitored through serial clinical photographs and anterior segment optical coherence tomography. Resolution began within 3 days of initiating treatment and was complete in 4 weeks. PMID:25311411

  11. Keratectasia following laser in situ keratomileusis in a low-risk patient with benign joint hypermobility syndrome.

    PubMed

    Galperin, Gustavo; Berra, Martin; Berra, Alejandro

    2014-04-01

    Here we present the case of a 27-year-old woman with benign joint hypermobility (BJHS) syndrome who developed keratectasia after laser in situ keratomileusis (LASIK) in both eyes. Both eyes had identical low Randleman risk factor scores. To our knowledge, this is the first report of such a complication in a patient with BJHS. It highlights our incomplete knowledge of the risk factors for keratectasia following LASIK and suggests that BJHS should be considered as a risk factor for keratectasia. PMID:25076479

  12. Accuracy of Corneal Power Measurements for Intraocular Lens Power Calculation after Myopic Laser In situ Keratomileusis

    PubMed Central

    Helaly, Hany A.; El-Hifnawy, Mohammad A. M.; Shaheen, Mohamed Shafik; Abou El-Kheir, Amr F.

    2016-01-01

    Purpose: To evaluate the accuracy of corneal power measurements for intraocular lens (IOL) power calculation after myopic laser in situ keratomileusis (LASIK). Methods: The study evaluated 45 eyes with a history of myopic LASIK. Corneal power was measured using manual keratometry, automated keratometry, optical biometry, and Scheimflug tomography. Different hypothetical IOL power calculation formulas were performed for each case. Results: The steepest mean K value was measured with manual keratometry (37.48 ± 2.86 D) followed by automated keratometry (37.31 ± 2.83 D) then optical biometry (37.06 ± 2.98 D) followed by Scheimflug tomography (36.55 ± 3.08). None of the K values generated by Scheimflug tomography were steeper than the measurements from the other 3 instruments. Using equivalent K reading (EKR) 4 mm with the Double-K SRK/T formula, the refractive outcome generated 97.8% of cases within ± 2 D, 80.0% of cases within ± 1 D, and 42.2% of cases within ± 0.5 D. The best combination of formulas was “Shammas-PL + Double-K SRK/T formula using EKR 4 mm.” Conclusion: Scheimflug tomography imaging using the Holladay EKR 4 mm improved the accuracy of IOL power calculation in post-LASIK eyes. The best option is a combination of formulas. We recommended the use the combined “Shammas-PL ± Double-K SRK/T formula using EKR 4 mm”h for optical outcomes. PMID:26957851

  13. Laser in-situ keratomileusis in patients with diabetes mellitus: a review of the literature

    PubMed Central

    Simpson, Rachel G; Moshirfar, Majid; Edmonds, Jason N; Christiansen, Steven M

    2012-01-01

    Purpose A growing number of diabetic patients request laser in situ keratomileusis (LASIK) for elective vision correction each year. While the United States Food and Drug Administration considers diabetes a relative contraindication to LASIK surgery, there are several reports in the literature of LASIK being performed safely in this patient population. The purpose of this review was to examine whether diabetes should still be considered a contraindication to LASIK surgery by reviewing the ocular and systemic complications of diabetes, and examining the existing data on the outcomes of LASIK in diabetic patients. Methods A literature review was conducted through PubMed, Medline, and Ovid to identify any study on LASIK surgery in patients with diabetes mellitus. This search was conducted without date restrictions. The search used the Medical Subject Headings (MeSH®) term LASIK linked by the word “and” to the following MeSH and natural language terms: diabetes, diabetes mellitus, systemic disease, and contraindications. Abstracts for all studies meeting initial search criteria were reviewed for relevance. There were no prospective clinical studies identified. Three retrospective studies were identified. Key sources from these papers were identified, reviewed, and included as appropriate. An additional literature search was conducted to identify any study of ocular surgery on patients with diabetes using the MeSH terms refractive surgery, photorefractive keratectomy, radial keratotomy, cataract surgery, vitrectomy, and iridectomy linked by the word “and” to the following MeSH terms: diabetes, diabetes mellitus, and systemic disease. This search was conducted without date restrictions. Abstracts of studies meeting the initial search criteria were reviewed and articles deemed relevant to the subject were included in this review. Conclusion LASIK may be safe in diabetic patients with tight glycemic control and no ocular or systemic complications. PMID:23109803

  14. Influence of transient intraocular pressure elevation during laser in situ keratomileusis on rabbit retina thickness

    PubMed Central

    Zhao, Hai-Xia; Liu, Hui; Niu, Chun-Mei; Guan, Wen-Ying

    2015-01-01

    AIM To utilize tissue micro measurement to study the effect of transient high intraocular pressure (IOP) induced by different durations of suction during laser in situ keratomileusis (LASIK) on rabbit retina thickness. METHODS Sixty healthy New Zealand white rabbits were randomly divided into a control group, and 3 negative-pressure suction groups (20s group, 45s group, and 3min group) and each group was comprised of 15 rabbits (30 eyes); the latter 3 groups were the transient high IOP models. The retinal tissue around the papilledema was separated. Hematoxylin and eosin (HE) staining was carried out to generate slices for light microscopy. The changes in the retina thickness values of each layer were measured for all animals in each group at different postoperative recovery periods and compared with the values recorded for the animals in the control group. The thickness of the retinal tissue showed a normal distribution. The ANOVA was performed by using SPSS13.0 statistic software. RESULTS In the comparison between the 20s and 45s negative-pressure suction groups and the control group, no significant differences were observed, except at 14d. Significant difference was observed between the 3min negative-pressure suction group and the control group, and the retina thickness value of each layer reached a peak at 14d after repair. CONCLUSION Conventional negative suction during LASIK may not lead to significant changes in retinal tissue thickness; however, if the suction duration is increased to 3min, it will cause significant changes in retinal tissue thickness. PMID:26682153

  15. Comparison of corneal sensitivity, tear function and corneal staining following laser in situ keratomileusis with two femtosecond laser platforms

    PubMed Central

    Petznick, Andrea; Chew, Annabel; Hall, Reece C; Chan, Cordelia ML; Rosman, Mohamad; Tan, Donald; Tong, Louis; Mehta, Jodhbir S

    2013-01-01

    Purpose To evaluate longitudinal changes in corneal sensitivity, tear function, and corneal staining in patients who underwent laser in situ keratomileusis (LASIK) using two different femtosecond lasers. Methods In a prospective, randomized clinical trial, contralateral eyes of 45 patients underwent flap creation by either VisuMax or IntraLase™ femtosecond laser. Corneal sensitivity, tear break up time (TBUT), Schirmer’s test, and corneal fluorescein staining were assessed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Results There were no statistical differences in any clinical outcome measure between the two femtosecond lasers (P > 0.05), although there was a trend towards slightly lower reductions for corneal sensitivity and TBUT in VisuMax-operated eyes. Overall, corneal sensitivity was significantly reduced at 1 week (P < 0.05), 1 month (P < 0 .001), and 3 months (P < 0.001) postoperatively. A significantly greater reduction of corneal sensitivity was noted in eyes with a myopic spherical equivalent of −6.00 diopters (D) to −11.25 D as compared with eyes that had a relatively lower level of myopia of less than −6.00 D (P < 0.001). TBUT and Schirmer’s test values were significantly diminished at 1 week postoperatively (P < 0.04). Overall, corneal staining was significantly increased at 1 week postoperatively (P < 0.001). The level of myopia did not significantly affect postoperative changes in TBUT, Schirmer’s test values, or corneal staining (P > 0.05). Conclusion This study showed that changes in corneal sensitivity, tear function, and corneal staining were statistically similar in LASIK using VisuMax and IntraLase femtosecond lasers for flap creation. However, the trend towards faster recovery of corneal sensitivity and TBUT observed in VisuMax-operated eyes may be attributable to improved technical specifications. PMID:23576858

  16. Wavefront-guided versus standard laser in situ keratomileusis to correct low to moderate myopia.

    PubMed

    Nuijts, Rudy M M A; Nabar, Vaishaly A; Hament, Willem J; Eggink, Fred A G J

    2002-11-01

    To evaluate the 6-month refractive outcomes of wavefront-guided laser in situ keratomileusis (LASIK) (Zyoptix, Bausch & Lomb) versus standard LASIK (PlanoScan, Bausch & Lomb). Department of Ophthalmology, University Hospital Maastricht, Maastricht, The Netherlands. In a prospective randomized study, 12 patients with myopia had Zyoptix wavefront-guided LASIK in 1 eye and PlanoScan LASIK in the contralateral eye. The safety, efficacy, predictability, stability, optical zone size, and ablation depth were evaluated. The mean preoperative spherical equivalent (SE) of the subjective manifest refraction was -3.88 diopters (D) +/- 1.92 (SD) (Zyoptix) and -4.35 +/- 2.11 D (PlanoScan). Six months postoperatively, 8% of PlanoScan patients and 16% of Zyoptix patients gained at least 2 lines of best corrected visual acuity; the safety index was 1.12 in the Zyoptix group and 1.08 in the PlanoScan group. An SE of +/-1.00 D and +/-0.50 D was achieved by 100% and 92%, respectively, in both groups. There were 2 undercorrections in the Zyoptix group and 1 undercorrection in the PlanoScan group. In the Zyoptix group, 100% had a UCVA of 20/40 and 67% of 20/20 and in the PlanoScan group, 100% and 83%, respectively. The efficacy index was 0.87 and 0.93 in the Zyoptix group and PlanoScan group, respectively. The mean optical zone 6 months postoperatively was 6.16 +/- 0.34 mm in the PlanoScan group and 6.23 +/- 0.41 mm in the Zyoptix group (P =.67). The ablation depth per diopter of defocus equivalent was 13.5 +/- 4.6 microm/D and 8.6 +/- 4.4 microm/D, respectively (P =.01).An excellent safety index was achieved with the Zyoptix and PlanoScan treatments. The efficacy index was marginally lower for Zyoptix treatments as a result of 2 undercorrections. The ablation depth in the Zyoptix group per diopter of defocus equivalent was significantly lower than in the PlanoScan group. Further refinements in defining the ablation algorithms may increase the efficacy index. PMID:12457662

  17. Excimer laser in-situ keratomileusis (LASIK) under a corneal flap for myopia of 2 to 20 D.

    PubMed Central

    Salah, T; Waring, G O; el-Maghraby, A; Moadel, K; Grimm, S B

    1995-01-01

    BACKGROUND: We report the results of a recent technique of keratomileusis for myopia: excimer laser in-situ keratomileusis (LASIK). METHODS: We studied retrospectively 88 eyes of 63 patients that received LASIK with the Chiron Automated Corneal Shaper and the Summit OmniMed excimer laser under a hinged corneal flap without sutures. RESULTS: Mean follow-up was 5.2 months. Mean spherical equivalent of the manifest refraction before surgery was -8.24 diopters (D)(range -2.00 to -20.00 D). Mean spherical equivalent refraction after surgery was +0.22 D (SD, 1.42 D). Of 40 eyes with a baseline refraction from -2.00 to -6.00 D, 25 (63%) had a refraction within +/- 0.50 D and 37 eyes (93%) within +/-1.00 D. In 29 eyes with baseline refraction of -6.12 to -12.00 D, postoperative refraction was within +/-1.00 D in 19 (65%). In 19 eyes with baseline refraction of -12.10 to -20.00 D postoperative refraction was +/-1.00 D in 8 (43%). Overall, 64 of 88 eyes (72.8%) had a refraction within +/-1.00 D after surgery. Between three weeks and five months after surgery the change in the mean spherical equivalent refraction was -0.61 D in the myopic direction. Uncorrected visual acuity after surgery was 20/20 or better in 31 eyes (36%) and 20/40 or better in 61 eyes (71%). Three eyes (3.6%) lost two lines or more of spectacle corrected visual acuity, two from progressive myopic maculopathy and one from irregular astigmatism. No eyes had vision threatening complications. CONCLUSION: Excimer laser in-situ keratomileusis (LASIK) under a corneal flap can be an effective method of reducing myopia between -2.00 to -20.00 D, with minimal complications. Current surgical algorithms need modification to improve predictability. Stability of refraction after surgery requires further study. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 PMID:8719677

  18. Incidence and Outcomes of Anterior Chamber Gas Bubble during Femtosecond Flap Creation for Laser-Assisted In Situ Keratomileusis.

    PubMed

    Rush, Sloan W; Cofoid, Philip; Rush, Ryan B

    2015-01-01

    Purpose. To report the incidence and outcomes of anterior chamber gas bubble formation during femtosecond laser flap creation for laser-assisted in situ keratomileusis (LASIK). Methods. The charts of 2,886 consecutive eyes that underwent femtosecond LASIK from May 2011 through August 2014 were retrospectively reviewed. The incidence, preoperative characteristics, intraoperative details, and postoperative outcomes were analyzed in subjects developing anterior chamber gas bubble formation during the procedure. Results. A total of 4 cases (0.14%) developed anterior chamber gas bubble formation during femtosecond laser flap creation. In all four cases, the excimer laser was unable to successfully track the pupil immediately following the anterior chamber bubble formation, temporarily postponing the completion of the procedure. There was an ethnicity predilection of anterior chamber gas formation toward Asians (p = 0.0055). An uncorrected visual acuity of 20/20 was ultimately achieved in all four cases without further complications. Conclusions. Anterior chamber gas bubble formation during femtosecond laser flap creation for LASIK is an uncommon event that typically results in a delay in treatment completion; nevertheless, it does influence final positive visual outcome. PMID:25954511

  19. Incidence and Outcomes of Anterior Chamber Gas Bubble during Femtosecond Flap Creation for Laser-Assisted In Situ Keratomileusis

    PubMed Central

    Rush, Sloan W.; Cofoid, Philip; Rush, Ryan B.

    2015-01-01

    Purpose. To report the incidence and outcomes of anterior chamber gas bubble formation during femtosecond laser flap creation for laser-assisted in situ keratomileusis (LASIK). Methods. The charts of 2,886 consecutive eyes that underwent femtosecond LASIK from May 2011 through August 2014 were retrospectively reviewed. The incidence, preoperative characteristics, intraoperative details, and postoperative outcomes were analyzed in subjects developing anterior chamber gas bubble formation during the procedure. Results. A total of 4 cases (0.14%) developed anterior chamber gas bubble formation during femtosecond laser flap creation. In all four cases, the excimer laser was unable to successfully track the pupil immediately following the anterior chamber bubble formation, temporarily postponing the completion of the procedure. There was an ethnicity predilection of anterior chamber gas formation toward Asians (p = 0.0055). An uncorrected visual acuity of 20/20 was ultimately achieved in all four cases without further complications. Conclusions. Anterior chamber gas bubble formation during femtosecond laser flap creation for LASIK is an uncommon event that typically results in a delay in treatment completion; nevertheless, it does influence final positive visual outcome. PMID:25954511

  20. Effect of Myopic Defocus on Visual Acuity after Phakic Intraocular Lens Implantation and Wavefront-guided Laser in Situ Keratomileusis.

    PubMed

    Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Kawamorita, Takushi

    2015-01-01

    This study aimed to investigate the effect of myopic defocus on visual acuity after phakic intraocular lens (IOL) implantation and wavefront-guided laser in situ keratomileusis (wfg-LASIK). Our prospective study comprised thirty eyes undergoing posterior chamber phakic IOL implantation and 30 eyes undergoing wfg-LASIK. We randomly measured visual acuity under myopic defocus after cycloplegic and non-cycloplegic correction. We also calculated the modulation transfer function by optical simulation and estimated visual acuity from Campbell &Green's retinal threshold curve. Visual acuity in the phakic IOL group was significantly better than that in the wfg-LASIK group at myopic defocus levels of 0, -1, and -2 D (p < 0.001, p < 0.001, and p = 0.02, Mann-Whitney U-test), but not at a defocus of -3 D (p = 0.30). Similar results were also obtained in a cycloplegic condition. Decimal visual acuity values at a myopic defocus of 0, -1, -2, and -3 D by optical simulation were estimated to be 1.95, 1.21, 0.97, and 0.75 in the phakic IOL group, and 1.39, 1.11, 0.94, and 0.71 in the wfg-LASIK group, respectively. From clinical and optical viewpoints, phakic IOL implantation was superior to wfg-LASIK in terms of the postoperative visual performance, even in the presence of low to moderate myopic regression. PMID:25994984

  1. Clinical outcomes of wavefront-guided laser in situ keratomileusis to treat moderate-to-high astigmatism

    PubMed Central

    Schallhorn, Steven C; Venter, Jan A; Hannan, Stephen J; Hettinger, Keith A

    2015-01-01

    Purpose The purpose of this study was to evaluate the refractive and visual outcomes of wavefront-guided laser in situ keratomileusis (LASIK) in eyes with myopic astigmatism and cylindrical component ≥2.0 diopter (D). Methods In this retrospective study, 611 eyes that underwent LASIK for simple or compound myopic astigmatism were analyzed. Preoperative refractive cylinder ranged from −2.00 D to −6.00 D (mean −2.76±0.81 D), and the sphere was between 0.00 D and −9.75 D (mean −2.79±2.32 D). Predictability, visual outcomes, and vector analysis of changes in refractive astigmatism were evaluated. Results At 3 months after LASIK, 83.8% of eyes had uncorrected distance visual acuity of 20/20 or better, 90.3% had manifest spherical equivalent within ±0.50 D, and 79.1% had residual refractive cylinder within ±0.50 D of intended correction. The mean correction ratio for refractive cylinder was 0.92±0.14, the mean error of angle was −0.45°±2.99°, and the mean error vector was 0.37±0.38 D. A statistically significant correlation was found between the error of magnitude (arithmetic difference in the magnitudes between surgically induced refractive correction and intended refractive correction) and the intended refractive correction (r=0.26, P<0.01). Conclusion Wavefront-guided LASIK for the correction of myopic astigmatism is safe, effective, and predictable. PMID:26203219

  2. Effect of Myopic Defocus on Visual Acuity after Phakic Intraocular Lens Implantation and Wavefront-guided Laser in Situ Keratomileusis

    PubMed Central

    Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Kawamorita, Takushi

    2015-01-01

    This study aimed to investigate the effect of myopic defocus on visual acuity after phakic intraocular lens (IOL) implantation and wavefront-guided laser in situ keratomileusis (wfg-LASIK). Our prospective study comprised thirty eyes undergoing posterior chamber phakic IOL implantation and 30 eyes undergoing wfg-LASIK. We randomly measured visual acuity under myopic defocus after cycloplegic and non-cycloplegic correction. We also calculated the modulation transfer function by optical simulation and estimated visual acuity from Campbell & Green’s retinal threshold curve. Visual acuity in the phakic IOL group was significantly better than that in the wfg-LASIK group at myopic defocus levels of 0, –1, and –2 D (p < 0.001, p < 0.001, and p = 0.02, Mann-Whitney U-test), but not at a defocus of –3 D (p = 0.30). Similar results were also obtained in a cycloplegic condition. Decimal visual acuity values at a myopic defocus of 0, −1, −2, and -3 D by optical simulation were estimated to be 1.95, 1.21, 0.97, and 0.75 in the phakic IOL group, and 1.39, 1.11, 0.94, and 0.71 in the wfg-LASIK group, respectively. From clinical and optical viewpoints, phakic IOL implantation was superior to wfg-LASIK in terms of the postoperative visual performance, even in the presence of low to moderate myopic regression. PMID:25994984

  3. Long-term evaluation of eyes with central corneal thickness <400 μm following laser in situ keratomileusis

    PubMed Central

    Djodeyre, Mohammad Reza; Beltran, Jaime; Ortega-Usobiaga, Julio; Gonzalez-Lopez, Felix; Ruiz-Rizaldos, Ana Isabel; Baviera, Julio

    2016-01-01

    Purpose To study long-term refractive and visual outcomes of laser in situ keratomileusis (LASIK) in eyes with a postoperative thin central cornea. Methods In this retrospective observational case series, we studied 282 myopic eyes with a normal preoperative topographic pattern and postoperative thin corneas (<400 μm) that had at least 3 years of follow-up after LASIK in three private clinics. The main outcome measures were safety, efficacy, predictability, percent tissue altered, and complications. Results The mean postoperative central corneal thickness was 392.05 μm (range: 363.00–399.00 μm). After a mean follow-up of 6.89±2.35 years (standard deviation), the safety index was 1.17, the efficacy index was 0.94, and predictability (±1.00 diopter [D]) was 73.49. The mean residual stromal bed thickness was 317.34±13.75 μm (range: 275–356 μm), the mean flap thickness was 74.76±13.57 μm (range: 55–124 μm), and the mean percent tissue altered was 37.12%±3.62% (range: 27.25%–49.26%). No major complications were recorded. Conclusion LASIK with a resultant central cornea thickness <400 μm seems to be effective, safe, and predictable provided that preoperative topography is normal and the residual stromal bed thickness is >275 μm. PMID:27099459

  4. Four-year follow-up of corneal aberrations and visual functions of myopic patients after laser in situ keratomileusis

    PubMed Central

    Liu, Tai-Xiang; Chen, Yong-Tao; Dan, Ting-Ting; Shi, Rong; Linghu, Shao-Rong; Li, Hai-Xiang

    2015-01-01

    Objective: To report on 4-year follow-up of corneal higher-order aberrations and daily visual functions of myopic patients after laser in situ keratomileusis (LASIK). Methods: One hundred thirty four eyes of 67 patients who underwent LASIK guided by aspherical ablation were included in this study. The vision, corneal spherical aberration (SphA) and Coma were recorded before LASIK and at 6 month and 4 year after LASIK. The evaluation of the questionnaire about daily visual functions was performed by the same physician after LASIK. Results: No eye decreased the BCVA during 4 year follow-up. The effect index and safety index were 1.08±0.16, 1.11±0.17 and 1.12±0.16, 1.13±0.14 respectively at 6 month and 4 year post-LASIK. After LASIK the corneal SphA and Coma were significantly increased, however the difference between 6 month and 4 year post-LASIK was no statistical significance. Most patients (94.3%-92.4%) felt satisfaction or high satisfaction about the ability to perform each daily visual function after LASIK. Meanwhile there was still about 7.4%-9.2% patients who complained that they could not drive at night. Further analysis showed that the score of driving at night was negative correlation with corneal SphA (r=-0.645, p=0.040; r=-0.688, p=0.040 at 6 month and 4 year post-LASIK respectively). Conclusions: Our four-year follow-up outcomes indicated that the myopic patients after LASIK had the long-term stable corneal aberration and satisfaction of daily visual functions. PMID:26870114

  5. A comparison of visual acuity, predictability, and visual function outcomes after intracorneal ring segments and laser in situ keratomileusis.

    PubMed Central

    Suiter, B G; Twa, M D; Ruckhofer, J; Schanzlin, D J

    2000-01-01

    PURPOSE: To compare correction of low myopia by intrastromal corneal ring segments (ICRS) and by laser in situ keratomileusis (LASIK) with respect to early visual recovery and refractive outcomes. METHODS: Eighty-two eyes implanted with ICRS in a phase III study for US Food and Drug Administration review were matched with 133 eyes treated with LASIK by criteria of age (> 18 years, < 65 years), preoperative myopia (-1.00 to -3.50 diopters [D]), astigmatism (< or = 1.00 D), single treatment, and attempted full correction. Examinations were performed preoperatively and postoperatively at days 1 and 7 and months 1 and 3. Visual acuity and manifest refraction data were collected retrospectively. Visual function scores were assigned, and summarized results were compared. RESULTS: Uncorrected visual acuity was 20/20 or better at day 1 in 24% of eyes (20/82) after ICRS and in 55% of eyes (73/133) after LASIK, and at month 3 in 75% of eyes (58/77) after ICRS and in 67% of eyes (84/126) after LASIK. Spherical equivalent refraction at month 3 was within +/- 1.00 D of intended correction in 99% of eyes (76/77) after ICRS and in 96% of eyes (121/126) after LASIK. Excellent visual function scores were noted at month 3 in 90% of eyes (69/77) after ICRS and in 78% of eyes (98/126) after LASIK. CONCLUSION: Patients treated with LASIK showed better uncorrected visual acuity immediately following surgery; however, beyond 1 month, patients treated with ICRS achieved better uncorrected visual acuity that continued to improve with time. Visual function scores indicate that ICRS eyes see at higher levels of uncorrected visual acuity than LASIK eyes do with the same refractive error. The ICRS and LASIK were comparable in the correction of mild myopia. PMID:11190040

  6. Clinical results of the laser-assisted in situ keratomileusis (LASIK) for myopia

    NASA Astrophysics Data System (ADS)

    Guo, Hai-ke; Yao, Da-qing; Gui, Lu-ping

    1998-11-01

    To observe and analyze the refractive and complications of the LASIK for corrections of myopia. With the microlamellar keratoplasty and the excimer laser, LASIK was performed on 194 cases. According to the preoperative spherical equivalent refraction, divide the patients into three groups.

  7. Modulation of corneal wound healing after excimer laser keratomileusis using topical mitomycin C and steroids

    SciTech Connect

    Talamo, J.H.; Gollamudi, S.; Green, W.R.; De La Cruz, Z.; Filatov, V.; Stark, W.J. )

    1991-08-01

    A 193-nm excimer laser system was used to create deep stromal ablations in seven New Zealand white rabbits and shallow ablations in three. Eyes were randomized for treatment with topical mitomycin C, steroids, and erythromycin; topical steroids and erythromycin; or topical erythromycin only. All treatment regimens were instituted twice daily for 14 days. All eyes reepithelialized normally within 3 to 5 days. During 10 weeks of follow-up, all eyes developed moderate reticular subepithelial haze without significant differences among treatment groups. Results of light, fluorescence, and electron microscopic examination showed anterior stromal scarring and markedly reduced new subepithelial collagen formation in the group treated with mitomycin C, corticosteroids, and erythromycin. Focal abnormalities of Descemet's membrane and endothelial abnormalities were present in all treatment groups. Combination therapy with topical steroids, mitomycin C, and erythromycin to control the corneal wound healing response after refractive laser surgery appears promising and warrants further study.

  8. Laser In Situ keratomileusis (LASIK) for the treatment of low moderate, and high myopia.

    PubMed Central

    Lindstrom, R L; Hardten, D R; Chu, Y R

    1997-01-01

    PURPOSE: To evaluate the efficacy, safety and predictability of LASIK in the treatment of low, moderate and high myopia. METHODS: A perspective study of LASIK for low myopia of -0.75 to -6.00 with less than +1 D of astigmatism and for moderate and high myopia of -6.12 to -20 D with astigmatism up to +4.50 D was performed at our institution from March through November, 1996. The Chiron automated corneal shaper was used for the initial flap, and either the Summit or VISX laser was used for the refractive ablation. Preoperative refraction, uncorrected and corrected visual acuity were compared to postoperative refraction, uncorrected and corrected visual acuity. One day and 1 month results were available on all patients. RESULTS: In the low myopia group 101 eyes underwent LASIK with a mean preoperative spherical equivalent of -4.16 +/- 1.41 D (-0.75 D to -6.00 D). Mean preoperative astigmatism was +0.4 +/- 1.29 D (0 to 0.75 D). At 1 day, 48% were 20/25 or better and 80% were 20/40 or better. The day 1 mean spherical equivalent was +0.4 +/- 0.75 D with 86% between +/- 1.00 D of emmetropia. At 1 month, 50% were 20/25 or better and 90% were 20/40 or better. The 1 month mean spherical equivalent was -0.26 +/- 0.65 D with 89% between +/- 1.00 D of emmetropia. In the high myopia group 198 eyes underwent LASIK with a preoperative mean spherical equivalent of -8.34 +/- 2.15 D)-6 to -20D) and a mean preoperative astigmatism of +1.18 +/- 0.88 D (0 to +4.5 D). At 1 day postoperatively, 17% were 20/25 or better, and 61% were 20/40 or better. The mean day one spherical equivalent was -0.26 +/- 1.56 D with 58% between +/- 1.00 D of emmetropia. At 1 month, 35% were 20/25 or better and 71% were 20/40 or better. The 1 month mean spherical equivalent was -0.28 +/- 1.18 with 63% within +/- 1.00 D of emmetropia. CONCLUSION: Early results of using LASIK to treat low, moderate and high degrees of myopia with and without astigmatism appear promising, although longer follow-up and nomogram

  9. Factors Affecting Long-term Myopic Regression after Laser In Situ Keratomileusis and Laser-assisted Subepithelial Keratectomy for Moderate Myopia

    PubMed Central

    Lim, Sung A; Park, Yooyeon; Cheong, Yu Jin; Na, Kyung Sun

    2016-01-01

    Purpose High myopia is known to be a risk factor for long-term regression after laser refractive surgery. There have been few studies about the correction of moderate myopias that did not need retreatment after long-term follow-up. We evaluated 10 years of change in visual acuity and refractive power in eyes with moderate myopia after laser refractive surgery. Methods We included patients that had undergone laser in situ keratomileusis (LASIK) or laser-assisted subepithelial keratectomy (LASEK) to correct their myopia and that had at least 10 years of follow-up. We evaluated the stability of visual acuity in terms of safety, efficacy, and refractive changes at examinations 6 months and 1, 2, 5, 7, and 10 years after surgery. Results The study evaluated 62 eyes (36 eyes in LASIK patients and 26 eyes in LASEK patients). In both groups, the efficacy index tended to decrease, and it was consistently higher in the LASEK group compared to the LASIK group over the 10 years of follow-up. The safety index improved over 10 years and was always higher than 0.9 in both groups. The difference between the spherical equivalent at 6 months postoperatively and later periods was statistically significant after 5, 7, and 10 years in both groups (LASIK, p = 0.036, p = 0.003, and p < 0.001, respectively; LASEK, p = 0.006, p = 0.002, and p = 0.001, respectively). Ten years after surgery,26 eyes (66.7%) in the LASIK group and 19 eyes (73.1%) in the LASEK group had myopia greater than 1 diopter. In comparison with the thickness at 6 months postoperatively, central corneal thickness was significantly increased after 5, 7, and 10 years in both LASIK and LASEK groups (LASIK, p < 0.001, p < 0.001, and p < 0.001, respectively; LASEK, p = 0.01, p < 0.001, and p < 0.001, respectively). Conclusions Moderately myopic eyes showed progressive myopic shifting and corneal thickening after LASIK and LASEK during 10 years of follow-up. We also found that early refractive regression may indicate the long

  10. Early Changes in Ocular Surface and Tear Inflammatory Mediators after Small-Incision Lenticule Extraction and Femtosecond Laser-Assisted Laser In Situ Keratomileusis

    PubMed Central

    Gao, Shaohui; Li, Saiqun; Liu, Liangping; Wang, Yong; Ding, Hui; Li, Lili; Zhong, Xingwu

    2014-01-01

    Purpose To characterize the early ocular-surface changes or tear inflammatory-mediators levels following small-incision lenticule extraction (ReLEx smile) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). Methods Forty-seven myopic subjects were recruited for this prospective study. Fifteen underwent ReLEx smile and thirty-two underwent FS-LASIK. Corneal fluorescein (FL) staining, tear break-up time (TBUT), Schirmer I test (SIT), ocular surface disease index (OSDI) and central corneal sensitivity were evaluated in all participants. Tears were collected and analyzed for interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF) and intercellular adhesion molecule-1 (ICAM-1) levels using multiplex magnetic beads. All measurements were preformed preoperatively and 1 day, 1 week, 1 month and 3 months postoperatively. Results FL scores in ReLEx smile group were lower than those of FS-LASIK group 1 week postoperatively (P = 0.010). Compared to the FS-LASIK group, longer TBUT were observed in ReLEx smile group 1 month (P = 0.029) and 3 months (P = 0.045) postoperatively. No significant differences were found in tear secretion for the two groups (P>0.05). OSDI scores were higher in FS-LASIK group 1 month after surgery (P = 0.020). Higher central corneal sensitivity was observed in ReLEx smile group 1 week, 1 month and 3 months (P<0.05) postoperatively. Compared to FS-LASIK group, lower and faster recovery of IL-6 and NGF levels in tears was observed in ReLEx smile group postoperatively (P<0.05). Tears TNF-α and ICAM-1 concentrations were not significantly different between the two groups at any follow-up time (P>0.05). Moreover, IL-6 and NGF levels correlated with ocular surface changes after ReLEx smile or FS-LASIK. Conclusions In the early postoperative period, ReLEx smile results in milder ocular surface changes than FS-LASIK. Furthermore, the tear inflammatory mediators IL-6 and NGF may play a crucial role

  11. Comparison of Intraocular Pressure before and after Laser In Situ Keratomileusis Refractive Surgery Measured with Perkins Tonometry, Noncontact Tonometry, and Transpalpebral Tonometry

    PubMed Central

    Cacho, Isabel; Sanchez-Naves, Juan; Batres, Laura; Pintor, Jesús; Carracedo, Gonzalo

    2015-01-01

    Purpose. To compare the intraocular pressure (IOP) before and after Laser In Situ Keratomileusis (LASIK), measured by Diaton, Perkins, and noncontact air pulse tonometers. Methods. Fifty-seven patients with a mean age of 34.88 were scheduled for myopia LASIK treatment. Spherical equivalent refraction (SER), corneal curvature (K), and central corneal thickness (CCT) and superior corneal thickness (SCT) were obtained before and after LASIK surgery. IOP values before and after surgery were measured using Diaton, Perkins, and noncontact air pulse tonometers. Results. The IOP values before and after LASIK surgery using Perkins tonometer and air tonometers were statistically significant (p < 0.05). However, no significant differences were found (p > 0.05) for IOP values measured with Diaton tonometer. CCT decreases significantly after surgery (p < 0.05) but no statistical differences were found in SCT (p = 0.08). Correlations between pre- and postsurgery were found for all tonometers used, with p = 0.001 and r = 0.434 for the air pulse tonometer, p = 0.008 and r = 0.355 for Perkins, and p < 0.001 and r = 0.637 for Diaton. Conclusion. Transpalpebral tonometry may be useful for measuring postsurgery IOP after myopic LASIK ablation because this technique is not influenced by the treatment. PMID:26167293

  12. Efficacy and Safety of Topical Timolol Eye Drops in the Treatment of Myopic Regression after Laser In Situ Keratomileusis: A Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Xiaochen; Zhao, Guiqiu; Lin, Jing; Jiang, Nan; Wang, Qian; Xu, Qiang

    2015-01-01

    Aims. The aim of this study was to assess the efficacy and safety of timolol in the treatment of myopic regression after laser in situ keratomileusis (LASIK). Methods. We searched MEDLINE, CENTRAL, EMBASE, China National Knowledge Infrastructure (CNKI), and Chinese Biological Medicine (CBM) from the inception to July 2015 for relevant randomized controlled trials that examined timolol therapy for myopic regression. The methodological quality of the studies included was assessed using the Revman 5.3 software. Results. We included six clinical trials involving 483 eyes in this review, including 246 eyes in treated group and 237 eyes in controlled group. We observed statistically significant improvements on the postoperative SE in the 3 months. However, the change of CCT was not statistically different between the control group and the experimental group. There were fewer cases of IOP, UDVA, and CDVA in treated group having significant difference from the controlled group. Conclusions. Topical timolol could be an effective treatment for reduction of myopic regression especially the spherical errors after myopic LASIK. Further RCTs with larger sample sizes for these trials are warranted to determine the efficacy and limitation for myopic regression after LASIK. PMID:26798507

  13. The Correlation Analysis between Corneal Biomechanical Properties and the Surgically Induced Corneal High-Order Aberrations after Small Incision Lenticule Extraction and Femtosecond Laser In Situ Keratomileusis

    PubMed Central

    Wu, Wenjing; Wang, Yan

    2015-01-01

    Background. To investigate the correlation between corneal biomechanics and the surgically induced corneal high-order aberrations (HOAs) after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). Methods. A total of 150 right myopic eyes that underwent SMILE or FS-LASIK surgery were included in this retrospective study, 75 eyes in each group. The corneal hysteresis (CH) and the corneal resistance factor (CRF) with the corneal HOAs of the anterior, posterior, and total cornea were assessed preoperatively and three months postoperatively. Multivariate linear regression was applied to determine the correlations. Results. The preoperative CRF was significantly correlated with the induced 3rd–6th-order HOAs and spherical aberration of the anterior surface and the total cornea after SMILE and FS-LASIK surgeries (P < 0.05), postoperatively. The CRF was significantly correlated with the induced vertical coma of the anterior and posterior surfaces and the total cornea after SMILE surgery (P < 0.05). There was a significant correlation between the CRF and the induced posterior corneal horizontal coma after FS-LASIK surgery (P = 0.013). Conclusions. The corneal biomechanics affect the surgically induced corneal HOAs after SMILE and FS-LASIK surgery, which may be meaningful for screening the patients preoperatively and optimizing the visual qualities postoperatively. PMID:26483975

  14. Wavefront-Guided Laser in Situ Keratomileusis (Lasik) versus Wavefront-Guided Photorefractive Keratectomy (Prk): A Prospective Randomized Eye-to-Eye Comparison (An American Ophthalmological Society Thesis)

    PubMed Central

    Manche, Edward E.; Haw, Weldon W.

    2011-01-01

    Purpose To compare the safety and efficacy of wavefront-guided laser in situ keratomileusis (LASIK) vs photorefractive keratectomy (PRK) in a prospective randomized clinical trial. Methods A cohort of 68 eyes of 34 patients with −0.75 to −8.13 diopters (D) of myopia (spherical equivalent) were randomized to receive either wavefront-guided PRK or LASIK in the fellow eye using the VISX CustomVue laser. Patients were evaluated at 1 day, 1 week, and months 1, 3, 6, and 12. Results At 1 month, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), 5% and 25% contrast sensitivity, induction of higher-order aberrations (HOAs), and subjective symptoms of vision clarity, vision fluctuation, ghosting, and overall self-assessment of vision were worse (P<0.05) in the PRK group. By 3 months, these differences had resolved (P>0.05). At 1 year, mean spherical equivalent was reduced 94% to −0.27 ± 0.31 D in the LASIK group and reduced 96% to −0.17 ± 0.41 D in the PRK group. At 1 year, 91% of eyes were within ±0.50 D and 97 % were within ±1.0 D in the PRK group. At 1 year, 88% of eyes were within ±0.50 D and 97% were within ±1.0 D in the LASIK group. At 1 year, 97% of eyes in the PRK group and 94% of eyes in the LASIK group achieved an UCVA of 20/20 or better (P=0.72). Refractive stability was achieved in both PRK and LASIK groups after 1 month. There were no intraoperative or postoperative flap complications in the LASIK group. There were no instances of corneal haze in the PRK group. Conclusions Wavefront-guided LASIK and PRK are safe and effective at reducing myopia. At 1 month postoperatively, LASIK demonstrates an advantage over PRK in UCVA, BSCVA, low-contrast acuity, induction of total HOAs, and several subjective symptoms. At postoperative month 3, these differences between PRK and LASIK results had resolved. PMID:22253488

  15. Small incision lenticule extraction (SMILE) versus laser in-situ keratomileusis (LASIK): study protocol for a randomized, non-inferiority trial

    PubMed Central

    2012-01-01

    Background Small incision lenticule extraction or SMILE is a novel form of ‘flapless’ corneal refractive surgery that was adapted from refractive lenticule extraction (ReLEx). SMILE uses only one femtosecond laser to complete the refractive surgery, potentially reducing surgical time, side effects, and cost. If successful, SMILE could potentially replace the current, widely practiced laser in-situ keratomileusis or LASIK. The aim of this study is to evaluate whether SMILE is non-inferior to LASIK in terms of refractive outcomes at 3 months post-operatively. Methods/Design Single tertiary center, parallel group, single-masked, paired-eye design, non-inferiority, randomized controlled trial. Participants who are eligible for LASIK will be enrolled for study after informed consent. Each participant will be randomized to receive SMILE and LASIK in each eye. Our primary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 diopter (D)) at a tertiary eye center in terms of refractive predictability at 3 months post-operatively. Our secondary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 D) at a tertiary eye center in terms of other refractive outcomes (efficacy, safety, higher-order aberrations) at 3 months post-operatively. Our primary outcome is refractive predictability, which is one of several standard refractive outcomes, defined as the proportion of eyes achieving a postoperative spherical equivalent (SE) within ±0.50 D of the intended target. Randomization will be performed using random allocation sequence generated by a computer with no blocks or restrictions, and implemented by concealing the number-coded surgery within sealed envelopes until just before the procedure. In this single-masked trial, subjects and their caregivers will be masked to the assigned

  16. A prospective comparison of phakic collamer lenses and wavefront-optimized laser-assisted in situ keratomileusis for correction of myopia

    PubMed Central

    Parkhurst, Gregory D

    2016-01-01

    Purpose The aim of this study was to evaluate and compare night vision and low-luminance contrast sensitivity (CS) in patients undergoing implantation of phakic collamer lenses or wavefront-optimized laser-assisted in situ keratomileusis (LASIK). Patients and methods This is a nonrandomized, prospective study, in which 48 military personnel were recruited. Rabin Super Vision Test was used to compare the visual acuity and CS of Visian implantable collamer lens (ICL) and LASIK groups under normal and low light conditions, using a filter for simulated vision through night vision goggles. Results Preoperative mean spherical equivalent was −6.10 D in the ICL group and −6.04 D in the LASIK group (P=0.863). Three months postoperatively, super vision acuity (SVa), super vision acuity with (low-luminance) goggles (SVaG), super vision contrast (SVc), and super vision contrast with (low luminance) goggles (SVcG) significantly improved in the ICL and LASIK groups (P<0.001). Mean improvement in SVaG at 3 months postoperatively was statistically significantly greater in the ICL group than in the LASIK group (mean change [logarithm of the minimum angle of resolution, LogMAR]: ICL =−0.134, LASIK =−0.085; P=0.032). Mean improvements in SVc and SVcG were also statistically significantly greater in the ICL group than in the LASIK group (SVc mean change [logarithm of the CS, LogCS]: ICL =0.356, LASIK =0.209; P=0.018 and SVcG mean change [LogCS]: ICL =0.390, LASIK =0.259; P=0.024). Mean improvement in SVa at 3 months was comparable in both groups (P=0.154). Conclusion Simulated night vision improved with both ICL implantation and wavefront-optimized LASIK, but improvements were significantly greater with ICLs. These differences may be important in a military setting and may also affect satisfaction with civilian vision correction. PMID:27418804

  17. Small Incision Lenticule Extraction (SMILE) versus Femtosecond Laser-Assisted In Situ Keratomileusis (FS-LASIK) for Myopia: A Systematic Review and Meta-Analysis

    PubMed Central

    Shen, Zeren; Shi, Keda; Yu, Yinhui; Yu, Xiaoning; Lin, Yuchen; Yao, Ke

    2016-01-01

    Purpose The goal of this study was to compare small incision lenticule extraction (SMILE) with femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for treating myopia. Methods The CENTRAL, EMBASE, PubMed databases and a Chinese database (SinoMed) were searched in May of 2016. Twelve studies with 1,076 eyes, which included three randomized controlled trials (RCTs) and nine cohorts, met our inclusion criteria. The overall quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group framework. Data were extracted and analysed at three to six months postoperatively. Primary outcome measures included a loss of one or more lines of best spectacle corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA) of 20/20 or better, mean logMAR UCVA, postoperative mean spherical equivalent (SE) and postoperative refraction within ±1.0 D of the target refraction. Secondary outcome measures included ocular surface disease index (OSDI), tear breakup time (TBUT) and Schirmer’s 1 test (S1T) as dry eye parameters, along with corneal sensitivity. Results The overall quality of evidence was considered to be low to very low. Pooled results revealed no significant differences between the two groups with regard to a loss of one or more lines in the BSCVA (OR 1.71; 95% CI: 0.81, 3.63; P = 0.16), UCVA of 20/20 or better (OR 0.71; 95% CI: 0.44, 1.15; P = 0.16), logMAR UCVA (MD 0.00; 95% CI: -0.03, 0.04; P = 0.87), postoperative refractive SE (MD -0.00; 95% CI: -0.05, 0.05; P = 0.97) or postoperative refraction within ±1.0 D of the target refraction (OR 0.78; 95% CI: 0.22, 2.77; P = 0.70) within six months postoperatively. The pooled analysis also indicated that the FS-LASIK group suffered more severely from dry eye symptoms (OSDI; MD -6.68; 95% CI: -11.76, -2.00; P = 0.006) and lower corneal sensitivity (MD 12.40; 95% CI: 10.23, 14.56; P < 0.00001) at six months postoperatively. Conclusions In conclusion

  18. A retrospective analysis of the postoperative use of loteprednol etabonate gel 0.5% following laser-assisted in situ keratomileusis or photorefractive keratectomy surgery

    PubMed Central

    Salinger, Clifford L; Gordon, Michael; Jackson, Mitchell A; Perl, Theodore; Donnenfeld, Eric

    2015-01-01

    Background While loteprednol etabonate ophthalmic gel 0.5% (LE gel) is approved for treatment of postoperative ocular inflammation and pain, there have been no reported studies in patients undergoing laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK). Methods This was a retrospective chart review conducted at five refractive surgical centers in the USA. Data were collected from primary LASIK or PRK surgery cases in which LE gel was used postoperatively as the clinician’s routine standard of care and in which patients were followed-up for up to 6 months. Data extracted from charts included patient demographics, surgical details, LE gel dosing regimen, pre- and postsurgical refractive characteristics, intraocular pressure (IOP) measurements, and visual acuity. Primary outcomes included postoperative IOP elevations, adverse events, and early discontinuations. Results Data were collected on 189 LASIK eyes (96 patients) and 209 PRK eyes (108 patients). Mean (standard deviation [SD]) years of age at surgery was 36.0 (11.7) and 33.9 (11.3) in LASIK and PRK patients. LE gel was prescribed most often four times daily during the first postoperative week, regardless of procedure; the most common treatment duration was 7–14 days in LASIK and ≥30 days in PRK patients. No unusual corneal findings or healing abnormalities were reported. Mean postoperative uncorrected distance visual acuity was 20/24 in LASIK and 20/30 in PRK eyes. Mild/trace corneal haze was reported in 20% of PRK patients; two PRK patients with moderate/severe corneal haze were switched to another corticosteroid. Mean postoperative IOP did not increase over time in either LASIK or PRK eyes (P≥0.331); clinically significant elevations from baseline in IOP (≥10 mmHg) were noted in only three eyes of two PRK patients. Conclusion LE gel appears to have a high level of safety and tolerability when used for the management of postoperative pain and inflammation following LASIK

  19. Spherical and aspherical photorefractive keratectomy and laser in-situ keratomileusis for moderate to high myopia: two prospective, randomized clinical trials. Summit technology PRK-LASIK study group.

    PubMed Central

    Steinert, R F; Hersh, P S

    1998-01-01

    OBJECTIVE: Determine the outcomes of single-zone photorefractive keratectomy (SZPRK), aspherical photorefractive keratectomy (ASPRK), and laser in-situ keratomileusis (LASIK) for the correction of myopia between -6 and -12 diopters. DESIGN: Two simultaneous prospective, randomized, multi-center clinical trials. PARTICIPANTS: 286 first-treated eyes of 286 patients enrolled in one of two studies. In Study I, 134 eyes were randomized to SZPRK (58 eyes) or ASPRK (76 eyes). In Study II, 152 eyes were randomized to ASPRK (76 eyes) or to LASIK (76 eyes). INTERVENTION: All eyes received spherical one-pass excimer laser ablation as part of PRK or LASIK performed with the Summit Technologies Apex laser under an investigational device exemption, with attempted corrections between -6 and -12 diopters. MAIN OUTCOME MEASURES: Data on uncorrected and best spectacle-corrected visual acuity, predictability and stability of refraction, and complications were analyzed. Follow-up was 12 months. RESULTS: At 1 month postoperatively, more eyes in the LASIK group achieved 20/20 and 20/25 or better uncorrected visual acuity than PRK-treated eyes; at the 20/25 or better level, the difference was significant for LASIK (29/76 eyes, 38%) over SZPRK (10/58 eyes, 17%) (P = .0064). At all subsequent postoperative intervals, no difference was seen between treatment groups. Similarly, best corrected visual acuities were better for LASIK than all PRK eyes at 1 month postoperatively, and LASIK was better than SZPRK at 3 months follow-up (e.g., for 20/20 or better at 1 month, LASIK 50/76 eyes (66%) versus SZPRK 24/57 eyes (42%), P = .0066). PRK eyes had a mean loss of BCVA through 6 months, while LASIK eyes had a slight gain of mean BCVA through month 6; at 12 months, both ASPRK groups but not SZPRK continued to have a small mean loss of BCVA (e.g., compared to preoperative, mean BCVA at 12 months for SZPRK was + 0.3, LASIK was +.21, ASPRK I was -0.11, and ASPRK II -0.31 (SZPRK versus ASPRK II, P

  20. Femtosecond laser-assisted in situ keratomileusis multifocal ablation profile using a mini-monovision approach for presbyopic patients with hyperopia

    PubMed Central

    Vastardis, Iraklis; Pajic-Eggspühler, Brigitte; Müller, Jörg; Cvejic, Zeljka; Pajic, Bojan

    2016-01-01

    Purpose To report the visual outcomes of the femtosecond laser-assisted multifocal aspheric corneal ablation profile using a mini-monovision approach and to evaluate if corneal multifocality was effective, and to report the relative benefits of this approach. Patients and methods Bilateral femtosecond laser-assisted in situ keratomileusis using a multifocal aspheric corneal ablation profile was performed on 19 hyperopic patients (38 eyes). They were divided into two groups based on eye dominance: dominant eye (DE) group targeting emmetropia and the nondominant eye (NDE) group targeting −0.5 D slight myopia. The uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), and retreatment rates were reported from baseline to 6 months. Results The UNVA, UIVA, and UDVA improved significantly in both groups (Kruskal–Wallis test, DE and NDE: P<0.00001, P<0.000005, and P=0.00001, respectively). Corrected distance visual acuity (CDVA) baseline was better in both groups in comparison to UDVA at 6 months (Wilcoxon test, DE: P<0.001, 95% confidence interval (CI) of the median 0.0–0.0 LogMAR and 0.1000–0.1218 LogMAR and NDE: P=0.010, 95% CI of the median 0.0–0.0 LogMAR and 0.00–0.10 LogMAR). There was a significant loss of lines between CDVA baseline and UDVA at 6 months in both groups (DE group: 68% of eyes lost one line or more; NDE group: 58% of eyes lost one line or more). The corrected near visual acuity baseline compared to UNVA at 6 months was not statistically important (Wilcoxon test, DE: P=0.8125, 95% CI of the median 0.0–0.0 LogMAR and 0.0–0.0 LogMAR and NDE: P=0.82, 95% CI of the median 0.0–0.0 LogMAR and 0.0–0.0 LogMAR). The comparison among the UDVA, UIVA, and UNVA between the two groups at baseline and during all follow-ups was not statistically important. Two cases from the DE group were retreated (6%). Conclusion Use of this multifocal aspheric corneal ablation profile in

  1. Preliminary results of tracked laser-assisted in-situ keratomileusis (T-LASIK) for myopia and hyperopia using the autonomous technologies excimer laser system

    NASA Astrophysics Data System (ADS)

    Maguen, Ezra I.; Nesburn, Anthony B.; Salz, James J.

    2000-06-01

    A study was undertaken to assess the safety and efficacy of LASIK with the LADARVision laser by Autonomous Technologies, (Orlando, FL). The study included four subsets: Spherical myopia -- up to -11.00D, spherical hyperopia -- up to +6.00D. Both myopic and hyperopic astigmatism could be corrected, up to 6.00D of astigmatism. A total of 105 patients participated. Sixty-six patients were myopic and 39 were hyperopic. The mean (+/- SD) age was 42.8 +/- 9.3 years for myopia and 53.2 +/- 9.9 years for hyperopia. At 3 months postop. Sixty-one myopic eyes were available for evaluation. Uncorrected visual acuity was 20/20 in 70% of eyes and 20/40 in 92.9% of all eyes. The refractive outcome was within +/- 0.50D in 73.8% of eyes and within +/- 1.00D in 96.7 of eyes. Thirty-eight hyperopic eyes were available. Uncorrected visual acuity was 20/20 in 42.1% of eyes and 20/40 in 88% of all eyes. The refractive outcome was within +/- 0.50D in 57.9% of eyes and within +/- 1.00D in 86.8% of eyes. Complications were not sight threatening and were discussed in detail. Lasik with the LADARVision laser appears to be safe and effective.

  2. In vitro inhibition of lens epithelial cell growth by continuous wave Nd:YAG laser

    SciTech Connect

    Miyake, K.; Iwata, S.; Ando, F.; Daikuzono, N.; Federman, J.L.

    1989-04-01

    Bovine lens epithelial cells were suspended in MEM medium and subjected to continuous wave, low power, pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation. The temperature of each suspension was maintained at 36 degrees C. Laser applications ranged from 1 to 10 watts and from 100 to 2000 seconds, but the total dose to each of the epithelial cell suspension was 2000 J. Six to thirty-nine percent of the cells were dead immediately after irradiation. Surviving cells, cultured for 15 days, showed decreased attachment and failed to grow. These preliminary results suggest that the Nd:YAG laser may be used during cataract surgery to prevent subsequent lens epithelial cell proliferation and the resulting vision reduction and glare.

  3. Low Power Laser Irradiation Stimulates the Proliferation of Adult Human Retinal Pigment Epithelial Cells in Culture

    PubMed Central

    Song, Qing; Uygun, Basak; Banerjee, Ipsita; Nahmias, Yaakov; Zhang, Quan; Berthiaume, François; Latina, Mark; Yarmush, Martin L.

    2015-01-01

    We investigated the effects of low power laser irradiation on the proliferation of retinal pigment epithelial (RPE) cells. Adult human RPE cells were artificially pigmented by preincubation with sepia melanin, and exposed to a single sublethal laser pulse (590 nm, 1 µs, <200 mJ/cm2). DNA synthesis, cell number, and growth factor activity in irradiated RPE cells were subsequently monitored. The effect of sublethal laser irradiation on the “wound” healing response of an RPE monolayer in an in vitro scratch assay was also investigated. Single pulsed laser irradiation increased DNA synthesis in pigmented RPE cells measured 6 h post-treatment. In the scratch assay, laser irradiation increased the rates of cell proliferation and wound closure. Conditioned medium, collected 48 h following laser treatment, increased cell proliferation of unirradiated cells. Irradiation increased RPE cell secretion of platelet-derived growth factor (PDGF)-B chain, and increased mRNA levels of several growth factors and their receptors, including PDGF, transforming growth factor-β1, basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor, as well as heat shock proteins. This demonstrates, for the first time, that low power single pulsed laser irradiation stimulates the proliferation of RPE cells, and upregulates growth factors that are mitogenic for RPE cells. PMID:26740823

  4. Optimised laser microdissection of the human ocular surface epithelial regions for microarray studies

    PubMed Central

    2013-01-01

    Background The most important challenge of performing insitu transcriptional profiling of the human ocular surface epithelial regions is obtaining samples in sufficient amounts, without contamination from adjacent tissue, as the region of interest is microscopic and closely apposed to other tissues regions. We have effectively collected ocular surface (OS) epithelial tissue samples from the Limbal Epithelial Crypt (LEC), limbus, cornea and conjunctiva of post-mortem cadaver eyes with laser microdissection (LMD) technique for gene expression studies with spotted oligonucleotide microarrays and Gene 1.0 ST arrays. Methods Human donor eyes (4 pairs for spotted oligonucleotide microarrays, 3 pairs for Gene 1.0 ST arrays) consented for research were included in this study with due ethical approval of the Nottingham Research Ethics Committee. Eye retrieval was performed within 36 hours of post-mortem period. The dissected corneoscleral buttons were immersed in OCT media and frozen in liquid nitrogen and stored at −80°C till further use. Microscopic tissue sections of interest were taken on PALM slides and stained with Toluidine Blue for laser microdissection with PALM microbeam systems. Optimisation of the laser microdissection technique was crucial for efficient and cost effective sample collection. Results The starting concentration of RNA as stipulated by the protocol of microarray platforms was taken as the cut-off concentration of RNA samples in our studies. The area of LMD tissue processed for spotted oligonucleotide microarray study ranged from 86,253 μm2 in LEC to 392,887 μm2 in LEC stroma. The RNA concentration of the LMD samples ranged from 22 to 92 pg/μl. The recommended starting concentration of the RNA samples used for Gene 1.0 ST arrays was 6 ng/5 μl. To achieve the desired RNA concentration the area of ocular surface epithelial tissue sample processed for the Gene 1.0 ST array experiments was approximately 100,0000 μm2 to 130,0000 μm2. RNA

  5. In vitro effect of phototherapy with low-intensity laser on HSV-1 and epithelial cells

    NASA Astrophysics Data System (ADS)

    Eduardo, Fernanda P.; Mehnert, Dolores U.; Monezi, Telma A.; Zezell, Denise M.; Schubert, Mark M.; Eduardo, Carlos P.; Marques, Márcia M.

    2007-02-01

    The effects of phototherapy on herpes lesions have been clinically demonstrated by either preventing the lesion formation or speeding their repair. The aim of this in vitro study was analyze the effect of phototherapy on epithelial cells and HSV-1 in culture. Cultures of HSV-1 and epithelial cells (Vero cell line) were used. The irradiations were done using a GaAlAs laser (660 e 780 nm, 4.0 mm2). One, two and three irradiations with 6 h-intervals were done. The experimental groups were: Control: non-irradiated; 660 nm and 3 J/cm2 (2.8 sec); 660 nm and 5 J/cm2 (3.8 sec); 780 nm and 3 J/cm2 (1.9 sec), and 780 nm and 5 J/cm2 (2.5 sec). The HSV-1 cytopatic effect and the cell viability of irradiated cultures and controls were analyzed in four different conditions: irradiation of non-infected epithelial cells; epithelial cells irradiated prior infection; virus irradiated prior infection; irradiation of HSV infected cells. The mitochondrial activity and cytopathic effects were assessed. The number of irradiations influenced the cell growth positively and proportionally, except for the 660 nm/ 3 J/cm2 group. Any variation in cytopathic effects was observed amongst the experimental groups. The viability of infected cells prior irradiation was significantly higher than that of non-irradiated cultures when 2 irradiations were done. Under the experimental conditions of this study we concluded that phototherapy is capable of enhancing epithelial cell growth and prolonging cell viability of HSV-1 infected cells. Positive benefits of phototherapy could be resultant from prolongation of infected cells viability, corroborating with host defenses.

  6. [Epithelial complications of sub-flap intrastromal photo-kerato ablation for correction of ametropia: causes, therapy, prophylaxis].

    PubMed

    Sheludchenko, V M; Smirennaia, E V

    2002-01-01

    The causes of epithelial complications are evaluated from clinical viewpoint and approaches to their elimination in laser operations are developed. The study included analysis of 3227 intrastromal ablation operations performed by the LASIK and REIK methods in 1725 patients with myopia (spheroequivalent -6.47 +/- 2.23 diopters) and hypermetropia (spheroequivalent +4.57 +/- 1.88 diopters). Laser keratoablation was carried out on an EC 5000 device (Nidek, Japan). Lamellar keratomileusis was carried out with a Hansatome Chiron Vision 230 HT-TM microkeratotome (USA). The incidence of epithelial complications was 5.2%. Intraoperative complications occurred in 3.2% cases. Corneal erosions of 1 x 3 mm were responsible for 51.2% complications, extensive erosions for 18.4%, horizontal ruptures of the epithelium for 22.4%, and stretching of epithelial plast for 9.8% complications. Other complications were epitheliopathy (6 cases), growth of epithelium under corneal flap (0.7%), and "dry islets" in the epithelium (22%). The probable causes of epithelial complications were microkeratotome design, toxic effects of anesthetics, congenital desmosomopathy, and insufficient adaptation of corneal flap. Prevention of complications should consist in additional protection of the epithelium before and after the operation. The protection can be realized by using low-toxic antibiotics, viscoelastic liquids during performance of the lamellar section of the cornea, soft contact lenses, tear substitutes, and lacrimal film stabilizers during the early postoperative period. PMID:12226970

  7. The Combination of Laser Therapy and Metal Nanoparticles in Cancer Treatment Originated From Epithelial Tissues: A Literature Review.

    PubMed

    Fekrazad, Reza; Naghdi, Nafiseh; Nokhbatolfoghahaei, Hanieh; Bagheri, Hossein

    2016-01-01

    Several methods have been employed for cancer treatment including surgery, chemotherapy and radiation therapy. Today, recent advances in medical science and development of new technologies, have led to the introduction of new methods such as hormone therapy, Photodynamic therapy (PDT), treatments using nanoparticles and eventually combinations of lasers and nanoparticles. The unique features of LASERs such as photo-thermal properties and the particular characteristics of nanoparticles, given their extremely small size, may provide an interesting combined therapeutic effect. The purpose of this study was to review the simultaneous application of lasers and metal nanoparticles for the treatment of cancers with epithelial origin. A comprehensive search in electronic sources including PubMed, Google Scholar and Science Direct was carried out between 2000 and 2013. Among the initial 400 articles, 250 articles applied nanoparticles and lasers in combination, in which more than 50 articles covered the treatment of cancer with epithelial origin. In the future, the combination of laser and nanoparticles may be used as a new or an alternative method for cancer therapy or diagnosis. Obviously, to exclude the effect of laser's wavelength and nanoparticle's properties more animal studies and clinical trials are required as a lack of perfect studies. PMID:27330701

  8. In vivo gene expression profiling of human intestinal epithelial cells: analysis by laser microdissection of formalin fixed tissues

    PubMed Central

    George, Michael D; Wehkamp, Jan; Kays, Robert J; Leutenegger, Christian M; Sabir, Sadiah; Grishina, Irina; Dandekar, Satya; Bevins, Charles L

    2008-01-01

    Background The small intestinal epithelium mediates vital functions of nutrient absorption and host defense. The spatial organization of the epithelial cells along the crypt-villus axis segregates them into regions of specialized function. However, the differences in transcriptional programming and the molecular machinery that governs the migration, adhesion, and differentiation of intestinal epithelial cell lineages in humans remain under-explored. To increase our understanding of these mechanisms, we have evaluated gene expression patterns of ileal epithelial cells isolated by laser capture microdissection from either the villus epithelial or crypt cell regions of healthy human small intestinal mucosa. Expression profiles in villus and crypt epithelium were determined by DNA microarray, quantitative real-time PCR, and immunohistochemistry based methods. The expression levels of selected epithelial biomarkers were also compared between gastrointestinal tissues. Results Previously established biomarkers as well as a novel and distinct set of genes believed to be linked to epithelial cell motility, adhesion, and differentiation were found to be enriched in each of the two corresponding cell populations (GEO accession: GSE10629). Additionally, high baseline expression levels of innate antimicrobials, alpha defensin 5 (HD5) and regenerating islet-derived 3 alpha (Reg3A), were detected exclusively within the small bowel crypt, most notably in the ileum in comparison to other sites along the gastrointestinal tract. Conclusion The elucidation of differential gene expression patterns between crypt and villus epithelial cell lineages in human ileal tissue provides novel insights into the molecular machinery that mediates their functions and spatial organization. Moreover, our findings establish an important framework of knowledge for future investigations of human gastrointestinal diseases. PMID:18457593

  9. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    NASA Astrophysics Data System (ADS)

    Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.

    2013-05-01

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.

  10. Laser phototherapy triggers the production of reactive oxygen species in oral epithelial cells without inducing DNA damage.

    PubMed

    Dillenburg, Caroline Siviero; Almeida, Luciana Oliveira; Martins, Manoela Domingues; Squarize, Cristiane Helena; Castilho, Rogerio Moraes

    2014-04-01

    Laser phototherapy (LPT) is widely used in clinical practice to accelerate healing. Although the use of LPT has advantages, the molecular mechanisms involved in the process of accelerated healing and the safety concerns associated with LPT are still poorly understood. We investigated the physiological effects of LPT irradiation on the production and accumulation of reactive oxygen species (ROS), genomic instability, and deoxyribose nucleic acid (DNA) damage in human epithelial cells. In contrast to a high energy density (20  J/cm²), laser administered at a low energy density (4  J/cm²) resulted in the accumulation of ROS. Interestingly, 4  J/cm² of LPT did not induce DNA damage, genomic instability, or nuclear influx of the BRCA1 DNA damage repair protein, a known genome protective molecule that actively participates in DNA repair. Our results suggest that administration of low energy densities of LPT induces the accumulation of safe levels of ROS, which may explain the accelerated healing results observed in patients. These findings indicate that epithelial cells have an endowed molecular circuitry that responds to LPT by physiologically inducing accumulation of ROS, which triggers accelerated healing. Importantly, our results suggest that low energy densities of LPT can serve as a safe therapy to accelerate epithelial healing. PMID:24781593

  11. Fluorescence and laser photon counting: measurements of epithelial [Ca2+]i or [Na+]i with ciliary beat frequency.

    PubMed

    Mao, H; Wong, L B

    1998-01-01

    We describe a system we developed that enabled simultaneous measurements of either epithelial calcium ion concentration ([Ca2+]i) or sodium ion concentration ([Na+]i) with the ciliary beat frequency (CBF) in native ciliated epithelia using either Fura-2 (AM) or SBFI (AM) ratiometric fluorescence photon counting along with nonstationary laser light scattering. Studies were performed using native epithelial tissues obtained from ovine tracheae. The dynamic range of the laser light-scattering system was determined by a simulated light "beating" experiment. The nonstationary CBF was demonstrated by the time-frequency analysis of the raw photon count sequences of backscattered heterodyne photons from cultured and native epithelia. Calibrations of calcium and sodium ion concentrations were performed using the respective Fura-2 and SBFI impermanent salts as well as in native epithelia. The cumulative responses of 10(-6), 10(-5), and 10(-4) M nifedipine on [Ca2+]i together with the CBF as well as the cumulative responses of 10(-5), 10(-4), and 10(-3) M amiloride on [Na+]i together with the CBF were also determined. Nifedipine decreased [Ca2+]i but had no effect on CBF. Amiloride decreased [Na+]i and CBF. Stimulation of CBF corresponded with either an increase of [Na+]i or an increase of [Ca2+]i. Decreases of [Na+]i or substantial decreases of [Ca2+]i were associated with decreases in the CBF. These data demonstrate the utility of this system for investigating the regulatory mechanisms of intracellular ions dynamics and the CBF in native epithelia. PMID:9662158

  12. Irradiation with a low-level diode laser induces the developmental endothelial locus-1 gene and reduces proinflammatory cytokines in epithelial cells.

    PubMed

    Fujimura, Takeki; Mitani, Akio; Fukuda, Mitsuo; Mogi, Makio; Osawa, Kazuhiro; Takahashi, Shinko; Aino, Makoto; Iwamura, Yuki; Miyajima, Shinichi; Yamamoto, Hiromitsu; Noguchi, Toshihide

    2014-05-01

    We demonstrated previously that low-level diode laser irradiation with an indocyanine green-loaded nanosphere coated with chitosan (ICG-Nano/c) had an antimicrobial effect, and thus could be used for periodontal antimicrobial photodynamic therapy (aPDT). Since little is known about the effects of aPDT on periodontal tissue, we here investigated the effect of low-level laser irradiation, with and without ICG-Nano/c, on cultured epithelial cells. Human oral epithelial cells were irradiated in a repeated pulse mode (duty cycle, 10 %; pulse width, 100 ms; peak power output, 5 W). The expression of the developmental endothelial locus 1 (Del-1), interleukin-6 (IL-6), IL-8, and the intercellular adhesion molecule-1 (ICAM-1) were evaluated in Ca9-22 cells stimulated by laser irradiation and Escherichia coli-derived lipopolysaccharide (LPS). A wound healing assay was carried out on SCC-25 cells irradiated by diode laser with or without ICG-Nano/c. The mRNA expression of Del-1, which is known to have anti-inflammatory activity, was significantly upregulated by laser irradiation (p < 0.01). Concurrently, LPS-induced IL-6 and IL-8 expression was significantly suppressed in the LPS + laser group (p < 0.01). ICAM-1 expression was significantly higher in the LPS + laser group than in the LPS only or control groups. Finally, compared with the control, the migration of epithelial cells was significantly increased by diode laser irradiation with or without ICG-Nano/c. These results suggest that, in addition to its antimicrobial effect, low-level diode laser irradiation, with or without ICG-Nano/c, can suppress excessive inflammatory responses via a mechanism involving Del-1, and assists in wound healing. PMID:24197516

  13. STR profiling of epithelial cells identified by X/Y-FISH labelling and laser microdissection using standard and elevated PCR conditions.

    PubMed

    Lynch, Laura; Gamblin, Amelia; Vintiner, Sue; Simons, Joanne L

    2015-05-01

    During the investigation of allegations of sexual assault, samples are frequently encountered that contain DNA from a female and a male donor. These may represent contributions of DNA from the complainant and potentially, the offender. Many semen stained samples successfully undergo DNA analysis and interpretation using a differential extraction method that separates sperm from the epithelial cells present in the stain. However, for those mixed cell samples that contain only epithelial cells, separation of any male cells from female cells is problematic. This paper describes the application of fluorescent in situ hybridisation (FISH) for the gender identification of epithelial cells and subsequent recovery of target cells using laser microdissection (LMD). The profiling results obtained from samples of known cell numbers using the Identifiler™ multiplex at standard 28-cycle PCR conditions and, when cell numbers are low, the SGM Plus™ multiplex at elevated 34-cycle PCR conditions (also known as Low Copy Number DNA analysis (LCN)) are described. PMID:25555139

  14. Combining Laser Microsurgery and Finite Element Modeling to Assess Cell-Level Epithelial Mechanics

    PubMed Central

    Hutson, M. Shane; Veldhuis, J.; Ma, Xiaoyan; Lynch, Holley E.; Cranston, P. Graham; Brodland, G. Wayne

    2009-01-01

    Abstract Laser microsurgery and finite element modeling are used to determine the cell-level mechanics of the amnioserosa—a morphogenetically crucial epithelium on the dorsal surface of fruit fly embryos (Drosophila melanogaster). In the experiments, a tightly focused laser ablates a subcellular hole (1 μm in diameter) that passes clean through the epithelium. The surrounding cells recoil from the wound site with a large range of initial recoil velocities. These depend on the embryo's developmental stage and the subcellular wound site. The initial recoil (up to 0.1 s) is well reproduced by a base finite element model, which assumes a uniform effective viscosity inside the cells, a constant tension along each cell-cell boundary, and a large, potentially anisotropic, far-field stress—one that far exceeds the stress equivalent of the cell-edge tensions. After 0.1 s, the experimental recoils slow dramatically. This observation can be reproduced by adding viscoelastic rods along cell edges or as a fine prestressed mesh parallel to the apical and basal membranes of the cell. The mesh also reproduces a number of double-wounding experiments in which successive holes are drilled in a single cell. PMID:20006944

  15. Excimer laser photorefractive surgery of the cornea

    NASA Astrophysics Data System (ADS)

    Gaster, Ronald N.

    1998-09-01

    The 193 nm argon fluoride (ArF) excimer laser can effectively be used to change the radius of curvature of the cornea and thus alter the refractive state of the eye. This change allows myopic (nearsighted) patients to see well with less dependence on glasses or contact lenses. The two major techniques of laser refractive surgery currently in effect in the United States are photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). This paper will discuss these refractive cornea surgical techniques.

  16. Helium-Neon Laser Irradiation Promotes the Proliferation and Migration of Human Epidermal Stem Cells In Vitro: Proposed Mechanism for Enhanced Wound Re-epithelialization

    PubMed Central

    Liao, Xuan; Xie, Guang-Hui; Cheng, Biao; Li, Sheng-Hong; Xie, Shan; Xiao, Li-Ling; Fu, Xiao-Bing

    2014-01-01

    Abstract Objective: The present study was conducted to investigate the effects of helium-neon (He-Ne) laser irradiation on the proliferation, migration, and differentiation of cultured human epidermal stem cells (ESCs). Background data: A He-Ne laser with a wavelength of 632.8 nm is known to have photobiological effects, and is widely used for accelerating wound healing; however, the cellular mechanisms involved have not been completely understood. Methods: The ESCs were prepared from human foreskin, and irradiated by using He-Ne laser at 632.8 nm with 2 J/cm2. The ESC proliferation, migration, and differentiation were examined by using XTT assay, scratch assay, and flow cytometry technology, respectively. The phosphorylation of extracellular signal-regulated kinases (ERK) was analyzed by using Western blotting. Results: He-Ne laser irradiation markedly promoted cell proliferation and migration accompanied by an increase in the phosphorylation of ERK, but did not significantly influence cell differentiation. Conclusion: Our data indicated that photostimulation with a He-Ne laser resulted in a significant increase in human ESC proliferation and migration in vitro, which might contribute, at least partially, to accelerated wound re-epithelialization by low-level laser therapy. PMID:24661127

  17. Femtosecond Lasers in Ophthalmology: Surgery and Imaging

    NASA Astrophysics Data System (ADS)

    Bille, J. F.

    Ophthalmology has traditionally been the field with prevalent laser applications in medicine. The human eye is one of the most accessible human organs and its transparency for visible and near-infrared light allows optical techniques for diagnosis and treatment of almost any ocular structure. Laser vision correction (LVC) was introduced in the late 1980s. Today, the procedural ease, success rate, and lack of disturbing side-effects in laser assisted in-situ keratomileusis (LASIK) have made it the most frequently performed refractive surgical procedure (keratomileusis(greek): cornea-flap-cutting). Recently, it has been demonstrated that specific aspects of LVC can take advantage of unique light-matter interaction processes that occur with femtosecond laser pulses.

  18. F 2 excimer laser (157 nm) radiation modification and surface ablation of PHEMA hydrogels and the effects on bioactivity: Surface attachment and proliferation of human corneal epithelial cells

    NASA Astrophysics Data System (ADS)

    Zainuddin; Chirila, Traian V.; Barnard, Zeke; Watson, Gregory S.; Toh, Chiong; Blakey, Idriss; Whittaker, Andrew K.; Hill, David J. T.

    2011-02-01

    Physical and chemical changes at the surface of poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels modified by ablation with an F 2 excimer laser were investigated experimentally. An important observation was that only the outer exposed surface layers of the hydrogel were affected by the exposure to 157 nm radiation. The effect of the surface changes on the tendency of cells to adhere to the PHEMA was also investigated. A 0.5 cm 2 area of the hydrogel surfaces was exposed to laser irradiation at 157 nm to fluences of 0.8 and 4 J cm -2. The changes in surface topography were analysed by light microscopy and atomic force microscopy, while the surface chemistry was characterized by attenuated total reflection infrared and X-ray photoelectron spectroscopies. Cell-interfacial interactions were examined based on the proliferation of human corneal limbal epithelial (HLE) cells cultured on the laser-modified hydrogels, and on the unexposed hydrogels and tissue culture plastic for comparison. It was observed that the surface topography of laser-exposed hydrogels showed rippled patterns with a surface roughness increasing at the higher exposure dose. The changes in surface chemistry were affected not only by an indirect effect of hydrogen and hydroxyl radicals, formed by water photolysis, on the PHEMA, but also by the direct action of laser radiation on PHEMA if the surface layers of the gel become depleted of water. The laser treatment led to a change in the surface characteristics, with a lower concentration of ester side-chains and the formation of new oxygenated species at the surface. The surface also became more hydrophobic. Most importantly, the surface chemistry and the newly created surface topographical features were able to improve the attachment, spreading and growth of HLE cells.

  19. The use of laser microdissection in the identification of suitable reference genes for normalization of quantitative real-time PCR in human FFPE epithelial ovarian tissue samples.

    PubMed

    Cai, Jing; Li, Tao; Huang, Bangxing; Cheng, Henghui; Ding, Hui; Dong, Weihong; Xiao, Man; Liu, Ling; Wang, Zehua

    2014-01-01

    Quantitative real-time PCR (qPCR) is a powerful and reproducible method of gene expression analysis in which expression levels are quantified by normalization against reference genes. Therefore, to investigate the potential biomarkers and therapeutic targets for epithelial ovarian cancer by qPCR, it is critical to identify stable reference genes. In this study, twelve housekeeping genes (ACTB, GAPDH, 18S rRNA, GUSB, PPIA, PBGD, PUM1, TBP, HRPT1, RPLP0, RPL13A, and B2M) were analyzed in 50 ovarian samples from normal, benign, borderline, and malignant tissues. For reliable results, laser microdissection (LMD), an effective technique used to prepare homogeneous starting material, was utilized to precisely excise target tissues or cells. One-way analysis of variance (ANOVA) and nonparametric (Kruskal-Wallis) tests were used to compare the expression differences. NormFinder and geNorm software were employed to further validate the suitability and stability of the candidate genes. Results showed that epithelial cells occupied a small percentage of the normal ovary indeed. The expression of ACTB, PPIA, RPL13A, RPLP0, and TBP were stable independent of the disease progression. In addition, NormFinder and geNorm identified the most stable combination (ACTB, PPIA, RPLP0, and TBP) and the relatively unstable reference gene GAPDH from the twelve commonly used housekeeping genes. Our results highlight the use of homogeneous ovarian tissues and multiple-reference normalization strategy, e.g. the combination of ACTB, PPIA, RPLP0, and TBP, for qPCR in epithelial ovarian tissues, whereas GAPDH, the most commonly used reference gene, is not recommended, especially as a single reference gene. PMID:24776823

  20. Changes in F-actin organization induced by hard metal particle exposure in rat pulmonary epithelial cells using laser scanning confocal microscopy.

    PubMed

    Antonini, J M; Starks, K; Roberts, J R; Millecchia, L; Yang, H M; Rao, K M

    2000-01-01

    Chronic inhalation of hard metal (WC-Co) particles causes alveolitis and the eventual development of pulmonary fibrosis. The initial inflammatory response includes a change in the alveolar epithelial cell-capillary barrier, which has been shown to be regulated by the state of assembly and organization of the actin cytoskeletal network. The objective of this study was to evaluate the effect WC-Co particles have on F-actin organization of lung epithelial cells in an in vitro culture system. Rat lung epithelial (L2) cells were exposed to 5, 25, and 100 microg/mL of WC-Co particles, as well as the individual components (Co and WC) of the hard metal mixture particles for 24 h. The effect on F-actin organization was visualized by laser scanning confocal microscopy (LSCM) following Bodipy-Phallacidin staining. Minimal changes in the F-actin microfilaments of L2 cells were observed by LSCM after exposure to WC and WC-Co at 5 and 25 microg/mL, while at 100 microg/mL, there was a noticeable disruption in the uniform distribution of L2 cell F-actin microfilaments. After exposure to Co, a dose-dependent change in the F-actin organization of the L2 cells was observed. Little change in F-actin assembly was observed after treatment with 5 microg/mL of Co (the concentration equivalent to the 5% amount of Co commonly present in 100 microg/mL of the WC-Co sample mixture). However, at 100 microg/mL of Co, the microfilaments aggregated into homogeneous masses within the cells, and a significant loss in the organization of L2 F-actin was observed. These dramatic alterations in F-actin organization seen after exposure to the higher doses of Co were attributed to an increase in L2 cell injury as measured by lactate dehydrogenase and trypan blue exclusion. We conclude the pulmonary response evoked in the lung by inhalation of high levels of WC-Co particles is unlikely due to alterations in the F-actin microfilaments of lung-epithelial cells. PMID:10900403

  1. [Is there a future for the Excimer laser in refractive surgery?].

    PubMed

    Pouliquen, Y; Hanna, K; Waring, G; Savoldelli, M

    1990-02-01

    The refractive surgery concerns all the surgical procedures implicated in the refractive power change of the cornea. Its clinical results are just known, and a new physical procedure is becoming capable to replace surgery: the Excimer laser. Without any instrumental contact with the corneal surface, the laser beam is able to remodel the corneal tissue, and to treat astigmatism, myopia, hypermetropia. Millions of people could be treated by such a laser, and could leave their glasses. Biological effects on rabbit and monkeys are presented. An argon fluoride excimer laser (193 nm) with a moving slit delivery system was used to perform anterior myopic keratomileusis in both eyes of 37 rabbits and 15 monkeys. Histological analysis of the corneas was made after ablation and at intervals up to 20 months. By slit examination at the longer follow up time, 60% of treated rabbits and 40% of treated monkeys keep a clear cornea, but the others had central spotty subepithelial haze. Light and electron microscopy documented corneal healing. In the clear corneas a good reconstitution of the epithelium, its basal lamina was observed, and anterior stromal corneas contained few active fibrocytes with a good preservation of the connective lamellar structure. On the contrary, in the cornea with opacification focal areas of 20 microns thick subepithelial scarring were present and the interface between epithelial cells and anterior stroma remained disturbed by incomplete, disrupted or duplicated basal lamina. Differences between the responses of monkeys, rabbits corneas to the same photoablation procedure remain unclear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2115392

  2. Lasers.

    ERIC Educational Resources Information Center

    Schewe, Phillip F.

    1981-01-01

    Examines the nature of laser light. Topics include: (1) production and characteristics of laser light; (2) nine types of lasers; (3) five laser techniques including holography; (4) laser spectroscopy; and (5) laser fusion and other applications. (SK)

  3. Bilateral diffuse lamellar keratitis following consecutive selective laser trabeculoplasty in LASIK patient.

    PubMed

    Holz, Huck; Pirouzian, Amir

    2010-05-01

    A 48-year-old man with a history of myopic laser in situ keratomileusis (LASIK) had selective laser trabeculoplasty (SLT) for the treatment of glaucoma in the right eye. He subsequently developed grade 2 diffuse lamellar keratitis (DLK). He then elected to have SLT in the left eye and developed grade 1 DLK. To our knowledge, this is the first report of bilateral consecutive late postoperative DLK following SLT after LASIK. PMID:20457380

  4. The Impact of Flap Creation Methods for Sub-Bowman’s Keratomileusis (SBK) on the Central Thickness of Bowman’s Layer

    PubMed Central

    Hu, Liang; Zhuang, Xiran; Peng, Mei; Hu, Di; Liu, Jing; Wang, Jianhua; Qu, Jia; Lu, Fan

    2015-01-01

    Purpose To determine the impact of flap creation methods for sub-Bowman’s keratomileusis (SBK) on central Bowman’s layer thickness. Methods SBK flaps were made by Moria microkeratome for 20 subjects and by femtosecond (FEMTO) laser for 21 subjects. Corneal sublayer thicknesses were measured by ultra-high resolution optical coherence tomography before SBK and at 1 day, 1 week, 2 weeks, and 1 month afterwards. Each subject was imaged twice on each visit. Thicknesses of central epithelium, Bowman’s layer, flap, and total cornea were calculated using a custom-made automated image processing algorithm. The repeatability of sublayer thickness measurements was tested by the intraclass correlation coefficient (ICC) and by the coefficient of repeatability (CoR) at 1 week post-SBK. Results ICCs of the Moria and FEMTO groups were ≥0.959 and ≥0.961 respectively for all sublayer measurements. The segmentation CoRs were less than 6.78% and 5.63% respectively. For both groups, microdistortions were present in the epithelium and Bowman’s layer after SKB. The flap thickness of the Moria group was 9.8 μm (95% confidence interval: 4.8 – 14.8μm) thinner than the FEMTO group one day after SBK (independent samples t-test, P < 0.05). Bowman’s layer became thicker by 1.6 ± 1.1 μm and 1.7 ± 1.6 μm one day post-SBK for the Moria and FEMTO groups (repeated ANOVA, P < 0.05) and then remained stable. Corneal and sublayer thickness were similar between the two groups. Conclusions Central Bowman’s layer thickness increased 1 day post-SBK. Flap creation by Moria microkeratome and femtosecond laser did not have significantly different impacts on Bowman’s layer thickness following SBK. Trial Registration Chinese Clinical Trial Registry (ChiCTR) NO: ChiCTR-OCH-14004525 PMID:25938492

  5. Role of epithelial hyperplasia in regression following photorefractive keratectomy.

    PubMed Central

    Gauthier, C. A.; Holden, B. A.; Epstein, D.; Tengroth, B.; Fagerholm, P.; Hamberg-Nyström, H.

    1996-01-01

    AIM--To determine the relation between epithelial hyperplasia and regression of effect after photorefractive keratectomy (PRK). METHODS--Seventy unilaterally treated patients with PRK were examined. All eyes had been treated with the Summit excimer laser 27 (SD 7) months previously with zone diameters of 4.1 to 5.0 mm. The untreated fellow eyes served as controls. Epithelial thickness was measured centrally with a thin slit optical pachometer and manifest subjective refraction was performed. RESULTS--The epithelium was 21% thicker in the treated eye (p < 0.0001). The relation between refractive regression and epithelial hyperplasia was significant (r = 0.41; p < 0.001). CONCLUSIONS--Epithelial hyperplasia after PRK correlated with the myopic shift (including hyperopia reduction) after treatment with the Summit laser. A model is proposed suggesting that both subepithelial and epithelial layers contribute to regression in the Summit treated eyes with 18 microns of epithelial hyperplasia contributing each dioptre of regression. PMID:8759267

  6. Effects of Laser Printer–Emitted Engineered Nanoparticles on Cytotoxicity, Chemokine Expression, Reactive Oxygen Species, DNA Methylation, and DNA Damage: A Comprehensive in Vitro Analysis in Human Small Airway Epithelial Cells, Macrophages, and Lymphoblasts

    PubMed Central

    Pirela, Sandra V.; Miousse, Isabelle R.; Lu, Xiaoyan; Castranova, Vincent; Thomas, Treye; Qian, Yong; Bello, Dhimiter; Kobzik, Lester; Koturbash, Igor; Demokritou, Philip

    2015-01-01

    Background Engineered nanomaterials (ENMs) incorporated into toner formulations of printing equipment become airborne during consumer use. Although information on the complex physicochemical and toxicological properties of both toner powders and printer-emitted particles (PEPs) continues to grow, most toxicological studies have not used the actual PEPs but rather have primarily used raw toner powders, which are not representative of current exposures experienced at the consumer level during printing. Objectives We assessed the biological responses of a panel of human cell lines to PEPs. Methods Three physiologically relevant cell lines—small airway epithelial cells (SAECs), macrophages (THP-1 cells), and lymphoblasts (TK6 cells)—were exposed to PEPs at a wide range of doses (0.5–100 μg/mL) corresponding to human inhalation exposure durations at the consumer level of 8 hr or more. Following treatment, toxicological parameters reflecting distinct mechanisms were evaluated. Results PEPs caused significant membrane integrity damage, an increase in reactive oxygen species (ROS) production, and an increase in pro-inflammatory cytokine release in different cell lines at doses equivalent to exposure durations from 7.8 to 1,500 hr. Furthermore, there were differences in methylation patterns that, although not statistically significant, demonstrate the potential effects of PEPs on the overall epigenome following exposure. Conclusions The in vitro findings obtained in this study suggest that laser printer–emitted engineered nanoparticles may be deleterious to lung cells and provide preliminary evidence of epigenetic modifications that might translate to pulmonary disorders. Citation Pirela SV, Miousse IR, Lu X, Castranova V, Thomas T, Qian Y, Bello D, Kobzik L, Koturbash I, Demokritou P. 2016. Effects of laser printer–emitted engineered nanoparticles on cytotoxicity, chemokine expression, reactive oxygen species, DNA methylation, and DNA damage: a comprehensive in

  7. Use of laser capture microdissection for the assessment of equine lamellar basal epithelial cell signalling in the early stages of laminitis

    PubMed Central

    Leise, B. S.; Watts, M.; Roy, S.; Yilmaz, S.; Alder, H.; Belknap, J. K.

    2016-01-01

    Summary Reason for performing study Dysadhesion of the laminar basal epithelial cells (LBEC) from the underlying dermis is the central event leading to structural failure in equine laminitis. Although many studies of sepsis-related laminitis have reported multiple events occurring throughout the lamellar tissue, there is minimal information regarding signalling events occurring specifically in the LBEC. Objectives To determine the signalling events in the LBECs during the early stages of carbohydrate induced laminitis. Study Design Experimental study. Methods Eight horses were given an overload of carbohydrate (corn starch mixture, CHO) via nasogastric tube. Prior to administration of CHO, lamellar biopsies were taken from the left fore foot (CON). Biopsies were taken from the left hind foot at the onset of fever (DEV) and from the right fore foot at the onset of lameness (OG1). Laminar basal epithelial cells (LBECs) were isolated from cryosections using a LCM microscope. Next generation sequencing (RNA-Seq) was used to identify transcripts expressed in the LBECs for each time point and bioinformatic analysis was performed with thresholds for between group comparisons set at a greater than 2-fold change and p-value ≤0.05. Results Forty genes (22 increased/18 decreased) were significantly different from DEV time vs. CON and 107 genes (57 increased/50 decreased) were significantly different from OG1 time vs. CON. Significant increases in inflammatory genes were present in addition to significantly altered expression of genes related to extracellular matrix composition, stability and turnover. Conclusions Inflammatory response and extracellular matrix regulation signalling was strongly represented at the DEV and OG1 times. These results indicate that the LBEC is not only a casualty but also an active participant in lamellar events leading to structural failure of the digital lamellae in equine laminitis. PMID:24750316

  8. Exposing human retinal pigmented epithelial cells to red light in vitro elicits an adaptive response to a subsequent 2-μm laser challenge

    NASA Astrophysics Data System (ADS)

    Schuster, K. J.; Estlack, L. E.; Wigle, J. C.

    2013-03-01

    The objective of this study was to elucidate cellular mechanisms of protection against laser-induced thermal killing utilizing an in vitro retina model. When exposed to a 1-sec pulse of 2-μm laser radiation 24 hr after illuminating hTERT-RPE cells with red light (preconditioning), the cells are more resistant to thermal challenge than unilluminated controls (adaptive response). Results of efforts to understand the physiology of this effect led us to two genes: Vascular Endothelial Growth Factor C (VEGF-C) and Micro RNA 146a (miR-146a). Transfecting wild type (WT) cells with siRNA for VEGF-C and miR-146a mRNA resulted in knockdown strains (VEGF-C(KD) and miR- 146a(-)) with 10% and 30% (respectively) of the constitutive levels expressed in the WT cells. To induce gene expression, WT or KD cells were preconditioned with 1.44 to 5.40 J/cm2, using irradiances between 0.40 and 1.60 mW/cm2 of either 671-nm (diode) or 637-nm (laser) radiation. Probit analysis was used to calculate threshold damage irradiance, expressed as ED50, between 10 and 100 W/cm2 for the 2-μm laser pulse. In the WT cells there is a significant increase in ED50 (p 0.05) with the maximum response occurring at 2.88 J/cm2 in the preconditioned cells. Neither KD cell strain showed a significant increase in the ED50, although some data suggest the response may just be decreased in the knockdown cells instead of absent. So far the response does not appear to be dependent upon either wavelength (637 vs. 671 nm) or coherence (laser vs. LED), but there is an irradiance dependence.

  9. Finite element model of the temperature increase in excised porcine cadaver iris during direct illumination by femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Sun, Hui; Kurtz, Ronald M.; Juhasz, Tibor

    2012-07-01

    In order to model the thermal effect of laser exposure of the iris during laser corneal surgery, we simulated the temperature increase in porcine cadaver iris. The simulation data for the 60 kHz FS60 Laser showed that the temperature increased up to 1.23°C and 2.45°C (at laser pulse energy 1 and 2 µJ, respectively) by the 24 second procedure time. Calculated temperature profiles show good agreement with data obtained from ex vivo experiments using porcine cadaver iris. Simulation results of different types of femtosecond lasers indicate that the Laser in situ keratomileusis procedure does not present a safety hazard to the iris.

  10. Simulation of the temperature increase in human cadaver retina during direct illumination by 150-kHz femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Sun, Hui; Hosszufalusi, Nora; Mikula, Eric R.; Juhasz, Tibor

    2011-10-01

    We have developed a two-dimensional computer model to predict the temperature increase of the retina during femtosecond corneal laser flap cutting. Simulating a typical clinical setting for 150-kHz iFS advanced femtosecond laser (0.8- to 1-μJ laser pulse energy and 15-s procedure time at a laser wavelength of 1053 nm), the temperature increase is 0.2°C. Calculated temperature profiles show good agreement with data obtained from ex vivo experiments using human cadaver retina. Simulation results obtained for different commercial femtosecond lasers indicate that during the laser in situ keratomileusis procedure the temperature increase of the retina is insufficient to induce damage.

  11. Bovine myocardial epithelial inclusions.

    PubMed

    Baker, D C; Schmidt, S P; Langheinrich, K A; Cannon, L; Smart, R A

    1993-01-01

    Light microscopic, histochemical, immunohistochemical, and ultrastructural methods were used to examine myocardial epithelial masses in the hearts of ten cattle. The tissues consisted of paraffin-embedded or formalin-fixed samples from eight hearts that were being inspected in slaughter houses and from two hearts from calves that died of septicemia. The ages of the cattle ranged from 4 days to 12 years; the breeds were unspecified for all but one Hereford female and the two Holstein calves; and there were three males, four females, and three steers. The masses in these cases were compared with similar appearing lesions found in other animal species. The lesions in the bovine hearts were single to multiple, well circumscribed, found in the left ventricle wall, and composed of squamous to cuboidal epithelial cells that formed tubular, ductular, and acinar structures with lumens that were void or filled with amorphous protein globules. Electron microscopic examination revealed epithelial cells that had sparse apical microvilli, tight apical intercellular junctions, perinuclear bundles of filaments, and rare cilia. Almost half of the bovine epithelial masses (4/9) had occasional diastase-resistant periodic acid-Schiff-positive granules in their cytoplasm, and few had hyaluronidase-resistant alcian blue-positive granules (2/9) or colloidal iron-positive granules (1/9). All myocardial masses had abundant collagen surrounding the tubular and acinar structures, and 2/9 had elastin fibers as well. None of the myocardial masses had Churukian-Schenk or Fontana Masson's silver staining granules in epithelial cells. Immunohistochemically, all bovine myocardial tumors stained positively for cytokeratin (8/8), and occasional masses stained positively for vimentin (3/8) or carcinoembryonic antigen (3/8). None of the masses stained positively for desmin. The myocardial epithelial tumors most likely represent endodermal rests of tissue misplaced during organogenesis. PMID:7680178

  12. The evolution of corneal and refractive surgery with the femtosecond laser.

    PubMed

    Aristeidou, Antonis; Taniguchi, Elise V; Tsatsos, Michael; Muller, Rodrigo; McAlinden, Colm; Pineda, Roberto; Paschalis, Eleftherios I

    2015-01-01

    The use of femtosecond lasers has created an evolution in modern corneal and refractive surgery. With accuracy, safety, and repeatability, eye surgeons can utilize the femtosecond laser in almost all anterior refractive procedures; laser in situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), penetrating keratoplasty (PKP), insertion of intracorneal ring segments, anterior and posterior lamellar keratoplasty (Deep anterior lamellar keratoplasty (DALK) and Descemet's stripping endothelial keratoplasty (DSEK)), insertion of corneal inlays and cataract surgery. As the technology matures, it will push surgical limits and open new avenues for ophthalmic intervention in areas not yet explored. As we witness the transition from femto-LASIK to femto-cataract surgery it becomes obvious that this innovation is here to stay. This article presents some of the most relevant advances of femtosecond lasers to modern corneal and refractive surgery. PMID:26605365

  13. Epithelial hyperplasia, airways —

    Cancer.gov

    Number of respiratory epithelial cells is increased diffusely or focally. Frequently luminal protrusions are observed, sometimes forming papillae. Mucous (goblet) cell metaplastic hyperplasia is a variant, in which the respiratory epithelium of conducting airways is replaced by mucous cells either as a single or a pseudostratified layer.

  14. Angiomyolipoma With Epithelial Cysts.

    PubMed

    LeRoy, Michael A; Rao, Priya

    2016-06-01

    Angiomyolipoma with epithelial cysts is a rare mesenchymal tumor of the kidney that enters in the differential diagnosis of adult cystic renal neoplasms. These tumors demonstrate a slight female predominance and can present either incidentally or with symptoms, commonly flank pain and hematuria. Unlike conventional angiomyolipoma, this variant is characterized grossly by both solid and cystic areas, and histologically by the presence of single or multiple cysts lined by epithelial cells, a subepithelial "cambium-like" layer of small stromal cells with a prominent capillary vasculature, and a thick exterior wall composed of poorly formed fascicles of smooth muscle and thick-walled dysplastic blood vessels. Tumors show a distinct immunohistochemical profile and are often reactive for melanocytic markers (HMB-45 and Melan-A), as well as estrogen receptor and progesterone receptor. These tumors have an indolent clinical course, with no reports of progression or metastasis in reported cases thus far. PMID:27232352

  15. Autokeratomileusis Laser

    NASA Astrophysics Data System (ADS)

    Kern, Seymour P.

    1987-03-01

    Refractive defects such as myopia, hyperopia, and astigmatism may be corrected by laser milling of the cornea. An apparatus combining automatic refraction/keratometry and an excimer type laser for precision reshaping of corneal surfaces has been developed for testing. When electronically linked to a refractometer or keratometer or holographic imaging device, the laser is capable of rapidly milling or ablating corneal surfaces to preselected dioptric power shapes without the surgical errors characteristic of radial keratotomy, cryokeratomileusis or epikeratophakia. The excimer laser simultaneously generates a synthetic Bowman's like layer or corneal condensate which appears to support re-epithelialization of the corneal surface. An electronic feedback arrangement between the measuring instrument and the laser enables real time control of the ablative milling process for precise refractive changes in the low to very high dioptric ranges. One of numerous options is the use of a rotating aperture wheel with reflective portions providing rapid alternate ablation/measurement interfaced to both laser and measurement instrumentation. The need for the eye to be fixated is eliminated or minimized. In addition to reshaping corneal surfaces, the laser milling apparatus may also be used in the process of milling both synthetic and natural corneal inlays for lamellar transplants.

  16. Epithelial Cell Adhesion Molecule

    PubMed Central

    Trzpis, Monika; McLaughlin, Pamela M.J.; de Leij, Lou M.F.H.; Harmsen, Martin C.

    2007-01-01

    The epithelial cell adhesion molecule (EpCAM, CD326) is a glycoprotein of ∼40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally lower level than carcinoma cells. In early studies, EpCAM was proposed to be a cell-cell adhesion molecule. However, recent insights revealed a more versatile role for EpCAM that is not limited only to cell adhesion but includes diverse processes such as signaling, cell migration, proliferation, and differentiation. Cell surface expression of EpCAM may actually prevent cell-cell adhesion. Here, we provide a comprehensive review of the current knowledge on EpCAM biology in relation to other cell adhesion molecules. We discuss the implications of the newly identified functions of EpCAM in view of its prognostic relevance in carcinoma, inflammatory pathophysiology, and tissue development and regeneration as well as its role in normal epithelial homeostasis. PMID:17600130

  17. Femtosecond all-solid-state laser for refractive surgery

    NASA Astrophysics Data System (ADS)

    Zickler, Leander; Han, Meng; Giese, G.'nter; Loesel, Frieder H.; Bille, Josef F.

    2003-06-01

    Refractive surgery in the pursuit of perfect vision (e.g. 20/10) requires firstly an exact measurement of abberations induced by the eye and then a sophisticated surgical approach. A recent extension of wavefront measurement techniques and adaptive optics to ophthalmology has quantitatively characterized the quality of the human eye. The next milestone towards perfect vision is developing a more efficient and precise laser scalpel and evaluating minimal-invasive laser surgery strategies. Femtosecond all-solid-state MOPA lasers based on passive modelocking and chirped pulse amplification are excellent candidates for eye surgery due to their stability, ultra-high intensity and compact tabletop size. Furthermore, taking into account the peak emission in the near IR and diffraction limited focusing abilities, surgical laser systems performing precise intrastromal incisions for corneal flap resection and intrastromal corneal reshaping promise significant improvement over today's Photorefractive Keratectomy (PRK) and Laser Assisted In Situ Keratomileusis (LASIK) techniques which utilize UV excimer lasers. Through dispersion control and optimized regenerative amplification, a compact femtosecond all-solid-state laser with pulsed energy well above LIOB threshold and kHz repetition rate is constructed. After applying a pulse sequence to the eye, the modified corneal morphology is investigated by high resolution microscopy (Multi Photon/SHG Confocal Microscope).

  18. Epithelial hyperplasia, alveoli —

    Cancer.gov

    Solitary or multiple foci of increased cellularity distal to terminal bronchioles. The background of broncho-alveolar architecture remains detectable, and epithelial cells are usually single layered. Round to oval hypertrophic type II pneumocytes with abundant eosinophilic cytoplasm line alveolar walls. In bronchiolar subvariant, also called bronchiolization of alveoli, alveolar walls are lined by cuboidal to columnar cells with features of bronchiolar differentiation, such as formation of cilia, Clara cell resemblance, and presence of mucous granules. Foci of consolidation may indicate early stages of adenoma formation. Macrophages may be present in the alveolar lumens.

  19. Epithelial stem cells.

    PubMed

    Draheim, Kyle M; Lyle, Stephen

    2011-01-01

    It is likely that adult epithelial stem cells will be useful in the treatment of diseases, such as ectodermal dysplasias, monilethrix, Netherton syndrome, Menkes disease, hereditary epidermolysis bullosa, and alopecias. Additionally, other skin problems such as burn wounds, chronic wounds, and ulcers will benefit from stem cell-related therapies. However, there are many questions that need to be answered before this goal can be realized. The most important of these questions is what regulates the adhesion of stem cells to the niche versus migration to the site of injury. We have started to identify the mechanisms involved in this decision-making process. PMID:21618097

  20. Hydraulic fracture during epithelial stretching

    NASA Astrophysics Data System (ADS)

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-03-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells’ cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

  1. Hydraulic fracture during epithelial stretching.

    PubMed

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-03-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics. PMID:25664452

  2. Hydraulic fracture during epithelial stretching

    PubMed Central

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-01-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells’ cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression maneuvers. After pressure equilibration cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics. PMID:25664452

  3. The Recovery of Optical Quality after Laser Vision Correction

    PubMed Central

    Jung, Hyeong-Gi

    2013-01-01

    Purpose To evaluate the optical quality after laser in situ keratomileusis (LASIK) or serial photorefractive keratectomy (PRK) using a double-pass system and to follow the recovery of optical quality after laser vision correction. Methods This study measured the visual acuity, manifest refraction and optical quality before and one day, one week, one month, and three months after laser vision correction. Optical quality parameters including the modulation transfer function, Strehl ratio and intraocular scattering were evaluated with a double-pass system. Results This study included 51 eyes that underwent LASIK and 57 that underwent PRK. The optical quality three months post-surgery did not differ significantly between these laser vision correction techniques. Furthermore, the preoperative and postoperative optical quality did not differ significantly in either group. Optical quality recovered within one week after LASIK but took between one and three months to recover after PRK. The optical quality of patients in the PRK group seemed to recover slightly more slowly than their uncorrected distance visual acuity. Conclusions Optical quality recovers to the preoperative level after laser vision correction, so laser vision correction is efficacious for correcting myopia. The double-pass system is a useful tool for clinical assessment of optical quality. PMID:23908570

  4. [Analysis of images in the prophylaxis and treatment of complications after kerato-refractive excimer laser surgeries].

    PubMed

    Makarov, I A

    2003-01-01

    A total of 236 eyes of patients with myopia and hypermetropia of different severity degrees after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) were observed. The densitometry and planimetry analysis of corneal images, obtained through storing them in the computer memory, was used to evaluate postoperatively the corneal condition. Planimetry was used to forecast the time of epithelization and to assess the efficiency of drug therapy. The optic density was found to increase, after excimer-laser surgeries, in all patients and it depended on a type of refraction and its degree. The optic-density dynamics of corneal images also depended on a degree and type of refraction as well as on a type of drug therapy. Hence, densitometry and planimetry, as objective methods used to follow up the patients after keratorefractive excimer-laser surgeries, make it possible to diagnose early enough the presence of complications related with disorders in transparency and healing of the cornea. PMID:12698885

  5. Theory of epithelial elasticity

    NASA Astrophysics Data System (ADS)

    Krajnc, Matej; Ziherl, Primož

    2015-11-01

    We propose an elastic theory of epithelial monolayers based on a two-dimensional discrete model of dropletlike cells characterized by differential surface tensions of their apical, basal, and lateral sides. We show that the effective tissue bending modulus depends on the apicobasal differential tension and changes sign at the transition from the flat to the fold morphology. We discuss three mechanisms that stabilize the finite-wavelength fold structures: Physical constraint on cell geometry, hard-core interaction between non-neighboring cells, and bending elasticity of the basement membrane. We show that the thickness of the monolayer changes along the waveform and thus needs to be considered as a variable rather than a parameter. Next we show that the coupling between the curvature and the thickness is governed by the apicobasal polarity and that the amplitude of thickness modulation along the waveform is proportional to the apicobasal differential tension. This suggests that intracellular stresses can be measured indirectly by observing easily measurable morphometric parameters. We also study the mechanics of three-dimensional structures with cylindrical symmetry.

  6. Epithelial Sodium Channels in Pulmonary Epithelial Progenitor and Stem Cells

    PubMed Central

    Liu, Yang; Jiang, Bi-Jie; Zhao, Run-Zhen; Ji, Hong-Long

    2016-01-01

    Regeneration of the epithelium of mammalian lungs is essential for restoring normal function following injury, and various cells and mechanisms contribute to this regeneration and repair. Club cells, bronchioalveolar stem cells (BASCs), and alveolar type II epithelial cells (ATII) are dominant stem/progenitor cells for maintaining epithelial turnover and repair. Epithelial Na+ channels (ENaC), a critical pathway for transapical salt and fluid transport, are expressed in lung epithelial progenitors, including club and ATII cells. Since ENaC activity and expression are development- and differentiation-dependent, apically located ENaC activity has therefore been used as a functional biomarker of lung injury repair. ENaC activity may be involved in the migration and differentiation of local and circulating stem/progenitor cells with diverse functions, eventually benefiting stem cells spreading to re-epithelialize injured lungs. This review summarizes the potential roles of ENaC expressed in native progenitor and stem cells in the development and regeneration of the respiratory epithelium. PMID:27570489

  7. Integrins and epithelial cell polarity

    PubMed Central

    Lee, Jessica L.; Streuli, Charles H.

    2014-01-01

    ABSTRACT Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell–matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical–basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity. For further reading, please see related articles: ‘ERM proteins at a glance’ by Andrea McClatchey (J. Cell Sci. 127, 3199–3204). ‘Establishment of epithelial polarity – GEF who's minding the GAP?’ by Siu Ngok et al. (J. Cell Sci. 127, 3205–3215). PMID:24994933

  8. Investigation of the formation mechanism and morphology of the features created in the interior of cornea by femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Guo, Yizang; Vukelic, Sinisa

    2015-03-01

    Laser assisted corneal surgeries often rely on the nonlinear absorption effect of ultrafast lasers to induce features in the interior of the cornea without affecting the surface. In particular, corneal flap formation in femtosecond assisted Laser- Assisted in situ Keratomileusis (LASIK) is based on the bubble creation. This study focuses on the interaction between the tissue and the femtosecond laser. Interior of cornea is treated with tightly focused femtosecond laser pulses. Due to the nature of the process, heating of the tissue within and around the focal volume is practically instantaneous. The affected region is subject to thermoelastic stress that arises with the steep temperature elevation. To predict the size of the region subject to the morphological changes due to the laser treatment, the temperature field is calculated. Cavitation bubble initiation and expansion process, which acts as precursor to the stress induced tissue trauma, is studied as well. Theoretical findings are compared against experimental results. High-speed camera is utilized to assess the laser treatment process, showing the temporal development of the cavitation bubbles. The results obtained in this study facilitate a better understanding of the effects of femtosecond laser assisted corneal surgeries and help in choosing optimal laser parameters.

  9. Optimization of the parameters for intrastromal refractive surgery with ultrashort laser pulses

    NASA Astrophysics Data System (ADS)

    Heisterkamp, Alexander; Ripken, Tammo; Lubatschowski, Holger; Welling, Herbert; Dommer, Wolfgang; Luetkefels, Elke; Mamom, Thanongsak; Ertmer, Wolfgang

    2001-06-01

    Focussing femtosecond laser pulses into a transparent media, such as corneal tissue, leads to optical breakdown, generation of a micro-plasma and, thus, a cutting effect inside the tissue. To proof the potential of fs-lasers in refractive surgery, three-dimensional cutting within the corneal stroma was evaluated. With the use of ultrashort laser pulses within the LASIK procedure (laser in situ keratomileusis) possible complications in handling of a mechanical knife, the microkeratome, can be reduced by using the treatment laser as the keratome itself. To study woundhealing effects, animal studies were carried out in rabbit specimen. The surgical outcome was analyzed by means of histological sections, as well as light and scanning electron microscopy. Dependencies on the dispersion caused by focussing optics were evaluated and optimized. Thus, pulse energies well below 1 (mu) J were sufficient to perform the intrastromal cuts. The laser pulses with a duration of 180 fs and energies of 0.5-100 (mu) J were provided by a modelocked frequency doubled erbium fiber-laser with subsequent chirped pulse amplification in a titanium sapphire amplifier at up to 3 kHz.

  10. NME genes in epithelial morphogenesis

    PubMed Central

    2012-01-01

    The NME family of genes encodes highly conserved multifunctional proteins that have been shown to participate in nucleic acid metabolism, energy homeostasis, cell signaling, and cancer progression. Some family members, particularly isoforms 1 and 2, have attracted extensive interests because of their potential anti-metastasis activity. Unfortunately, there have been few consensus mechanistic explanations for this critical function because of the numerous molecular functions ascribed to these proteins, including nucleoside diphosphate kinase, protein kinase, nuclease, transcription factor, growth factor, among others. In addition, different studies showed contradictory prognostic correlations between NME expression levels and tumor progression in clinical samples. Thus, analyses using pliable in vivo systems have become critical for unraveling at least some aspects of the complex functions of this family of genes. Recent works using the Drosophila genetic system have suggested a role for NME in regulating epithelial cell motility and morphogenesis, which has also been demonstrated in mammalian epithelial cell culture. This function is mediated by promoting internalization of growth factor receptors in motile epithelial cells, and the adherens junction components such as E-cadherin and β-catenin in epithelia that form the tissue linings. Interestingly, NME genes in epithelial cells appear to function in a defined range of expression levels. Either down-regulation or over-expression can perturb epithelial integrity, resulting in different aspects of epithelial abnormality. Such biphasic functions provide a plausible explanation for the documented anti-metastatic activity and the suspected oncogenic function. This review summarizes these recent findings and discusses their implications. PMID:21336542

  11. Ion Channels in Epithelial Cells

    NASA Astrophysics Data System (ADS)

    Palmer, Lawrence G.

    Ion channels in epithelial cells serve to move ions, and in some cases fluid, between compartments of the body. This function of the transfer of material is fundamentally different from that of the transfer of information, which is the main job of most channels in excitable cells. Nevertheless the basic construction of the channels is similar in many respects in the two tissue types. This chapter reviews the nature of channels in epithelia and discusses how their functions have evolved to accomplish the basic tasks for which they are responsible. I will focus on three channel types: epithelial Na+ channels, inward-rectifier K+ channels, and CFTR Cl- channels.

  12. Evaluation of thermal load during laser corneal refractive surgery using infrared thermography

    NASA Astrophysics Data System (ADS)

    Brunsmann, U.; Sauer, U.; Arba-Mosquera, S.; Magnago, T.; Triefenbach, N.

    2010-09-01

    Infrared thermography is used for evaluation of the mean temperature as a measure of thermal load during corneal refractive surgery. An experimental method to determine emissivity and to calibrate the thermografic system is presented. In a case study on the porcine eye two dimensional temperature distributions with lateral resolution of 170 μm and line scans with temporal resolution of 13 μs are discussed with respect to the meaning of mean temperature. Using the newest generation of surgery equipment it is shown, that the mean temperature rise can be kept below 5 °C during myopic laser in situ keratomileusis (LASIK) treatments corresponding to an aberration-free correction of -2.75 diopter.

  13. Epithelial histogenesis during tooth development.

    PubMed

    Lesot, H; Brook, A H

    2009-12-01

    This paper reviews the current understanding of the progressive changes mediating dental epithelial histogenesis as a basis for future collaborative studies. Tooth development involves morphogenesis, epithelial histogenesis and cell differentiation. The consecutive morphological stages of lamina, bud, cap and bell are also characterized by changes in epithelial histogenesis. Differential cell proliferation rates, apoptosis, and alterations in adhesion and shape lead to the positioning of groups of cells with different functions. During tooth histo-morphogenesis changes occur in basement membrane composition, expression of signalling molecules and the localization of cell surface components. Cell positional identity may be related to cell history. Another important parameter is cell plasticity. Independently of signalling molecules, which play a major role in inducing or modulating specific steps, cell-cell and cell-matrix interactions regulate the plasticity/rigidity of particular domains of the enamel organ. This involves specifying in space the differential growth and influences the progressive tooth morphogenesis by shaping the epithelial-mesenchymal junction. Deposition of a mineralized matrix determines the final shape of the crown. All data reviewed in this paper were investigated in the mouse. PMID:18656852

  14. MicroRNAs and Epithelial Immunity

    PubMed Central

    Liu, Jun; Drescher, Kristen M.; Chen, Xian-Ming

    2009-01-01

    MicroRNAs are required for development and maintenance of the epithelial barrier. It is hypothesized that microRNAs are involved in regulating epithelial anti-microbial defenses by targeting key epithelial effector molecules and/or influencing intracellular signaling pathways. Additionally, aberrant microRNA expression has been implicated in the pathogenesis of various diseases at the skin and mucosa. Increased understanding of the role of microRNAs in epithelial immunoregulation and identification of microRNAs of pathogenetic significance will enhance our understanding of epithelial immunobiology and immunopathology. PMID:19811319

  15. Endomicroscopy imaging of epithelial structures using tissue autofluorescence

    NASA Astrophysics Data System (ADS)

    Lin, Bevin; Urayama, Shiro; Saroufeem, Ramez M. G.; Matthews, Dennis L.; Demos, Stavros G.

    2011-04-01

    We explore autofluorescence endomicroscopy as a potential tool for real-time visualization of epithelial tissue microstructure and organization in a clinical setting. The design parameters are explored using two experimental systems--an Olympus Medical Systems Corp. stand-alone clinical prototype probe, and a custom built bench-top rigid fiber conduit prototype. Both systems entail ultraviolet excitation at 266 nm and/or 325 nm using compact laser sources. Preliminary results using ex vivo animal and human tissue specimens suggest that this technology can be translated toward in vivo application to address the need for real-time histology.

  16. Epithelial TRPV1 signaling accelerates gingival epithelial cell proliferation.

    PubMed

    Takahashi, N; Matsuda, Y; Yamada, H; Tabeta, K; Nakajima, T; Murakami, S; Yamazaki, K

    2014-11-01

    Transient receptor potential cation channel subfamily V member 1 (TRPV1), a member of the calcium-permeable thermosensitive transient receptor potential superfamily, is a sensor of thermal and chemical stimuli. TRPV1 is activated by noxious heat (> 43°C), acidic conditions (pH < 6.6), capsaicin, and endovanilloids. This pain receptor was discovered on nociceptive fibers in the peripheral nervous system. TRPV1 was recently found to be expressed by non-neuronal cells, such as epithelial cells. The oral gingival epithelium is exposed to multiple noxious stimuli, including heat and acids derived from endogenous and exogenous substances; however, whether gingival epithelial cells (GECs) express TRPV1 is unknown. We show that both TRPV1 mRNA and protein are expressed by GECs. Capsaicin, a TRPV1 agonist, elevated intracellular Ca(2+) levels in the gingival epithelial cell line, epi 4. Moreover, TRPV1 activation in epi 4 cells accelerated proliferation. These responses to capsaicin were inhibited by a specific TRPV1 antagonist, SB-366791. We also observed GEC proliferation in capsaicin-treated mice in vivo. No effects were observed on GEC apoptosis by epithelial TRPV1 signaling. To examine the molecular mechanisms underlying this proliferative effect, we performed complementary (c)DNA microarray analysis of capsaicin-stimulated epi 4 cells. Compared with control conditions, 227 genes were up-regulated and 232 genes were down-regulated following capsaicin stimulation. Several proliferation-related genes were validated by independent experiments. Among them, fibroblast growth factor-17 and neuregulin 2 were significantly up-regulated in capsaicin-treated epi 4 cells. Our results suggest that functional TRPV1 is expressed by GECs and contributes to the regulation of cell proliferation. PMID:25266715

  17. Refractive surgery: keratomileusis and keratophakia.

    PubMed

    Werner, D L

    1986-08-01

    This paper reviews the non-radial keratotomy surgeries that are being performed. The author reviews the literature and suggests an approach toward counseling patients who may be considering these approaches. The paucity of reported studies makes the choice of these alternate procedures somewhat risky, particularly in their refractive predictability. PMID:3528269

  18. Photodynamic treatment of lens epithelial cells for cataract surgery

    NASA Astrophysics Data System (ADS)

    Lingua, Robert W.; Parel, Jean-Marie A.; Simon, Gabriel; Li, Kam

    1991-06-01

    Photodynamic therapy (PDT) eiiploying Dihematopor*iyrin ethers (DHE) (Photofrin II) at pharmacologic lvels, has been denonstrate3 to kill rabbit lens epithelial cells, in vivo. This in vitro study, reports on the minimal necessary parameters for rabbit lens epithelial cell death. Explants of rabbit lenses were incubated in various concentrations of DHE (1O,, 100, 500, 1000 ug/ml) for 1, 2, or 5 minutes. 30 to 120 Joules/an of collimated 514.5 nm Argon laser light re delivered to the locier concentrations of 10, 50, and 100 ug,'ml DHE treated cells. One hundre1 fifteen explants were treated, in all. Higher concentrations of DHE alone (500 and 1000 ug/ml) were sufficient to induce cellular swelling. Lower concentrations required light for cellular effect. Trypan blue staining revealed cell death at these minimal pa9ieters: DHE 50 ug/ml, incubation 1 minute, 514.5 r Argon light 1.0 Watt/an for 30 sec (30 Joules) . In future studies, these rameters will be tested in vivo, for their ability to eliminate lens epithelial proliferation after cataract surgery.

  19. Quantitative Morphology of Epithelial Folds.

    PubMed

    Štorgel, Nick; Krajnc, Matej; Mrak, Polona; Štrus, Jasna; Ziherl, Primož

    2016-01-01

    The shape of spatially modulated epithelial morphologies such as villi and crypts is usually associated with the epithelium-stroma area mismatch leading to buckling. We propose an alternative mechanical model based on intraepithelial stresses generated by differential tensions of apical, lateral, and basal sides of cells as well as on the elasticity of the basement membrane. We use it to theoretically study longitudinal folds in simple epithelia and we identify four types of corrugated morphologies: compact, invaginated, evaginated, and wavy. The obtained tissue contours and thickness profiles are compared to epithelial folds observed in invertebrates and vertebrates, and for most samples, the agreement is within the estimated experimental error. Our model establishes the groove-crest modulation of tissue thickness as a morphometric parameter that can, together with the curvature profile, be used to estimate the relative differential apicobasal tension in the epithelium. PMID:26745429

  20. Epithelial and stromal-specific immune pathway activation in the murine endometrium post-coitum.

    PubMed

    Field, S L; Cummings, M; Orsi, N M

    2015-08-01

    The endometrium is a dynamic tissue, demonstrating cyclical growth/remodelling in preparation for implantation. In mice, seminal constituents trigger mechanisms to prepare the endometrium, a process dubbed 'seminal priming' that modifies immune system components and mediates endometrial remodelling in preparation for pregnancy. An array of cytokines has been reported to mediate this interaction, although much of the literature relates to in vitro studies on isolated endometrial epithelial cells. This study measured changes in immune-related gene expression in endometrial epithelial and stromal cells in vivo following natural mating. CD1 mice were naturally mated and sacrificed over the first 4 days post-coitum (n=3 each day). Endometrial epithelial and stromal compartments were isolated by laser capture microdissection. Labelled cRNA was generated and hybridised to genome-wide expression microarrays. Pathway analysis identified several immune-related pathways active within epithelial and stromal compartments, in particular relating to cytokine networks, matrix metalloproteinases and prostaglandin synthesis. Cluster analysis demonstrated that the expression of factors involved in immunomodulation/endometrial remodelling differed between the epithelial and stromal compartments in a temporal fashion. This study is the first to examine the disparate responses of the endometrial epithelial and stromal compartments to seminal plasma in vivo in mice, and demonstrates the complexity of the interactions between these two compartments needed to create a permissive environment for implantation. PMID:26015594

  1. [Epithelial hepatoblastomas in the adult].

    PubMed

    Mondragón Sánchez, R; Bernal Maldonado, R; Sada Navarro, L A; Hernández, A I; Hurtado Andrade, H; Cortés Espinoza, T; Sánchez Cisneros, R

    1994-01-01

    Hepatoblastoma is the most frequent primary malignant liver neoplasm in childhood; in adults it is extremely rare and only 27 cases have been published. The prognosis of this neoplasm is poor because it is usually discovered late. Surgery, chemotherapy and liver transplantation have been tried with poor results. We present two adult patients who were diagnosed with an epithelial hepatoblastoma. The pathogenesis, histologic features and current management is reviewed. PMID:7716366

  2. Treatment of focal epithelial hyperplasia with topical imiquimod: report of three cases.

    PubMed

    Yasar, Sirin; Mansur, Ayse Tulin; Serdar, Zehra Asiran; Goktay, Fatih; Aslan, Canan

    2009-01-01

    Focal epithelial hyperplasia (Heck disease) is a rare disorder caused by specific types of HPV. It mainly involves oral mucosa and children are affected more frequently. It may persist for years, producing a significant reduction in quality of life. Several treatment modalities such as surgical excision, laser ablation, cryotherapy, electrocauterization, topical, intralesional, systemic interferon, and systemic retinoic acid have been used with inconsistent results and many side effects. Here we report three children of Turkish origin with focal epithelial hyperplasia successfully treated with imiquimod 5% cream. No serious side effects were observed and recurrence did not occur during the 1-year follow-up period. PMID:19689526

  3. Epithelial cells and Von Gierke's disease.

    PubMed

    Negishi, H; Benke, P J

    1977-08-01

    Epithelial cells and not fibroblasts from human liver and amniotic fluid contain inducible glucose-6-phosphatase (G-6-Pase) activity. The diagnosis of Von Gierke's disease has been made in a patient with hepatomegaly utilizing cultured epithelial cells grown from a liver biopsy. G-6-Pase activity in epithelial cells from this patient could not be induced by dibutyryl cyclic AMP and theophylline. This is the first use of epithelial cells for diagnosis of a metabolic disease. G-6-Pase activity in cloned epithelial cells from amniotic fluid increases 2- to 3-fold after 24-hr exposure to dibutyryl cyclic AMP and theophylline. The prenatal diagnosis of Von Gierke's disease may be possible in a laboratory experienced with these techniques if epithelial cell growth is obtained from amniotic fluid. PMID:196249

  4. Towards femtosecond laser surgery guidance in the posterior eye: utilization of optical coherence tomography and adaptive optics for focus positioning and shaping

    NASA Astrophysics Data System (ADS)

    Krüger, Alexander; Hansen, Anja; Matthias, Ben; Ripken, Tammo

    2014-02-01

    Although fs-laser surgery is clinically established in the field of corneal flap cutting for laser in situ keratomileusis, surgery with fs-laser in the posterior part of the eye is impaired by focus degradation due to aberrations. Precise targeting and keeping of safety distance to the retina also relies on an intraoperative depth resolved imaging. We demonstrate a concept for image guided fs-laser surgery in the vitreous body combining adaptive optics (AO) for focus reshaping and optical coherence tomography (OCT) for focus position guidance. The setup of the laboratory system consist of an 800 nm fs-laser which is focused into a simple eye model via a closed loop adaptive optics system with Hartmann-Shack sensor and a deformable mirror to correct for wavefront aberrations. A spectral domain optical coherence tomography system is used to target phantom structures in the eye model. Both systems are set up to share the same scanner and focusing optics. The use of adaptive optics results in a lowered threshold energy for laser induced breakdown and an increased cutting precision. 3D OCT imaging of porcine retinal tissue prior and immediately after fs-laser cutting is also demonstrated. In the near future OCT and AO will be two essential assistive components in possible clinical systems for fs-laser based eye surgery beyond the cornea.

  5. Epithelial ovarian cancer: An overview

    PubMed Central

    Desai, Arpita; Xu, Jingyao; Aysola, Kartik; Qin, Yunlong; Okoli, Chika; Hariprasad, Ravipati; Chinemerem, Ugorji; Gates, Candace; Reddy, Avinash; Danner, Omar; Franklin, Geary; Ngozi, Anachebe; Cantuaria, Guilherme; Singh, Karan; Grizzle, William; Landen, Charles; Partridge, Edward E; Rice, Valerie Montgomery; Reddy, E Shyam P; Rao, Veena N

    2014-01-01

    Ovarian cancer is the second most common gynecological cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions. PMID:25525571

  6. Shape Transformations of Epithelial Shells.

    PubMed

    Misra, Mahim; Audoly, Basile; Kevrekidis, Ioannis G; Shvartsman, Stanislav Y

    2016-04-12

    Regulated deformations of epithelial sheets are frequently foreshadowed by patterning of their mechanical properties. The connection between patterns of cell properties and the emerging tissue deformations is studied in multiple experimental systems, but the general principles remain poorly understood. For instance, it is in general unclear what determines the direction in which the patterned sheet is going to bend and whether the resulting shape transformation will be discontinuous or smooth. Here these questions are explored computationally, using vertex models of epithelial shells assembled from prismlike cells. In response to rings and patches of apical cell contractility, model epithelia smoothly deform into invaginated or evaginated shapes similar to those observed in embryos and tissue organoids. Most of the observed effects can be captured by a simpler model with polygonal cells, modified to include the effects of the apicobasal polarity and natural curvature of epithelia. Our models can be readily extended to include the effects of multiple constraints and used to describe a wide range of morphogenetic processes. PMID:27074691

  7. Epithelialization in Wound Healing: A Comprehensive Review

    PubMed Central

    Pastar, Irena; Stojadinovic, Olivera; Yin, Natalie C.; Ramirez, Horacio; Nusbaum, Aron G.; Sawaya, Andrew; Patel, Shailee B.; Khalid, Laiqua; Isseroff, Rivkah R.; Tomic-Canic, Marjana

    2014-01-01

    Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure. PMID:25032064

  8. Maximum imaging depth of two-photon autofluorescence microscopy in epithelial tissues

    PubMed Central

    Durr, Nicholas J.; Weisspfennig, Christian T.; Holfeld, Benjamin A.; Ben-Yakar, Adela

    2011-01-01

    Endogenous fluorescence provides morphological, spectral, and lifetime contrast that can indicate disease states in tissues. Previous studies have demonstrated that two-photon autofluorescence microscopy (2PAM) can be used for noninvasive, three-dimensional imaging of epithelial tissues down to approximately 150 μm beneath the skin surface. We report ex-vivo 2PAM images of epithelial tissue from a human tongue biopsy down to 370 μm below the surface. At greater than 320 μm deep, the fluorescence generated outside the focal volume degrades the image contrast to below one. We demonstrate that these imaging depths can be reached with 160 mW of laser power (2-nJ per pulse) from a conventional 80-MHz repetition rate ultrafast laser oscillator. To better understand the maximum imaging depths that we can achieve in epithelial tissues, we studied image contrast as a function of depth in tissue phantoms with a range of relevant optical properties. The phantom data agree well with the estimated contrast decays from time-resolved Monte Carlo simulations and show maximum imaging depths similar to that found in human biopsy results. This work demonstrates that the low staining inhomogeneity (∼20) and large scattering coefficient (∼10 mm−1) associated with conventional 2PAM limit the maximum imaging depth to 3 to 5 mean free scattering lengths deep in epithelial tissue. PMID:21361692

  9. Epithelial organization, cell polarity and tumorigenesis.

    PubMed

    McCaffrey, Luke Martin; Macara, Ian G

    2011-12-01

    Epithelial cells comprise the foundation for the majority of organs in the mammalian body, and are the source of approximately 90% of all human cancers. Characteristically, epithelial cells form intercellular adhesions, exhibit apical/basal polarity, and orient their mitotic spindles in the plane of the epithelial sheet. Defects in these attributes result in the tissue disorganization associated with cancer. Epithelia undergo self-renewal from stem cells, which might in some cases be the cell of origin for cancers. The PAR polarity proteins are master regulators of epithelial organization, and are closely linked to signaling pathways such as Hippo, which orchestrate proliferation and apoptosis to control organ size. 3D ex vivo culture systems can now faithfully recapitulate epithelial organ morphogenesis, providing a powerful approach to study both normal development and the initiating events in carcinogenesis. PMID:21782440

  10. [Recent studies on corneal epithelial barrier function].

    PubMed

    Liu, F F; Li, W; Liu, Z G; Chen, W S

    2016-08-01

    Corneal epithelium, the outermost layer of eyeball, is the main route for foreign materials to enter the eye. Under physiological conditions, the corneal epithelial superficial cells form a functionally selective permeability barrier. Integral corneal epithelial barrier function not only ensures the enrolling of nutrients which is required for regular metabolism, but also prevents foreign bodies, or disease-causing microorganism invasion. Recently, a large number of clinical and experimental studies have shown that abnormal corneal epithelial barrier function is the pathological basis for many ocular diseases. In addition, some study found that corneal epithelial barrier constitutes a variety of proteins involved in cell proliferation, differentiation, apoptosis, and a series of physiological and pathological processes. This paper reviewed recent studies specifically on the corneal epithelial barrier, highlights of its structure, function and influence factors. (Chin J Ophthalmol, 2016, 52: 631-635). PMID:27562284

  11. Intracellular insulin-like growth factor-1 induces Bcl-2 expression in airway epithelial cells.

    PubMed

    Chand, Hitendra S; Harris, Jennifer Foster; Mebratu, Yohannes; Chen, Yangde; Wright, Paul S; Randell, Scott H; Tesfaigzi, Yohannes

    2012-05-01

    Bcl-2, a prosurvival protein, regulates programmed cell death during development and repair processes, and it can be oncogenic when cell proliferation is deregulated. The present study investigated what factors modulate Bcl-2 expression in airway epithelial cells and identified the pathways involved. Microarray analysis of mRNA from airway epithelial cells captured by laser microdissection showed that increased expression of IL-1β and insulin-like growth factor-1 (IGF-1) coincided with induced Bcl-2 expression compared with controls. Treatment of cultured airway epithelial cells with IL-1β and IGF-1 induced Bcl-2 expression by increasing Bcl-2 mRNA stability with no discernible changes in promoter activity. Silencing the IGF-1 expression using short hairpin RNA showed that intracellular IGF-1 (IC-IGF-1) was increasing Bcl-2 expression. Blocking epidermal growth factor receptor or IGF-1R activation also suppressed IC-IGF-1 and abolished the Bcl-2 induction. Induced expression and colocalization of IC-IGF-1 and Bcl-2 were observed in airway epithelial cells of mice exposed to LPS or cigarette smoke and of patients with cystic fibrosis and chronic bronchitis but not in the respective controls. These studies demonstrate that IC-IGF-1 induces Bcl-2 expression in epithelial cells via IGF-1R and epidermal growth factor receptor pathways, and targeting IC-IGF-1 could be beneficial to treat chronic airway diseases. PMID:22461702

  12. Concept for image-guided vitreo-retinal fs-laser surgery: adaptive optics and optical coherence tomography for laser beam shaping and positioning

    NASA Astrophysics Data System (ADS)

    Matthias, Ben; Brockmann, Dorothee; Hansen, Anja; Horke, Konstanze; Knoop, Gesche; Gewohn, Timo; Zabic, Miroslav; Krüger, Alexander; Ripken, Tammo

    2015-03-01

    Fs-lasers are well established in ophthalmic surgery as high precision tools for corneal flap cutting during laser in situ keratomileusis (LASIK) and increasingly utilized for cutting the crystalline lens, e.g. in assisting cataract surgery. For addressing eye structures beyond the cornea, an intraoperative depth resolved imaging is crucial to the safety and success of the surgical procedure due to interindividual anatomical disparities. Extending the field of application even deeper to the posterior eye segment, individual eye aberrations cannot be neglected anymore and surgery with fs-laser is impaired by focus degradation. Our demonstrated concept for image-guided vitreo-retinal fs-laser surgery combines adaptive optics (AO) for spatial beam shaping and optical coherence tomography (OCT) for focus positioning guidance. The laboratory setup comprises an adaptive optics assisted 800 nm fs-laser system and is extended by a Fourier domain optical coherence tomography system. Phantom structures are targeted, which mimic tractional epiretinal membranes in front of excised porcine retina within an eye model. AO and OCT are set up to share the same scanning and focusing optics. A Hartmann-Shack sensor is employed for aberration measurement and a deformable mirror for aberration correction. By means of adaptive optics the threshold energy for laser induced optical breakdown is lowered and cutting precision is increased. 3D OCT imaging of typical ocular tissue structures is achieved with sufficient resolution and the images can be used for orientation of the fs-laser beam. We present targeted dissection of the phantom structures and its evaluation regarding retinal damage.

  13. Esophageal epithelial cells acquire functional characteristics of activated myofibroblasts after undergoing an epithelial to mesenchymal transition

    PubMed Central

    Muir, Amanda B.; Dods, Kara; Noah, Yuli; Toltzis, Sarit; Chandramouleeswaran, Prasanna Modayur; Lee, Anna; Benitez, Alain; Bedenbaugh, Adam; Falk, Gary W.; Wells, Rebecca G.; Nakagawa, Hiroshi; Wang, Mei-Lun

    2015-01-01

    Background and Aims Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that leads to esophageal fibrosis and stricture. We have recently shown that in EoE, esophageal epithelial cells undergo an epithelial to mesenchymal transition (EMT), characterized by gain of mesenchymal markers and loss of epithelial gene expression. Whether epithelial cells exposed to profibrotic cytokines can also acquire the functional characteristics of activated myofibroblasts, including migration, contraction, and extracellular matrix deposition, is relevant to our understanding and treatment of EoE-associated fibrogenesis. In the current study, we characterize cell migration, contraction, and collagen production by esophageal epithelial cells that have undergone cytokine-induced EMT in vitro. Methods and Results Stimulation of human non-transformed immortalized esophageal epithelial cells (EPC2-hTERT) with profibrotic cytokines TNFα, TGFβ, and IL1β for three weeks led to acquisition of mesenchymal αSMA and vimentin, and loss of epithelial E-cadherin expression. Upon removal of the profibrotic stimulus, epithelial characteristics were partially rescued. TGFβ stimulation had a robust effect upon epithelial collagen production. Surprisingly, TNFα stimulation had the most potent effect upon cell migration and contraction, exceeding the effects of the prototypical profibrotic cytokine TGFβ. IL1β stimulation alone had minimal effect upon esophageal epithelial migration, contraction, and collagen production. Conclusions Esophageal epithelial cells that have undergone EMT acquire functional characteristics of activated myofibroblasts in vitro. Profibrotic cytokines exert differential effects upon esophageal epithelial cells, underscoring complexities of fibrogenesis in EoE, and implicating esophageal epithelial cells as effector cells in EoE-associated fibrogenesis. PMID:25183431

  14. The comparison of glycosphingolipids isolated from an epithelial ovarian cancer cell line and a nontumorigenic epithelial ovarian cell line using MALDI-MS and MALDI-MS/MS.

    PubMed

    Rajanayake, Krishani K; Taylor, William R; Isailovic, Dragan

    2016-08-01

    Glycosphingolipids (GSLs) are important biomolecules, which are linked to many diseases such as GSL storage disorders and cancer. Consequently, the expression of GSLs may be altered in ovarian cancer cell lines in comparison to apparently healthy cell lines. Here, differential expressions of GSLs in an epithelial ovarian cancer cell line SKOV3 and a nontumorigenic epithelial ovarian cell line T29 were studied using matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and MALDI-MS/MS. The isolation of GSLs from SKOV3 and T29 cell lines was carried out using Folch partition. GSLs were successfully detected by MALDI-MS, and structurally assigned by a comparison of their MALDI-MS/MS fragmentation patterns with MS/MS data found in SimLipid database. Additionally, LIPID MAPS was used to assign GSL ion masses in MALDI-MS spectra. Seventeen neutral GSLs were identified in Folch partition lower (chloroform/methanol) phases originating from both cell lines, while five globo series neutral GSLs were identified only in the Folch partition lower phase of SKOV3 cell line. Several different sialylated GSLs were detected in Folch partition upper (water/methanol) phases of SKOV3 and T29 cell lines. Overall, this study demonstrates the alteration and increased glycosylation of GSLs in an epithelial ovarian cancer cell line in comparison to a nontumorigenic epithelial ovarian cell line. PMID:27267063

  15. Airway epithelial cell responses to ozone injury

    SciTech Connect

    Leikauf, G.D.; Simpson, L.G.; Zhao, Qiyu

    1995-03-01

    The airway epithelial cell is an important target in ozone injury. Once activated, the airway epithelium responds in three phases. The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis products-hydroxyhydroperoxides, aldehydes, and hydrogen peroxide. Recently, we found hydroxyhydroperoxides to be potent agonists; of bioactive eicosanoid formation by human airway epithelial cells in culture. Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase). During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines-macrophage inflammatory protein-2, RANTES, and interleukin-8. Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation. The third (late) phase of ozone injury is characterized by eosinophil or monocyte infiltration. Cytokine expression leads to alteration of structural protein synthesis, with increases in fibronectin evident by in situ hybridization. Synthesis of epithelial antiproteases, e.g., secretary leukocyte protease inhibitor, may also increase locally 24 to 48 hr after elastase concentrations become excessive. Thus, the epithelium is not merely a passive barrier to ozone injury but has a dynamic role in directing the migration, activating, and then counteracting inflammatory cells. Through these complex interactions, epithelial cells can be viewed as the initiators (alpha) and the receptors (omega) of ozone-induced airway disease. 51 refs., 2 figs., 3 tabs.

  16. Femtosecond laser beam propagation through corneal tissue: Evaluation of therapeutic laser-stimulated second and third- harmonic generation

    NASA Astrophysics Data System (ADS)

    Calhoun, William R., III

    One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction. The application of FSLs in medical therapeutics is a recent development, and although they offer many benefits, FSLs also stimulate nonlinear optical effects (NOEs), many of which were insignificant with previously developed lasers. NOEs can change the laser characteristics during propagation through a medium, which can subsequently introduce unique safety concerns for the surrounding tissues. Traditional approaches for characterizing optical effects, laser performance, safety and efficacy do not properly account for NOEs, and there remains a lack of data that describe NOEs in clinically relevant procedures and tissues. As FSL technology continues to expand towards new applications, FSL induced NOEs need to be better understood in order to ensure safety as FSL medical devices and applications continue to evolve at a rapid pace. In order to improve the understanding of FSL-tissue interactions related to NOEs stimulated during laser beam propagation though corneal tissue, research investigations were conducted to evaluate corneal optical properties and determine how corneal tissue properties including corneal layer, collagen orientation and collagen crosslinking, and laser parameters including pulse energy, repetition rate and numerical aperture affect second and third-harmonic generation (HG) intensity, duration and efficiency. The results of

  17. Epithelial Inclusion Cyst in Conjunctival Melanoma.

    PubMed

    Esposito, Evangelina; Zoroquiain, Pablo; Mastromonaco, Christina; Morales, Melina C; Belfort Neto, Rubens; Burnier, Miguel

    2016-09-01

    Conjunctival melanoma is the second most common conjunctival malignancy. Its differential diagnosis with other conjunctival melanocytic neoplasms is inherently difficult. The presence of epithelial cysts is a useful feature in conjunctival tumors and favors a benign lesion. Herein 2 cases of conjunctival melanoma with cysts are presented. To the best of our knowledge, this is the first series of conjunctival melanoma with epithelial inclusion cysts. This series emphasizes the importance of considering several malignant features when reviewing conjunctival melanocytic lesions, as malignancy can exist even in the presence of epithelial inclusion cysts. PMID:27160434

  18. Comparison of self-reported quality of vision outcomes after myopic LASIK with two femtosecond lasers: a prospective, eye-to-eye study

    PubMed Central

    Sáles, Christopher S; Manche, Edward E

    2016-01-01

    Purpose To compare self-reported quality of vision (QoV) outcomes after myopic LASIK (laser-assisted in situ keratomileusis) with two femtosecond lasers. Design Prospective, randomized, eye-to-eye study. Methods Consecutive myopic patients were treated with wavefront-guided LASIK bilaterally. Eyes were randomized according to ocular dominance. The flap of one eye was made with the IntraLase FS 60 kHz femtosecond laser with a conventional 70° side-cut, and the flap of the fellow eye was made with the IntraLase iFS 150 kHz femtosecond laser with an inverted 130° side-cut. Patients completed the validated, Rasch-tested, linear-scaled 30-item QoV questionnaire preoperatively and at Months 1, 3, 6, and 12. Results The study enrolled 120 fellow eyes in 60 patients. None of the measured QoV parameters exhibited statistically significant differences between the groups preoperatively or at any postoperative time point. Conclusion Creating LASIK flaps with an inverted side-cut using a 150 kHz femtosecond laser and with a conventional 70° side-cut using a 60 kHz femtosecond laser resulted in no significant differences in self-reported QoV assessed by the QoV questionnaire. PMID:27621589

  19. Laser Technology.

    ERIC Educational Resources Information Center

    Gauger, Robert

    1993-01-01

    Describes lasers and indicates that learning about laser technology and creating laser technology activities are among the teacher enhancement processes needed to strengthen technology education. (JOW)

  20. Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic behavior of epithelial malignancies

    PubMed Central

    Talbot, Lindsay J; Bhattacharya, Syamal D; Kuo, Paul C

    2012-01-01

    Objective The mechanisms of cancer metastasis have been intensely studied recently and may provide vital therapeutic targets for metastasis prevention. We sought to review the contribution of epithelial-mesenchymal transition and the tumor microenvironment to cancer metastasis. Summary Background Data Epithelial-mesenchymal transition is the process by which epithelial cells lose cell-cell junctions and baso-apical polarity and acquire plasticity, mobility, invasive capacity, stemlike characteristics, and resistance to apoptosis. This cell biology program is active in embryology, wound healing, and pathologically in cancer metastasis, and along with the mechanical and cellular components of the tumor microenvironment, provides critical impetus for epithelial malignancies to acquire metastatic capability. Methods A literature review was performed using PubMed for “epithelial-mesenchymal transition”, “tumor microenvironment”, “TGF-β and cancer”, “Wnt and epithelial-mesenchymal transition”, “Notch and epithelial-mesenchymal transition”, “Hedgehog and epithelial-mesenchymal transition” and “hypoxia and metastasis”. Relevant primary studies and review articles were assessed. Results Major signaling pathways involved in epithelial-mesenchymal transition include TGF-β, Wnt, Notch, Hedgehog, and others. These pathways converge on several transcription factors, including zinc finger proteins Snail and Slug, Twist, ZEB 1/2, and Smads. These factors interact with one another and others to provide crosstalk between the relevant signaling pathways. MicroRNA suppression and epigenetic changes also influence the changes involved in epithelial-mesenchymal transition. Cellular and mechanical components of the tumor microenvironment are also critical in determining metastatic potential. Conclusions While the mechanisms promoting metastasis are extremely wide ranging and still under intense investigation, the epithelial-mesenchymal transition program and

  1. Epithelial self-organization in fruit fly embryogenesis

    NASA Astrophysics Data System (ADS)

    Hutson, M. Shane

    2010-03-01

    During fruit fly embryogenesis, there are several morphogenetic events in which sheets of epithelial cells expand, contract and bend due to coordinated intra- and intercellular forces. This tissue-level reshaping is accompanied by changes in the shape and arrangement of individual cells -- changes that can be measured quantitatively and dynamically using modern live-cell imaging techniques. Such data sets represent rich targets for computational modeling of self-organization; however, reproducing the observed cell- and tissue-level reshaping is not enough. The inverse problem of using cell shape changes to determine cell-level forces is ill-posed -- yielding non-unique solutions that cannot discriminate between active changes in cell shape and passive deformation. These non-unique solutions can be tested experimentally using in vivo laser-microsurgery -- i.e., cutting a targeted region of an epithelium and carefully tracking the temporal and spatial dependence of the subsequent strain relaxation. This technique uses a variety of incisions (hole, line or closed curve) to probe different aspects of epithelial mechanics: the local mesoscopic strain; the distribution of intracellular forces; changes in the cell-level power-law rheology; and the question of active versus passive deformation. I will discuss my group's work using laser-microsurgery to investigate two morphogenetic events in fruit fly embryogenesis: germband retraction and dorsal closure. In both cases, we find a substantial active mechanical role for the amnioserosa -- an epithelium that undergoes apoptosis near the end of embryogenesis and makes no part of the fly larva -- in reshaping an adjacent epithelium that becomes the larval epidermis. In these examples, self-organization of the fly embryo relies not only on self-organization of individual tissues, but also on the mechanical interactions between tissues.

  2. Regulation of angiogenin expression and epithelial-mesenchymal transition by HIF-1α signaling in hypoxic retinal pigment epithelial cells.

    PubMed

    Lai, Kairan; Luo, Chenqi; Zhang, Xiaobo; Ye, Panpan; Zhang, Yidong; He, Jiliang; Yao, Ke

    2016-09-01

    Choroidal neovascularization (CNV) is a major cause of vision loss in many retinal diseases. Hypoxia is determined to be a key inducer of CNV and hypoxia-inducible factor-1 (HIF-1) is an important transcription factor. Epithelial-mesenchymal transition (EMT) and the synthesis of proangiogenic cytokines make great contributions to the development of CNV. In the present study, the role of HIF-1α signaling in the regulation of angiogenin (ANG) expression and EMT in hypoxic retinal pigment epithelial cells was investigated. A significant elevation expression of ANG expression level in a mouse model of laser-induced CNV was demonstrated. In a hypoxic model of ARPE-19, an increased expression level of ANG and induction of EMT accompanied with stabilization and nucleus translocation of HIF-1α. Blockage of HIF-1α signaling resulted in inhibition of high expression of ANG and EMT features. The direct interaction between HIF-1α and ANG promoter region was identified by ChIP-qPCR. The association of RNase 4 mRNA level with HIF-1α signaling was also clarified in APRE-19. Moreover, the exogenous ANG translocated into the nucleus, enhanced 45S rRNA transcription, promoted cell proliferation and tube formation in human retinal microvascular endothelial cells. In conclusion, the hypoxic conditions regulate the expression of ANG and EMT via an activation of HIF-1α signaling. It provides molecular evidence for potential therapy strategies of treating CNV. PMID:27259982

  3. General Information about Ovarian Epithelial Cancer

    MedlinePlus

    ... Primary Peritoneal Cancer Treatment (PDQ®)–Patient Version General Information About Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  4. Symmetry breaking mechanism for epithelial cell polarization

    NASA Astrophysics Data System (ADS)

    Veglio, A.; Gamba, A.; Nicodemi, M.; Bussolino, F.; Serini, G.

    2009-09-01

    In multicellular organisms, epithelial cells form layers separating compartments responsible for different physiological functions. At the early stage of epithelial layer formation, each cell of an aggregate defines an inner and an outer side by breaking the symmetry of its initial state, in a process known as epithelial polarization. By integrating recent biochemical and biophysical data with stochastic simulations of the relevant reaction-diffusion system, we provide evidence that epithelial cell polarization is a chemical phase-separation process induced by a local bistability in the signaling network at the level of the cell membrane. The early symmetry breaking event triggering phase separation is induced by adhesion-dependent mechanical forces localized in the point of convergence of cell surfaces when a threshold number of confluent cells is reached. The generality of the emerging phase-separation scenario is likely common to many processes of cell polarity formation.

  5. Respiratory epithelial cysts of the orbit.

    PubMed

    Goh, Rachel L Z; Hardy, Thomas G; Williams, Richard A; McNab, Alan A

    2016-10-01

    To describe post-traumatic and congenital respiratory epithelial cysts in the orbit, which are rare lesions with only 5 and 13 published cases, respectively. We reviewed all cases of respiratory epithelial cysts diagnosed at three institutions (two tertiary referral hospitals, one private clinic) between 1995 and 2015. We describe 10 cases of post-traumatic respiratory epithelial cyst (age range 23 - 82), presenting a mean of 17.4 years after their original trauma; and 3 congenital cases (age range 17-34). All but one case underwent surgical excision of the cyst and its lining, along with any surgical implant within the cyst. Two were recurrent after incomplete excision. Three presented with acute infection within the cyst. Respiratory epithelial orbital cysts are probably commoner than the paucity of published reports would suggest. Post-traumatic cysts often present many years after trauma, and may become secondarily infected. Complete surgical removal is recommended to prevent future recurrence. PMID:27468088

  6. Understanding lasers

    SciTech Connect

    Gibilisco, S.

    1989-01-01

    Covering all different types of laser applications-Gibilisco offers an overview of this fascinating phenomenon of light. Here he describes what lasers are and how they work and examines in detail the different kinds of lasers in use today. Topics of particular interest include: the way lasers work; the different kinds of lasers; infrared, ultraviolet and x-ray lasers; use of lasers in industry and manufacturing; use of lasers for long-distance communications; fiberoptic communications; the way laser shows work; the reality of Star Wars; lasers in surgical and medical applications; and holography and the future of laser technology.

  7. Alveolar epithelial disintegrity in pulmonary fibrosis.

    PubMed

    Kulkarni, Tejaswini; de Andrade, Joao; Zhou, Yong; Luckhardt, Tracy; Thannickal, Victor J

    2016-08-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive decline in lung function, resulting in significant morbidity and mortality. Current concepts of the pathogenesis of IPF primarily center on dysregulated epithelial cell repair and altered epithelial-mesenchymal communication and extracellular matrix deposition following chronic exposure to cigarette smoke or environmental toxins. In recent years, increasing attention has been directed toward the role of the intercellular junctional complex in determining the specific properties of epithelia in pulmonary diseases. Additionally, recent genomewide association studies suggest that specific genetic variants predictive of epithelial cell dysfunction may confer susceptibility to the development of sporadic idiopathic pulmonary fibrosis. A number of genetic disorders linked to pulmonary fibrosis and familial interstitial pneumonias are associated with loss of epithelial integrity. However, the potential links between extrapulmonary clinical syndromes associated with defects in epithelial cells and the development of pulmonary fibrosis are not well understood. Here, we report a case of hereditary mucoepithelial dysplasia that presented with pulmonary fibrosis and emphysema on high-resolution computed tomography. This case illustrates a more generalizable concept of epithelial disintegrity in the development of fibrotic lung diseases, which is explored in greater detail in this review article. PMID:27233996

  8. Transcriptome Analysis of Epithelial and Stromal Contributions to Mammogenesis in Three Week Prepartum Cows

    PubMed Central

    Casey, Theresa; Dover, Heather; Liesman, James; DeVries, Lindsey; Kiupel, Matti; VandeHaar, Michael; Plaut, Karen

    2011-01-01

    Transcriptome analysis of bovine mammary development has provided insight into regulation of mammogenesis. However, previous studies primarily examined expression of epithelial and stromal tissues combined, and consequently did not account for tissue specific contribution to mammary development. Our objective was to identify differences in gene expression in epithelial and intralobular stromal compartments. Tissue was biopsied from non-lactating dairy cows 3 weeks prepartum, cut into explants and incubated for 2 hr with insulin and hydrocortisone. Epithelial and intralobular stromal tissues were isolated with laser capture microdissection. Global gene expression was measured with Bovine Affymetrix GeneChips, and data were preprocessed using RMA method. Moderated t-tests from gene-specific linear model analysis with cell type as a fixed effect showed more than 3,000 genes were differentially expressed between tissues (P<0.05; FDR<0.17). Analysis of epithelial and stromal transcriptomes using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathways Analysis (IPA) showed that epithelial and stromal cells contributed distinct molecular signatures. Epithelial signatures were enriched with gene sets for protein synthesis, metabolism and secretion. Stromal signatures were enriched with genes that encoded molecules important to signaling, extracellular matrix composition and remodeling. Transcriptome differences also showed evidence for paracrine interactions between tissues in stimulation of IGF1 signaling pathway, stromal reaction, angiogenesis, neurogenesis, and immune response. Molecular signatures point to the dynamic role the stroma plays in prepartum mammogenesis and highlight the importance of examining the roles of cell types within the mammary gland when targeting therapies and studying mechanisms that affect milk production. PMID:21829467

  9. Forces driving epithelial wound healing

    NASA Astrophysics Data System (ADS)

    Brugués, Agustí; Anon, Ester; Conte, Vito; Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier

    2014-09-01

    A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and `purse-string’ contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate.

  10. Forces driving epithelial wound healing

    PubMed Central

    Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier

    2015-01-01

    A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and “purse-string” contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate. PMID:27340423

  11. A histological study of rabbit corneas after transepithelial corneal crosslinking using partial epithelial photoablation or ethanol treatment

    PubMed Central

    Ozmen, Mehmet Cuneyt; Hondur, Ahmet; Yilmaz, Guldal; Bilgihan, Kamil; Hasanreisoglu, Berati

    2014-01-01

    AIM To evaluate the histological changes after transepithelial corneal crosslinking (CXL) using partial thickness excimer laser ablation or epithelial ethanol application in an experimental rabbit study. METHODS Right eyes of twenty-four rabbits were studied. Four eyes received total epithelial debridement (group I). Four eyes received partial thickness epithelial ablation with excimer laser (group II). Twelve eyes were treated with different durations (30s and 60s) and concentrations (18% to 48%) of ethanol (group III). Riboflavin was applied for 30min intervals along with topical proparacaine drops with benzalkonium chloride, and 370 nm irradiation was performed for 30min, while riboflavin was instilled every 3min. Four eyes (group IV) received 48% ethanol for 30s without riboflavin and irradiation. Eyes were collected after 24h and examined histologically. RESULTS All eyes in group I showed keratocyte loss in the superficial 300 µ of corneal storma. In group II, 1-4 layers of epithelium were preserved and no keratocyte loss occurred. In group III, CXL after treatment with ethanol up to 24% concentration and up to 60s revealed no keratocyte loss. CXL after treatment with 48% and higher ethanol concentrations yielded keratocyte loss in the superficial 200 µ to 300 µ of cornea. CONCLUSION Incomplete excimer laser ablation of the epithelium or treatment with ethanol up to 24% concentration and up to 60s duration yielded no stromal keratocyte loss. To get the same histological appearance seen in epithelial debridement group, partial thickness excimer laser epithelial ablation or ethanol application is not adequate for transepithelial CXL. PMID:25540746

  12. Epithelial phenotype in total sclerocornea

    PubMed Central

    Yeh, Lung-Kun; Chen, Hung-Chi; Chang, Anna Marie; Ho, Yi-Ju; Chang, Shirley H.L.; Yang, Unique

    2014-01-01

    Purpose To understand whether the epithelial phenotype in total sclerocornea is corneal or conjunctival in origin. Methods Four cases of total sclerocornea (male:female = 1:3; mean age = 5.4±4.3; 1–11 years old) who received penetrating keratoplasty (PKP) at our hospital between 2008 and 2011 were included. Corneal buttons obtained during PKP were used for transmission electron microscopy (TEM) as well as immunoconfocal microscopy for cytokeratins 3, 12, and 13, goblet cell mucin MUC5AC, connexin 43, stem cell markers p63 and ABCG2, laminin-5, and fibronectin. Results After a mean follow-up period of 38.8±14.0 (12–54) months, the grafts remained clear in half of the patients. TEM examination revealed a markedly attenuated Bowman’s layer in the scleralized corneas, with irregular and variably thinned collagen lamellar layers, and disorganization and random distribution of collagen fibrils, which were much larger in diameter compared with a normal cornea. Immunoconfocal microscopy showed that keratin 3 was expressed in all four patients, while p63, ABCG2, and MUC5AC were all absent. Cornea-specific keratin 12 was universally expressed in Patients 1 to 3, while mucosa (including conjunctiva)-specific keratin 13 was negative in these patients. Interestingly, keratin 12 and 13 were expressed in Patient 4 in a mutually exclusive manner. Linear expression of laminin-5 in the basement membrane zone and similar expression of fibronectin were observed. Conclusions The epithelia in total sclerocornea are essentially corneal in phenotype, but in the event of massive corneal angiogenesis, invasion by the conjunctival epithelium is possible. PMID:24744607

  13. Intestinal epithelial dysplasia (tufting enteropathy).

    PubMed

    Goulet, Olivier; Salomon, Julie; Ruemmele, Frank; de Serres, Natacha Patey-Mariaud; Brousse, Nicole

    2007-01-01

    Intestinal epithelial dysplasia (IED), also known as tufting enteropathy, is a congenital enteropathy presenting with early-onset severe intractable diarrhea causing sometimes irreversible intestinal failure. To date, no epidemiological data are available, however, the prevalence can be estimated at around 1/50,000-100,000 live births in Western Europe. The prevalence seems higher in areas with high degree of consanguinity and in patients of Arabic origin. Infants develop within the first days after birth a watery diarrhea persistent in spite of bowel rest and parenteral nutrition. Some infants are reported to have associated choanal rectal or esophageal atresia. IED is thought to be related to abnormal enterocytes development and/or differentiation. Nonspecific punctuated keratitis was reported in more than 60% of patients. Histology shows various degree of villous atrophy, with low or without mononuclear cell infiltration of the lamina propria but specific histological abnormalities involving the epithelium with disorganization of surface enterocytes with focal crowding, resembling tufts. Several associated specific features were reported, including abnormal deposition of laminin and heparan sulfate proteoglycan (HSPG) in the basement membrane, increased expression of desmoglein and ultrastructural changes in the desmosomes, and abnormal distribution of alpha2beta1 integrin adhesion molecules. One model of transgenic mice in which the gene encoding the transcription factor Elf3 is disrupted have morphologic features resembling IED. Parental consanguinity and/or affected siblings suggest an autosomal recessive transmission but the causative gene(s) have not been yet identified making prenatal diagnosis unavailable. Some infants have a milder phenotype than others but in most patients, the severity of the intestinal malabsorption even with enteral feeding make them totally dependent on daily long-term parenteral nutrition with a subsequent risk of complications

  14. The Na+/H+ exchange inhibitor HOE642 prevents stress-induced epithelial barrier dysfunction.

    PubMed

    Nowak, Peter; Blaheta, Roman; Schuller, Alina; Cinatl, Jindrich; Wimmer-Greinecker, Gerhard; Moritz, Anton; Scholz, Martin

    2004-08-01

    Recently, evidence has been obtained that the Na+/H+ exchange (NHE) inhibitor HOE642 may stabilize endothelial and epithelial barrier function in vivo. However, the underlying mechanisms are not known. Therefore, we studied the influence of HOE642 on the barrier function of the epithelial cell line CaCo2. The phorbolester phorbol 12-myristate 13-acetate (PMA) was used to induce hyperpermeability of the epithelial layer which was indirectly determined by measuring the transepithelial electrical resistance (TER). Confocal laser scan microscopy (LSM) served to analyze the intracellular localization of adherens and tight junction molecules. In five independent experiments we found that HOE642 increased TER in non-treated CaCo2 cells (control: 350 +/- 28 Omega/cm2; HOE642: 444 +/- 53 Omega/cm2) and prevented PMA-induced barrier dysfunction (PMA: 33 +/- 12 Omega/cm2; PMA plus HOE642: 496 +/- 47 Omega/cm2). LSM showed that HOE642 prevented the PMA-induced disassociation of the zonula adherens molecule beta-catenin from the cell membrane and the decreased expression of the zonula occludens molecule ZO-1. From our data we conclude that HOE642 may prevent stress-induced epithelial dysfunction by stabilization of cell membrane-associated junction molecules. PMID:15254761

  15. Ultrastructure of tracheal epithelial cells migrating in an in vivo environment.

    PubMed

    Sawada, Hajime; Tanaka, Hideo; Ono, Michio

    2008-12-01

    The tracheal epithelium can be induced to move as a cellular sheet by heterotopic transplantation, which offers the opportunity to observe migrating cells as a group in an in vivo environment. We therefor investigated the ultrastructural characteristics of migrating tracheal epithelial cells with special reference to the moving front using this transplantation. The migrating epithelial cells underwent squamous metaplasia and lost their differentiated characteristics such as cilia or secretory granules. Several unique observations were made concerning the mechanism of mobility: one is that epithelial cells in the front were elongated in a direction perpendicular to the course of movement, different from previous reports in vitro. The second is that lamellipodia, which are regarded as the major locomotive machinery in the adult wound epithelium, did not make up the major part of the front; the major portion of the anterior fringe of the moving front was usually smooth and gently curved, and actin cables parallel to the elongated cells were observed by confocal laser microscopy, indicating that the purse-string mechanism of epithelial wound healing takes place. The third finding is that the cells in the front had irregular bleb-like structures on their antero-basal surface, which were formed even in the portion where the cells did not attach to the matrix. Few organelles were recognized in these structures. From their location, one might propose that these bleb-like structures play a role in the recognition of the substrate and thus the movement of the cell sheet. PMID:19359805

  16. Epithelial Cell Shedding and Barrier Function

    PubMed Central

    Williams, J. M.; Duckworth, C. A.; Burkitt, M. D.; Watson, A. J. M.; Campbell, B. J.

    2015-01-01

    The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed. PMID:25428410

  17. Epithelial dynamics of pancreatic branching morphogenesis

    PubMed Central

    Villasenor, Alethia; Chong, Diana C.; Henkemeyer, Mark; Cleaver, Ondine

    2010-01-01

    The mammalian pancreas is a highly branched gland, essential for both digestion and glucose homeostasis. Pancreatic branching, however, is poorly understood, both at the ultrastructural and cellular levels. In this article, we characterize the morphogenesis of pancreatic branches, from gross anatomy to the dynamics of their epithelial organization. We identify trends in pancreatic branch morphology and introduce a novel mechanism for branch formation, which involves transient epithelial stratification and partial loss of cell polarity, changes in cell shape and cell rearrangements, de novo tubulogenesis and epithelial tubule remodeling. In contrast to the classical epithelial budding and tube extension observed in other organs, a pancreatic branch takes shape as a multi-lumen tubular plexus coordinately extends and remodels into a ramifying, single-lumen ductal system. Moreover, our studies identify a role for EphB signaling in epithelial remodeling during pancreatic branching. Overall, these results illustrate distinct, step-wise cellular mechanisms by which pancreatic epithelium shapes itself to create a functional branching organ. PMID:21098570

  18. Epithelial repair mechanisms in the lung.

    PubMed

    Crosby, Lynn M; Waters, Christopher M

    2010-06-01

    The recovery of an intact epithelium following lung injury is critical for restoration of lung homeostasis. The initial processes following injury include an acute inflammatory response, recruitment of immune cells, and epithelial cell spreading and migration upon an autologously secreted provisional matrix. Injury causes the release of factors that contribute to repair mechanisms including members of the epidermal growth factor and fibroblast growth factor families (TGF-alpha, KGF, HGF), chemokines (MCP-1), interleukins (IL-1beta, IL-2, IL-4, IL-13), and prostaglandins (PGE(2)), for example. These factors coordinate processes involving integrins, matrix materials (fibronectin, collagen, laminin), matrix metalloproteinases (MMP-1, MMP-7, MMP-9), focal adhesions, and cytoskeletal structures to promote cell spreading and migration. Several key signaling pathways are important in regulating these processes, including sonic hedgehog, Rho GTPases, MAP kinase pathways, STAT3, and Wnt. Changes in mechanical forces may also affect these pathways. Both localized and distal progenitor stem cells are recruited into the injured area, and proliferation and phenotypic differentiation of these cells leads to recovery of epithelial function. Persistent injury may contribute to the pathology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. For example, dysregulated repair processes involving TGF-beta and epithelial-mesenchymal transition may lead to fibrosis. This review focuses on the processes of epithelial restitution, the localization and role of epithelial progenitor stem cells, the initiating factors involved in repair, and the signaling pathways involved in these processes. PMID:20363851

  19. 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.

  20. Epithelial Cell Regulation of Allergic Diseases.

    PubMed

    Gour, Naina; Lajoie, Stephane

    2016-09-01

    Allergic diseases, which have escalated in prevalence in recent years, arise as a result of maladaptive immune responses to ubiquitous environmental stimuli. Why only certain individuals mount inappropriate type 2 immune responses to these otherwise harmless allergens has remained an unanswered question. Mounting evidence suggests that the epithelium, by sensing its environment, is the central regulator of allergic diseases. Once considered to be a passive barrier to allergens, epithelial cells at mucosal surfaces are now considered to be the cornerstone of the allergic diathesis. Beyond their function as maintaining barrier at mucosal surfaces, mucosal epithelial cells through the secretion of mediators like IL-25, IL-33, and TSLP control the fate of downstream allergic immune responses. In this review, we will discuss the advances in recent years regarding the process of allergen recognition and secretion of soluble mediators by epithelial cells that shape the development of the allergic response. PMID:27534656

  1. Gap geometry dictates epithelial closure efficiency

    PubMed Central

    Ravasio, Andrea; Cheddadi, Ibrahim; Chen, Tianchi; Pereira, Telmo; Ong, Hui Ting; Bertocchi, Cristina; Brugues, Agusti; Jacinto, Antonio; Kabla, Alexandre J.; Toyama, Yusuke; Trepat, Xavier; Gov, Nir; Neves de Almeida, Luís; Ladoux, Benoit

    2015-01-01

    Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity. PMID:26158873

  2. Epithelial-Mesenchymal Transition and Breast Cancer.

    PubMed

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V

    2016-01-01

    Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges. PMID:26821054

  3. Epithelial-Mesenchymal Transition and Breast Cancer

    PubMed Central

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V.

    2016-01-01

    Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges. PMID:26821054

  4. Gap geometry dictates epithelial closure efficiency.

    PubMed

    Ravasio, Andrea; Cheddadi, Ibrahim; Chen, Tianchi; Pereira, Telmo; Ong, Hui Ting; Bertocchi, Cristina; Brugues, Agusti; Jacinto, Antonio; Kabla, Alexandre J; Toyama, Yusuke; Trepat, Xavier; Gov, Nir; Neves de Almeida, Luís; Ladoux, Benoit

    2015-01-01

    Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity. PMID:26158873

  5. Odontogenic epithelial stem cells: hidden sources.

    PubMed

    Padma Priya, Sivan; Higuchi, Akon; Abu Fanas, Salem; Pooi Ling, Mok; Kumari Neela, Vasantha; Sunil, P M; Saraswathi, T R; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Kumar, Suresh

    2015-12-01

    The ultimate goal of dental stem cell research is to construct a bioengineered tooth. Tooth formation occurs based on the well-organized reciprocal interaction of epithelial and mesenchymal cells. The dental mesenchymal stem cells are the best explored, but because the human odontogenic epithelium is lost after the completion of enamel formation, studies on these cells are scarce. The successful creation of a bioengineered tooth is achievable only when the odontogenic epithelium is reconstructed to produce a replica of natural enamel. This article discusses the untapped sources of odontogenic epithelial stem cells in humans, such as those present in the active dental lamina in postnatal life, in remnants of dental lamina (the gubernaculum cord), in the epithelial cell rests of Malassez, and in reduced enamel epithelium. The possible uses of these stem cells in regenerative medicine, not just for enamel formation, are discussed. PMID:26367485

  6. Laser vaccine adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

  7. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells

    PubMed Central

    Celià-Terrassa, Toni; Meca-Cortés, Óscar; Mateo, Francesca; Martínez de Paz, Alexia; Rubio, Nuria; Arnal-Estapé, Anna; Ell, Brian J.; Bermudo, Raquel; Díaz, Alba; Guerra-Rebollo, Marta; Lozano, Juan José; Estarás, Conchi; Ulloa, Catalina; ρlvarez-Simón, Daniel; Milà, Jordi; Vilella, Ramón; Paciucci, Rosanna; Martínez-Balbás, Marian; García de Herreros, Antonio; Gomis, Roger R.; Kang, Yibin; Blanco, Jerónimo; Fernández, Pedro L.; Thomson, Timothy M.

    2012-01-01

    Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs. PMID:22505459

  8. Nitric Oxide and Airway Epithelial Barrier Function: Regulation of Tight Junction Proteins and Epithelial Permeability

    PubMed Central

    Olson, Nels; Greul, Anne-Katrin; Hristova, Milena; Bove, Peter F.; Kasahara, David I.; van der Vliet, Albert

    2008-01-01

    Acute airway inflammation is associated with enhanced production of nitric oxide (NO•) and altered airway epithelial barrier function, suggesting a role of NO• or its metabolites in epithelial permeability. While high concentrations of S-nitrosothiols disrupted transepithelial resistance (TER) and increased permeability in 16HBE14o- cells, no significant barrier disruption was observed by NONOates, in spite of altered distribution and expression of some TJ proteins. Barrier disruption of mouse tracheal epithelial (MTE) cell monolayers in response to inflammatory cytokines was independent of NOS2, based on similar effects in MTE cells from NOS2-/- mice and a lack of effect of the NOS2-inhibitor 1400W. Cell pre-incubation with LPS protected MTE cells from TER loss and increased permeability by H2O2, which was independent of NOS2. However, NOS2 was found to contribute to epithelial wound repair and TER recovery after mechanical injury. Overall, our results demonstrate that epithelial NOS2 is not responsible for epithelial barrier dysfunction during inflammation, but may contribute to restoration of epithelial integrity. PMID:19100237

  9. 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

  10. Claudins: Gatekeepers of lung epithelial function.

    PubMed

    Schlingmann, Barbara; Molina, Samuel A; Koval, Michael

    2015-06-01

    The lung must maintain a proper barrier between airspaces and fluid filled tissues in order to maintain lung fluid balance. Central to maintaining lung fluid balance are epithelial cells which create a barrier to water and solutes. The barrier function of these cells is mainly provided by tight junction proteins known as claudins. Epithelial barrier function varies depending on the different needs within the segments of the respiratory tree. In the lower airways, fluid is required to maintain mucociliary clearance, whereas in the terminal alveolar airspaces a thin layer of surfactant enriched fluid lowers surface tension to prevent airspace collapse and is critical for gas exchange. As the epithelial cells within the segments of the respiratory tree differ, the composition of claudins found in these epithelial cells is also different. Among these differences is claudin-18 which is uniquely expressed by the alveolar epithelial cells. Other claudins, notably claudin-4 and claudin-7, are more ubiquitously expressed throughout the respiratory epithelium. Claudin-5 is expressed by both pulmonary epithelial and endothelial cells. Based on in vitro and in vivo model systems and histologic analysis of lungs from human patients, roles for specific claudins in maintaining barrier function and protecting the lung from the effects of acute injury and disease are being identified. One surprising finding is that claudin-18 and claudin-4 control lung cell phenotype and inflammation beyond simply maintaining a selective paracellular permeability barrier. This suggests claudins have more nuanced roles for the control of airway and alveolar physiology in the healthy and diseased lung. PMID:25951797

  11. Functional imaging and assessment of the glucose diffusion rate in epithelial tissues in optical coherence tomography

    SciTech Connect

    Larin, K V; Tuchin, V V

    2008-06-30

    Functional imaging, monitoring and quantitative description of glucose diffusion in epithelial and underlying stromal tissues in vivo and controlling of the optical properties of tissues are extremely important for many biomedical applications including the development of noninvasive or minimally invasive glucose sensors as well as for therapy and diagnostics of various diseases, such as cancer, diabetic retinopathy, and glaucoma. Recent progress in the development of a noninvasive molecular diffusion biosensor based on optical coherence tomography (OCT) is described. The diffusion of glucose was studied in several epithelial tissues both in vitro and in vivo. Because OCT provides depth-resolved imaging of tissues with high in-depth resolution, the glucose diffusion is described not only as a function of time but also as a function of depth. (special issue devoted to application of laser technologies in biophotonics and biomedical studies)

  12. Respiratory epithelial cells orchestrate pulmonary innate immunity.

    PubMed

    Whitsett, Jeffrey A; Alenghat, Theresa

    2015-01-01

    The epithelial surfaces of the lungs are in direct contact with the environment and are subjected to dynamic physical forces as airway tubes and alveoli are stretched and compressed during ventilation. Mucociliary clearance in conducting airways, reduction of surface tension in the alveoli, and maintenance of near sterility have been accommodated by the evolution of a multi-tiered innate host-defense system. The biophysical nature of pulmonary host defenses are integrated with the ability of respiratory epithelial cells to respond to and 'instruct' the professional immune system to protect the lungs from infection and injury. PMID:25521682

  13. Physiology of Epithelial Chloride and Fluid Secretion

    PubMed Central

    Frizzell, Raymond A.; Hanrahan, John W.

    2012-01-01

    Epithelial salt and water secretion serves a variety of functions in different organ systems, such as the airways, intestines, pancreas, and salivary glands. In cystic fibrosis (CF), the volume and/or composition of secreted luminal fluids are compromised owing to mutations in the gene encoding CFTR, the apical membrane anion channel that is responsible for salt secretion in response to cAMP/PKA stimulation. This article examines CFTR and related cellular transport processes that underlie epithelial anion and fluid secretion, their regulation, and how these processes are altered in CF disease to account for organ-specific secretory phenotypes. PMID:22675668

  14. Propagating Stress Waves During Epithelial Expansion

    NASA Astrophysics Data System (ADS)

    Banerjee, Shiladitya; Utuje, Kazage J. C.; Marchetti, M. Cristina

    2015-06-01

    Coordinated motion of cell monolayers during epithelial wound healing and tissue morphogenesis involves mechanical stress generation. Here we propose a model for the dynamics of epithelial expansion that couples mechanical deformations in the tissue to contractile activity and polarization in the cells. A new ingredient of our model is a feedback between local strain, polarization, and contractility that naturally yields a mechanism for viscoelasticity and effective inertia in the cell monolayer. Using a combination of analytical and numerical techniques, we demonstrate that our model quantitatively reproduces many experimental findings [Nat. Phys. 8, 628 (2012)], including the buildup of intercellular stresses, and the existence of traveling mechanical waves guiding the oscillatory monolayer expansion.

  15. Small incision lenticule extraction (SMILE) and femtosecond laser LASIK: comparison of corneal wound healing and inflammation

    PubMed Central

    Dong, Zixian; Zhou, Xingtao; Wu, Jihong; Zhang, Zhehuan; Li, Tao; Zhou, Zimei; Zhang, Shenghai; Li, Gang

    2014-01-01

    Aim To evaluate and compare early corneal wound healing and inflammatory responses after small incision lenticule extraction (SMILE) versus femtosecond laser laser in situ keratomileusis (LASIK). Methods Thirty-six eyes of 36 rabbits underwent SMILE, while another 36 eyes of 36 rabbits were treated with femtosecond laser LASIK. All the eyes were subjected to the same refractive correction of −6.00 DS/−1.00 DC. Twelve eyes that had no surgery were included for control. After euthanisation, corneal tissue sections were evaluated with terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay to detect apoptosis at postoperative 4 and 24 h, immunocytochemistry for Ki67 to detect keratocyte proliferation at postoperative day 3, week 1 and month 1, and immunocytochemistry for CD11b to detect inflammation at postoperative day 1, day 3 and week 1, respectively. Results No adverse effects were noted after SMILE or LASIK. Corneal healing postoperatively was uneventful in all cases. There were significantly fewer TUNEL-positive corneal stromal cells after the SMILE procedure at 4 and 24 h postoperatively (p<0.01) compared with the LASIK procedure. In addition, immunocytochemistry showed significantly fewer Ki67-positive cells in the SMILE group than those in the femtosecond laser LASIK group at day 3 and week 1 postoperatively (p<0.05), but there was little expression of Ki67 at month 1 postoperatively in both groups. The CD11b-positive cells were significantly fewer in the SMILE group at day 1, day 3 and week 1 postoperatively (p<0.01). Conclusions SMILE induces less keratocyte apoptosis, proliferation and inflammation compared with femtosecond laser LASIK. PMID:24227802

  16. Effect of laser polarization and pulse energy on therapeutic, femtosecond laser-induced second harmonic generation in corneal tissue (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Calhoun, William R.; Ilev, Ilko K.

    2016-03-01

    Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (e.g. cataract surgery), and keratoplasty (cornea transplant), now employ therapeutic infrared femtosecond lasers (FSLs) for their extreme precision, low energy delivered into tissue and advanced ablation characteristics. Although the widely exploited applications of FSLs in medical therapeutics offer significant benefits, FSLs must generate very high intensities in order to achieve optical breakdown, the predominant tissue ablative mechanism, which can also stimulate nonlinear optical effects such as harmonic generation, an effect that generates coherent visible and UV light in the case of second- (SHG) and third-harmonic generation (THG), respectively. In order to improve the understanding of HG in corneal tissue, the effect of FSL polarization and pulse energy were investigated. FSL stimulated SHG intensity in corneal tissue was measured as the laser polarization was rotated 360 degrees. Further, the pulse energy at the SHG wavelength were measured for single FSL pulses as the pulse energy at the fundamental wavelength was varied through a range of clinically relevant values. The results of this study revealed SHG intensity oscillated with laser polarization, having a variation greater than 20%. This relationship seems to due to the intrinsic anisotropy of collagen fibril hyperpolarizability, not related to tissue birefringence. SHG pulse energy measurements showed an increase in SHG pulse energy with increasing FSL pulse energy, however conversion efficiency decreased. This may be related to the dynamic relationship between optical breakdown leading to tissue destruction and HG evolution.

  17. Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

    EPA Science Inventory

    The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

  18. Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling.

    PubMed

    Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru

    2016-01-01

    Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity. PMID:27431614

  19. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    SciTech Connect

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  20. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation

    PubMed Central

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2016-01-01

    Summary Cellular senescence suppresses cancer by arresting cells at risk of malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation and branching morphogenesis. Furthermore, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts – the ability to alter epithelial differentiation – that might also explain the loss of tissue function and organization that is a hallmark of aging. PMID:15657080

  1. Iris pigment epithelial cysts in a newborn

    PubMed Central

    Zargar, Shabnam; Prendiville, Kevin John; Martinez, Eladio

    2016-01-01

    Purpose: We report a case of iris pigment epithelial cysts in a newborn and discuss the importance of an accurate diagnosis for prevention of amblyopia. Methods: We describe a case of an abnormal red reflex seen on a newborn exam. Results: A full-term female born via normal spontaneous vaginal delivery without any complications was seen in the newborn nursery. She was noted to have an abnormal eye exam. Pupils were large with circular dark excrescences of the iris pigment epithelium. She was referred to a pediatric ophthalmologist where she was noted to fixate and follow faces. No afferent pupillary defect was seen. OD red reflex was normal whereas OS red reflex was blocked mostly by dark excrescences. A 2–3 mm dark brown lesion was seen in the OD iris and a 3–5 mm dark brown lesion was seen in the OS iris, consistent with a pupillary iris pigment epithelial cyst. Central visual axis was clear OU. Glaucoma was not present and patching was not performed. Observations and clinical photographs were recommended with follow-up in three months. Conclusion: Iris pigment epithelial cysts are uncommonly seen in children. The primary care provider first seeing a newborn must be aware of lesions obscuring a red reflex with appropriate follow-up. Follow-up in three months with IOP measurements is recommended. Iris pigment epithelial cysts in children may be a cause of amblyopia, thus prompt evaluation is important for prognostic purposes and the prevention of amblyopia. PMID:27625966

  2. The buffer capacity of airway epithelial secretions

    PubMed Central

    Kim, Dusik; Liao, Jie; Hanrahan, John W.

    2014-01-01

    The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF). The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 μl) volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO−3 is the major buffer. Peak buffer capacity (β) increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR)-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO−3 secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO−3 secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions. PMID:24917822

  3. Thrombomodulin Promotes Corneal Epithelial Wound Healing

    PubMed Central

    Huang, Yi-Hsun; I, Ching-Chang; Kuo, Cheng-Hsiang; Hsu, Yun-Yan; Lee, Fang-Tzu; Shi, Guey-Yueh; Tseng, Sung-Huei; Wu, Hua-Lin

    2015-01-01

    Purpose To determine the role of thrombomodulin (TM) in corneal epithelial wound healing, and to investigate whether recombinant TM epidermal growth factor-like domain plus serine/threonine-rich domain (rTMD23) has therapeutic potential in corneal epithelial wound healing. Methods TM localization and expression in the murine cornea were examined by immunofluorescence staining. TM expression after injury was also studied. The effect of rTMD23 on corneal wound healing was evaluated by in vitro and in vivo assays. Results TM was expressed in the cornea in normal adult mice. TM expression increased in the early phase of wound healing and decreased after wound recovery. In the in vitro study, platelet-derived growth factor-BB (PDGF-BB) induced TM expression in murine corneal epithelial cells by mediating E26 transformation-specific sequence-1 (Ets-1) via the mammalian target of rapamycin (mTOR) signaling pathway. The administration of rTMD23 increased the rate of corneal epithelial wound healing. Conclusions TM expression in corneal epithelium was modulated during the corneal wound healing process, and may be regulated by PDGF-BB. In addition, rTMD23 has therapeutic potential in corneal injury. PMID:25816372

  4. Odontogenic epithelial hamartomas in periodontal structures.

    PubMed

    Moskow, B S; Baden, E

    1989-02-01

    4 hamartomas apparently derived from remnants of the dental lamina and enamel organ are reported in a collection of human jaw specimens. These epithelial lesions represent a transitional stage between a developmental anomaly and a distinct odontogenic neoplasm. Earlier reports indicated that such lesions with clinical symptoms are rare; however, this study suggests a more common occurrence on a microscopic level. PMID:2921378

  5. Epithelial-mesenchymal transition in liver fibrosis

    PubMed Central

    ZHAO, YA-LEI; ZHU, RONG-TAO; SUN, YU-LING

    2016-01-01

    Liver fibrosis is the result of a sustained wound healing response to sustained chronic liver injury, which includes viral, alcoholic and autoimmune hepatitis. Hepatic regeneration is the dominant outcome of liver damage. The outcomes of successful repair are the replacement of dead epithelial cells with healthy epithelial cells, and reconstruction of the normal hepatic structure and function. Prevention of the development of epithelial-mesenchymal transition (EMT) may control and even reverse liver fibrosis. EMT is a critical process for an epithelial cell to undergo a conversion to a mesenchymal phenotype, and is believed to be an inflammation-induced response, which may have a central role in liver fibrosis. The origin of fibrogenic cells in liver fibrosis remains controversial. Numerous studies have investigated the origin of all fibrogenic cells within the liver and the mechanism of the signaling pathways that lead to the activation of EMT programs during numerous chronic liver diseases. The present study aimed to summarize the evidence to explain the possible role of EMT in liver fibrosis. PMID:26998262

  6. Multifocal epithelial hyperplasia. Report of nine cases.

    PubMed

    Ledesma-Montes, Constantino; Vega-Memije, Elisa; Garcés-Ortíz, Maricela; Cardiel-Nieves, Maritza; Juárez-Luna, Claudia

    2005-01-01

    Multifocal epithelial hyperplasia (MEH) is also known as focal epithelial hyperplasia, Heck's disease or multifocal papillomavirus-induced epithelial hyperplasia. It is characterised by the presence of multiple lesions in the oral mucosa of children and it has been associated with the presence of the human papillomavirus. The aim of this study was to determine the clinico-pathological features of the cases diagnosed as MEH in the Service of Dermatology of the Hospital Manuel Gea González (SDHMGG). The files of the SDHMGG were reviewed and all cases diagnosed as MEH were retrieved. Nine MEH cases were found. Most of the patients were 20 year-old or younger (67%) and females were more commonly affected (78%). All patients presented multiple lesions and always, close relatives with similar lesions were found. Lesions were located most commonly in the buccal mucosa, lower lip and commissures. MEH is a soft tissue intraoral condition that needs treatment solely of the traumatised lesions or those with cosmetic problems. Remaining lesions will disappear with the age of the patients. It is suggested that this entity should be named multifocal epithelial hyperplasia since this name describes better the clinico-pathological and microscopic features of the disease. PMID:16264387

  7. Adaptive epithelial cytoplasm segmentation and epithelial unit separation in immunoflurorescent images

    NASA Astrophysics Data System (ADS)

    Ramachandran, Janakiramanan; Scott, Richard; Ajemba, Peter; Karvir, Hrishikesh; Khan, Faisal; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

    2012-02-01

    Tissue segmentation is one of the key preliminary steps in the morphometric analysis of tissue architecture. In multi-channel immunoflurorescent biomarker images, the primary segmentation steps consist of segmenting the nuclei (epithelial and stromal) and epithelial cytoplasm from 4',6-diamidino-2-phenylindole (DAPI) and cytokeratin 18 (CK18) biomarker images respectively. The epithelial cytoplasm segmentation can be very challenging due to variability in cytoplasm morphology and image staining. A robust and adaptive segmentation algorithm was developed for the purpose of both delineating the boundaries and separating thin gaps that separate the epithelial unit structures. This paper discusses novel methods that were developed for adaptive segmentation of epithelial cytoplasm and separation of epithelial units. The adaptive segmentation was performed by computing the non-epithelial background texture of every CK18 biomarker image. The epithelial unit separation was performed using two complementary techniques: a marker based, center-initialized watershed transform and a boundary initialized fast marching-watershed segmentation. The adaptive segmentation algorithm was tested on 926 CK18 biomarker biopsy images (326 patients) with limited background noise and 1030 prostatectomy images (374 patients) with noisy to very noisy background. The segmentation performance was measured using two different methods, namely; stability and background textural metrics. It was observed that the database of 1030 noisy prostatectomy images had a lower mean value (using stability and three background texture performance metrics) compared to the biopsy dataset of 926 images that had limited background noise. The average of all four performance metrics yielded 94.32% accuracy for prostatectomy images compared to 99.40% accuracy for biopsy images.

  8. Epithelial tight junctions in intestinal inflammation.

    PubMed

    Schulzke, Joerg D; Ploeger, Svenja; Amasheh, Maren; Fromm, Anja; Zeissig, Sebastian; Troeger, Hanno; Richter, Jan; Bojarski, Christian; Schumann, Michael; Fromm, Michael

    2009-05-01

    The epithelium in inflamed intestinal segments of patients with Crohn's disease is characterized by a reduction of tight junction strands, strand breaks, and alterations of tight junction protein content and composition. In ulcerative colitis, epithelial leaks appear early due to micro-erosions resulting from upregulated epithelial apoptosis and in addition to a prominent increase of claudin-2. Th1-cytokine effects by interferon-gamma in combination with TNFalpha are important for epithelial damage in Crohn's disease, while interleukin-13 (IL-13) is the key effector cytokine in ulcerative colitis stimulating apoptosis and upregulation of claudin-2 expression. Focal lesions caused by apoptotic epithelial cells contribute to barrier disturbance in IBD by their own conductivity and by confluence toward apoptotic foci or erosions. Another type of intestinal barrier defect can arise from alpha-hemolysin harboring E. coli strains among the physiological flora, which can gain pathologic relevance in combination with proinflammatory cytokines under inflammatory conditions. On the other hand, intestinal barrier impairment can also result from transcellular antigen translocation via an initial endocytotic uptake into early endosomes, and this is intensified by proinflammatory cytokines as interferon-gamma and may thus play a relevant role in the onset of IBD. Taken together, barrier defects contribute to diarrhea by a leak flux mechanism (e.g., in IBD) and can cause mucosal inflammation by luminal antigen uptake. Immune regulation of epithelial functions by cytokines may cause barrier dysfunction not only by tight junction impairments but also by apoptotic leaks, transcytotic mechanisms, and mucosal gross lesions. PMID:19538319

  9. Protons Sensitize Epithelial Cells to Mesenchymal Transition

    PubMed Central

    Wang, Minli; Hada, Megumi; Saha, Janapriya; Sridharan, Deepa M.; Pluth, Janice M.; Cucinotta, Francis A.

    2012-01-01

    Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1. PMID:22844446

  10. Epithelial odontogenic tumours in domestic animals.

    PubMed

    Walsh, K M; Denholm, L J; Cooper, B J

    1987-09-01

    Epithelial odontogenic tumours are uncommon, poorly understood and often difficult to diagnose, oral neoplasms. Dental organ pre-ameloblasts and basal lamina induce development of mesenchymal cells into odontoblasts, which produce dentin and induce pre-ameloblasts to mature into secretory ameloblasts. These reciprocal sequential inductive interactions between dental epithelium and mesenchyme form the basis for classifying epithelial odontogenic tumours. There are three tumours classified as non-inductive: ameloblastoma characterized by cords and islands of stellate reticulum with peripheral palisades of polarized columnar cells, adenomatoid ameloblastoma which has acini, rosettes and ducts of polarized columnar cells and stellate reticulum and calcifying epithelial odontogenic tumour which contains foci of Congo-red-positive material surrounded by pleomorphic polygonal epithelial cells. There are five tumours in which induction of mesenchymal tissue is evident: ameloblastic fibroma with characteristics of ameloblastoma plus proliferation of closely associated pulp-like mesenchyme; dentinoma consisting of masses of dentin, often with minimal cellular component; ameloblastic odontoma which contains palisaded epithelium and stellate reticulum as in ameloblastoma, as well as foci of dentin and/or enamel; complex odontoma which is a disorderly array of dentin, enamel, ameloblastic epithelium and odontoblasts; and compound odontoma containing denticles with well-organized tooth morphology. This paper reviews the embryogenesis of teeth and describes six types of epithelial odontogenic tumours in 13 animals. The literature concerning these tumours in nearly 250 animals is reviewed. The most commonly reported tumour is ameloblastoma and the species in which all types are most commonly reported is the dog. PMID:3316314

  11. Klebsiella pneumoniae Is Able to Trigger Epithelial-Mesenchymal Transition Process in Cultured Airway Epithelial Cells

    PubMed Central

    Leone, Laura; Mazzetta, Francesca; Martinelli, Daniela; Valente, Sabatino; Alimandi, Maurizio; Raffa, Salvatore; Santino, Iolanda

    2016-01-01

    The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells. PMID:26812644

  12. Alveolar Epithelial Cells Undergo Epithelial-to-Mesenchymal Transition in Response to Endoplasmic Reticulum Stress*

    PubMed Central

    Tanjore, Harikrishna; Cheng, Dong-Sheng; Degryse, Amber L.; Zoz, Donald F.; Abdolrasulnia, Rasul; Lawson, William E.; Blackwell, Timothy S.

    2011-01-01

    Expression of mutant surfactant protein C (SFTPC) results in endoplasmic reticulum (ER) stress in type II alveolar epithelial cells (AECs). AECs have been implicated as a source of lung fibroblasts via epithelial-to-mesenchymal transition (EMT); therefore, we investigated whether ER stress contributes to EMT as a possible mechanism for fibrotic remodeling. ER stress was induced by tunicamyin administration or stable expression of mutant (L188Q) SFTPC in type II AEC lines. Both tunicamycin treatment and mutant SFTPC expression induced ER stress and the unfolded protein response. With tunicamycin or mutant SFTPC expression, phase contrast imaging revealed a change to a fibroblast-like appearance. During ER stress, expression of epithelial markers E-cadherin and Zonula occludens-1 decreased while expression of mesenchymal markers S100A4 and α-smooth muscle actin increased. Following induction of ER stress, we found activation of a number of pathways, including MAPK, Smad, β-catenin, and Src kinase. Using specific inhibitors, the combination of a Smad2/3 inhibitor (SB431542) and a Src kinase inhibitor (PP2) blocked EMT with maintenance of epithelial appearance and epithelial marker expression. Similar results were noted with siRNA targeting Smad2 and Src kinase. Together, these studies reveal that induction of ER stress leads to EMT in lung epithelial cells, suggesting possible cross-talk between Smad and Src kinase pathways. Dissecting pathways involved in ER stress-induced EMT may lead to new treatment strategies to limit fibrosis. PMID:21757695

  13. Clinical Use of Laser-Microtextured Abutments: A Case Series.

    PubMed

    Shapoff, Cary A; Babushkin, Jeffrey A; Wohl, David J

    2016-01-01

    This article discusses the clinical use of laser-microtextured abutments on dental implant restorations. Four cases are presented, each using one of the four commercially available laser-microtextured abutment styles. Numerous preclinical and clinical studies have shown the positive effects of laser microtexturing on the implant platform in limiting crestal bone loss and benefiting soft tissue stability. Other histologic studies of laser microtexturing on the implant abutment have demonstrated the ability of this specific feature to block epithelial downgrowth and provide a functional connective tissue attachment to the abutment surface. Other abutment designs, styles, and materials have only demonstrated a soft tissue seal with epithelial adhesion and a circular ring of connective tissue fibers around the abutment without direct contact. This article presents clinical and radiographic case examples from a private practice perspective on the longterm successful use of microtextured abutments with respect to crestal bone levels, exceptional soft tissue health, and stability with minimal sulcular depth. PMID:27560683

  14. Laser-assisted hair transplantation: histologic comparison between holmium:YAG and CO2 lasers

    NASA Astrophysics Data System (ADS)

    Chu, Eugene A.; Rabinov, C. Rose; Wong, Brian J.; Krugman, Mark E.

    1999-06-01

    The histological effects of flash-scanned CO2 (λ=10.6μm) and pulsed Holmium:YAG (Ho:YAG, λ=2.12μm) lasers were evaluated in human scalp following the creation of hair transplant recipient channels. Ho:YAG laser irradiation created larger zones of thermal injury adjacent to the laser channels than irradiation with the CO2 laser device. When the two lasers created recipient sites of nearly equal depth, the Holmium:YAG laser caused a larger region of lateral thermal damage (589.30μm) than the CO2 laser (118.07μm). In addition, Holmium:YAG irradiated specimens exhibited fractures or discontinuities beyond the region of clear thermal injury. This shearing effect is consistent with the photoacoustic mechanism of ablation associated with pulsed mid-IR laser irradiation. In contrast, channels created with the CO2 exhibited minimal epithelial disruption and significantly less lateral thermal damage. While the Holmium:YAG laser is a useful tool for ablation soft tissue with minimal char in select applications (sinus surgery, arthroscopic surgery), this study suggests that the use of the CO2 laser for the creation of transplantation recipient channels result in significantly less lateral thermal injury for the laser parameters employed.

  15. CO2 laser biopsies of oral mucosa: an immunocytological and histological comparative study

    NASA Astrophysics Data System (ADS)

    Vitale, Marina C.; Botticelli, Annibale R.; Zaffe, Davide; Martignone, Alessandra; Cisternino, Aurelia; Vezzoni, Franco; Scarpelli, Francesco

    2001-04-01

    The relationship between bioptic technique and tissue preservation has been studied in 18 oral biopsies of young patients obtained by electro surgery or CO2 laser surgery. Biopsies were formalin fixed, paraffin embedded and histologically, histochemically and immunocytochemically treated. All the biopsies show inflammatory cell infiltration, epithelial spongiosis, trichocariosis, supra basal small blisters, and epithelial clefts with lamina detaching from the corium. Histochemistry shows both the presence of edema and acid mucopolysaccharides inside the corium, and variable glycogen content in epithelial cells. Trichocariotic cells show a positive MiB1/Ki67 expression, when they are present. Nevertheless, laser biopsies show a lower amount of basophilic fibrous tissue and of bc12 bodies detection, connected with a higher amount of glycogen, Cytokeratin and MiB1/Ki67 expression in epithelial cells, compared to bovie biopsies. The result show a higher degree of damages in particular at the epithelial level, in electro surgery biopsies rather than laser biopsies. The best epithelial and corium preservation showed by laser biopsies suggest a chance of reversible condition, which can lead to a complete recovery due to its higher capability of restoring tissues.

  16. Non-Muscle Myosin II Regulation of Lung Epithelial Morphology

    PubMed Central

    Plosa, Erin J.; Gooding, Kimberly A.; Zent, Roy; Prince, Lawrence S.

    2012-01-01

    Background The regulation of epithelial cell shape and orientation during lung branching morphogenesis is not clearly understood. Non-muscle myosins regulate cell size, morphology, and planar cell polarity. Here we test the hypothesis that non-muscle myosin II (NM II) regulates lung epithelial morphology in a spatially restricted manner. Results Epithelial cell orientation at airway tips in fetal mouse lungs underwent a significant transformation at E17. Treatment of E15 lung explants with the NM II inhibitor blebbistatin increased airway branching, epithelial cell size, and the degree of anisotropy in epithelial cells lining the airway stalks. In cultured MLE-12 lung epithelial cells, blebbistatin increased cell velocity, but left the migratory response to FGF-10 unchanged. Conclusions In the developing lung, NM II acts to constrain cell morphology and orientation, but may be suppressed at sites of branching and cell migration. The regulation of epithelial orientation may therefore undergo dynamic variations from E15 to E17. PMID:22972683

  17. Comparison of corneal flaps created by Wavelight FS200 and Intralase FS60 femtosecond lasers

    PubMed Central

    Liu, Qian; Zhou, Yue-Hua; Zhang, Jing; Zheng, Yan; Zhai, Chang-Bin; Liu, Jing

    2016-01-01

    AIM To assess and compare the morphology of corneal flaps created by the Wavelight FS200 and Intralase FS60 femtosecond lasers in laser in situ keratomileusis (LASIK). METHODS Four hundred eyes of 200 patients were enrolled in this study and divided into Wavelight FS200 groups (200 eyes) and Intralase FS60 groups (200 eyes). Fourier-domain optical coherence tomography (RTVue OCT) was used to measure the corneal flap thickness of 36 specified measurements on each flap one week after surgery. Results were used to analyze the regularity, uniformity and accuracy of the two types of LASIK flaps. RESULTS The mean thickness of corneal flap and central flap was 105.71±4.72 µm and 105.39±4.50 µm in Wavelight FS200 group and 109.78±11.42 µm and 109.15 ±11.59 µm in Intralase FS60 group, respectively. The flaps made with the Wavelight FS200 femtosecond laser were thinner than those created by the Intralase FS60 femtosecond laser (P=0.000). Corneal flaps in the 2 groups were uniform and regular, showing an almost planar configuration. But the Wavelight FS200 group has more predictability and uniformity of flap creation. The mean deviation between achieved and attempted flap thickness was smaller in the Wavelight FS200 group than that in the Intralase FS60 group, which were 5.18±3.71 µm and 8.68±7.42 µm respectively. The deviation of more than 20 µm was 0.2% measurements in Wavelight FS200 group and 8.29% measurements in Intralase FS60 group. CONCLUSION The morphologies of flaps created by Wavelight FS200 are more uniform and thinner than those created by Intralase FS60. PMID:27500109

  18. Induced pluripotency of human prostatic epithelial cells.

    PubMed

    Zhao, Hongjuan; Sun, Ning; Young, Sarah R; Nolley, Rosalie; Santos, Jennifer; Wu, Joseph C; Peehl, Donna M

    2013-01-01

    Induced pluripotent stem (iPS) cells are a valuable resource for discovery of epigenetic changes critical to cell type-specific differentiation. Although iPS cells have been generated from other terminally differentiated cells, the reprogramming of normal adult human basal prostatic epithelial (E-PZ) cells to a pluripotent state has not been reported. Here, we attempted to reprogram E-PZ cells by forced expression of Oct4, Sox2, c-Myc, and Klf4 using lentiviral vectors and obtained embryonic stem cell (ESC)-like colonies at a frequency of 0.01%. These E-PZ-iPS-like cells with normal karyotype gained expression of pluripotent genes typical of iPS cells (Tra-1-81, SSEA-3, Nanog, Sox2, and Oct4) and lost gene expression characteristic of basal prostatic epithelial cells (CK5, CK14, and p63). E-PZ-iPS-like cells demonstrated pluripotency by differentiating into ectodermal, mesodermal, and endodermal cells in vitro, although lack of teratoma formation in vivo and incomplete demethylation of pluripotency genes suggested only partial reprogramming. Importantly, E-PZ-iPS-like cells re-expressed basal epithelial cell markers (CD44, p63, MAO-A) in response to prostate-specific medium in spheroid culture. Androgen induced expression of androgen receptor (AR), and co-culture with rat urogenital sinus further induced expression of prostate-specific antigen (PSA), a hallmark of secretory cells, suggesting that E-PZ-iPS-like cells have the capacity to differentiate into prostatic basal and secretory epithelial cells. Finally, when injected into mice, E-PZ-iPS-like cells expressed basal epithelial cell markers including CD44 and p63. When co-injected with rat urogenital mesenchyme, E-PZ-iPS-like cells expressed AR and expression of p63 and CD44 was repressed. DNA methylation profiling identified epigenetic changes in key pathways and genes involved in prostatic differentiation as E-PZ-iPS-like cells converted to differentiated AR- and PSA-expressing cells. Our results suggest that

  19. Expression analysis of Matrix Metalloproteinase-9 in epithelialized and non-epithelialized apical periodontitis lesions

    PubMed Central

    Carneiro, Everdan; Menezes, Renato; Garlet, Gustavo Pompermaier; Garcia, Roberto Brandão; Bramante, Clóvis Monteiro; Figueira, Rita; Sogayar, Mari; Granjeiro, José Mauro

    2009-01-01

    OBJECTIVE To determine the expression of matrix metalloproteinase-9 (MMP-9) in apical periodontitis lesions. STUDY DESIGN Nineteen epithelialized and eighteen non-epithelialized apical periodontitis lesions were collected after periapical surgery. After histological processing, serial sectioning, H&E staining and microscopic analysis, 10 epithelialized and 10 non-epithelialized lesions were selected for immunohistochemical analysis for MMP-9 and CD 68. At least 1/3 of each specimen was frozen at −70°C for further mRNA isolation and reverse transcription into cDNA for Real-Time-PCR procedures. The relative expression of a target gene was determined in comparison with reference genes (GAPDH, HPRT, β-actin and BCRP). RESULTS Polymorphonuclear neutrophils, macrophages and lymphocytes were stained for MMP-9 in both types of lesions, and when present, epithelial cells were also stained. The number and the ratio of MMP-9+/total cells were greater in non-epithelialized than epithelialized lesions (p=0.0001) and showed a positive correlation to CD68+/total cells (p=0.045). No significant differences were observed for MMP-9 mRNA expression between ephithelized and non-ephithelized lesions. However, when compared to healthy periapical ligaments, both types of lesions presented increased MMP-9 expression (p<0.0001). CONCLUSION The present data suggest the participation of several inflammatory cells, mainlly CD68+ cells, in the MMP-9 expression in apical periodontitis lesions. MMP-9 could be actively enroled in the ECM degradation in apical periodontitis lesions. PMID:18926740

  20. Establishment of Hertwig's epithelial root sheath/epithelial rests of Malassez cell line from human periodontium.

    PubMed

    Nam, Hyun; Kim, Ji-Hye; Kim, Jae-Won; Seo, Byoung-Moo; Park, Joo-Cheol; Kim, Jung-Wook; Lee, Gene

    2014-07-01

    Human Hertwig's epithelial root sheath/epithelial rests of Malassez (HERS/ERM) cells are epithelial remnants of teeth residing in the periodontium. Although the functional roles of HERS/ERM cells have yet to be elucidated, they are a unique epithelial cell population in adult teeth and are reported to have stem cell characteristics. Therefore, HERS/ERM cells might play a role as an epithelial component for the repair or regeneration of dental hard tissues; however, they are very rare population in periodontium and the primary isolation of them is considered to be difficult. To overcome these problems, we immortalized primary HERS/ERM cells isolated from human periodontium using SV40 large T antigen (SV40 LT) and performed a characterization of the immortalized cell line. Primary HERS/ERM cells could not be maintained for more than 6 passages; however, immortalized HERS/ERM cells were maintained for more than 20 passages. There were no differences in the morphological and immunophenotypic characteristics of HERS/ERM cells and immortalized HERS/ERM cells. The expression of epithelial stem cell and embryonic stem cell markers was maintained in immortalized HERS/ERM cells. Moreover, immortalized HERS/ERM cells could acquire mesenchymal phenotypes through the epithelial-mesenchymal transition via TGF-β1. In conclusion, we established an immortalized human HERS/ERM cell line with SV40 LT and expect this cell line to contribute to the understanding of the functional roles of HERS/ERM cells and the tissue engineering of teeth. PMID:25081036

  1. Desialylation of Spermatozoa and Epithelial Cell Glycocalyx Is a Consequence of Bacterial Infection of the Epididymis.

    PubMed

    Khosravi, Farhad; Michel, Vera; Galuska, Christina E; Bhushan, Sudhanshu; Christian, Philipp; Schuppe, Hans-Christian; Pilatz, Adrian; Galuska, Sebastian P; Meinhardt, Andreas

    2016-08-19

    Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in humans. In men, pathogens can also spread to the genital tract via the continuous ductal system, eliciting bacterial prostatitis and/or epididymo-orchitis. Antibiotic treatment usually clears pathogens in acute epididymitis; however, the fertility of patients can be permanently impaired. Because a premature acrosome reaction was observed in an UPEC epididymitis mouse model, and sialidases on the sperm surface are considered to be activated via proteases of the acrosome, we aimed to investigate whether alterations of the sialome of epididymal spermatozoa and surrounding epithelial cells occur during UPEC infection. In UPEC-elicited acute epididymitis in mice, a substantial loss of N-acetylneuraminic acid residues was detected in epididymal spermatozoa and epithelial cells using combined laser microdissection/HPLC-ESI-MS analysis. In support, a substantial reduction of sialic acid residues bound to the surface of spermatozoa was documented in men with a recent history of E. coli-associated epididymitis. In vitro, such an UPEC induced N-acetylneuraminic acid release from human spermatozoa was effectively counteracted by a sialidase inhibitor. These findings strongly suggest a substantial remodeling of the glycocalyx of spermatozoa and epididymal epithelial cells by endogenous sialidases after a premature acrosome reaction during acute epididymitis. PMID:27339898

  2. Lactobacilli require physical contact to reduce staphylococcal TSST-1 secretion and vaginal epithelial inflammatory response.

    PubMed

    Younes, Jessica A; Reid, Gregor; van der Mei, Henny C; Busscher, Henk J

    2016-06-01

    ITALIC! Staphylococcus aureusbiofilms can be found on vaginal epithelia, secreting toxins and causing inflammation. The co-vaginal species ITALIC! Lactobacilluscan alter staphylococcal-induced epithelial secretion of inflammatory cytokines and quench staphylococcal toxic shock syndrome toxin-1 secretion. It is hypothesized that these effects of lactobacilli require direct physical contact between lactobacilli, staphylococci and the epithelium. Indeed, lactobacilli only reduced ITALIC! S. aureus-induced inflammatory cytokine expression when allowed physical contact with vaginal epithelial cells. Furthermore, a reduction in toxic shock syndrome toxin-1 secretion only occurred when a probiotic ITALIC! Lactobacillusstrain was allowed contact, but not when being physically separated from ITALIC! S. aureus Bacterial-probe atomic force microscopy demonstrated that lactobacilli and staphylococci strongly adhere to epithelial cells, while lactobacilli adhere stronger to staphylococci than staphylococci to each other, giving lactobacilli opportunity to penetrate and reside in staphylococcal biofilms, as visualized using confocal laser scanning microscopy with fluorescence ITALIC! in situhybridization probes. These results identify that physical contact and biochemical signaling by lactobacilli are intrinsically linked mechanisms that reduce virulence of ITALIC! S. aureusbiofilm. PMID:27060097

  3. Goat uterine epithelial cells are susceptible to infection with Caprine Arthritis Encephalitis Virus (CAEV) in vivo

    PubMed Central

    2012-01-01

    The aim of this study was to determine, using immunofluorescence and in situ hybridization, whether CAEV is capable of infecting goat uterine epithelial cells in vivo. Five CAEV seropositive goats confirmed as infected using double nested polymerase chain reaction (dnPCR) on leucocytes and on vaginal secretions were used as CAEV positive goats. Five CAEV-free goats were used as controls. Samples from the uterine horn were prepared for dnPCR, in situ hybridization, and immunofluorescence. The results from dnPCR confirmed the presence of CAEV proviral DNA in the uterine horn samples of infected goats whereas no CAEV proviral DNA was detected in samples taken from the uninfected control goats. The in situ hybridization probe was complementary to part of the CAEV gag gene and confirmed the presence of CAEV nucleic acids in uterine samples. The positively staining cells were seen concentrated in the mucosa of the lamina propria of uterine sections. Finally, laser confocal analysis of double p28/cytokeratin immunolabelled transverse sections of CAEV infected goat uterus, demonstrated that the virus was localized in glandular and epithelial cells. This study clearly demonstrates that goat uterine epithelial cells are susceptible to CAEV infection in vivo. This finding could help to further our understanding of the epidemiology of CAEV, and in particular the possibility of vertical transmission. PMID:22276529

  4. DNA typing of epithelial cells after strangulation.

    PubMed

    Wiegand, P; Kleiber, M

    1997-01-01

    DNA typing was carried out on epithelial cells which were transferred from the hands of the suspect onto the neck of the victim. In an experimental study 16 suspect-victim combinations were investigated for estimating the typing success. Alternatively to an attack against the neck, the upper arm was used for "strangulation". PCR typing was carried out using the short tandem repeat systems (STRs) HumCD4, HumVWF31A (VWA) and Hum-FIBRA (FGA) and the success rate was > 70% for all 3 systems. In most of the cases mixed patterns containing the phenotype of the suspect and the victim were obtained. In a case where strangulation was the cause of death, epithelial cells could be removed from the neck of the victim. The DNA pattern of the suspect could be successfully amplified using four STRs, demonstrating the applicability of this approach for practical casework. PMID:9274940

  5. Probiotic bacteria and intestinal epithelial barrier function.

    PubMed

    Ohland, Christina L; Macnaughton, Wallace K

    2010-06-01

    The intestinal tract is a diverse microenvironment where more than 500 species of bacteria thrive. A single layer of epithelium is all that separates these commensal microorganisms and pathogens from the underlying immune cells, and thus epithelial barrier function is a key component in the arsenal of defense mechanisms required to prevent infection and inflammation. The epithelial barrier consists of a dense mucous layer containing secretory IgA and antimicrobial peptides as well as dynamic junctional complexes that regulate permeability between cells. Probiotics are live microorganisms that confer benefit to the host and that have been suggested to ameliorate or prevent diseases including antibiotic-associated diarrhea, irritable bowel syndrome, and inflammatory bowel disease. Probiotics likely function through enhancement of barrier function, immunomodulation, and competitive adherence to the mucus and epithelium. This review summarizes the evidence about effects of the many available probiotics with an emphasis on intestinal barrier function and the mechanisms affected by probiotics. PMID:20299599

  6. Epithelial Proliferation on Curved Toroidal Surfaces

    NASA Astrophysics Data System (ADS)

    Chang, Ya-Wen; Cruz, Ricardo; Fragkopoulos, Alexandros; Marquez, Samantha; Garcia, Andres; Fernandez-Nieves, Alberto

    Cellular environment influences a multitude of cellular functions by providing chemical and physical signals that modulate cell behavior, dynamics, development, and eventually survival. In strongly interacting epithelial cells, cells coordinate their behavior to respond to mechanical constraints in 2D. Local differences in tissue tension has also been shown to impact cell reproduction within an epithelial-cell sheet. Much less is known about how cells respond to out-of-plane curvatures. Here, we describe the proliferation of MDCK on toroidal hydrogel substrates, which unlike spheres or planes, have regions of both positive and negative Gaussian curvature. Additionally, the range of curvatures can be controlled by varying the size and aspect ratio of the torus, allowing us to quantify the relation between substrate curvature and cell proliferation.

  7. Retinal pigment epithelial change and partial lipodystrophy.

    PubMed Central

    Davis, T. M.; Holdright, D. R.; Schulenberg, W. E.; Turner, R. C.; Joplin, G. F.

    1988-01-01

    Cuticular drusen and retinal pigment epithelial changes were found incidentally in a 27 year old Lebanese woman during assessment of partial lipodystrophy. Her vision was normal despite involvement of both maculae. The patient had hypocomplementaemia, but serum C3 nephritic factor was absent and renal function was normal. She had impaired glucose tolerance and a continuous infusion of glucose with model assessment (CIGMA) test revealed low normal tissue insulin sensitivity and high normal pancreatic beta cell function. Mild fasting hypertriglyceridaemia (2.0 mmol/l) may have been secondary to impaired insulin sensitivity. Endocrine function was otherwise normal apart from a completely absent growth hormone response to adequate hypoglycaemia. The simultaneous occurrence of partial lipodystrophy and retinal pigmentary epithelial and basement membrane changes appears to be a newly recognized syndrome. Images Figure 1 Figure 2 PMID:3255937

  8. Extensive Focal Epithelial Hyperplasia: A Case Report

    PubMed Central

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck’s disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis. PMID:26351501

  9. Laser therapy as the method of choice in treating young women with CIN lesions of the uterine cervix and VIN lesions of the vulva

    NASA Astrophysics Data System (ADS)

    Knapp, Piotr A.

    1996-03-01

    The aim of the studies was to attempt to investigate the results of treating young women with CIN I - III of the cervix and epithelial VIN I - III lesions of the vulva by means of the laser technique (vaporization).

  10. [Complications of corneal lamellar refractive surgery].

    PubMed

    Kohnen, T; Remy, M

    2015-12-01

    Techniques available for corneal lamellar refractive surgery are laser-assisted in situ keratomileusis (LASIK) using a microkeratome or femtosecond laser incision followed by excimer laser corneal ablation, and femtosecond laser-assisted refractive lenticule extraction (ReLEx). These treatments are nowadays considered to be safe and effective standard procedures for surgical correction of mild to moderate ametropia. Possible complications include too small or decentered optical zones, intraoperative flap cutting errors and postoperative inflammation (e.g. diffuse lamellar keratitis, DLK), epithelial or flap folds, epithelial ingrowths or iatrogenic ectasia. The occurrence of complications may be significantly reduced by compliance to corresponding standards of indication and treatment that are based on current scientific knowledge. PMID:26613941

  11. Entry of genital Chlamydia trachomatis into polarized human epithelial cells.

    PubMed Central

    Wyrick, P B; Choong, J; Davis, C H; Knight, S T; Royal, M O; Maslow, A S; Bagnell, C R

    1989-01-01

    To study the initial invasion process(es) of genital chlamydiae, a model system consisting of hormonally maintained primary cultures of human endometrial gland epithelial cells (HEGEC), grown in a polarized orientation on collagen-coated filters, was utilized. After Chlamydia trachomatis inoculation of the apical surface of polarized HEGEC, chlamydiae were readily visualized, by transmission electron microscopy, in coated pits and coated vesicles. This was true for HEGEC maintained in physiologic concentrations of estrogen (proliferative phase) and of estrogen plus progesterone (secretory phase), despite the finding that association of chlamydiae with secretory-phase HEGEC is significantly reduced (P = 0.025; A.S. Maslow, C.H. Davis, J. Choong, and P.B. Wyrick, Am. J. Obstet. Gynecol. 159:1006-1014, 1988). In contrast, chlamydiae were rarely observed in the clathrin-associated structures if the HEGEC were cultured on plastic surfaces. The same pattern of coated pit versus noncoated pit entry was reproducible in HeLa cells. The quantity of coated pits associated with isolated membrane sheets derived from HeLa cells, grown on poly-L-lysine-coated cover slips in medium containing the female hormones, was not significantly different as monitored by radiolabeling studies and by laser scanning microscopy. These data suggest that culture conditions which mimic in vivo cellular organization may enhance entry into coated pits for some obligate intracellular pathogens. Images PMID:2744852

  12. Ontogeny of Intestinal Epithelial Innate Immune Responses

    PubMed Central

    Hornef, Mathias W.; Fulde, Marcus

    2014-01-01

    Emerging evidence indicates that processes during postnatal development might significantly influence the establishment of mucosal host-microbial homeostasis. Developmental and adaptive immunological processes but also environmental and microbial exposure early after birth might thus affect disease susceptibility and health during adult life. The present review aims at summarizing the current understanding of the intestinal epithelial innate immune system and its developmental and adaptive changes after birth. PMID:25346729

  13. Fibro-epithelial hyperplasia mimicking mucocele.

    PubMed

    Jain, K; Singh, B D; Dubey, A; Avinash, A

    2014-01-01

    The effects of chronic local irritation have been seen commonly in the form of fibroma or mucocele in children. We report a ten year old girl with the chief complaint of swelling in the lower right region of labial mucosa which was diagnosed clinically as mucocele and histologically as fibro-epithelial hyperplasia. Surgical excision was done under local anesthesia with no post-operative complication. PMID:25552222

  14. Epithelial Notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity.

    PubMed

    Tsao, Po-Nien; Matsuoka, Chisa; Wei, Shu-Chen; Sato, Atsuyasu; Sato, Susumu; Hasegawa, Koichi; Chen, Hung-Kuan; Ling, Thai-Yen; Mori, Munemasa; Cardoso, Wellington V; Morimoto, Mitsuru

    2016-07-19

    Abnormal enlargement of the alveolar spaces is a hallmark of conditions such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. Notch signaling is crucial for differentiation and regeneration and repair of the airway epithelium. However, how Notch influences the alveolar compartment and integrates this process with airway development remains little understood. Here we report a prominent role of Notch signaling in the epithelial-mesenchymal interactions that lead to alveolar formation in the developing lung. We found that alveolar type II cells are major sites of Notch2 activation and show by Notch2-specific epithelial deletion (Notch2(cNull)) a unique contribution of this receptor to alveologenesis. Epithelial Notch2 was required for type II cell induction of the PDGF-A ligand and subsequent paracrine activation of PDGF receptor-α signaling in alveolar myofibroblast progenitors. Moreover, Notch2 was crucial in maintaining the integrity of the epithelial and smooth muscle layers of the distal conducting airways. Our data suggest that epithelial Notch signaling regulates multiple aspects of postnatal development in the distal lung and may represent a potential target for intervention in pulmonary diseases. PMID:27364009

  15. Andrographolide suppresses epithelial mesenchymal transition by inhibition of MAPK signalling pathway in lens epithelial cells.

    PubMed

    Kayastha, Forum; Johar, Kaid; Gajjar, Devarshi; Arora, Anshul; Madhu, Hardik; Ganatra, Darshini; Vasavada, Abhay

    2015-06-01

    Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown. The purpose of this study is to evaluate the effect of andrographolide on EMT induced by growth factors in the fetal human lens epithelial cell line (FHL 124). Initially the LECs were treated with growth factors (TGF-beta 2 and bFGF) to induce EMT. Subsequently these EMT-induced cells were treated with andrographolide at 100 and 500 nM concentrations for 24 h. Our results showed that FHL 124 cells treated with growth factors had a significant decrease in protein and m-RNA levels of epithelial markers pax6 and E-Cadherin. After administering andrographolide, these levels significantly increased. It was noticed that EMT markers alpha-SMA, fibronectin and collagen IV significantly decreased after treatment with andrographolide when compared to the other group. Treatment with andrographolide significantly inhibited phosphorylation of ERK and JNK. Cell cycle analysis showed that andrographolide did not arrest cells at G0/G1 or G2/M at tested concentrations. Our findings suggest that andrographolide helps sustain epithelial characteristics by modulating EMT markers and inhibiting the mitogen-activated protein kinase (MAPK) signalling pathway in LECs. Hence it can prove to be useful in curbing EMT-mediated PCO. PMID:25963259

  16. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update

    PubMed Central

    Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan

    2015-01-01

    Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514

  17. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    SciTech Connect

    Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  18. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update.

    PubMed

    Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan

    2015-05-16

    Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514

  19. An epithelial armamentarium to sense the microbiota.

    PubMed

    Prescott, David; Lee, Jooeun; Philpott, Dana J

    2013-11-30

    Intestinal epithelial cells were once thought to be inert, non-responsive cells that simply acted as a physical barrier that prevents the contents of the intestinal lumen from accessing the underlying tissue. However, it is now clear that these cells express a full repertoire of Toll- and Nod-like receptors, and that their activation by components of the microbiota is vital for the development of a functional epithelium, maintenance of barrier integrity, and defense against pathogenic organisms. Additionally, mounting evidence suggests that epithelial sensing of bacteria plays a significant role in the management of the numbers and types of microbes present in the gut microbiota via the production of antimicrobial peptides and other microbe-modulatory products. This is a critical process, as it is now becoming apparent that alterations in the composition of the microbiota can predispose an individual to a wide variety of chronic diseases. In this review, we will discuss the bacterial pattern recognition receptors that are known to be expressed by the intestinal epithelium, and how each of them individually contributes to these vital protective functions. Moreover, we will review what is known about the communication between epithelial cells and various classes of underlying leukocytes, and discuss how they interact with the microbiota to form a three-part relationship that maintains homeostasis in the gut. PMID:24169517

  20. Epithelial-mesenchymal transition in gastric cancer

    PubMed Central

    Huang, Lei; Wu, Ruo-Lin; Xu, A-Man

    2015-01-01

    Gastric cancer (GC) is one of the most common malignancies worldwide with poor prognosis for lack of early detection and effective treatment modalities. The significant influence of tumor microenvironment on malignant cells has been extensively investigated in this targeted-therapy era. Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process that is critical for embryogenesis and some other pathophysiological processes, especially tumor genesis and progression. Aberrant gastric EMT activation could endow gastric epithelial cells with increased mesenchymal characteristics and less epithelial features, and promote cancer cell stemness, initiation, invasion, metastasis, and chemo-resistance with cellular adhesion molecules especially E-cadherin concomitantly repressed, which allows tumor cells to disseminate and spread throughout the body. Some pathogens, stress, and hypoxia could induce and aggravate GC via EMT, which is significantly correlated with prognosis. GC EMT is modulated by diverse micro-environmental, membrane, and intracellular cues, and could be triggered by various overexpressed transcription factors, which are downstream of several vital cross-talking signaling pathways including TGF-β, Wnt/β-catenin, Notch, etc. microRNAs also contribute significantly to GC EMT modulation. There are currently some agents which could suppress GC EMT, shedding light on novel anti-malignancy strategies. Investigating potential mechanisms modulating GC cell EMT and discovering novel EMT regulators will further elucidate GC biology, and may provide new biomarkers for early GC detection and potentially efficient targets for preventative and curative anti-GC intervention approaches to prevent local and distant invasions. PMID:26807164

  1. Normal and Abnormal Epithelial Differentiation in the Female Reproductive Tract

    PubMed Central

    Kurita, Takeshi

    2011-01-01

    In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences. PMID:21612855

  2. Laser ignition

    DOEpatents

    Early, James W.; Lester, Charles S.

    2002-01-01

    In the apparatus of the invention, a first excitation laser or other excitation light source is used in tandem with an ignitor laser to provide a compact, durable, engine deployable fuel ignition laser system. The beam from the excitation light source is split with a portion of it going to the ignitor laser and a second portion of it being recombined with the first portion after a delay before injection into the ignitor laser. Reliable fuel ignition is provided over a wide range of fuel conditions by using a single remote excitation light source for one or more small lasers located proximate to one or more fuel combustion zones.

  3. ABCG2 Transporter Identifies a Population of Clonogenic Human Limbal Epithelial Cells

    PubMed Central

    de Paiva, Cintia S.; Chen, Zhuo; Corrales, Rosa M.; Pflugfelder, Stephen C.; Li, De-Quan

    2010-01-01

    ABCG2, a member of the ATP binding cassette (ABC) transporters, has been identified as a molecular determinant for bone marrow stem cells and proposed as a universal marker for stem cells. This study investigates ABCG2 expression and its potential as a marker that identifies human limbal epithelial stem cells. ABCG2 expression was evaluated by immunofluorescent and immunohistochemical staining, laser scanning confocal microscopy, flow cytometry, and semiquantitative reverse transcription–polymerase chain reaction. Cells selected from primary limbal epithelial cultures by flow cytometry with ABCG2 monoclonal antibody (mAb) or Hoechst 33342 dye staining were evaluated for their gene expression and colony-forming efficiency (CFE). ABCG2 protein was mainly located in the basal cells of limbal epithelia but not in the limbal suprabasal and corneal epithelia. ABCG2 staining was also observed in primary limbal epithelial cultures. Limbal epithelia express higher levels of ABCG2 and ΔNp63 mRNAs than corneal epithelia. Labeling with ABCG2 mAb yielded 2.5%–3.0% positive cells by flow cytometry. The ABCG2-positive cells exhibited greater CFE on a 3T3 fibroblast feeder layer than ABCG2-negative cells. A side population (SP) was detected by the Hoechst 33342 exclusion assay. SP cells displayed stronger expression of ABCG2 and ΔNp63 mRNA and greater CFE than the non-SP cells. In conclusion, these findings demonstrate that ABCG2 transporter was exclusively expressed by limbal basal cells and that the ABCG2-positive and SP cells possess enriched stem cell properties, suggesting for the first time that ABCG2 could serve as a marker to identify the putative limbal epithelial stem cells. PMID:15625123

  4. In vitro ultraviolet–induced damage in human corneal, lens, and retinal pigment epithelial cells

    PubMed Central

    Youn, Hyun-Yi; Sivak, Jacob G.; Jones, Lyndon W.

    2011-01-01

    Purpose The purpose was to develop suitable in vitro methods to detect ocular epithelial cell damage when exposed to UV radiation, in an effort to evaluate UV-absorbing ophthalmic biomaterials. Methods Human corneal epithelial cells (HCEC), lens epithelial cells (HLEC), and retinal pigment epithelial cells (ARPE-19) were cultured and Ultraviolet A/Ultraviolet B (UVA/UVB) blocking filters and UVB-only blocking filters were placed between the cells and a UV light source. Cells were irradiated with UV radiations at various energy levels with and without filter protections. Cell viability after exposure was determined using the metabolic dye alamarBlue and by evaluating for changes in the nuclei, mitochondria, membrane permeability, and cell membranes of the cells using the fluorescent dyes Hoechst 33342, rhodamine 123, calcein AM, ethidium homodimer-1, and annexin V. High-resolution images of the cells were taken with a Zeiss 510 confocal laser scanning microscope. Results The alamarBlue assay results of UV-exposed cells without filters showed energy level-dependent decreases in cellular viability. However, UV treated cells with 400 nm LP filter protection showed the equivalent viability to untreated control cells at all energy levels. Also, UV irradiated cells with 320 nm LP filter showed lower cell viability than the unexposed control cells, yet higher viability than UV-exposed cells without filters in an energy level-dependent manner. The confocal microscopy results also showed that UV radiation can cause significant dose-dependent degradations of nuclei and mitochondria in ocular cells. The annexin V staining also showed an increased number of apoptotic cells after UV irradiation. Conclusions The findings suggest that UV-induced HCEC, HLEC, and ARPE-19 cell damage can be evaluated by bioassays that measure changes in the cell nuclei, mitochondria, cell membranes, and cell metabolism, and these assay methods provide a valuable in vitro model for evaluating the

  5. Lasers of All Sizes

    NASA Astrophysics Data System (ADS)

    Balcou, Philippe; Forget, Sébastien Robert-Philip, Isabelle

    2015-10-01

    * Introduction * The Laser in All Its Forms * Gas lasers * Dye lasers * Solid-state lasers * Lasers for Every Taste * The rise of lasers * Lasers of all sizes * The colors of the rainbow... and beyond * Shorter and shorter lasers * Increasingly powerful lasers * Lasers: A Universal Tool? * Cutting, welding, and cleaning * Communicating * Treating illnesses * Measuring * Supplying energy? * Entertaining * Understanding * Conclusion

  6. Refractive surgery: the future of perfect vision?

    PubMed

    Fong, C S

    2007-08-01

    The history of refractive eye surgery is recent, but has seen rapid advancement. Older technologies, such as radial keratectomy, had the problem of overcorrection and epithelial complications. Newer technologies, such as photorefractive keratectomy, laser-assisted in-situ keratomileusis (LASIK) and laser-assisted subepithelial keratomileusis (LASEK), which require the use of laser, has revolutionised eye surgery. However, there are complications, such as corneal hazing, postoperative pain, regression, and poorer correction for high myopes. If not contraindicated, wavefront analysis and femtosecond laser are useful adjuncts to laser photoablation for better visual results. Wavefront analysis improves the precision of laser photoablation by measuring the individual's wavefront aberrations, while femtosecond laser offers an instrument-free means of creating the corneal hinge. Lastly, implantation of intraocular lenses, with or without extraction of the crystalline lens, provides an alternative to laser photoablation for the treatment of high myopia. Clear lens exchange offers refractive correction to presbyopes and people with cataracts. However, complications, such as endothelial cell loss, cataract formation and retinal detachment, exist. In conclusion, refractive eye surgery provides an alternative to wearing spectacles or contact lenses. However, potential patients must be warned of the complications and long-term effects on the eyes. PMID:17657376

  7. Control of local immunity by airway epithelial cells.

    PubMed

    Weitnauer, M; Mijošek, V; Dalpke, A H

    2016-03-01

    The lung is ventilated by thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbial compounds, most of them harmless contaminants. Airway epithelial cells are known to have innate sensor functions, thus being able to detect microbial danger. To avoid chronic inflammation, the pulmonary system has developed specific means to control local immune responses. Even though airway epithelial cells can act as proinflammatory promoters, we propose that under homeostatic conditions airway epithelial cells are important modulators of immune responses in the lung. In this review, we discuss epithelial cell regulatory functions that control reactivity of professional immune cells within the microenvironment of the airways and how these mechanisms are altered in pulmonary diseases. Regulation by epithelial cells can be divided into two mechanisms: (1) mediators regulate epithelial cells' innate sensitivity in cis and (2) factors are produced that limit reactivity of immune cells in trans. PMID:26627458

  8. Innate lymphoid cells regulate intestinal epithelial cell glycosylation.

    PubMed

    Goto, Yoshiyuki; Obata, Takashi; Kunisawa, Jun; Sato, Shintaro; Ivanov, Ivaylo I; Lamichhane, Aayam; Takeyama, Natsumi; Kamioka, Mariko; Sakamoto, Mitsuo; Matsuki, Takahiro; Setoyama, Hiromi; Imaoka, Akemi; Uematsu, Satoshi; Akira, Shizuo; Domino, Steven E; Kulig, Paulina; Becher, Burkhard; Renauld, Jean-Christophe; Sasakawa, Chihiro; Umesaki, Yoshinori; Benno, Yoshimi; Kiyono, Hiroshi

    2014-09-12

    Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosylation are unknown. Here, we show that type 3 innate lymphoid cells (ILC3) induced intestinal epithelial Fut2 expression and fucosylation in mice. This induction required the cytokines interleukin-22 and lymphotoxin in a commensal bacteria-dependent and -independent manner, respectively. Disruption of intestinal fucosylation led to increased susceptibility to infection by Salmonella typhimurium. Our data reveal a role for ILC3 in shaping the gut microenvironment through the regulation of epithelial glycosylation. PMID:25214634

  9. Polarized Protein Transport and Lumen Formation During Epithelial Tissue Morphogenesis

    PubMed Central

    Blasky, Alex J.; Mangan, Anthony; Prekeris, Rytis

    2015-01-01

    One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo. PMID:26359775

  10. Epithelial Anion Transport as Modulator of Chemokine Signaling

    PubMed Central

    Schnúr, Andrea; Hegyi, Péter; Rousseau, Simon; Lukacs, Gergely L.; Veit, Guido

    2016-01-01

    The pivotal role of epithelial cells is to secrete and absorb ions and water in order to allow the formation of a luminal fluid compartment that is fundamental for the epithelial function as a barrier against environmental factors. Importantly, epithelial cells also take part in the innate immune system. As a first line of defense they detect pathogens and react by secreting and responding to chemokines and cytokines, thus aggravating immune responses or resolving inflammatory states. Loss of epithelial anion transport is well documented in a variety of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, pancreatitis, and cholestatic liver disease. Here we review the effect of aberrant anion secretion with focus on the release of inflammatory mediators by epithelial cells and discuss putative mechanisms linking these transport defects to the augmented epithelial release of chemokines and cytokines. These mechanisms may contribute to the excessive and persistent inflammation in many respiratory and gastrointestinal diseases. PMID:27382190

  11. Cell Division Drives Epithelial Cell Rearrangements during Gastrulation in Chick.

    PubMed

    Firmino, Joao; Rocancourt, Didier; Saadaoui, Mehdi; Moreau, Chloe; Gros, Jerome

    2016-02-01

    During early embryonic development, cells are organized as cohesive epithelial sheets that are continuously growing and remodeled without losing their integrity, giving rise to a wide array of tissue shapes. Here, using live imaging in chick embryo, we investigate how epithelial cells rearrange during gastrulation. We find that cell division is a major rearrangement driver that powers dramatic epithelial cell intercalation events. We show that these cell division-mediated intercalations, which represent the majority of epithelial rearrangements within the early embryo, are absolutely necessary for the spatial patterning of gastrulation movements. Furthermore, we demonstrate that these intercalation events result from overall low cortical actomyosin accumulation within the epithelial cells of the embryo, which enables dividing cells to remodel junctions in their vicinity. These findings uncover a role for cell division as coordinator of epithelial growth and remodeling that might underlie various developmental, homeostatic, or pathological processes in amniotes. PMID:26859350

  12. Laser therapy

    MedlinePlus

    ... be used for many medical purposes. Because the laser beam is so small and precise, it allows health care providers to safely treat tissue without injuring the surrounding area. Lasers are often used to: Treat varicose veins Improve ...

  13. Laser microphone

    DOEpatents

    Veligdan, James T.

    2000-11-14

    A microphone for detecting sound pressure waves includes a laser resonator having a laser gain material aligned coaxially between a pair of first and second mirrors for producing a laser beam. A reference cell is disposed between the laser material and one of the mirrors for transmitting a reference portion of the laser beam between the mirrors. A sensing cell is disposed between the laser material and one of the mirrors, and is laterally displaced from the reference cell for transmitting a signal portion of the laser beam, with the sensing cell being open for receiving the sound waves. A photodetector is disposed in optical communication with the first mirror for receiving the laser beam, and produces an acoustic signal therefrom for the sound waves.

  14. Chromatin-based Mechanisms of Renal Epithelial Differentiation

    PubMed Central

    2011-01-01

    Successful regenerative renal medicine depends on understanding the molecular mechanisms by which diverse phenotypes of epithelial cells differentiate from metanephric mesenchyme to populate nephrons. Whereas many genes are maintained in a poised state within the population of pluripotent progenitors, specialized epithelial functions reflect the selective expression of a subset of genes and the repression of all others. Here we highlight some common mechanisms of cell differentiation and epigenetic regulation to discuss their implications for renal epithelial development, repair, and disease. PMID:21700830

  15. Nonablative lasers.

    PubMed

    Nouri, Keyvan; Rivas, Maria Patricia; Bouzari, Navid; Faghih, Sahar

    2006-06-01

    The trend toward minimally invasive rejuvenation techniques has led to the widespread use of nonablative lasers. Nonablative lasers can be classified in two groups based on their wavelengths: lasers emitting light in the visible range, and those emitting in the infrared range. In this review, different laser and intense pulsed light (IPL) systems are presented and critically discussed along with findings of the studies in the literature. PMID:17173583

  16. An in vitro model for retinal laser damage

    NASA Astrophysics Data System (ADS)

    Denton, Michael L.; Foltz, Michael S.; Schuster, Kurt J.; Estlack, Larry E.; Hodnett, Harvey M.; Noojin, Gary D.; Thomas, Robert J.

    2007-02-01

    Ocular laser exposures resulting in damage at the retina typically involve cellular alterations in the retinal pigment epithelial (RPE) layer. To provide guidelines for eye-safe exposure to lasers, the laser safety community has relied on damage assessment in nonhuman primate studies. Simple and reliable model systems for laser bioeffects that use cultured RPE cells, rather than animals, are thus desirable. We have characterized our artificially pigmented hTERT-RPE1 model by identifying ED 50 thresholds over a wide range of laser parameters and cell culture conditions. When summarized as action spectra and temporal action profiles (log threshold fluence versus log exposure duration), trends (pigment-dependent) in our cell model data are strikingly similar to the threshold trends reported for animal models (literature). In addition, the rapidity and flexibility (laser delivery) with which studies are performed in our culture model has benefited computational modeling efforts.

  17. Is the inflammasome relevant for epithelial cell function?

    PubMed

    Santana, Patricia T; Martel, Jan; Lai, Hsin-Chih; Perfettini, Jean-Luc; Kanellopoulos, Jean M; Young, John D; Coutinho-Silva, Robson; Ojcius, David M

    2016-02-01

    Inflammasomes are intracellular protein complexes that sense microbial components and damage of infected cells. Following activation by molecules released by pathogens or injured cells, inflammasomes activate caspase-1, allowing secretion of the pro-inflammatory cytokines IL-1β and IL-18 from innate immune cells. Inflammasomes are also expressed in epithelial cells, where their function has attracted less attention. Nonetheless, depending on the tissue, epithelial inflammasomes can mediate inflammation, wound healing, and pain sensitivity. We review here recent findings on inflammasomes found in epithelial tissues, highlighting the importance of these protein complexes in the response of epithelial tissues to microbial infections. PMID:26546965

  18. Laser driver

    SciTech Connect

    Culpepper, C.F.

    1989-03-14

    A laser driver for a laser diode is described, consisting of: an impedance matched input buffer amplifier to which a modulation signal is applied; and a current source coupled to the output of the impedance matched input buffer amplifier, the output of the current source providing an essentially constant amplitude a.c. current component coupled to drive the laser diode.

  19. Laser ignition

    DOEpatents

    Early, James W.; Lester, Charles S.

    2004-01-13

    Sequenced pulses of light from an excitation laser with at least two resonator cavities with separate output couplers are directed through a light modulator and a first polarzing analyzer. A portion of the light not rejected by the first polarizing analyzer is transported through a first optical fiber into a first ignitor laser rod in an ignitor laser. Another portion of the light is rejected by the first polarizing analyzer and directed through a halfwave plate into a second polarization analyzer. A first portion of the output of the second polarization analyzer passes through the second polarization analyzer to a second, oscillator, laser rod in the ignitor laser. A second portion of the output of the second polarization analyzer is redirected by the second polarization analyzer to a second optical fiber which delays the beam before the beam is combined with output of the first ignitor laser rod. Output of the second laser rod in the ignitor laser is directed into the first ignitor laser rod which was energized by light passing through the first polarizing analyzer. Combined output of the first ignitor laser rod and output of the second optical fiber is focused into a combustible fuel where the first short duration, high peak power pulse from the ignitor laser ignites the fuel and the second long duration, low peak power pulse directly from the excitation laser sustains the combustion.

  20. Anti-Apoptotic Gene Delivery with cyclo-(d-Trp-Tyr) Peptide Nanotube via Eye Drop Following Corneal Epithelial Debridement

    PubMed Central

    Lee, Yu-Hsing; Chang, Shwu-Fen; Liaw, Jiahorng

    2015-01-01

    Corneal keratocyte apoptosis triggered by cornel debridement is one mechanism of corneal disorders. In this study, the feasibility of cyclo-(d-Trp-Tyr) peptide nanotubes (PNTs) as carriers of caspase 3 silence shRNA delivery was assessed. A model of epithelial injury by epithelial debridement was applied to investigate the feasibility of PNTs as gene delivery carriers on corneal injury. First, the PNTs were found within 2 μm in length and 300 nm in width by an atomic force microscope and confocal laser microscope system. Plasmid DNAs were observed to be associated with PNTs by atomic force microscope and confocal laser scanning microscope. The plasmids were associated with tyrosine of PNTs with a binding constant of 2.7 × 108 M−1. The stability of plasmid DNA with PNTs against the DNase was found at 60 min. Using thioflavin T pre-stained PNTs on the corneal eye drop delivery, the distribution of PNTs was in the epithelial and stroma regions. After corneal debridement, the rhodamine-labeled plasmid DNA and thioflavin T pre-stained PNTs were also delivered and could be observed in the stroma of cornea. PNTs complexed with anti-apoptotic plasmid caspase 3 silencing shRNA eye drop delivery decreased 41% of caspase 3 activity after the first dose by caspase 3 activity and Western blot analysis. PMID:26193308

  1. Effects of CO/sub 2/ laser irradiation on gingiva

    SciTech Connect

    Rossmann, J.A.; Gottlieb, S.; Koudelka, B.M.; McQuade, M.J.

    1987-06-01

    A CO/sub 2/ laser (Coherent Medical Model 400) was used to irradiate the gingival tissue of a cynomolgous monkey to determine laser effects on the epithelium and underlying connective tissue. A focal length of 400 mm and a 10-watt power setting at 0.2- and 0.5-second exposure was used. Biopsy results indicated that a 0.2-second duration of CO/sub 2/ laser irradiation was inadequate to completely de-epithelialize the gingival tissue. A 0.5-second exposure exhibited complete epithelial destruction with little or no disturbance of the underlying connective tissue layer and viable connective tissue 1.0 mm below the impact site.

  2. Epithelial function and dysfunction in asthma.

    PubMed

    Loxham, M; Davies, D E; Blume, C

    2014-11-01

    Asthma was previously defined as an allergic Th2-mediated inflammatory immune disorder. Recently, this paradigm has been challenged because not all pathological changes observed in the asthmatic airways are adequately explained simply as a result of Th2-mediated processes. Contemporary thought holds that asthma is a complex immune disorder involving innate as well as adaptive immune responses, with the clinical heterogeneity of asthma perhaps a result of the different relative contribution of these two systems to the disease. Epidemiological studies show that exposure to certain environmental substances is strongly associated with the risk of developing asthma. The airway epithelium is first barrier to interact with, and respond to, environmental agents (pollution, viral infection, allergens), suggesting that it is a key player in the pathology of asthma. Epithelial cells play a key role in the regulation of tissue homeostasis by the modulation of numerous molecules, from antioxidants and lipid mediators to growth factors, cytokines, and chemokines. Additionally, the epithelium is also able to suppress mechanisms involved in, for example, inflammation in order to maintain homeostasis. An intrinsic alteration or defect in these regulation mechanisms compromises the epithelial barrier, and therefore, the barrier may be more prone to environmental substances and thus more likely to exhibit an asthmatic phenotype. In support of this, polymorphisms in a number of genes that are expressed in the bronchial epithelium have been linked to asthma susceptibility, while environmental factors may affect epigenetic mechanisms that can alter epithelial function and response to environmental insults. A detailed understanding of the regulatory role of the airway epithelium is required to develop new therapeutic strategies for asthma that not only address the symptoms but also the underlining pathogenic mechanism(s) and prevent airway remodelling. PMID:24661647

  3. Expression of the FGFR2 mesenchymal splicing variant in epithelial cells drives epithelial-mesenchymal transition

    PubMed Central

    Ranieri, Danilo; Rosato, Benedetta; Nanni, Monica; Magenta, Alessandra

    2016-01-01

    The FGFRs are receptor tyrosine kinases expressed by tissue-specific alternative splicing in epithelial IIIb or mesenchymal IIIc isoforms. Deregulation of FGF/FGFR signaling unbalances the epithelial-stromal homeostasis and may lead to cancer development. In the epithelial-context, while FGFR2b/KGFR acts as tumor suppressor, FGFR2c appears to play an oncogenic role. Based on our recent observation that the switching of FGFR2b versus FGFR2c induces EMT, here we investigated the biological outcome of the ectopic expression of FGFR2c in normal human keratinocytes. Morphological analysis showed that, differently from FGFR2b overexpression, the forced expression and activation of FGFR2c drive the epithelial cells to acquire a mesenchymal-like shape and actin reorganization. Moreover, the appearance of invasiveness and anchorage-independent growth ability in FGFR2c transfected keratinocytes was consistent with the potential tumorigenic role proposed for this receptor variant. Biochemical and molecular approaches revealed that the observed phenotypic changes were accompanied by modulation of EMT biomarkers and indicated the involvement of EMT transcription factors and miRs. Finally, the analysis of the expression pattern of discriminating markers strongly suggested that activation of FGFR2c triggers a process corresponding to the initiation of the pathological type III EMT, but not to the more physiological type II EMT occurring during FGFR2b-mediated wound healing. PMID:26713601

  4. Topographic confinement of epithelial clusters induces epithelial-to-mesenchymal transition in compliant matrices

    NASA Astrophysics Data System (ADS)

    Nasrollahi, Samila; Pathak, Amit

    2016-01-01

    Epithelial cells disengage from their clusters and become motile by undergoing epithelial-to-mesenchymal transition (EMT), an essential process for both embryonic development and tumor metastasis. Growing evidence suggests that high extracellular matrix (ECM) stiffness induces EMT. In reality, epithelial clusters reside in a heterogeneous microenvironment whose mechanical properties vary not only in terms of stiffness, but also topography, dimensionality, and confinement. Yet, very little is known about how various geometrical parameters of the ECM might influence EMT. Here, we adapt a hydrogel-microchannels based matrix platform to culture mammary epithelial cell clusters in ECMs of tunable stiffness and confinement. We report a previously unidentified role of ECM confinement in EMT induction. Surprisingly, confinement induces EMT even in the cell clusters surrounded by a soft matrix, which otherwise protects against EMT in unconfined environments. Further, we demonstrate that stiffness-induced and confinement-induced EMT work through cell-matrix adhesions and cytoskeletal polarization, respectively. These findings highlight that both the structure and the stiffness of the ECM can independently regulate EMT, which brings a fresh perspective to the existing paradigm of matrix stiffness-dependent dissemination and invasion of tumor cells.

  5. Amniotic epithelial cells promote wound healing in mice through high epithelialization and engraftment.

    PubMed

    Jin, Enze; Kim, Tae-Hee; Han, Seongho; Kim, Sung-Whan

    2016-07-01

    Although human amniotic epithelial cells (AMEs) are an attractive source of stem cells, their therapeutic potential in wound healing has not been fully investigated. We evaluated the therapeutic potential of AMEs for wound healing. Real-time PCR showed that the epithelialization growth factors epidermal growth factor (EGF), platelet-derived growth factor (PDGF)-B and chemotactic factors interleukin-8 (IL-8 or CXCL8) and neutrophil-activating protein-2 (NAP-2 or CXCL7) were upregulated in AMEs compared with adipose-derived mesenchymal stem cells (ADMs). In vitro scratch wound assays revealed that AME-derived conditioned medium substantially accelerated wound closure. Wounds in NOD/SCID mice were created by skin excision, followed by AME transplantation. AMEs implantation significantly accelerated wound healing and increased cellularity and re-epithelialization. Transplanted AMEs exhibited high engraftment rates and expressed keratinocyte-specific proteins and cytokeratin in the wound area, suggesting direct benefits for cutaneous closure. Taken together, these data indicate that AMEs possess therapeutic capability for wound healing through the secretion of epithelialization growth factors and enhanced engraftment properties. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26174407

  6. Topographic confinement of epithelial clusters induces epithelial-to-mesenchymal transition in compliant matrices

    PubMed Central

    Nasrollahi, Samila; Pathak, Amit

    2016-01-01

    Epithelial cells disengage from their clusters and become motile by undergoing epithelial-to-mesenchymal transition (EMT), an essential process for both embryonic development and tumor metastasis. Growing evidence suggests that high extracellular matrix (ECM) stiffness induces EMT. In reality, epithelial clusters reside in a heterogeneous microenvironment whose mechanical properties vary not only in terms of stiffness, but also topography, dimensionality, and confinement. Yet, very little is known about how various geometrical parameters of the ECM might influence EMT. Here, we adapt a hydrogel-microchannels based matrix platform to culture mammary epithelial cell clusters in ECMs of tunable stiffness and confinement. We report a previously unidentified role of ECM confinement in EMT induction. Surprisingly, confinement induces EMT even in the cell clusters surrounded by a soft matrix, which otherwise protects against EMT in unconfined environments. Further, we demonstrate that stiffness-induced and confinement-induced EMT work through cell-matrix adhesions and cytoskeletal polarization, respectively. These findings highlight that both the structure and the stiffness of the ECM can independently regulate EMT, which brings a fresh perspective to the existing paradigm of matrix stiffness-dependent dissemination and invasion of tumor cells. PMID:26728047

  7. MFGE8 regulates TGF-β-induced epithelial mesenchymal transition in endometrial epithelial cells in vitro.

    PubMed

    Yu, Liang; Hu, Rong; Sullivan, Claretta; Swanson, R James; Oehninger, Sergio; Sun, Ying-Pu; Bocca, Silvina

    2016-09-01

    This study investigated the role of milk fat globule-epidermal growth factor-factor 8 (MFGE8) in TGF-β-induced epithelial-mesenchymal transition (EMT) of endometrial epithelial cells. These were in vitro studies using human endometrial epithelial cells and mouse blastocysts. We investigated the ability of TGF-β to induce EMT in endometrial epithelial cells (HEC-1A) by assessment of cytological phenotype (by light and atomic force microscopy), changes in expression of the markers of cell adhesion/differentiation E- and N-cadherin, and of the transcription factor Snail (by immunofluorescence and immunoblotting), and competence to support embryo attachment in a mouse blastocyst outgrowth assay. We also studied the effects of E-cadherin expression in cells transfected by retroviral shRNA vectors specifically silencing MFGE8. Results demonstrated that TGF-β induced EMT as demonstrated by phenotypic cell changes, by a switch of cadherin expression as well as by upregulation of the expression of the mesenchymal markers Snail and Vimentin. Upon MFGE8 knockdown, these processes were interfered with, suggesting that MFGE8 and TGF-β together may participate in regulation of EMT. This study demonstrated for the first time that endometrial MFGE8 modulates TGF-β-induced EMT in human endometrium cells. PMID:27340235

  8. Epithelial Notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity

    PubMed Central

    Tsao, Po-Nien; Matsuoka, Chisa; Wei, Shu-Chen; Sato, Atsuyasu; Sato, Susumu; Hasegawa, Koichi; Chen, Hung-kuan; Ling, Thai-Yen; Mori, Munemasa; Cardoso, Wellington V.; Morimoto, Mitsuru

    2016-01-01

    Abnormal enlargement of the alveolar spaces is a hallmark of conditions such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. Notch signaling is crucial for differentiation and regeneration and repair of the airway epithelium. However, how Notch influences the alveolar compartment and integrates this process with airway development remains little understood. Here we report a prominent role of Notch signaling in the epithelial–mesenchymal interactions that lead to alveolar formation in the developing lung. We found that alveolar type II cells are major sites of Notch2 activation and show by Notch2-specific epithelial deletion (Notch2cNull) a unique contribution of this receptor to alveologenesis. Epithelial Notch2 was required for type II cell induction of the PDGF-A ligand and subsequent paracrine activation of PDGF receptor-α signaling in alveolar myofibroblast progenitors. Moreover, Notch2 was crucial in maintaining the integrity of the epithelial and smooth muscle layers of the distal conducting airways. Our data suggest that epithelial Notch signaling regulates multiple aspects of postnatal development in the distal lung and may represent a potential target for intervention in pulmonary diseases. PMID:27364009

  9. Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling

    PubMed Central

    Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru

    2016-01-01

    Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity. DOI: http://dx.doi.org/10.7554/eLife.15034.001 PMID:27431614

  10. Surgical treatment of thymic epithelial neoplasms.

    PubMed

    Kaiser, Larry R

    2008-06-01

    Resection continues to be the mainstay of treatment for epithelial lesions of the thymus. This has never been in doubt for encapsulated stage I and II lesions, but we recently have come to a greater appreciation of the role of preoperative therapy for locally advanced lesions, particularly stage III disease. For any lesion that presents in the anterior mediastinum and on CT scan does not appear to be eminently resectable, a biopsy should be performed to rule out lymphoma after serum germ cell markers have been obtained to rule out the rare primary mediastinal or metastatic germ cell tumor. PMID:18514128

  11. Macrophage-epithelial interactions in pulmonary alveoli.

    PubMed

    Bhattacharya, Jahar; Westphalen, Kristin

    2016-07-01

    Alveolar macrophages have been investigated for years by approaches involving macrophage extraction from the lung by bronchoalveolar lavage, or by cell removal from lung tissue. Since extracted macrophages are studied outside their natural milieu, there is little understanding of the extent to which alveolar macrophages interact with the epithelium, or with one another to generate the lung's innate immune response to pathogen challenge. Here, we review new evidence of macrophage-epithelial interactions in the lung, and we address the emerging understanding that the alveolar epithelium plays an important role in orchestrating the macrophage-driven immune response. PMID:27170185

  12. Tyrosine kinase gene rearrangements in epithelial malignancies

    PubMed Central

    Shaw, Alice T.; Hsu, Peggy P.; Awad, Mark M.; Engelman, Jeffrey A.

    2014-01-01

    Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as ‘druggable’ targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours. PMID:24132104

  13. 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

  14. Transcriptional Landscape of Glomerular Parietal Epithelial Cells

    PubMed Central

    Gharib, Sina A.; Pippin, Jeffrey W.; Ohse, Takamoto; Pickering, Scott G.; Krofft, Ronald D.; Shankland, Stuart J.

    2014-01-01

    Very little is known about the function of glomerular parietal epithelial cells (PECs). In this study, we performed genome-wide expression analysis on PEC-enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the transcriptional state of PECs under normal conditions. We identified hundreds of differentially expressed genes that mapped to distinct biologic modules including development, tight junction, ion transport, and metabolic processes. Since developmental programs were highly enriched in PECs, we characterized several of their candidate members at the protein level. Collectively, our findings confirm that PECs are multifaceted cells and help define their diverse functional repertoire. PMID:25127402

  15. Active Tensile Modulus of an Epithelial Monolayer

    NASA Astrophysics Data System (ADS)

    Vincent, Romaric; Bazellières, Elsa; Pérez-González, Carlos; Uroz, Marina; Serra-Picamal, Xavier; Trepat, Xavier

    2015-12-01

    A general trait of cell monolayers is their ability to exert contractile stresses on their surroundings. The scaling laws that link such contractile stresses with the size and geometry of constituent cells remain largely unknown. In this Letter, we show that the active tension of an epithelial monolayer scales linearly with the size of the constituent cells, a surprisingly simple relationship. The slope of this relationship defines an active tensile modulus, which depends on the concentration of myosin and spans more than 2 orders of magnitude across cell types and molecular perturbations.

  16. CW laser pumped emerald laser

    SciTech Connect

    Shand, M.L.; Lai, S.T.

    1984-02-01

    A CW laser-pumped emerald laser is reported. A 34 percent output power slope efficiency is observed with longitudinal pumping by a krypton laser in a nearly concentric cavity. The laser has been tuned from 728.8 to 809.0 nm. Losses in emerald are larger than those of alexandrite determined in a similar cavity. The present data also indicate that the excited state absorption minimum is shifted from that of alexandrite. 13 references.

  17. Fabrication of transplantable corneal epithelial and oral mucosal epithelial cell sheets using a novel temperature-responsive closed culture device.

    PubMed

    Nakajima, Ryota; Kobayashi, Toyoshige; Kikuchi, Tetsutaro; Kitano, Yuriko; Watanabe, Hiroya; Mizutani, Manabu; Nozaki, Takayuki; Senda, Naoko; Saitoh, Kazuo; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Takeda, Shizu

    2015-05-01

    Temperature-responsive culture surfaces make it possible to harvest transplantable carrier-free cell sheets. Here, we applied temperature-responsive polymer for polycarbonate surfaces with previously developed closed culture devices for an automated culture system in order to fabricate transplantable stratified epithelial cell sheets. Histological and immunohistochemical analyses and colony-forming assays revealed that corneal epithelial and oral mucosal epithelial cell sheets could be harvested with the temperature-responsive closed culture devices. The results were similar to those obtained using temperature-responsive culture inserts. These results indicate that the novel temperature-responsive closed culture device is useful for fabricating transplantable stratified epithelial cell sheets. PMID:23475606

  18. Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pal, Rahul; Yang, Jinping; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2016-03-01

    The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .

  19. High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells.

    PubMed

    Chen, Yu-Ching; Statt, Sarah; Wu, Reen; Chang, Hao-Teng; Liao, Jiunn-Wang; Wang, Chien-Neng; Shyu, Woei-Cherng; Lee, Chen-Chen

    2016-01-01

    Epithelial-mesenchymal transition (EMT) is implicated in bronchial remodeling and loss of lung function in chronic inflammatory airway diseases. Previous studies showed the involvement of the high mobility group box 1 (HMGB1) protein in the pathology of chronic pulmonary inflammatory diseases. However, the role of HMGB1 in EMT of human airway epithelial cells is still unclear. In this study, we used RNA sequencing to show that HMGB1 treatment regulated EMT-related gene expression in human primary-airway epithelial cells. The top five upregulated genes were SNAI2, FGFBP1, VIM, SPARC (osteonectin), and SERPINE1, while the downregulated genes included OCLN, TJP1 (ZO-1), FZD7, CDH1 (E-cadherin), and LAMA5. We found that HMGB1 induced downregulation of E-cadherin and ZO-1, and upregulation of vimentin mRNA transcription and protein translation in a dose-dependent manner. Additionally, we observed that HMGB1 induced AKT phosphorylation, resulting in GSK3β inactivation, cytoplasmic accumulation, and nuclear translocation of β-catenin to induce EMT in human airway epithelial cells. Treatment with PI3K inhibitor (LY294006) and β-catenin shRNA reversed HMGB1-induced EMT. Moreover, HMGB1 induced expression of receptor for advanced glycation products (RAGE), but not that of Toll-like receptor (TLR) 2 or TLR4, and RAGE shRNA inhibited HMGB1-induced EMT in human airway epithelial cells. In conclusion, we found that HMGB1 induced EMT through RAGE and the PI3K/AKT/GSK3β/β-catenin signaling pathway. PMID:26739898

  20. Laser device

    DOEpatents

    Scott, Jill R.; Tremblay, Paul L.

    2004-11-23

    A laser device includes a target position, an optical component separated a distance J from the target position, and a laser energy source separated a distance H from the optical component, distance H being greater than distance J. A laser source manipulation mechanism exhibits a mechanical resolution of positioning the laser source. The mechanical resolution is less than a spatial resolution of laser energy at the target position as directed through the optical component. A vertical and a lateral index that intersect at an origin can be defined for the optical component. The manipulation mechanism can auto align laser aim through the origin during laser source motion. The laser source manipulation mechanism can include a mechanical index. The mechanical index can include a pivot point for laser source lateral motion and a reference point for laser source vertical motion. The target position can be located within an adverse environment including at least one of a high magnetic field, a vacuum system, a high pressure system, and a hazardous zone. The laser source and an electro-mechanical part of the manipulation mechanism can be located outside the adverse environment. The manipulation mechanism can include a Peaucellier linkage.

  1. Laser device

    DOEpatents

    Scott, Jill R.; Tremblay, Paul L.

    2007-07-10

    A laser device includes a target position, an optical component separated a distance J from the target position, and a laser energy source separated a distance H from the optical component, distance H being greater than distance J. A laser source manipulation mechanism exhibits a mechanical resolution of positioning the laser source. The mechanical resolution is less than a spatial resolution of laser energy at the target position as directed through the optical component. A vertical and a lateral index that intersect at an origin can be defined for the optical component. The manipulation mechanism can auto align laser aim through the origin during laser source motion. The laser source manipulation mechanism can include a mechanical index. The mechanical index can include a pivot point for laser source lateral motion and a reference point for laser source vertical motion. The target position can be located within an adverse environment including at least one of a high magnetic field, a vacuum system, a high pressure system, and a hazardous zone. The laser source and an electro-mechanical part of the manipulation mechanism can be located outside the adverse environment. The manipulation mechanism can include a Peaucellier linkage.

  2. Glass lasers.

    PubMed

    Snitzer, E

    1966-10-01

    After a general discussion of the merits of glass vs. crystals as host materials for laser ions, a summary is given of the various glass lasers. Because of its importance as an efficient, room temperature laser the properties of neodymium are considered in greater detail. This includes the nonlaser properties of Nd(3+) in glass, the spectral and temporal emission characteristics of Nd(3+) lasers, and Nd(3+) laser configurations. Separate sections deal with the other two room temperature lasers which use Yb(3+) or Er(3+). The problem of thermal stability of laser cavities is also discussed. Finally, a survey is given of the glasses that are useful as Faraday rotators. PMID:20057584

  3. Laser ignition

    DOEpatents

    Early, James W.; Lester, Charles S.

    2003-01-01

    In the apparatus of the invention, a first excitation laser or other excitation light source is used in tandem with an ignitor laser to provide a compact, durable, engine deployable fuel ignition laser system. Reliable fuel ignition is provided over a wide range of fuel conditions by using a single remote excitation light source for one or more small lasers located proximate to one or more fuel combustion zones. In a third embodiment, alternating short and long pulses of light from the excitation light source are directed into the ignitor laser. Each of the embodiments of the invention can be multiplexed so as to provide laser light energy sequentially to more than one ignitor laser.

  4. Histopathology of laser skin resurfacing

    NASA Astrophysics Data System (ADS)

    Thomsen, Sharon L.; Baldwin, Bonnie; Chi, Eric; Ellard, Jeff; Schwartz, Jon A.

    1997-05-01

    Pulsed carbon-dioxide laser skin resurfacing is a purportedly 'non-thermal' procedure enjoying wide application as a cosmetic treatment for skin wrinkles. Treatment success has been based on clinical assessments of skin smoothness. Skin lesions (1 cm2) created by one, two or three superimposed carbon-dioxide laser passes were placed on the backs of 28 'fuzzy' Harlan Sprague Dawley rats. The variable laser irradiation parameters included measured energies ranging from 112 to 387/pulse with pulse widths of 65 and 125 microseconds and a repetition rate of 8 Hz. The square, flat laser beam measured 3 mm2 at the focal point. The lesions were collected from 0 to 10 days after treatment for qualitative and quantitative histopathology. Thermal damage and treatment effect tended to increase in severity and, to a lesser extent, depth with increased delivery parameters. In acute lesions, the vacuolated and fragmented, desiccated and thermally coagulated epidermis was partially removed exposing the underlying thermally coagulated dermal collagen and cells. Epidermal and dermal necrosis and slough occurred between 24 to 72 hours after treatment. Epithelial regeneration originated from the adnexa and the lesion edges. Dermal fibrous scar formation began at 5 days below the regenerated epidermis and became more prominent at 7 and 10 days.

  5. Ouabain modulates ciliogenesis in epithelial cells

    PubMed Central

    Larre, Isabel; Castillo, Aida; Flores-Maldonado, Catalina; Contreras, Ruben G.; Galvan, Ivan; Muñoz-Estrada, Jesus; Cereijido, Marcelino

    2011-01-01

    The exchange of substances between higher organisms and the environment occurs across transporting epithelia whose basic features are tight junctions (TJs) that seal the intercellular space, and polarity, which enables cells to transport substances vectorially. In a previous study, we demonstrated that 10 nM ouabain modulates TJs, and we now show that it controls polarity as well. We gauge polarity through the development of a cilium at the apical domain of Madin-Darby canine kidney cells (MDCK, epithelial dog kidney). Ouabain accelerates ciliogenesis in an ERK1/2-dependent manner. Claudin-2, a molecule responsible for the Na+ and H2O permeability of the TJs, is also present at the cilium, as it colocalizes and coprecipitates with acetylated α-tubulin. Ouabain modulates claudin-2 localization at the cilium through ERK1/2. Comparing wild-type and ouabain-resistant MDCK cells, we show that ouabain acts through Na+,K+-ATPase. Taken together, our previous and present results support the possibility that ouabain constitutes a hormone that modulates the transporting epithelial phenotype, thereby playing a crucial role in metazoan life. PMID:22143774

  6. Epithelial NAIPs protect against colonic tumorigenesis.

    PubMed

    Allam, Ramanjaneyulu; Maillard, Michel H; Tardivel, Aubry; Chennupati, Vijaykumar; Bega, Hristina; Yu, Chi Wang; Velin, Dominique; Schneider, Pascal; Maslowski, Kendle M

    2015-03-01

    NLR family apoptosis inhibitory proteins (NAIPs) belong to both the Nod-like receptor (NLR) and the inhibitor of apoptosis (IAP) families. NAIPs are known to form an inflammasome with NLRC4, but other in vivo functions remain unexplored. Using mice deficient for all NAIP paralogs (Naip1-6(Δ/Δ)), we show that NAIPs are key regulators of colorectal tumorigenesis. Naip1-6(Δ/Δ) mice developed increased colorectal tumors, in an epithelial-intrinsic manner, in a model of colitis-associated cancer. Increased tumorigenesis, however, was not driven by an exacerbated inflammatory response. Instead, Naip1-6(Δ/Δ) mice were protected from severe colitis and displayed increased antiapoptotic and proliferation-related gene expression. Naip1-6(Δ/Δ) mice also displayed increased tumorigenesis in an inflammation-independent model of colorectal cancer. Moreover, Naip1-6(Δ/Δ) mice, but not Nlrc4-null mice, displayed hyper-activation of STAT3 and failed to activate p53 18 h after carcinogen exposure. This suggests that NAIPs protect against tumor initiation in the colon by promoting the removal of carcinogen-elicited epithelium, likely in a NLRC4 inflammasome-independent manner. Collectively, we demonstrate a novel epithelial-intrinsic function of NAIPs in protecting the colonic epithelium against tumorigenesis. PMID:25732303

  7. Nuclear microscopy of rat colon epithelial cells

    NASA Astrophysics Data System (ADS)

    Ren, M.; Rajendran, Reshmi; Ng, Mary; Udalagama, Chammika; Rodrigues, Anna E.; Watt, Frank; Jenner, Andrew Michael

    2011-10-01

    Using Nuclear microscopy, we have investigated iron distributions in the colons of Sprague Dawley rats, in order to elucidate heme uptake. Four groups of five Sprague Dawley rats (mean weight 180 g) were fed different purified diets containing either heme diet (2.5% w/w hemoglobin), high fat diet (HFD) (18% w/w fat, 1% w/w cholesterol), 'western' diet (combination of hemoglobin 2.5% and 18% fat, 1% cholesterol) or control diet (7% w/w fat). After 4 weeks, animals were sacrificed by exsanguination after anaesthesia. Thin sections of frozen colon tissue were taken, freeze dried and scanned using nuclear microscopy utilising the techniques PIXE, RBS and STIM. The new data acquisition system (IonDaq) developed in CIBA was used to obtain high resolution images and line scans were used to map the iron distributions across the colon boundaries. The nuclear microscope results indicate that when HFD is given in addition to heme, the iron content of the epithelial cells that line the colon decreases, and the zinc in the smooth muscle wall increases. This implies that the level of heme and fat in diet has an important role in colon health, possibly by influencing epithelial cells directly or changing luminal composition such as bacterial flora or levels of metabolites and cytotoxins.

  8. Modeling continuum of epithelial mesenchymal transition plasticity.

    PubMed

    Mandal, Mousumi; Ghosh, Biswajoy; Anura, Anji; Mitra, Pabitra; Pathak, Tanmaya; Chatterjee, Jyotirmoy

    2016-02-01

    Living systems respond to ambient pathophysiological changes by altering their phenotype, a phenomenon called 'phenotypic plasticity'. This program contains information about adaptive biological dynamism. Epithelial-mesenchymal transition (EMT) is one such process found to be crucial in development, wound healing, and cancer wherein the epithelial cells with restricted migratory potential develop motile functions by acquiring mesenchymal characteristics. In the present study, phase contrast microscopy images of EMT induced HaCaT cells were acquired at 24 h intervals for 96 h. The expression study of relevant pivotal molecules viz. F-actin, vimentin, fibronectin and N-cadherin was carried out to confirm the EMT process. Cells were intuitively categorized into five distinct morphological phenotypes. A population of 500 cells for each temporal point was selected to quantify their frequency of occurrence. The plastic interplay of cell phenotypes from the observations was described as a Markovian process. A model was formulated empirically using simple linear algebra, to depict the possible mechanisms of cellular transformation among the five phenotypes. This work employed qualitative, semi-quantitative and quantitative tools towards illustration and establishment of the EMT continuum. Thus, it provides a newer perspective to understand the embedded plasticity across the EMT spectrum. PMID:26762753

  9. Clinical significance of epithelial-mesenchymal transition

    PubMed Central

    2014-01-01

    The concept of epithelial-mesenchymal transition (EMT), a process where cells change their epithelial towards a mesenchymal phenotype, has gained overwhelming attention especially in the cancer research community. Thousands of scientific reports investigated changes in gene, mRNA and protein expression compatible with EMT and their possible correlation with tumor invasion, metastatic spread or patient prognosis; however, up to now, a proof of clinical significance of the concept is still missing. This review, with a main focus on the role of EMT in tumors, will summarize the basic molecular events underlying EMT including the signaling pathways capable of its induction as well as changes in EMT-associated protein expression and will very briefly touch the role of microRNAs in EMT. We then outline protein markers that are used most frequently for the assessment of EMT in research and diagnostic evaluation of tumor specimens and depict the link between EMT, a cancer stem cell (CSC) phenotype and resistance to conventional antineoplastic therapies. Furthermore, we evaluate a possible correlation between EMT marker expression and patient prognosis as well as current therapeutic concepts targeting the EMT process to slow down or prevent metastatic spread of malignant tumors. PMID:25050175

  10. Epithelial Transport in Inflammatory Bowel Diseases

    PubMed Central

    Ghishan, Fayez K.; Kiela, Pawel R.

    2014-01-01

    The epithelium of the gastrointestinal tract is one of the most versatile tissues in the organism, responsible for providing a tight barrier between dietary and bacterial antigens and the mucosal and systemic immune system, while maintaining efficient digestive and absorptive processes to ensure adequate nutrient and energy supply. Inflammatory Bowel Diseases (IBD; Crohn’s disease and ulcerative colitis) are associated with a breakdown of both functions, which in some cases are clearly interrelated. In this updated literature review, we focus on the effects of intestinal inflammation and the associated immune mediators on selected aspects of the transepithelial transport of macro- and micronutrients. The mechanisms responsible for nutritional deficiencies are not always clear and could be related to decreased intake, malabsorption and excess losses. We summarize the known causes of nutrient deficiencies and the mechanism of IBD-associated diarrhea. We also overview the consequences of impaired epithelial transport, which infrequently transcend its primary purpose to affect the gut microbial ecology and epithelial integrity. While some of those regulatory mechanisms are relatively well established, more work needs to be done to determine how inflammatory cytokines can alter the transport process of nutrients across the gastrointestinal and renal epithelia. PMID:24691115

  11. Generation of Mouse Lung Epithelial Cells

    PubMed Central

    Kasinski, Andrea L.; Slack, Frank J.

    2016-01-01

    Although in vivo models are excellent for assessing various facets of whole organism physiology, pathology, and overall response to treatments, evaluating basic cellular functions, and molecular events in mammalian model systems is challenging. It is therefore advantageous to perform these studies in a refined and less costly setting. One approach involves utilizing cells derived from the model under evaluation. The approach to generate such cells varies based on the cell of origin and often the genetics of the cell. Here we describe the steps involved in generating epithelial cells from the lungs of KrasLSL-G12D/+; p53LSL-R172/+ mice (Kasinski and Slack, 2012). These mice develop aggressive lung adenocarcinoma following cre-recombinase dependent removal of a stop cassette in the transgenes and subsequent expression of Kra-G12D and p53R172. While this protocol may be useful for the generation of epithelial lines from other genetic backgrounds, it should be noted that the Kras; p53 cell line generated here is capable of proliferating in culture without any additional genetic manipulation that is often needed for less aggressive backgrounds.

  12. Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-05-02

    Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  13. 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

  14. Inhibition of corneal epithelial cell migration by cadmium and mercury

    SciTech Connect

    Ubels, J.L.; Osgood, T.B. Medical Coll. of Wisconsin, Milwaukee )

    1991-02-01

    In a previous comparative study of corneal healing in fish, the authors observed that corneal epithelial healing occurs very rapidly in vivo in the marine teleost Myoxocephalus octodecimspinosus (longhorn sculpin) with a 6-mm diameter wound on the mammalian cornea. This rapid healing which permits prompt restoration of the epithelial barrier is apparently an adaptation to the large ionic and osmotic gradients between the environment and the intraocular fluids of the fish. These observations suggested that epithelial healing in the sculpin cornea might be useful model in aquatic biomedical toxicology if an in vitro method for measurement of healing rates could be developed. In this report the authors demonstrate that sculpin eyes maintained in short-term organ culture have a rapid corneal epithelial healing response and that this model can be used to demonstrate the toxic effects of heavy metals on epithelial cell migration.

  15. Multi-functionality and plasticity characterize epithelial cells in Hydra

    PubMed Central

    Buzgariu, W; Al Haddad, S; Tomczyk, S; Wenger, Y; Galliot, B

    2015-01-01

    Epithelial sheets, a synapomorphy of all metazoans but porifers, are present as 2 layers in cnidarians, ectoderm and endoderm, joined at their basal side by an extra-cellular matrix named mesoglea. In the Hydra polyp, epithelial cells of the body column are unipotent stem cells that continuously self-renew and concomitantly express their epitheliomuscular features. These multifunctional contractile cells maintain homeostasis by providing a protective physical barrier, by digesting nutrients, by selecting a stable microbiota, and by rapidly closing wounds. In addition, epithelial cells are highly plastic, supporting the adaptation of Hydra to physiological and environmental changes, such as long starvation periods where survival relies on a highly dynamic autophagy flux. Epithelial cells also play key roles in developmental processes as evidenced by the organizer activity they develop to promote budding and regeneration. We propose here an integrative view of the homeostatic and developmental aspects of epithelial plasticity in Hydra. PMID:26716072

  16. Formation of a Neurosensory Organ by Epithelial Cell Slithering.

    PubMed

    Kuo, Christin S; Krasnow, Mark A

    2015-10-01

    Epithelial cells are normally stably anchored, maintaining their relative positions and association with the basement membrane. Developmental rearrangements occur through cell intercalation, and cells can delaminate during epithelial-mesenchymal transitions and metastasis. We mapped the formation of lung neuroepithelial bodies (NEBs), innervated clusters of neuroendocrine/neurosensory cells within the bronchial epithelium, revealing a targeted mode of cell migration that we named "slithering," in which cells transiently lose epithelial character but remain associated with the membrane while traversing neighboring epithelial cells to reach cluster sites. Immunostaining, lineage tracing, clonal analysis, and live imaging showed that NEB progenitors, initially distributed randomly, downregulate adhesion and polarity proteins, crawling over and between neighboring cells to converge at diametrically opposed positions at bronchial branchpoints, where they reestablish epithelial structure and express neuroendocrine genes. There is little accompanying progenitor proliferation or apoptosis. Activation of the slithering program may explain why lung cancers arising from neuroendocrine cells are highly metastatic. PMID:26435104

  17. Multi-functionality and plasticity characterize epithelial cells in Hydra.

    PubMed

    Buzgariu, W; Al Haddad, S; Tomczyk, S; Wenger, Y; Galliot, B

    2015-01-01

    Epithelial sheets, a synapomorphy of all metazoans but porifers, are present as 2 layers in cnidarians, ectoderm and endoderm, joined at their basal side by an extra-cellular matrix named mesoglea. In the Hydra polyp, epithelial cells of the body column are unipotent stem cells that continuously self-renew and concomitantly express their epitheliomuscular features. These multifunctional contractile cells maintain homeostasis by providing a protective physical barrier, by digesting nutrients, by selecting a stable microbiota, and by rapidly closing wounds. In addition, epithelial cells are highly plastic, supporting the adaptation of Hydra to physiological and environmental changes, such as long starvation periods where survival relies on a highly dynamic autophagy flux. Epithelial cells also play key roles in developmental processes as evidenced by the organizer activity they develop to promote budding and regeneration. We propose here an integrative view of the homeostatic and developmental aspects of epithelial plasticity in Hydra. PMID:26716072

  18. Macrophage-derived LIF and IL1B regulate alpha(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy.

    PubMed

    Jasper, Melinda J; Care, Alison S; Sullivan, Brad; Ingman, Wendy V; Aplin, John D; Robertson, Sarah A

    2011-01-01

    Macrophages accumulate within stromal tissue subjacent to the luminal epithelium in the mouse uterus during early pregnancy after seminal fluid exposure at coitus. To investigate their role in regulating epithelial cell expression of fucosylated structures required for embryo attachment and implantation, fucosyltransferase enzymes Fut1, Fut2 (Enzyme Commission number [EC] 2.4.1.69), and Fut4 (EC 2.4.1.214) and Muc1 and Muc4 mRNAs were quantified by quantitative real-time PCR in uterine epithelial cells after laser capture microdissection in situ or after epithelial cell coculture with macrophages or macrophage-secreted factors. When uterine macrophage recruitment was impaired by mating with seminal plasma-deficient males, epithelial cell Fut2 expression on Day 3.5 postcoitus (pc) was reduced compared to intact-mated controls. Epithelial cell Fut2 was upregulated in vitro by coculture with macrophages or macrophage-conditioned medium (MCM). Macrophage-derived cytokines LIF, IL1B, and IL12 replicated the effect of MCM on Fut2 mRNA expression, and MCM-stimulated expression was inhibited by anti-LIF and anti-IL1B neutralizing antibodies. The effects of acute macrophage depletion on fucosylated structures detected with lectins Ulex europaeus 1 (UEA-1) and Lotus tetragonolobus purpureas (LTP), or LewisX immunoreactivity, were quantified in vivo in Cd11b-dtr transgenic mice. Depletion of macrophages caused a 30% reduction in luminal epithelial UEA-1 staining and a 67% reduction in LewisX staining in uterine tissues of mice hormonally treated to mimic early pregnancy. Together, these data demonstrate that uterine epithelial Fut2 mRNA expression and terminal fucosylation of embryo attachment ligands is regulated in preparation for implantation by factors including LIF and IL1B secreted from macrophages recruited during the inflammatory response to insemination. PMID:20864644

  19. Epithelial restitution and wound healing in inflammatory bowel disease.

    PubMed

    Sturm, Andreas; Dignass, Axel U

    2008-01-21

    Inflammatory bowel disease is characterized by a chronic inflammation of the intestinal mucosa. The mucosal epithelium of the alimentary tract constitutes a key element of the mucosal barrier to a broad spectrum of deleterious substances present within the intestinal lumen including bacterial microorganisms, various dietary factors, gastrointestinal secretory products and drugs. In addition, this mucosal barrier can be disturbed in the course of various intestinal disorders including inflammatory bowel diseases. Fortunately, the integrity of the gastrointestinal surface epithelium is rapidly reestablished even after extensive destruction. Rapid resealing of the epithelial barrier following injuries is accomplished by a process termed epithelial restitution, followed by more delayed mechanisms of epithelial wound healing including increased epithelial cell proliferation and epithelial cell differentiation. Restitution of the intestinal surface epithelium is modulated by a range of highly divergent factors among them a broad spectrum of structurally distinct regulatory peptides, variously described as growth factors or cytokines. Several regulatory peptide factors act from the basolateral site of the epithelial surface and enhance epithelial cell restitution through TGF-beta-dependent pathways. In contrast, members of the trefoil factor family (TFF peptides) appear to stimulate epithelial restitution in conjunction with mucin glycoproteins through a TGF-beta-independent mechanism from the apical site of the intestinal epithelium. In addition, a number of other peptide molecules like extracellular matrix factors and blood clotting factors and also non-peptide molecules including phospholipids, short-chain fatty acids (SCFA), adenine nucleotides, trace elements and pharmacological agents modulate intestinal epithelial repair mechanisms. Repeated damage and injury of the intestinal surface are key features of various intestinal disorders including inflammatory bowel

  20. Documentation of angiotensin II receptors in glomerular epithelial cells

    NASA Technical Reports Server (NTRS)

    Sharma, M.; Sharma, R.; Greene, A. S.; McCarthy, E. T.; Savin, V. J.; Cowley, A. W. (Principal Investigator)

    1998-01-01

    Angiotensin II decreases glomerular filtration rate, renal plasma flow, and glomerular capillary hydraulic conductivity. Although angiotensin II receptors have been demonstrated in mesangial cells and proximal tubule cells, the presence of angiotensin II receptors in glomerular epithelial cells has not previously been shown. Previously, we have reported that angiotensin II caused an accumulation of cAMP and a reorganization of the actin cytoskeleton in cultured glomerular epithelial cells. Current studies were conducted to verify the presence of angiotensin II receptors by immunological and non-peptide receptor ligand binding techniques and to ascertain the activation of intracellular signal transduction in glomerular epithelial cells in response to angiotensin II. Confluent monolayer cultures of glomerular epithelial cells were incubated with angiotensin II, with or without losartan and/or PD-123,319 in the medium. Membrane vesicle preparations were obtained by homogenization of washed cells followed by centrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins followed by multiscreen immunoblotting was used to determine the presence of angiotensin II receptor type 1 (AT1) or type 2 (AT2). Angiotensin II-mediated signal transduction in glomerular epithelial cells was studied by measuring the levels of cAMP, using radioimmunoassay. Results obtained in these experiments showed the presence of both AT1 and AT2 receptor types in glomerular epithelial cells. Angiotensin II was found to cause an accumulation of cAMP in glomerular epithelial cells, which could be prevented only by simultaneous use of losartan and PD-123,319, antagonists for AT1 and AT2, respectively. The presence of both AT1 and AT2 receptors and an increase in cAMP indicate that glomerular epithelial cells respond to angiotensin II in a manner distinct from that of mesangial cells or proximal tubular epithelial cells. Our results suggest that glomerular epithelial

  1. Epithelial restitution and wound healing in inflammatory bowel disease

    PubMed Central

    Sturm, Andreas; Dignass, Axel U

    2008-01-01

    Inflammatory bowel disease is characterized by a chronic inflammation of the intestinal mucosa. The mucosal epithelium of the alimentary tract constitutes a key element of the mucosal barrier to a broad spectrum of deleterious substances present within the intestinal lumen including bacterial microorganisms, various dietary factors, gastrointestinal secretory products and drugs. In addition, this mucosal barrier can be disturbed in the course of various intestinal disorders including inflammatory bowel diseases. Fortunately, the integrity of the gastrointestinal surface epithelium is rapidly reestablished even after extensive destruction. Rapid resealing of the epithelial barrier following injuries is accomplished by a process termed epithelial restitution, followed by more delayed mechanisms of epithelial wound healing including increased epithelial cell proliferation and epithelial cell differentiation. Restitution of the intestinal surface epithelium is modulated by a range of highly divergent factors among them a broad spectrum of structurally distinct regulatory peptides, variously described as growth factors or cytokines. Several regulatory peptide factors act from the basolateral site of the epithelial surface and enhance epithelial cell restitution through TGF-β-dependent pathways. In contrast, members of the trefoil factor family (TFF peptides) appear to stimulate epithelial restitution in conjunction with mucin glycoproteins through a TGF-β-independent mechanism from the apical site of the intestinal epithelium. In addition, a number of other peptide molecules like extracellular matrix factors and blood clotting factors and also non-peptide molecules including phospholipids, short-chain fatty acids (SCFA), adenine nucleotides, trace elements and pharmacological agents modulate intestinal epithelial repair mechanisms. Repeated damage and injury of the intestinal surface are key features of various intestinal disorders including inflammatory bowel

  2. The physiological expression of scavenger receptor SR-B1 in canine endometrial and placental epithelial cells and its potential involvement in pathogenesis of pyometra.

    PubMed

    Gabriel, C; Becher-Deichsel, A; Hlavaty, J; Mair, G; Walter, I

    2016-06-01

    Pyometra, the purulent inflammation of the uterus, is a common uterine disease of bitches that has potentially life-threatening consequences. The opportunistic bacterial infection of the uterus often progresses into the serious systemic inflammatory response syndrome. In a previous study, we characterized epithelial foam cells in the canine endometrial surface occurring in metestrus, and we regularly observed pronounced epithelial foam-cell formations in pyometra-affected uteri. Therefore, it was assumed that the mechanism behind lipid droplet accumulation in surface epithelial cells might even increase bacterial binding capacity and promote pyometra development. Lipid droplet accumulation in epithelial cells is accomplished via specialized lipid receptors called scavenger receptors (SR). Scavenger receptor class B type 1 (SR-B1) is an important receptor for lipid accumulation in diverse cell types, but it is also a strong binding partner for bacteria, and thereby enhances bacterial adhesion and clinical signs of systemic inflammatory response syndrome. In the present study, after the isolation of metestrous surface epithelial cells from canine uteri by laser capture microdissection, SR-B1 was identified at the messenger RNA (mRNA) level by quantitative real time polymerase chain reaction and also at the protein level by means of immunohistochemistry. In pyometra-affected uteri, SR-B1 mRNA expression was higher than that in the healthy control samples, and SR-B1 protein was expressed in the surface and crypt epithelial cells. Furthermore, to understand the physiological role of SR-B1 expression in the metestrus surface epithelial cells, we investigated its expression in the epithelial cells of the glandular chambers of canine placenta in different stages of gestation because these cells are also characterized by lipid droplet accumulation. SR-B1 was present in the placental epithelial cells of the glandular chambers from 25 to 30 and 45 to 50 days of gestation

  3. Laser ignition

    DOEpatents

    Early, James W.; Lester, Charles S.

    2002-01-01

    In the apparatus of the invention, a first excitation laser or other excitation light source is used in tandem with an ignitor laser to provide a compact, durable, engine deployable fuel ignition laser system. Reliable fuel ignition is provided over a wide range of fuel conditions by using a single remote excitation light source for one or more small lasers located proximate to one or more fuel combustion zones. In the embodiment of the invention claimed herein, the beam from the excitation light source is split with a portion of it going to the ignitor laser and a second portion of it being combined with either the first portion after a delay before injection into the ignitor laser.

  4. Laser pyrometry

    NASA Technical Reports Server (NTRS)

    Stein, Alexander

    1988-01-01

    A method of determining the emissivity of a hot target from a laser-based reflectance measurement which is conducted simultaneously with a measurement of the target radiance is described. Once the correct radiance and emissivity are determined, one calculates the true target temperature from these parameters via the Planck equations. The design and performance of a laser pyrometer is described. The accuracy of laser pyrometry and the effect of ambient radiance are addressed.

  5. 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

  6. EDAC: Epithelial defence against cancer-cell competition between normal and transformed epithelial cells in mammals.

    PubMed

    Kajita, Mihoko; Fujita, Yasuyuki

    2015-07-01

    During embryonic development or under certain pathological conditions, viable but suboptimal cells are often eliminated from the cellular society through a process termed cell competition. Cell competition was originally identified in Drosophila where cells with different properties compete for survival; 'loser' cells are eliminated from tissues and consequently 'winner' cells become dominant. Recent studies have shown that cell competition also occurs in mammals. While apoptotic cell death is the major fate for losers in Drosophila, outcompeted cells show more variable phenotypes in mammals, such as cell death-independent apical extrusion and cellular senescence. Molecular mechanisms underlying these processes have been recently revealed. Especially, in epithelial tissues, normal cells sense and actively eliminate the neighbouring transformed cells via cytoskeletal proteins by the process named epithelial defence against cancer (EDAC). Here, we introduce this newly emerging research field: cell competition in mammals. PMID:25991731

  7. Laser ignition

    DOEpatents

    Early, James W.; Lester, Charles S.

    2002-01-01

    In the apparatus of the invention, a first excitation laser or other excitation light source capable of producing alternating beams of light having different wavelengths is used in tandem with one or more ignitor lasers to provide a compact, durable, engine deployable fuel ignition laser system. Reliable fuel ignition is provided over a wide range of fuel conditions by using the single remote excitation light source for pumping one or more small lasers located proximate to one or more fuel combustion zones with alternating wavelengths of light.

  8. Laser polishing

    NASA Astrophysics Data System (ADS)

    Temmler, A.; Willenborg, E.; Wissenbach, K.

    2012-03-01

    A new approach to polish metallic freeform surfaces is polishing by means of laser radiation. In this technology a thin surface layer is molten and the surface tension leads to a material flow from the peaks to the valleys. No material is removed but reallocated while molten. As the typical processing time is 1 min/cm2 laser polishing is up to 30 times faster than manual polishing. Reducing the roughness by laser polishing is achieved for several different materials such as hot work steels for the die and molding industries or titanium alloys for medical engineering. Enhancing the appearance of design surfaces is achieved by creating a dual-gloss effect by selective laser polishing (SLP). In comparison to conventional polishing processes laser polishing opens up the possibility of selective processing of small areas (< 0.1 mm2). A dual-gloss effect is based on a space-resolved change in surface roughness. In comparison to the initial surface the roughness of the laser polished surface is reduced significantly up to spatial wavelengths of 80 microns and therefore the gloss is raised considerably. The surface roughness is investigated by a spectral analysis which is achieved by a discrete convolution of the surface profile with a Gaussian loaded function. The surfaces roughness is split into discrete wavelength intervals and can be evaluated and optimized. Laser polishing is carried out by using a special tailored five-axis mechanical handling system, combined with a three axis laser scanning system and a fibre laser.

  9. Biocavity Lasers

    SciTech Connect

    Gourley, P.L.; Gourley, M.F.

    2000-10-05

    Laser technology has advanced dramatically and is an integral part of today's healthcare delivery system. Lasers are used in the laboratory analysis of human blood samples and serve as surgical tools that kill, burn or cut tissue. Recent semiconductor microtechnology has reduced the size o f a laser to the size of a biological cell or even a virus particle. By integrating these ultra small lasers with biological systems, it is possible to create micro-electrical mechanical systems that may revolutionize health care delivery.

  10. Laser apparatus

    DOEpatents

    Lewis, Owen; Stogran, Edmund M.

    1980-01-01

    Laser apparatus is described wherein an active laser element, such as the disc of a face-pumped laser, is mounted in a housing such that the weight of the element is supported by glass spheres which fill a chamber defined in the housing between the walls of the housing and the edges of the laser element. The uniform support provided by the spheres enable the chamber and the pump side of the laser element to be sealed without affecting the alignment or other optical properties of the laser element. Cooling fluid may be circulated through the sealed region by way of the interstices between the spheres. The spheres, and if desired also the cooling fluid may contain material which absorbs radiation at the wavelength of parasitic emissions from the laser element. These parasitic emissions enter the spheres through the interface along the edge surface of the laser element and it is desirable that the index of refraction of the spheres and cooling fluid be near the index of refraction of the laser element. Thus support, cooling, and parasitic suppression functions are all accomplished through the use of the arrangement.

  11. The SCFA butyrate stimulates the epithelial production of retinoic acid via inhibition of epithelial HDAC.

    PubMed

    Schilderink, Ronald; Verseijden, Caroline; Seppen, Jurgen; Muncan, Vanesa; van den Brink, Gijs R; Lambers, Tim T; van Tol, Eric A; de Jonge, Wouter J

    2016-06-01

    In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA. Functional RA conversion was analyzed by Adlefluor activity assays. Butyrate (0-20 mM), in contrast to other SCFAs, dose dependently induced aldh1a1 or aldh1a3 transcript expression and increased RA conversion in human and mouse epithelial cells. Epithelial cell line data were replicated in intestinal organoids. In these organoids, butyrate (2-5 mM) upregulated aldh1a3 expression (36-fold over control), whereas aldh1a1 was not significantly affected. Butyrate enhanced maturation markers (Mucin-2 and villin) but did not consistently affect stemness markers or other Wnt target genes (lgr5, olfm4, ascl2, cdkn1). In enteroids, the stimulation of RA production by SCFA was mimicked by inhibitors of histone deacetylase 3 (HDAC3) but not by HDAC1/2 inhibitors nor by agonists of butyrate receptors G-protein-coupled receptor (GPR)43 or GPR109A, indicating that butyrate stimulates RA production via HDAC3 inhibition. We conclude that the SCFA butyrate inhibits HDAC3 and thereby supports epithelial RA production. PMID:27151945

  12. High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells

    PubMed Central

    Chen, Yu-Ching; Statt, Sarah; Wu, Reen; Chang, Hao-Teng; Liao, Jiunn-Wang; Wang, Chien-Neng; Shyu, Woei-Cherng; Lee, Chen-Chen

    2016-01-01

    Epithelial–mesenchymal transition (EMT) is implicated in bronchial remodeling and loss of lung function in chronic inflammatory airway diseases. Previous studies showed the involvement of the high mobility group box 1 (HMGB1) protein in the pathology of chronic pulmonary inflammatory diseases. However, the role of HMGB1 in EMT of human airway epithelial cells is still unclear. In this study, we used RNA sequencing to show that HMGB1 treatment regulated EMT-related gene expression in human primary-airway epithelial cells. The top five upregulated genes were SNAI2, FGFBP1, VIM, SPARC (osteonectin), and SERPINE1, while the downregulated genes included OCLN, TJP1 (ZO-1), FZD7, CDH1 (E-cadherin), and LAMA5. We found that HMGB1 induced downregulation of E-cadherin and ZO-1, and upregulation of vimentin mRNA transcription and protein translation in a dose-dependent manner. Additionally, we observed that HMGB1 induced AKT phosphorylation, resulting in GSK3β inactivation, cytoplasmic accumulation, and nuclear translocation of β-catenin to induce EMT in human airway epithelial cells. Treatment with PI3K inhibitor (LY294006) and β-catenin shRNA reversed HMGB1-induced EMT. Moreover, HMGB1 induced expression of receptor for advanced glycation products (RAGE), but not that of Toll-like receptor (TLR) 2 or TLR4, and RAGE shRNA inhibited HMGB1-induced EMT in human airway epithelial cells. In conclusion, we found that HMGB1 induced EMT through RAGE and the PI3K/AKT/GSK3β/β-catenin signaling pathway. PMID:26739898

  13. Radical-containing ultrafine particulate matter initiates epithelial-to-mesenchymal transitions in airway epithelial cells.

    PubMed

    Thevenot, Paul T; Saravia, Jordy; Jin, Nili; Giaimo, Joseph D; Chustz, Regina E; Mahne, Sarah; Kelley, Matthew A; Hebert, Valeria Y; Dellinger, Barry; Dugas, Tammy R; Demayo, Francesco J; Cormier, Stephania A

    2013-02-01

    Environmentally persistent free radicals (EPFRs) in combustion-generated particulate matter (PM) are capable of inducing pulmonary pathologies and contributing to the development of environmental asthma. In vivo exposure of infant rats to EPFRs demonstrates their ability to induce airway hyperresponsiveness to methacholine, a hallmark of asthma. However, the mechanisms by which combustion-derived EPFRs elicit in vivo responses remain elusive. In this study, we used a chemically defined EPFR consisting of approximately 0.2 μm amorphrous silica containing 3% cupric oxide with the organic pollutant 1,2-dichlorobenzene (DCB-230). DCB-230 possesses similar radical content to urban-collected EPFRs but offers several advantages, including lack of contaminants and chemical uniformity. DCB-230 was readily taken up by BEAS-2B and at high doses (200 μg/cm(2)) caused substantial necrosis. At low doses (20 μg/cm(2)), DCB-230 particles caused lysosomal membrane permeabilization, oxidative stress, and lipid peroxidation within 24 hours of exposure. During this period, BEAS-2B underwent epithelial-to-mesenchymal transition (EMT), including loss of epithelial cell morphology, decreased E-cadherin expression, and increased α-smooth muscle actin (α-SMA) and collagen I production. Similar results were observed in neonatal air-liquid interface culture (i.e., disruption of epithelial integrity and EMT). Acute exposure of infant mice to DCB-230 resulted in EMT, as confirmed by lineage tracing studies and evidenced by coexpression of epithelial E-cadherin and mesenchymal α-SMA proteins in airway cells and increased SNAI1 expression in the lungs. EMT in neonatal mouse lungs after EPFR exposure may provide an explanation for epidemiological evidence supporting PM exposure and increased risk of asthma. PMID:23087054

  14. Forces driving epithelial spreading in zebrafish gastrulation.

    PubMed

    Behrndt, Martin; Salbreux, Guillaume; Campinho, Pedro; Hauschild, Robert; Oswald, Felix; Roensch, Julia; Grill, Stephan W; Heisenberg, Carl-Philipp

    2012-10-12

    Contractile actomyosin rings drive various fundamental morphogenetic processes ranging from cytokinesis to wound healing. Actomyosin rings are generally thought to function by circumferential contraction. Here, we show that the spreading of the enveloping cell layer (EVL) over the yolk cell during zebrafish gastrulation is driven by a contractile actomyosin ring. In contrast to previous suggestions, we find that this ring functions not only by circumferential contraction but also by a flow-friction mechanism. This generates a pulling force through resistance against retrograde actomyosin flow. EVL spreading proceeds normally in situations where circumferential contraction is unproductive, indicating that the flow-friction mechanism is sufficient. Thus, actomyosin rings can function in epithelial morphogenesis through a combination of cable-constriction and flow-friction mechanisms. PMID:23066079

  15. Mechanochemical actuators of embryonic epithelial contractility.

    PubMed

    Kim, YongTae; Hazar, Melis; Vijayraghavan, Deepthi S; Song, Jiho; Jackson, Timothy R; Joshi, Sagar D; Messner, William C; Davidson, Lance A; LeDuc, Philip R

    2014-10-01

    Spatiotemporal regulation of cell contractility coordinates cell shape change to construct tissue architecture and ultimately directs the morphology and function of the organism. Here we show that contractility responses to spatially and temporally controlled chemical stimuli depend much more strongly on intercellular mechanical connections than on biochemical cues in both stimulated tissues and adjacent cells. We investigate how the cell contractility is triggered within an embryonic epithelial sheet by local ligand stimulation and coordinates a long-range contraction response. Our custom microfluidic control system allows spatiotemporally controlled stimulation with extracellular ATP, which results in locally distinct contractility followed by mechanical strain pattern formation. The stimulation-response circuit exposed here provides a better understanding of how morphogenetic processes integrate responses to stimulation and how intercellular responses are transmitted across multiple cells. These findings may enable one to create a biological actuator that actively drives morphogenesis. PMID:25246549

  16. Needlescopic decapsulation of a splenic epithelial cyst

    PubMed Central

    Seshadri, Pieter A.; Poulin, Eric C.; Mamazza, Joseph; Schlachta, Christopher M.

    2000-01-01

    As technology advances, the techniques of laparoscopic surgery are being refined and their aplication is expanding to include many disease processes and organs. The new-generation laparoscopic instruments are becoming smaller (less than 5 mm). Expected advantages include improvements in cosmesis and patient satisfaction, and decreased postoperative analgesic requirements. Non-neoplastic cysts of the spleen are rare, and their management has evolved from total open splenectomy to laparoscopic cyst decapsulation. A 22-year-old woman with a symptomatic 10-cm epithelial cyst was treated by splenic decapsulation with needlescopic instruments (3 mm or smaller). Three trocars were used: one 12-mm umbilical and two 3-mm subcostal ports. The cyst was punctured by a Veress needle, and after drainage of straw-coloured fluid, circumferential decapsulation with 5-mm laparoscopic shears through the umbilical port site was done. The patient was discharged within 24 hours, having had a single intramuscular injection of meperidine and an excellent cosmetic result. PMID:10948693

  17. Sparfloxacin-associated corneal epithelial toxicity.

    PubMed

    Agarwal, Aniruddha Kishandutt; Ram, Jagat; Singh, Ramandeep

    2014-01-01

    Sparfloxacin is a broad-spectrum fluoroquinolone antibiotic commonly used for various bacterial corneal infections. Topical use of fluoroquinolones is considered to be safe leading to their widespread use. Common indications include blepharitis, conjunctivitis and corneal ulcers. However, unsupervised prolonged use is associated with deposition of crystalline material in the epithelial and anterior stromal layers of the cornea. These may be associated with significant visual symptoms including diminution of vision and glare/photophobia. We present a case of a 40-year-old man who was treated with topical 0.3% sparfloxacin unsupervised for a long time. The patient developed significant visual impairment due to diffuse epitheliopathy. Cessation of the drug was slowly followed by reversal of manifestations and normalisation of corneal morphology. PMID:25239984

  18. Analyzing epithelial and endothelial kisses in Merida

    PubMed Central

    Nusrat, Asma; Quiros, Miguel; González-Mariscal, Lorenza

    2013-01-01

    Last November a group of principal investigators, postdoctoral fellows and PhD students from around the world got together in the city of Merida in Southeastern Mexico in a State of the Art meeting on the “Molecular structure and function of the apical junctional complex in epithelial and endothelia.” They analyzed diverse tissue barriers including those in the gastrointestinal tract, the blood brain barrier, blood neural and blood retinal barriers. The talks revealed exciting new findings in the field, novel technical approaches and unpublished data and highlighted the importance of studying junctional complexes to better understand several pathogenesis and to develop therapeutic approaches that can be utilized for drug delivery. This meeting report has the purpose of highlighting the results and advances discussed by the speakers at the Merida Meeting.

  19. Advent of complex flows in epithelial tissues

    NASA Astrophysics Data System (ADS)

    Lee, Pilhwa; Wolgemuth, Charles

    2011-06-01

    The collective migration of cells in tissue pervades many important biological processes, such as wound healing, organism development, and cancer metastasis. Recent experiments on wound healing show that the collective migratory behavior of cells can be quite complex, including transient vortices and long-range correlations. Here, we explore cellular flows in epithelial tissues using a model that considers the force distribution and polarity of a single cell along with cell-cell adhesion. We show that the dipole nature of a crawling cell’s force distribution destabilizes steady cellular motion. We determine the values of the physical parameters that are necessary to produce these complex motions and use numerical simulation to verify the linear analysis and to demonstrate the complex flows. We find that the tendency for cells to align is the dominant physical parameter that determines the stability of steady flows in the epithelium.

  20. SGK1 regulation of epithelial sodium transport.

    PubMed

    Pearce, David

    2003-01-01

    Epithelial ion transport is regulated in vertebrates by a variety of hormonal and non-hormonal factors, including mineralocorticoids, insulin, and osmotic shock. SGK1 has been established as an important convergence point for multiple regulators of Na+transport. Unlike most serine-threonine kinases, SGK1 is under dual control: protein levels are controlled through effects on its gene transcription, while its activity is dependent on phosphatidylinositol-3-kinase (PI3K) activity. Aldosterone is the most notable regulator of SGK1 protein level in ion transporting epithelia, while insulin and other activators of the of PI3K are key regulators of its activity. Activated SGK1 regulates a variety of ion transporters, the best characterized of which is the epithelial sodium channel (ENaC). The apical targeting of ENaC is controlled by the ubiquitin ligase, Nedd4-2, and SGK1 acts, at least in part, through phosphorylation-dependent inhibition of Nedd4-2. This effect of SGK1 requires physical associations of Nedd4-2 with both SGK1 and ENaC. Moreover, direct physical association between SGK1 and ENaC may also be implicated in the formation of a tertiary complex. Osmotic shock is likely the most important non-hormonal regulator of SGK1 expression, and surprisingly, SGK1 expression can be induced by hypotonic or hypertonic stress in a cell-type dependent fashion. The SGK family represents an ancient arm of the serine-threonine kinase family, present in all eukaryotes that have been examined, including yeast. SGK1 appears to have been implicated in membrane trafficking and possibly in the control of ion transport and cell volume in early single cell eukaryotes. In metazoan epithelia, it seems likely that SGK1 was adapted to the regulation of ion transport in response to hormonal and osmotic signals. PMID:12649598

  1. [The molecular biology of epithelial ovarian cancer].

    PubMed

    Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

    2012-12-01

    Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research. PMID:23238064

  2. Henipavirus Pathogenesis in Human Respiratory Epithelial Cells

    PubMed Central

    Escaffre, Olivier; Borisevich, Viktoriya; Carmical, J. Russ; Prusak, Deborah; Prescott, Joseph; Feldmann, Heinz

    2013-01-01

    Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. Henipavirus infection causes severe respiratory illness and encephalitis. Although the exact route of transmission in human is unknown, epidemiological studies and in vivo studies suggest that the respiratory tract is important for virus replication. However, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can cause disease. In this study, we characterized henipavirus pathogenesis using primary cells derived from the human respiratory tract. The growth kinetics of NiV-Malaysia, NiV-Bangladesh, and HeV were determined in bronchial/tracheal epithelial cells (NHBE) and small airway epithelial cells (SAEC). In addition, host responses to infection were assessed by gene expression analysis and immunoassays. Viruses replicated efficiently in both cell types and induced large syncytia. The host response to henipavirus infection in NHBE and SAEC highlighted a difference in the inflammatory response between HeV and NiV strains as well as intrinsic differences in the ability to mount an inflammatory response between NHBE and SAEC. These responses were highest during HeV infection in SAEC, as characterized by the levels of key cytokines (interleukin 6 [IL-6], IL-8, IL-1α, monocyte chemoattractant protein 1 [MCP-1], and colony-stimulating factors) responsible for immune cell recruitment. Finally, we identified virus strain-dependent variability in type I interferon antagonism in NHBE and SAEC: NiV-Malaysia counteracted this pathway more efficiently than NiV-Bangladesh and HeV. These results provide crucial new information in the understanding of henipavirus pathogenesis in the human respiratory tract at an early stage of infection. PMID:23302882

  3. Epithelial topography for repetitive tooth formation

    PubMed Central

    Gaete, Marcia; Fons, Juan Manuel; Popa, Elena Mădălina; Chatzeli, Lemonia; Tucker, Abigail S.

    2015-01-01

    ABSTRACT During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2+ cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2+/Sox9+ cells. PMID:26538639

  4. Henipavirus pathogenesis in human respiratory epithelial cells.

    PubMed

    Escaffre, Olivier; Borisevich, Viktoriya; Carmical, J Russ; Prusak, Deborah; Prescott, Joseph; Feldmann, Heinz; Rockx, Barry

    2013-03-01

    Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. Henipavirus infection causes severe respiratory illness and encephalitis. Although the exact route of transmission in human is unknown, epidemiological studies and in vivo studies suggest that the respiratory tract is important for virus replication. However, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can cause disease. In this study, we characterized henipavirus pathogenesis using primary cells derived from the human respiratory tract. The growth kinetics of NiV-Malaysia, NiV-Bangladesh, and HeV were determined in bronchial/tracheal epithelial cells (NHBE) and small airway epithelial cells (SAEC). In addition, host responses to infection were assessed by gene expression analysis and immunoassays. Viruses replicated efficiently in both cell types and induced large syncytia. The host response to henipavirus infection in NHBE and SAEC highlighted a difference in the inflammatory response between HeV and NiV strains as well as intrinsic differences in the ability to mount an inflammatory response between NHBE and SAEC. These responses were highest during HeV infection in SAEC, as characterized by the levels of key cytokines (interleukin 6 [IL-6], IL-8, IL-1α, monocyte chemoattractant protein 1 [MCP-1], and colony-stimulating factors) responsible for immune cell recruitment. Finally, we identified virus strain-dependent variability in type I interferon antagonism in NHBE and SAEC: NiV-Malaysia counteracted this pathway more efficiently than NiV-Bangladesh and HeV. These results provide crucial new information in the understanding of henipavirus pathogenesis in the human respiratory tract at an early stage of infection. PMID:23302882

  5. Epithelial topography for repetitive tooth formation.

    PubMed

    Gaete, Marcia; Fons, Juan Manuel; Popa, Elena Mădălina; Chatzeli, Lemonia; Tucker, Abigail S

    2015-01-01

    During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2(+) cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2(+)/Sox9(+) cells. PMID:26538639

  6. Enhanced detection of bladder cancer using the epithelial surface marker epithelial membrane antigen: a preliminary report.

    PubMed

    Ring, K S; Karp, F; Benson, M C

    1990-09-01

    The flow cytometry (FCM) technique allows for the rapid quantitative analysis of the DNA content of individual cells. In a variety of genitourinary tumors, DNA ploidy has a significant impact upon prognosis and ultimate patient survival. In patients having transitional cell cancer (TCC) of the bladder, FCM of voided urine and bladder barbotage specimens is highly correlated with cytologic analysis in the detection of malignant cells. One problem with this technique has been decreased sensitivity in samples containing large numbers of inflammatory cells. To improve FCM detection of TCC in bladder wash specimens, we developed a technique using a monoclonal antibody (Mab) specific to human, epithelial membrane antigen (EMA). The EMA cell-surface marker enabled us to differentiate bladder epithelial cells from lymphocytes and cellular debris. In combination with DNA analysis using propidium iodide, the EMA Mab increased the sensitivity and specificity of FCM compared to conventional analysis using propidium iodide alone. We conclude that epithelial cell-surface antigen staining using both EMA Mab and DNA staining can increase the FCM detection of TCC in bladder wash specimens. PMID:2074517

  7. Automatic detection of spermatozoa for laser capture microdissection.

    PubMed

    Vandewoestyne, Mado; Van Hoofstat, David; Van Nieuwerburgh, Filip; Deforce, Dieter

    2009-03-01

    In sexual assault crimes, differential extraction of spermatozoa from vaginal swab smears is often ineffective, especially when only a few spermatozoa are present in an overwhelming amount of epithelial cells. Laser capture microdissection (LCM) enables the precise separation of spermatozoa and epithelial cells. However, standard sperm-staining techniques are non-specific and rely on sperm morphology for identification. Moreover, manual screening of the microscope slides is time-consuming and labor-intensive. Here, we describe an automated screening method to detect spermatozoa stained with Sperm HY-LITER. Different ratios of spermatozoa and epithelial cells were used to assess the automatic detection method. In addition, real postcoital samples were also screened. Detected spermatozoa were isolated using LCM and DNA analysis was performed. Robust DNA profiles without allelic dropout could be obtained from as little as 30 spermatozoa recovered from postcoital samples, showing that the staining had no significant influence on DNA recovery. PMID:18661142

  8. Comparison of the femtosecond laser and mechanical microkeratome for flap cutting in LASIK

    PubMed Central

    Xia, Li-Kun; Yu, Jie; Chai, Guang-Rui; Wang, Dang; Li, Yang

    2015-01-01

    AIM To compare refractive results, higher-order aberrations (HOAs), contrast sensitivity and dry eye after laser in situ keratomileusis (LASIK) performed with a femtosecond laser versus a mechanical microkeratome for myopia and astigmatism. METHODS In this prospective, non-randomized study, 120 eyes with myopia received a LASIK surgery with the VisuMax femtosecond laser for flap cutting, and 120 eyes received a conventional LASIK surgery with a mechanical microkeratome. Flap thickness, visual acuity, manifest refraction, contrast sensitivity function (CSF) curves, HOAs and dry-eye were measured at 1wk; 1, 3, 6mo after surgery. RESULTS At 6mo postoperatively, the mean central flap thickness in femtosecond laser procedure was 113.05±5.89 µm (attempted thickness 110 µm), and 148.36±21.24 µm (attempted thickness 140 µm) in mechanical microkeratome procedure. An uncorrected distance visual acuity (UDVA) of 4.9 or better was obtained in more than 98% of eyes treated by both methods, a gain in logMAR lines of corrected distance visual acuity (CDVA) occurred in more than 70% of eyes treated by both methods, and no eye lost ≥1 lines of CDVA in both groups. The difference of the mean UDVA and CDVA between two groups at any time post-surgery were not statistically significant (P>0.05). The postoperative changes of spherical equivalent occurred markedly during the first month in both groups. The total root mean square values of HOAs and spherical aberrations in the femtosecond treated eyes were markedly less than those in the microkeratome treated eyes during 6mo visit after surgery (P<0.01). The CSF values of the femtosecond treated eyes were also higher than those of the microkeratome treated eyes at all space frequency (P<0.01). The mean ocular surface disease index scores in both groups were increased at 1wk, and recovered to preoperative level at 1mo after surgery. The mean tear breakup time (TBUT) of the femtosecond treated eyes were markedly longer than those of

  9. Quantitative Assessment of Cytosolic Salmonella in Epithelial Cells

    PubMed Central

    Knodler, Leigh A.; Nair, Vinod; Steele-Mortimer, Olivia

    2014-01-01

    Within mammalian cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) inhabits a membrane-bound vacuole known as the Salmonella-containing vacuole (SCV). We have recently shown that wild type S. Typhimurium also colonizes the cytosol of epithelial cells. Here we sought to quantify the contribution of cytosolic Salmonella to the total population over a time course of infection in different epithelial cell lines and under conditions of altered vacuolar escape. We found that the lysosomotropic agent, chloroquine, acts on vacuolar, but not cytosolic, Salmonella. After chloroquine treatment, vacuolar bacteria are not transcriptionally active or replicative and appear degraded. Using a chloroquine resistance assay, in addition to digitonin permeabilization, we found that S. Typhimurium lyses its nascent vacuole in numerous epithelial cell lines, albeit with different frequencies, and hyper-replication in the cytosol is also widespread. At later times post-infection, cytosolic bacteria account for half of the total population in some epithelial cell lines, namely HeLa and Caco-2 C2Bbe1. Both techniques accurately measured increased vacuole lysis in epithelial cells upon treatment with wortmannin. By chloroquine resistance assay, we also determined that Salmonella pathogenicity island-1 (SPI-1), but not SPI-2, the virulence plasmid nor the flagellar apparatus, was required for vacuolar escape and cytosolic replication in epithelial cells. Together, digitonin permeabilization and the chloroquine resistance assay will be useful, complementary tools for deciphering the mechanisms of SCV lysis and Salmonella replication in the epithelial cell cytosol. PMID:24400108

  10. Technical note: Isolation and characterization of porcine mammary epithelial cells.

    PubMed

    Dahanayaka, S; Rezaei, R; Porter, W W; Johnson, G A; Burghardt, R C; Bazer, F W; Hou, Y Q; Wu, Z L; Wu, G

    2015-11-01

    Within the mammary gland, functional synthesis of milk is performed by its epithelial (alveolar) cells. The availability of a stable mammary epithelial cell line is essential for biochemical studies to elucidate cellular and molecular mechanisms responsible for nutritional regulation of lactation. Therefore, porcine mammary epithelial cells (PMEC) were isolated from mammary glands of a 9-mo-old nonpregnant and nonlactating gilt and cultured to establish a nonimmortalized cell line. These cells were characterized by expression of cytokeratin-18 (an intermediate filament specific for epithelial cells), β-casein (a specific marker for mammary epithelial cells), and α-lactalbumin. In culture, the PMEC doubled in number every 24 h and maintained a cobblestone morphology, typical for cultured epithelial cells, for at least 15 passages. Addition of 0.2 to 2 μg/mL prolactin to culture medium for 3 d induced the production of β-casein and α-lactalbumin by PMEC in a dose-dependent manner. Thus, we have successfully developed a useful PMEC line for future studies of cellular and molecular regulation of milk synthesis by mammary epithelial cells of the sow. PMID:26641038

  11. Clinical implications of epithelial cell plasticity in cancer progression.

    PubMed

    Aparicio, Luis A; Blanco, Moisés; Castosa, Raquel; Concha, Ángel; Valladares, Manuel; Calvo, Lourdes; Figueroa, Angélica

    2015-09-28

    In the last few years, the role of epithelial cell plasticity in cancer biology research has gained increasing attention. This concept refers to the ability of the epithelial cells to dynamically switch between different phenotypic cellular states. This programme is particularly relevant during the epithelial-to-mesenchymal transition (EMT) in cancer progression. During colonization, epithelial cells first activate the EMT programme to disseminate from a primary tumour to reach a distant tissue site. During this process, cells are transported into the circulation and are able to escape the immune system of the host. Then, a reverse process called mesenchymal-to-epithelial transition (MET) occurs on cells that settle in the distant organs. Although epithelial cell plasticity has an important impact on tumour biology, the clinical relevance of this concept remains to be recapitulated. In this review, we will update the current state of epithelial cell plasticity in cancer progression and its clinical implications for the design of therapeutic strategies, the acquisition of multidrug resistance, and future perspectives for the management of cancer patients. PMID:26099173

  12. Heterodyne laser spectroscopy system

    DOEpatents

    Wyeth, Richard W.; Paisner, Jeffrey A.; Story, Thomas

    1990-01-01

    A heterodyne laser spectroscopy system utilizes laser heterodyne techniques for purposes of laser isotope separation spectroscopy, vapor diagnostics, processing of precise laser frequency offsets from a reference frequency, and provides spectral analysis of a laser beam.

  13. Heterodyne laser spectroscopy system

    DOEpatents

    Wyeth, Richard W.; Paisner, Jeffrey A.; Story, Thomas

    1989-01-01

    A heterodyne laser spectroscopy system utilizes laser heterodyne techniques for purposes of laser isotope separation spectroscopy, vapor diagnostics, processing of precise laser frequency offsets from a reference frequency and the like, and provides spectral analysis of a laser beam.

  14. Lasers in Cancer Treatment

    MedlinePlus

    ... Cancer Treatment On This Page What is laser light? What is laser therapy, and how is it ... future hold for laser therapy? What is laser light? The term “ laser ” stands for light amplification by ...

  15. Triennial Lactation Symposium: Bovine mammary epithelial cell lineages and parenchymal development.

    PubMed

    Ellis, S; Akers, R M; Capuco, A V; Safayi, S

    2012-05-01

    Mammary development proceeds from an aggregation of cells in the ventral ectoderm to the establishment of an elaborate tree of alveoli, ducts, and cisternae. However, despite abundant data on endocrine regulation of ruminant mammary growth, we know comparatively little about cell lineages, expression of differentiation markers, and plasticity in mammary cell phenotype. Histologic analyses have revealed cell populations with distinct histochemical profiles, but functional assessment of cell populations during development has been limited to analysis of proliferation and frequency estimations of morphotypes. The lack of transplantation models, limited availability of validated antibodies with reactivity to bovine antigens, and similar technical challenges have generally hindered the pace of discovery, but the application of new technologies such as laser microdissection, transcriptional profiling, and multispectral image analysis are yielding important clues into bovine mammary cell ontogeny and developmental regulation. Our analyses have shown that prepubertal ovariectomy affects epithelial architecture, increases the proportion of cells expressing the estrogen receptor, and increases myoepithelial cell development, all concomitant with a dramatic reduction in the mass of parenchymal tissue. Our observations point to a dual role for ovarian secretions in the control of not only the rate of epithelial development, but also the nature of the parenchymal development. The balance of stimulus and inhibition pathways cooperatively regulates mammary growth. The increased reliance on objective staining analyses and quantitative approaches will ensure broader repeatability, application, and extension of the findings regarding the impact of the ovary and other regulatory entities and factors. Advances in understanding the ontogeny of mammary epithelial cells, coupled with established and increasing knowledge of endocrine factors affecting mammary development, may yield

  16. Mechanism underlying insulin uptake in alveolar epithelial cell line RLE-6TN.

    PubMed

    Oda, Keisuke; Yumoto, Ryoko; Nagai, Junya; Katayama, Hirokazu; Takano, Mikihisa

    2011-12-15

    For the development of efficient pulmonary delivery systems for protein and peptide drugs, it is important to understand their transport mechanisms in alveolar epithelial cells. In this study, the uptake mechanism for FITC-insulin in cultured alveolar epithelial cell line RLE-6TN was elucidated. FITC-insulin uptake by RLE-6TN cells was time-dependent, temperature-sensitive, and concentration-dependent. The uptake was inhibited by metabolic inhibitors, cytochalasin D, clathrin-mediated endocytosis inhibitors, and dynasore, an inhibitor of dynamin GTPase. On the other hand, no inhibitory effect was observed with caveolae-mediated endocytosis inhibitors and a macropinocytosis inhibitor. Intracellular FITC-insulin was found to be partly transported to the basal side of the epithelial cell monolayers. In addition, colocalization of FITC-insulin and LysoTracker Red was observed on confocal laser scanning microscopy, indicating that FITC-insulin was partly targeted to lysosomes. In accordance with these findings, SDS-PAGE/fluoroimage analysis showed that intact FITC-insulin in the cells was eliminated with time. The possible receptor involved in FITC-insulin uptake by RLE-6TN cells was examined by using siRNA. Transfection of the cells with megalin or insulin receptor siRNA successfully reduced the corresponding mRNA expression. FITC-insulin uptake decreased on the transfection with insulin receptor siRNA, but not that with megalin siRNA. These results suggest that insulin is taken up through endocytosis in RLE-6TN cells, and after the endocytosis, the intracellular insulin is partly degraded in lysosomes and partly transported to the basal side. Insulin receptor, but not megalin, may be involved at least partly in insulin endocytosis in RLE-6TN cells. PMID:22004610

  17. Lipopolysaccharide-induced epithelial monoamine oxidase mediates alveolar bone loss in a rat chronic wound model.

    PubMed

    Ekuni, Daisuke; Firth, James D; Nayer, Tarun; Tomofuji, Takaaki; Sanbe, Toshihiro; Irie, Koichiro; Yamamoto, Tatsuo; Oka, Takashi; Liu, Zhenzi; Vielkind, Juergen; Putnins, Edward E

    2009-10-01

    Reactive oxygen species (ROS) production is an antimicrobial response to pathogenic challenge that may, in the case of persistent infection, have deleterious effects on the tissue of origin. A rat periodontal disease model was used to study ROS-induced chronic epithelial inflammation and bone loss. Lipopolysaccharide (LPS) was applied for 8 weeks into the gingival sulcus, and histological analysis confirmed the onset of chronic disease. Junctional epithelium was collected from healthy and diseased animals using laser-capture microdissection, and expression microarray analysis was performed. Of 19,730 genes changed in disease, 42 were up-regulated >/=4-fold. Three of the top 10 LPS-induced genes, monoamine oxidase B (MAO/B) and flavin-containing monooxygenase 1 and 2, are implicated in ROS signaling. LPS-associated induction of the ROS mediator H(2)O(2), as well as MAO/B and tumor necrosis factor (TNF)-alpha levels were validated in the rat histological sections and a porcine junctional epithelial cell culture model. Topical MAO inhibitors significantly counteracted LPS-associated elevation of H(2)O(2) production and TNF-alpha expression in vivo and in vitro, inhibited disease-associated apical migration and proliferation of junctional epithelium and inhibited induced systemic H(2)O(2) levels and alveolar bone loss in vivo. These results suggest that LPS induces chronic wounds via elevated MAO/B-mediated increases in H(2)O(2) and TNF-alpha activity by epithelial cells and is further associated with more distant effects on systemic oxidative stress and alveolar bone loss. PMID:19779138

  18. Epithelial cells as alternative human biomatrices for comet assay

    PubMed Central

    Rojas, Emilio; Lorenzo, Yolanda; Haug, Kristiane; Nicolaissen, Bjørn; Valverde, Mahara

    2014-01-01

    The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many organs, have the potential to serve as biomatrices that can be used to evaluate genotoxicity and may also serve as early effect biomarkers. Furthermore, 80% of solid cancers are of epithelial origin, which points to the importance of studying DNA damage in these tissues. Indeed, studies including comet assay in epithelial cells have either clear clinical applications (lens and corneal epithelial cells) or examine genotoxicity within human biomonitoring and in vitro studies. We here review improvements in determining DNA damage using the comet assay by employing lens, corneal, tear duct, buccal, and nasal epithelial cells. For some of these tissues invasive sampling procedures are needed. Desquamated epithelial cells must be obtained and dissociated prior to examination using the comet assay, and such procedures may induce varying amounts of DNA damage. Buccal epithelial cells require lysis enriched with proteinase K to obtain free nucleosomes. Over a 30 year period, the comet assay in epithelial cells has been little employed, however its use indicates that it could be an extraordinary tool not only for risk assessment, but also for diagnosis, prognosis of treatments and diseases. PMID:25506353

  19. Laser Therapy

    MedlinePlus

    ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ...

  20. Fungal glycan interactions with epithelial cells in allergic airway disease

    PubMed Central

    Roy, René M.; Klein, Bruce S.

    2014-01-01

    Human exposure to fungi results in a wide range of health outcomes, from invasive disease or allergy to immune tolerance. Inhaled fungi contact airway epithelial cells as an early event, and this host:fungal interaction can shape the eventual immunological outcome. Emerging evidence points to exposure to fungal cell wall carbohydrates in the development of allergic airway disease. Herein, we describe determinants of fungal allergenicity, and review the responses of airway epithelial cells to fungal carbohydrates. A greater understanding of the recognition of and response to fungal carbohydrates by airway epithelial cells may lead to the development of targeted therapies that ameliorate allergic airway disease. PMID:23602359

  1. Probing the luminal microenvironment of reconstituted epithelial microtissues.

    PubMed

    Cerchiari, Alec E; Samy, Karen E; Todhunter, Michael E; Schlesinger, Erica; Henise, Jeff; Rieken, Christopher; Gartner, Zev J; Desai, Tejal A

    2016-01-01

    Polymeric microparticles can serve as carriers or sensors to instruct or characterize tissue biology. However, incorporating microparticles into tissues for in vitro assays remains a challenge. We exploit three-dimensional cell-patterning technologies and directed epithelial self-organization to deliver microparticles to the lumen of reconstituted human intestinal microtissues. We also develop a novel pH-sensitive microsensor that can measure the luminal pH of reconstituted epithelial microtissues. These studies offer a novel approach for investigating luminal microenvironments and drug-delivery across epithelial barriers. PMID:27619235

  2. Epithelial in vitro cell systems in carcinogenesis studies

    SciTech Connect

    Borek, C.

    1983-01-01

    The development of epithelial cells systems to study oncogenic transformation has presented a major challenge in the field of carcinogenesis. Because there exists in man a preponderance of carcinomas over sarcomas, the importance of studying oncogenic transformation in epithelial cells is of great relevance to human disease. The difficulty lies in the fact that different tissues contain epithelial cells with singular differentiated characteristics, which must be defined to assert the different nature of the cells being used. Liver cells in culture are a case in point. By careful maintenance and optimal culture conditions, one can maintain many of the differentiated characteristics of the cells for prolonged periods of time.

  3. Depth sensitive oblique polarized reflectance spectroscopy of oral epithelial tissue

    NASA Astrophysics Data System (ADS)

    Jimenez, Maria K.; Lam, Sylvia; Poh, Catherine; Sokolov, Konstantin

    2014-05-01

    Identifying depth-dependent alterations associated with epithelial cancerous lesions can be challenging in the oral cavity where variable epithelial thicknesses and troublesome keratin growths are prominent. Spectroscopic methods with enhanced depth resolution would immensely aid in isolating optical properties associated with malignant transformation. Combining multiple beveled fibers, oblique collection geometry, and polarization gating, oblique polarized reflectance spectroscopy (OPRS) achieves depth sensitive detection. We report promising results from a clinical trial of patients with oral lesions suspected of dysplasia or carcinoma demonstrating the potential of OPRS for the analysis of morphological and architectural changes in the context of multilayer, epithelial oral tissue.

  4. Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis

    PubMed Central

    Ewald, Andrew J.; Brenot, Audrey; Duong, Myhanh; Chan, Bianca S.; Werb, Zena

    2009-01-01

    Summary Epithelial organs are built through the movement of groups of interconnected cells. We observed cells in elongating mammary ducts reorganize into a multilayered epithelium, migrate collectively, and rearrange dynamically, all without forming leading cellular extensions. Duct initiation required proliferation, Rac, and myosin light-chain kinase, whereas repolarization to a bilayer depended on Rho kinase. We observed that branching morphogenesis results from the active motility of both luminal and myoepithelial cells. Luminal epithelial cells advanced collectively, whereas myoepithelial cells appeared to restrain elongating ducts. Significantly, we observed that normal epithelium and neoplastic hyperplasias are organized similarly during morphogenesis, suggesting common mechanisms of epithelial growth. PMID:18410732

  5. Genetics and epithelial cell dysfunction in cystic fibrosis

    SciTech Connect

    Riordan, J.R.; Buchwald, M.

    1987-01-01

    This book examines the advances being made in the study of the physiology, cell biology, and molecular genetics of cystic fibrosis. Emphasis is placed on various areas of research that involve epithelial cells (e.g., the CF-specific phenotypes exhibited by epithelial cells, abnormalities in epithelium ion transport, chloride channel regulation in CF epithelial.) Coverage is presented on the current status of CF, including data on the incidence of the disease, its mode of inheritance, chromosomal localization, genetic heterogeneity, and screening and management.

  6. Laser device

    DOEpatents

    Scott, Jill R.; Tremblay, Paul L.

    2008-08-19

    A laser device includes a virtual source configured to aim laser energy that originates from a true source. The virtual source has a vertical rotational axis during vertical motion of the virtual source and the vertical axis passes through an exit point from which the laser energy emanates independent of virtual source position. The emanating laser energy is collinear with an orientation line. The laser device includes a virtual source manipulation mechanism that positions the virtual source. The manipulation mechanism has a center of lateral pivot approximately coincident with a lateral index and a center of vertical pivot approximately coincident with a vertical index. The vertical index and lateral index intersect at an index origin. The virtual source and manipulation mechanism auto align the orientation line through the index origin during virtual source motion.

  7. Enhancement effect of poly(amino acid)s on insulin uptake in alveolar epithelial cells.

    PubMed

    Oda, Keisuke; Yumoto, Ryoko; Nagai, Junya; Katayama, Hirokazu; Takano, Mikihisa

    2012-01-01

    In this study, we elucidated the effect of poly(amino acid)s such as poly-L-ornithine (PLO) on FITC-insulin uptake in cultured alveolar type II epithelial cells, RLE-6TN. FITC-insulin uptake by RLE-6TN cells as well as its cell surface binding was markedly increased by PLO without cytotoxicity. The uptake of FITC-insulin in the presence of PLO was shown to be mediated by endocytosis, but in contrast to the uptake in the absence of PLO, the contribution of macropinocytosis emerged. Colocalization of FITC-insulin and LysoTracker Red was observed by confocal laser scanning microscopy both in the absence and presence of PLO, indicating that FITC-insulin was partly targeted to lysosomes in the cells and degraded. The half-life of the intracellular degradation of FITC-insulin was, however, prolonged by the presence of PLO. PLO also stimulated the uptake of other FITC-labeled compounds. Among them, the enhancement effects of PLO on FITC-albumin and FITC-insulin uptake were prominent. The effect of PLO on insulin absorption was also examined in in-vivo pulmonary administration in rats, and co-administration of PLO enhanced the hypoglycemic action of insulin. These findings suggest that co-administration of poly(amino acid)s such as PLO is a useful strategy for enhancing insulin uptake by alveolar epithelial cells and subsequent absorption from the lung. PMID:22510869

  8. Physical characterization and profiling of airway epithelial derived exosomes using light scattering.

    PubMed

    Kesimer, Mehmet; Gupta, Richa

    2015-10-01

    Exosomes and other extracellular vesicles have been gaining interest during the last decade due to their emerging role in biology and, disease pathogenesis and their biomarker potential. Almost all published research related to exosomes and other extracellular vesicles include some form of physical characterization. Therefore, these vesicles should be precisely profiled and characterized physically before studying their biological role as intercellular messengers, biomarkers or therapeutic tools. Using a combination of light scattering techniques, including dynamic light scattering (DLS) and multi-angle laser light scattering combined with size exclusion separation (SEC-MALLS), we physically characterized and compared distinct extracellular vesicles derived from the apical secretions of two different cultured airway epithelial cells. The results indicated that epithelial cells release vesicles with distinct physical properties and sizes. Human primary tracheobronchial cell culture (HTBE) derived vesicles have a hydrodynamic radius (Rh) of approximately 340 nm while their radius of gyration (Rg) is approximately 200 nm. Electron microscopy analysis, however, revealed that their spherical component is 40-100 nm in size, and they carry filamentous, entangled membrane mucins on their surface that increases their overall radius. The mucin decoration on the surface defines their size and charge as measured using light scattering techniques. Their surface properties mirror the properties of the cells from which they are derived. This may provide a unique tool for researchers to elucidate the unanswered questions in normal airway biology and innate and adaptive defense, including the remodeling of airways during inflammation, tumorigenesis and metastasis. PMID:25823850

  9. Ciliary neurotrophic factor promotes the activation of corneal epithelial stem/progenitor cells and accelerates corneal epithelial wound healing.

    PubMed

    Zhou, Qingjun; Chen, Peng; Di, Guohu; Zhang, Yangyang; Wang, Yao; Qi, Xia; Duan, Haoyun; Xie, Lixin

    2015-05-01

    Ciliary neurotrophic factor (CNTF), a well-known neuroprotective cytokine, has been found to play an important role in neurogenesis and functional regulations of neural stem cells. As one of the most innervated tissue, however, the role of CNTF in cornea epithelium remains unclear. This study was to explore the roles and mechanisms of CNTF in the activation of corneal epithelial stem/progenitor cells and wound healing of both normal and diabetic mouse corneal epithelium. In mice subjecting to mechanical removal of corneal epithelium, the corneal epithelial stem/progenitor cell activation and wound healing were promoted by exogenous CNTF application, while delayed by CNTF neutralizing antibody. In cultured corneal epithelial stem/progenitor cells, CNTF enhanced the colony-forming efficiency, stimulated the mitogenic proliferation, and upregulated the expression levels of corneal epithelial stem/progenitor cell-associated transcription factors. Furthermore, the promotion of CNTF on the corneal epithelial stem/progenitor cell activation and wound healing was mediated by the activation of STAT3. Moreover, in diabetic mice, the content of CNTF in corneal epithelium decreased significantly when compared with that of normal mice, and the supplement of CNTF promoted the diabetic corneal epithelial wound healing, accompanied with the advanced activation of corneal epithelial stem/progenitor cells and the regeneration of corneal nerve fibers. Thus, the capability of expanding corneal epithelial stem/progenitor cells and promoting corneal epithelial wound healing and nerve regeneration indicates the potential application of CNTF in ameliorating limbal stem cell deficiency and treating diabetic keratopathy. PMID:25546438

  10. Characteristics of functionalized nano-hydroxyapatite and internalization by human epithelial cell

    PubMed Central

    2011-01-01

    Hydroxyapatite is the main inorganic component of biological bone and tooth enamel, and synthetic hydroxyapatite has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of arginine-functionalized and europium-doped hydroxyapatite nanoparticles (Arg-Eu-HAP). The synthesized nanoparticles characterized by transmission electron microscopy, X-ray diffractometry, Fourier transform infrared, and Zeta potential analyzer. Its biological properties with DNA binding, cell toxicity, cell binding and intracellular distribution were tested by agarose gel electrophoresis assay, flow cytometry, and fluorescence microscope and laser scanning confocal microscope. The synthesized Arg-Eu-HAP could effectively bind DNA without any cytotoxicity and be internalized into the cytoplasm and perinuclear of human lung epithelial cells. PMID:22108000

  11. Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells.

    PubMed

    Han, Meng; Bindewald-Wittich, Almut; Holz, Frank G; Giese, Guenter; Niemz, Markolf H; Snyder, Sarah; Sun, Hui; Yu, Jiayi; Agopov, Michael; La Schiazza, Olivier; Bille, Josef F

    2006-01-01

    Degeneration of retinal pigment epithelial (RPE) cells severely impairs the visual function of retina photoreceptors. However, little is known about the events that trigger the death of RPE cells at the subcellular level. Two-photon excited autofluorescence (TPEF) imaging of RPE cells proves to be well suited to investigate both the morphological and the spectral characteristics of the human RPE cells. The dominant fluorophores of autofluorescence derive from lipofuscin (LF) granules that accumulate in the cytoplasm of the RPE cells with increasing age. Spectral TPEF imaging reveals the existence of abnormal LF granules with blue shifted autofluorescence in RPE cells of aging patients and brings new insights into the complicated composition of the LF granules. Based on a proposed two-photon laser scanning ophthalmoscope, TPEF imaging of the living retina may be valuable for diagnostic and pathological studies of age related eye diseases. PMID:16526877

  12. Characteristics of functionalized nano-hydroxyapatite and internalization by human epithelial cell

    NASA Astrophysics Data System (ADS)

    Yan-Zhong, Zhao; Yan-Yan, Huang; Jun, Zhu; Shai-Hong, Zhu; Zhi-You, Li; Ke-Chao, Zhou

    2011-11-01

    Hydroxyapatite is the main inorganic component of biological bone and tooth enamel, and synthetic hydroxyapatite has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of arginine-functionalized and europium-doped hydroxyapatite nanoparticles (Arg-Eu-HAP). The synthesized nanoparticles characterized by transmission electron microscopy, X-ray diffractometry, Fourier transform infrared, and Zeta potential analyzer. Its biological properties with DNA binding, cell toxicity, cell binding and intracellular distribution were tested by agarose gel electrophoresis assay, flow cytometry, and fluorescence microscope and laser scanning confocal microscope. The synthesized Arg-Eu-HAP could effectively bind DNA without any cytotoxicity and be internalized into the cytoplasm and perinuclear of human lung epithelial cells.

  13. Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells.

    PubMed

    Macho-Fernandez, E; Koroleva, E P; Spencer, C M; Tighe, M; Torrado, E; Cooper, A M; Fu, Y-X; Tumanov, A V

    2015-03-01

    The immune mechanisms regulating epithelial cell repair after injury remain poorly defined. We demonstrate here that lymphotoxin beta receptor (LTβR) signaling in intestinal epithelial cells promotes self-repair after mucosal damage. Using a conditional gene-targeted approach, we demonstrate that LTβR signaling in intestinal epithelial cells is essential for epithelial interleukin-23 (IL-23) production and protection against epithelial injury. We further show that epithelial-derived IL-23 promotes mucosal wound healing by inducing the IL-22-mediated proliferation and survival of epithelial cells and mucus production. Additionally, we identified CD4(-)CCR6(+)T-bet(-) RAR-related orphan receptor gamma t (RORγt)(+) lymphoid tissue inducer cells as the main producers of protective IL-22 after epithelial damage. Thus, our results reveal a novel role for LTβR signaling in epithelial cells in the regulation of intestinal epithelial cell homeostasis to limit mucosal damage. PMID:25183367

  14. Noncontraceptive estrogen use and epithelial ovarian cancer.

    PubMed

    Kaufman, D W; Kelly, J P; Welch, W R; Rosenberg, L; Stolley, P D; Warshauer, M E; Lewis, J; Woodruff, J; Shapiro, S

    1989-12-01

    The relation of noncontraceptive estrogen use to epithelial ovarian cancer was evaluated in a case-control study conducted in hospitals mainly in the northeastern United States. There were 377 cases diagnosed within the year before hospital admission and 2,030 hospital controls; data were collected by interview in the hospital. Compared with women who never took noncontraceptive estrogens, the overall relative risk estimate for women whose estrogen use lasted at least one year and was not combined with progestogens or testosterone was 1.2 (95% confidence interval (CI) 0.8-1.9), after taking into account risk factors for ovarian cancer. There were 55 cases of the endometrioid, clear cell, or malignant mixed mesodermal cell type; the corresponding relative risk estimate was 0.9 (95% CI 0.3-3.0). There were 26 cases of undifferentiated cell type, with a relative risk estimate of 3.6 (95% CI 1.2-11). Relative risk estimates were similar in a subset of the cases (57%) for which pathology slides were reviewed. For estrogen use of long duration, use of high-dose preparations, or use in the distant past, the relative risk estimates were not significantly different from 1.0. The estimates were elevated for some categories of use, but not consistently--for example, for an interval of 5-9 years since estrogen use began (relative risk (RR) = 2.7), but not after shorter or longer intervals, and for use of conjugated estrogens with a dose of 0.3 mg (RR = 3.2) or 1.25 mg (RR = 2.4), but not for doses of 0.625 mg or 2.5 mg. The relative risk estimate was also elevated for use by nulliparous women (RR = 2.4). The results suggest that, overall, noncontraceptive estrogen use is not associated with the risk of epithelial ovarian cancer. Furthermore, our data do not support the hypothesis that estrogens increase the risk of endometrioid ovarian cancer. The elevated estimates could be due to multiple stratification of the data, but they should be explored in further studies, given the

  15. Sodium selectivity of Reissner's membrane epithelial cells

    PubMed Central

    2011-01-01

    Background Sodium absorption by Reissner's membrane is thought to contribute to the homeostasis of the volume of cochlear endolymph. It was previously shown that the absorptive transepithelial current was blocked by amiloride and benzamil. The most commonly-observed target of these drugs is the epithelial sodium channel (ENaC), which is composed of the three subunits α-,β- and γ-ENaC. However, other less-selective cation channels have also been observed to be sensitive to benzamil and amiloride. The aim of this study was to determine whether Reissner's membrane epithelial cells could support parasensory K+ absorption via amiloride- and benzamil-sensitive electrogenic pathways. Results We determined the molecular and functional expression of candidate cation channels with gene array (GEO GSE6196), RT-PCR, and whole-cell patch clamp. Transcript expression analysis of Reissner's membrane detected no amiloride-sensitive acid-sensing ion channels (ASIC1a, ASIC2a, ASIC2b) nor amiloride-sensitive cyclic-nucleotide gated channels (CNGA1, CNGA2, CNGA4, CNGB3). By contrast, α-,β- and γ-ENaC were all previously reported as present in Reissner's membrane. The selectivity of the benzamil-sensitive cation currents was observed in whole-cell patch clamp recordings under Cl--free conditions where cations were the only permeant species. The currents were carried by Na+ but not K+, and the permeability of Li+ was greater than that of Na+ in Reissner's membrane. Complete replacement of bath Na+ with the inpermeable cation NMDG+ led to the same inward current as with benzamil in a Na+ bath. Conclusions These results are consistent with the amiloride/benzamil-sensitive absorptive flux of Reissner's membrane mediated by a highly Na+-selective channel that has several key characteristics in common with αβγ-ENaC. The amiloride-sensitive pathway therefore absorbs only Na+ in this epithelium and does not provide a parasensory K+ efflux route from scala media. PMID:21284860

  16. Epithelial discrimination of commensal and pathogenic Candida albicans.

    PubMed

    Tang, S X; Moyes, D L; Richardson, J P; Blagojevic, M; Naglik, J R

    2016-04-01

    All mucosal surfaces are lined by epithelial cells and are colonised by opportunistic microbes. In health, these opportunistic microbes remain commensal and are tolerated by the immune system. However, when the correct environmental conditions arise, these microbes can become pathogenic and need to be controlled or cleared by the immune system to prevent disease. The mechanisms that enable epithelial cells to initiate the 'danger' signals activated specifically by pathogenic microbes are critical to mucosal defence and homeostasis but are not well understood. Deciphering these mechanisms will provide essential understanding to how mucosal tissues maintain health and activate immunity, as well as how pathogens promote disease. This review focuses on the interaction of the human fungal pathogen Candida albicans with epithelial cells and the epithelial mechanisms that enable mucosal tissues to discriminate between the commensal and pathogenic state of this medically important fungus. PMID:26843519

  17. Sarcoma with true epithelial differentiation secondary to irradiated glioblastoma

    PubMed Central

    Pimentel, J.; Marques, J.; Pereira, P.; Roque, L.; Martins, C.; Campos, A.

    2011-01-01

    Glioblastoma multiforme rarely shows true, immunohistochemically confirmed, epithelial differentiation. Furthermore, radiotherapy may induce cerebral sarcomatous tumors, and postsurgery glioblastoma irradiation may give rise to secondary gliosarcomas. We report a case of a 48-year-old male operated on a primary glioblastoma, followed by radiotherapy. A local recurrence occurred 23 months later that was operated too, and a second diagnosis of a fibrosarcoma with true epithelial differentiation was made. Primary systemic neoplasms were largely excluded. The patient died shortly after, and postmortem showed another cerebral dural-attached mass corresponding to a sarcoma without epithelial differentiation, and leptomeningeal seeding composed of malignant epithelial elements only. Cytogenetics, however, disclosed the second tumor to be similar to the primary one.

  18. Lung epithelial cells modulate the inflammatory response of alveolar macrophages.

    PubMed

    Rubovitch, Vardit; Gershnabel, Shoham; Kalina, Moshe

    2007-12-01

    The goal of this study was to examine the effect of alveolar epithelial cells on inflammatory responses in macrophages. Lung epithelial cells (either rat RLE-6TN or human A549 cells) reduced LPS-induced NO production in alveolar macrophages (AM) in a contact-independent mechanism. The inhibitory effect of the epithelial cells was present already at the transcriptional level: LPS-induced inducible NO synthase (iNOS) expression was significantly smaller. Surfactant protein A (SP-A)-induced NO production by alveolar macrophages was also reduced in the presence of A549 cells, though, by a different kinetics. LPS-induced interleukin-6 (IL-6) production (another inflammatory pathway) by alveolar macrophages was also reduced in the presence of RLE-6TN cells. These data suggest a role for lung epithelial cells in the complicated modulation of inflammatory processes, and provide an insight into the mechanism underlying. PMID:17851743

  19. Molecular responses of rat tracheal epithelial cells to transmembrane pressure.

    PubMed

    Ressler, B; Lee, R T; Randell, S H; Drazen, J M; Kamm, R D

    2000-06-01

    Smooth muscle constriction in asthma causes the airway to buckle into a rosette pattern, folding the epithelium into deep crevasses. The epithelial cells in these folds are pushed up against each other and thereby experience compressive stresses. To study the epithelial cell response to compressive stress, we subjected primary cultures of rat tracheal epithelial cells to constant elevated pressures on their apical surface (i.e., a transmembrane pressure) and examined changes in the expression of genes that are important for extracellular matrix production and maintenance of smooth muscle activation. Northern blot analysis of RNA extracted from cells subjected to transmembrane pressure showed induction of early growth response-1 (Egr-1), endothelin-1, and transforming growth factor-beta1 in a pressure-dependent and time-dependent manner. Increases in Egr-1 protein were detected by immunohistochemistry. Our results demonstrate that airway epithelial cells respond rapidly to compressive stresses. Potential transduction mechanisms of transmembrane pressure were also investigated. PMID:10835333

  20. Applications of mouse airway epithelial cell culture for asthma research.

    PubMed

    Horani, Amjad; Dickinson, John D; Brody, Steven L

    2013-01-01

    Primary airway epithelial cell culture provides a valuable tool for studying cell differentiation, cell-cell interactions, and the role of immune system factors in asthma pathogenesis. In this chapter, we discuss the application of mouse tracheal epithelial cell cultures for the study of asthma biology. A major advantage of this system is the ability to use airway epithelial cells from mice with defined genetic backgrounds. The in vitro proliferation and differentiation of mouse airway epithelial cells uses the air-liquid interface condition to generate well-differentiated epithelia with characteristics of native airways. Protocols are provided for manipulation of differentiation, induction of mucous cell metaplasia, genetic modification, and cell and pathogen coculture. Assays for the assessment of gene expression, responses of cells, and analysis of specific cell subpopulations within the airway epithelium are included. PMID:23943446

  1. Autoantibodies to tumor-associated antigens in epithelial ovarian carcinoma.

    PubMed

    Piura, Benjamin; Piura, Ettie

    2009-01-01

    This review will focus on recent knowledge related to circulating autoantibodies (AAbs) to tumor-associated antigens (TAAs) in epithelial ovarian carcinoma. So far, the following TAAs have been identified to elicit circulating AAbs in epithelial ovarian carcinoma: p53, homeobox proteins (HOXA7, HOXB7), heat shock proteins (HSP-27, HSP-90), cathepsin D, cancer-testis antigens (NY-ESO-1/LAGE-1), MUC1, GIPC-1, IL-8, Ep-CAM, and S100A7. Since AAbs to TAAs have been identified in the circulation of patients with early-stage cancer, it has been speculated that the assessment of a panel of AAbs specific for epithelial ovarian carcinoma TAAs might hold great potential as a novel tool for early diagnosis of epithelial ovarian carcinoma. PMID:20145720

  2. Apoptosis and autophagy induced by TGF-B1 in bovine mammary epithelial BME-UV1 cells.

    PubMed

    Gajewska, M; Gajkowska, B; Motyl, T

    2005-06-01

    Mammary gland growth and involution is based on a dynamic equilibrium between proliferation and apoptosis of mammary gland epithelial cells (MEC). TGF-beta1 is an important antiproliferative and apoptogenic factor for mammary gland epithelial cells, acting in auto/paracrine matter and thus considered an important local regulator of mammary tissue involution. So far the studies on mammary gland involution concerned only apoptosis as a type I of MEC programmed cell death (PCD). Autophagy is known to be type II of PCD and this paper is the first, supporting evidence for the TGF-beta1-induced autophagy in bovine mammary epithelial cell line BME-UV1, as a distinct to apoptosis type of PCD. Laser scanning cytometry and confocal microscopy were used for analysis of MAP1 LC3 and Beclin 1 expression - two proteins considered being the most reliable biochemical markers of autophagy. The significant increase of MAP1 LC3 and Beclin 1 expression in cells treated with TGF-beta1 (2 ng/ml) was observed. Ultrastructural observation in electron microscopy revealed that autophagy is not only alternative, but also complementary to apoptosis type of cell death in TGF-beta1-treated bovine MEC. It was manifested by typical morphological features of apoptosis (cell shrinkage, margination and condensation of chromatin) and autophagy (autophagosomes, autophagic vacuoles) in the same cell. PMID:16077200

  3. A Novel Human Cytomegalovirus Glycoprotein, gpUS9, Which Promotes Cell-to-Cell Spread in Polarized Epithelial Cells, Colocalizes with the Cytoskeletal Proteins E-Cadherin and F-Actin

    PubMed Central

    Maidji, Ekaterina; Tugizov, Sharof; Abenes, Gerardo; Jones, Thomas; Pereira, Lenore

    1998-01-01

    Processes by which human herpesviruses penetrate and are released from polarized epithelial cells, which have distinct apical and basolateral membrane domains differing in protein and lipid content, are poorly understood. We recently reported that human cytomegalovirus (CMV) mutants with deletions of the gene US9 formed wild-type plaques in cultures of human fibroblasts but were impaired in the capacity for cell-to-cell spread in polarized human retinal pigment epithelial cells. Unlike the glycoproteins that are required for infection, the protein encoded by CMV US9 plays an accessory role by promoting dissemination of virus across cell-cell junctions of polarized epithelial cells. To identify the product and investigate its specialized functions, we selected Madine-Darby canine kidney II (MDCK) epithelial cells that constitutively express CMV US9 or, as a control, US8. The gene products, designated gpUS9 and gpUS8, were glycosylated proteins of comparable molecular masses but differed considerably in intracellular distribution and solubility. Immunofluorescence laser scanning confocal microscopy indicated that, like gpUS8, gpUS9 was present in the endoplasmic reticulum and Golgi compartments of nonpolarized cells. In polarized epithelial cells, gpUS9 also accumulated along lateral membranes, colocalizing with cadherin and actin, and was insoluble in Triton X-100, a property shared with proteins that associate with the cytoskeleton. We hypothesize that gpUS9 may enhance the dissemination of CMV in infected epithelial tissues by associating with the cytoskeletal matrix. PMID:9621030

  4. Stress-Derived Corticotropin Releasing Factor Breaches Epithelial Endotoxin Tolerance

    PubMed Central

    Yu, Yong; Geng, Xiao-Rui; Yang, Gui; Liu, Zhi-Gang; Zheng, Peng-Yuan; Yang, Ping-Chang

    2013-01-01

    Background and aims Loss of the endotoxin tolerance of intestinal epithelium contributes to a number of intestinal diseases. The etiology is not clear. Psychological stress is proposed to compromise the intestinal barrier function. The present study aims to elucidate the role of the stress-derived corticotropin releasing factor (CRF) in breaching the established intestinal epithelial endotoxin tolerance. Methods Epithelial cells of HT-29, T84 and MDCK were exposed to lipopolysaccharide to induce the endotoxin tolerance; the cells were then stimulated with CRF. The epithelial barrier function was determined using as indicators of the endotoxin tolerant status. A water-avoid stress mouse model was employed to test the role of CRF in breaching the established endotoxin tolerance in the intestine. Results The established endotoxin tolerance in the epithelial cell monolayers was broken down by a sequent exposure to CRF and LPS manifesting a marked drop of the transepithelial resistance (TER) and an increase in the permeability to a macromolecular tracer, horseradish peroxidase (HRP). The exposure to CRF also increased the expression of Cldn2 in the epithelial cells, which could be mimicked by over expression of TLR4 in epithelial cells. Over expression of Cldn2 resulted in low TER in epithelial monolayers and high permeability to HRP. After treating mice with the 10-day chronic stress, the intestinal epithelial barrier function was markedly compromised, which could be prevented by blocking either CRF, or TLR4, or Cldn2. Conclusions Psychological stress-derived CRF can breach the established endotoxin tolerance in the intestinal mucosa. PMID:23840363

  5. Isolation of Cancer Epithelial Cells from Mouse Mammary Tumors

    PubMed Central

    Johnson, Sara; Chen, Hexin; Lo, Pang-Kuo

    2016-01-01

    The isolation of cancer epithelial cells from mouse mammary tumor is accomplished by digestion of the solid tumor. Red blood cells and other contaminates are removed using several washing techniques such that primary epithelial cells can further enriched. This procedure yields primary tumor cells that can be used for in vitro tissue culture, fluorescence-activated cell sorting (FACS) and a wide variety of other experiments (Lo et al., 2012).

  6. Response of corneal epithelial cells to Staphylococcus aureus

    PubMed Central

    2010-01-01

    Staphylococcus aureus is a leading cause of invasive infection. It also infects wet mucosal tissues including the cornea and conjunctiva. Conflicting evidence exists on the expression of Toll-like receptors by human corneal epithelial cells. It was therefore of interest to determine how epithelial cells from this immune privileged tissue respond to S. aureus. Further, it was of interest to determine whether cytolytic toxins, with the potential to cause ion flux or potentially permit effector molecule movement across the target cell membrane, alter the response. Microarrays were used to globally assess the response of human corneal epithelial cells to S. aureus. A large increase in abundance of transcripts encoding the antimicrobial dendritic cell chemokine, CCL20, was observed. CCL20 release into the medium was detected, and this response was found to be largely TLR2 and NOD2 independent. Corneal epithelial cells also respond to S. aureus by increasing the intracellular abundance of mRNA for inflammatory mediators, transcription factors, and genes related to MAP kinase pathways, in ways similar to other cell types. The corneal epithelial cell response was surprisingly unaffected by toxin exposure. Toxin exposure did, however, induce a stress response. Although model toxigenic and non-toxigenic strains of S. aureus were employed in the present study, the results obtained were strikingly similar to those reported for stimulation of vaginal epithelial cells by clinical toxic shock toxin expressing isolates, demonstrating that the initial epithelial cellular responses to S. aureus are largely independent of strain as well as epithelial cell tissue source. PMID:21178447

  7. The microenvironmental determinants for kidney epithelial cyst morphogenesis

    PubMed Central

    Guo, Qiusha; Xia, Bing; Moshiach, Simon; Xu, Congfeng; Jiang, Yongde; Chen, Yuanjian; Sun, Yao; Lahti, Jill M.; Zhang, Xin A.

    2011-01-01

    Although epithelial morphogenesis is tightly controlled by intrinsic genetic programs, the microenvironment in which epithelial cells proliferate and differentiate also contributes to the morphogenetic process. The roles of the physical microenvironment in epithelial morphogenesis, however, have not been well dissected. In this study, we assessed the impact of the microenvironment on epithelial cyst formation, which often marks the beginning or end step of morphogenesis of epithelial tissues and the pathological characteristic of some diseases. Previous studies have demonstrated that Madin-Darby canine kidney (MDCK) epithelial cells form cysts when grown in a three-dimensional (3D) extracellullar matrix (ECM) environment. We have now further demonstrated that the presence of ECM in the 3D scaffold is required for the formation of properly polarized cysts. Also, we have found that the full interface of epithelial cells with the ECM environment (in-3D) is not essential for cyst formation, since partial contact (on-3D) is sufficient to induce cystogenesis. In addition, we have defined the minimal ECM environment or the physical threshold for cystogenesis under the on-3D condition. Only above the threshold can the morphological cues from the ECM environment induce cyst formation. Moreover, cyst formation under the on-3D condition described in this study actually defines a novel and more feasible model to analyze in vitro morphogenesis. Finally, we have found that, during cystogenesis, MDCK cells generate basal microprotrusions and produce vesicle-like structures to the basal extracellular space, which are specific to and correlated with cyst formation. For the first time, we have systematically elucidated the microenvironmental determinants for epithelial cystogenesis. PMID:18191498

  8. Expression and Function of CD44 in Epithelial Ovarian Carcinoma

    PubMed Central

    Sacks, Joelle D.; Barbolina, Maria V.

    2015-01-01

    CD44, a cell surface glycoprotein, has been increasingly implicated in the pathogenesis and progression of epithelial ovarian cancer, the deadliest gynecologic malignancy in women. Here, we review recent reports on the expression and function of CD44 in epithelial ovarian carcinoma. Further functional data for CD44 in peritoneal adhesion and metastatic progression and its association with stem cells is highlighted. Recent studies utilizing CD44 for therapeutic targeting are also discussed. PMID:26569327

  9. Laser propulsion

    NASA Technical Reports Server (NTRS)

    Rom, F. E.; Putre, H. A.

    1972-01-01

    The use of an earth-based high-power laser beam to provide energy for earth-launched rocket vehicle is investigated. The laser beam energy is absorbed in an opaque propellant gas and is converted to high-specific-impulse thrust by expanding the heated propellant to space by means of a nozzle. This laser propulsion scheme can produce specific impulses of several thousand seconds. Payload to gross-weight fractions about an order of magnitude higher than those for conventional chemical earth-launched vehicles appear possible. There is a potential for a significant reduction in cost per payload mass in earth orbit.

  10. Laser goniometer

    DOEpatents

    Fairer, George M.; Boernge, James M.; Harris, David W.; Campbell, DeWayne A.; Tuttle, Gene E.; McKeown, Mark H.; Beason, Steven C.

    1993-01-01

    The laser goniometer is an apparatus which permits an operator to sight along a geologic feature and orient a collimated lamer beam to match the attitude of the feature directly. The horizontal orientation (strike) and the angle from horizontal (dip), are detected by rotary incremental encoders attached to the laser goniometer which provide a digital readout of the azimuth and tilt of the collimated laser beam. A microprocessor then translates the square wave signal encoder outputs into an ASCII signal for use by data recording equipment.

  11. Explosive laser

    DOEpatents

    Robinson, C.P.; Jensen, R.J.; Davis, W.C.; Sullivan, J.A.

    1975-09-01

    This patent relates to a laser system wherein reaction products from the detonation of a condensed explosive expand to form a gaseous medium with low translational temperature but high vibration population. Thermal pumping of the upper laser level and de-excitation of the lower laser level occur during the expansion, resulting in a population inversion. The expansion may be free or through a nozzle as in a gas-dynamic configuration. In one preferred embodiment, the explosive is such that its reaction products are CO$sub 2$ and other species that are beneficial or at least benign to CO$sub 2$ lasing. (auth)

  12. Chemical lasers

    NASA Astrophysics Data System (ADS)

    Khariton, Y.

    1984-08-01

    The application and the advances of quantum electronics, specifically, of optical quantum generators lasers is reviewed. Materials are cut, their surfaces are machined, chemical transformations of substances are carried out, surgical operations are performed, data are transmitted, three dimensional images are produced and the content of microimpurities, in the atmosphere, are analyzed by use of a beam. Laser technology is used in conducting investigations in the most diverse fields of the natural and technical sciences from controlled thermonuclear fusion to genetics. Many demands are placed on lasers as sources of light energy. The importance of low weight, compactness of the optical generator and the efficiency of energy conversion processes is emphasized.

  13. Laser arthroscopy.

    PubMed

    Sherk, H H; Lane, G J; Black, J D

    1992-09-01

    Lasers have become widely used in several medical and surgical disciplines. In ophthalmology and plastic surgery, their use has permitted the development of therapeutic modalities that would have been otherwise impossible. In such specialties as gynecology and general surgery, lasers provide advantages that make certain procedures more convenient and easier to perform. In contrast, orthopaedic surgeons have, to date, been slow to accept these devices into the therapeutic armamentarium. The purpose of this paper is to describe the status of laser use in the orthopaedic subspecialty of arthroscopy. PMID:1437258

  14. Sunitinib Malate in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-01-15

    Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

  15. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk.

    PubMed

    Amankwah, Ernest K; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chen, Zhihua; Chen, Y Ann; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Ian; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Pike, Malcolm C; Poole, Elizabeth M; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Thomsen, Lotte; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vierkant, Robert A; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E; Berchuck, Andrew; Schildkraut, Joellen M; Ramus, Susan J; Goode, Ellen L; Monteiro, Alvaro N A; Gayther, Simon A; Narod, Steven A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

    2015-12-01

    Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC. PMID:26399219

  16. The epithelial barrier is maintained by in vivo tight junction expansion during pathologic intestinal epithelial shedding

    PubMed Central

    Marchiando, Amanda M.; Shen, Le; Graham, W. Vallen; Edelblum, Karen L.; Duckworth, Carrie A.; Guan, Yanfang; Montrose, Marshall H.; Turner, Jerrold R.; Watson, Alastair J.M.

    2011-01-01

    BACKGROUND & AIMS Tumor necrosis factor (TNF) increases intestinal epithelial cell shedding and apoptosis, potentially challenging the barrier between the gastrointestinal lumen and internal tissues. We investigated the mechanism of tight junction remodeling and barrier maintenance, as well as the roles of cytoskeletal regulatory molecules during TNF-induced shedding. METHODS We studied wild-type and transgenic mice that express the fluorescent-tagged proteins enhanced green fluorescent protein–occludin or monomeric red fluorescent protein1–ZO-1. After injection of high doses of TNF (7.5µg, i.p.), laparotomies were performed and segments of small intestine were opened to visualize the mucosa by video confocal microscopy. Pharmacologic inhibitors and knockout mice were used to determine the roles of caspase activation, actomyosin, and microtubule remodeling and membrane trafficking in epithelial shedding. RESULTS Changes detected included redistribution of the tight junction proteins ZO-1 and occluding to lateral membranes of shedding cells. These proteins ultimately formed a funnel around the shedding cell that defined the site of barrier preservation. Claudins, E-cadherin, F-actin, myosin II, Rho-associated kinase (ROCK), and myosin light chain kinase (MLCK) were also recruited to lateral membranes. Caspase activity, myosin motor activity, and microtubules were required to initiate shedding, whereas completion of the process required microfilament remodeling and ROCK, MLCK, and dynamin II activities. CONCLUSIONS Maintenance of the epithelial barrier during TNF-induced cell shedding is a complex process that involves integration of microtubules, microfilaments, and membrane traffic to remove apoptotic cells. This process is accompanied by redistribution of apical junctional complex proteins to form intercellular barriers between lateral membranes and maintain mucosal function. PMID:21237166

  17. Regulation of intestinal epithelial cells transcriptome by enteric glial cells: impact on intestinal epithelial barrier functions

    PubMed Central

    2009-01-01

    Background Emerging evidences suggest that enteric glial cells (EGC), a major constituent of the enteric nervous system (ENS), are key regulators of intestinal epithelial barrier (IEB) functions. Indeed EGC inhibit intestinal epithelial cells (IEC) proliferation and increase IEB paracellular permeability. However, the role of EGC on other important barrier functions and the signalling pathways involved in their effects are currently unknown. To achieve this goal, we aimed at identifying the impact of EGC upon IEC transcriptome by performing microarray studies. Results EGC induced significant changes in gene expression profiling of proliferating IEC after 24 hours of co-culture. 116 genes were identified as differentially expressed (70 up-regulated and 46 down-regulated) in IEC cultured with EGC compared to IEC cultured alone. By performing functional analysis of the 116 identified genes using Ingenuity Pathway Analysis, we showed that EGC induced a significant regulation of genes favoring both cell-to-cell and cell-to-matrix adhesion as well as cell differentiation. Consistently, functional studies showed that EGC induced a significant increase in cell adhesion. EGC also regulated genes involved in cell motility towards an enhancement of cell motility. In addition, EGC profoundly modulated expression of genes involved in cell proliferation and cell survival, although no clear functional trend could be identified. Finally, important genes involved in lipid and protein metabolism of epithelial cells were shown to be differentially regulated by EGC. Conclusion This study reinforces the emerging concept that EGC have major protective effects upon the IEB. EGC have a profound impact upon IEC transcriptome and induce a shift in IEC phenotype towards increased cell adhesion and cell differentiation. This concept needs to be further validated under both physiological and pathophysiological conditions. PMID:19883504

  18. Trek1 contributes to maintaining nasal epithelial barrier integrity.

    PubMed

    Jiang, Jing; Liu, Jiang-Qi; Li, Jing; Li, Meng; Chen, Hong-Bin; Yan, Hao; Mo, Li-Hua; Qiu, Shu-Qi; Liu, Zhi-Gang; Yang, Ping-Chang

    2015-01-01

    Epithelial barrier integrity is critical to maintain the homeostasis in the body. The regulatory mechanism of the epithelial barrier function has not been fully understood. This study aims to elucidate the role of the TWIK-related potassium channel-1 (Trek1) in the regulation of the epithelial barrier function of the nasal mucosa. In this study, the levels of Trek1 were assessed by real time RT-PCR and Western blotting. The epithelial barrier function of the rat nasal epithelia was evaluated by the Ussing chamber system. The results showed that Trek1 was detected in the human and rat nasal epithelia, which were significantly lower in patients and rats with allergic rhinitis than that in healthy controls. Exposure to the signature T helper 2 cytokine, interleukin (IL)-4, markedly suppressed the expression of Trek1 in the nasal mucosa via up regulating the expression of the histone deacetylase (HDAC)1. The IL-4-induced rat nasal epithelial barrier dysfunction could be blocked by HDAC1 inhibitor (Trichostatin A), or sodium butyrate, or administration of Clostridium Butyricum. We conclude that Trek1 is critical to maintain the nasal epithelial barrier function. PMID:25778785

  19. Strengthening of the intestinal epithelial tight junction by Bifidobacterium bifidum

    PubMed Central

    Hsieh, Chen-Yu; Osaka, Toshifumi; Moriyama, Eri; Date, Yasuhiro; Kikuchi, Jun; Tsuneda, Satoshi

    2015-01-01

    Epithelial barrier dysfunction has been implicated as one of the major contributors to the pathogenesis of inflammatory bowel disease. The increase in intestinal permeability allows the translocation of luminal antigens across the intestinal epithelium, leading to the exacerbation of colitis. Thus, therapies targeted at specifically restoring tight junction barrier function are thought to have great potential as an alternative or supplement to immunology-based therapies. In this study, we screened Bifidobacterium, Enterococcus, and Lactobacillus species for beneficial microbes to strengthen the intestinal epithelial barrier, using the human intestinal epithelial cell line (Caco-2) in an in vitro assay. Some Bifidobacterium and Lactobacillus species prevented epithelial barrier disruption induced by TNF-α, as assessed by measuring the transepithelial electrical resistance (TER). Furthermore, live Bifidobacterium species promoted wound repair in Caco-2 cell monolayers treated with TNF-α for 48 h. Time course 1H-NMR-based metabonomics of the culture supernatant revealed markedly enhanced production of acetate after 12 hours of coincubation of B. bifidum and Caco-2. An increase in TER was observed by the administration of acetate to TNF-α-treated Caco-2 monolayers. Interestingly, acetate-induced TER-enhancing effect in the coculture of B. bifidum and Caco-2 cells depends on the differentiation stage of the intestinal epithelial cells. These results suggest that Bifidobacterium species enhance intestinal epithelial barrier function via metabolites such as acetate. PMID:25780093

  20. Intrinsic epithelial cells repair the kidney after injury.

    PubMed

    Humphreys, Benjamin D; Valerius, M Todd; Kobayashi, Akio; Mugford, Joshua W; Soeung, Savuth; Duffield, Jeremy S; McMahon, Andrew P; Bonventre, Joseph V

    2008-03-01

    Understanding the mechanisms of nephron repair is critical for the design of new therapeutic approaches to treat kidney disease. The kidney can repair after even a severe insult, but whether adult stem or progenitor cells contribute to epithelial renewal after injury and the cellular origin of regenerating cells remain controversial. Using genetic fate-mapping techniques, we generated transgenic mice in which 94%-95% of tubular epithelial cells, but no interstitial cells, were labeled with either beta-galactosidase (lacZ) or red fluorescent protein (RFP). Two days after ischemia-reperfusion injury (IRI), 50.5% of outer medullary epithelial cells coexpress Ki67 and RFP, indicating that differentiated epithelial cells that survived injury undergo proliferative expansion. After repair was complete, 66.9% of epithelial cells had incorporated BrdU, compared to only 3.5% of cells in the uninjured kidney. Despite this extensive cell proliferation, no dilution of either cell-fate marker was observed after repair. These results indicate that regeneration by surviving tubular epithelial cells is the predominant mechanism of repair after ischemic tubular injury in the adult mammalian kidney. PMID:18371453

  1. Diversity of epithelial stem cell types in adult lung.

    PubMed

    Li, Feng; He, Jinxi; Wei, Jun; Cho, William C; Liu, Xiaoming

    2015-01-01

    Lung is a complex organ lined with epithelial cells. In order to maintain its homeostasis and normal functions following injuries caused by varied extraneous and intraneous insults, such as inhaled environmental pollutants and overwhelming inflammatory responses, the respiratory epithelium normally undergoes regenerations by the proliferation and differentiation of region-specific epithelial stem/progenitor cells that resided in distinct niches along the airway tree. The importance of local epithelial stem cell niches in the specification of lung stem/progenitor cells has been recently identified. Studies using cell differentiating and lineage tracing assays, in vitro and/or ex vivo models, and genetically engineered mice have suggested that these local epithelial stem/progenitor cells within spatially distinct regions along the pulmonary tree contribute to the injury repair of epithelium adjacent to their respective niches. This paper reviews recent findings in the identification and isolation of region-specific epithelial stem/progenitor cells and local niches along the airway tree and the potential link of epithelial stem cells for the development of lung cancer. PMID:25810726

  2. Serum-Induced Differentiation of Human Meibomian Gland Epithelial Cells

    PubMed Central

    Sullivan, David A.; Liu, Yang; Kam, Wendy R.; Ding, Juan; Green, Karin M.; Shaffer, Scott A.; Hatton, Mark P.; Liu, Shaohui

    2014-01-01

    Purpose. We hypothesize that culturing immortalized human meibomian gland epithelial cells in serum-containing medium will induce their differentiation. The purpose of this investigation was to begin to test our hypothesis, and explore the impact of serum on gene expression and lipid accumulation in human meibomian gland epithelial cells. Methods. Immortalized and primary human meibomian gland epithelial cells were cultured in the presence or absence of serum. Cells were evaluated for lysosome and lipid accumulation, polar and neutral lipid profiles, and gene expression. Results. Our results support our hypothesis that serum stimulates the differentiation of human meibomian gland epithelial cells. This serum-induced effect is associated with a significant increase in the expression of genes linked to cell differentiation, epithelium development, the endoplasmic reticulum, Golgi apparatus, vesicles, and lysosomes, and a significant decrease in gene activity related to the cell cycle, mitochondria, ribosomes, and translation. These cellular responses are accompanied by an accumulation of lipids within lysosomes, as well as alterations in the fatty acid content of polar and nonpolar lipids. Of particular importance, our results show that the molecular and biochemical changes of immortalized human meibomian gland epithelial cells during differentiation are analogous to those of primary cells. Conclusions. Overall, our findings indicate that immortalized human meibomian gland epithelial cells may serve as an ideal preclinical model to identify factors that control cellular differentiation in the meibomian gland. PMID:24867579

  3. A Case of Solitary Nonvascularized Corneal Epithelial Dysplasia

    PubMed Central

    Morii, Tomoya; Sumioka, Takayoshi; Izutani-Kitano, Ai; Takada, Yukihisa; Okada, Yuka; Kao, Winston W.-Y.; Saika, Shizuya

    2016-01-01

    Background. Epithelial dysplasia is categorized as conjunctival/corneal intraepithelial neoplasia which is a precancerous lesion. The lesion is usually developed at the limbal region and grows towards central cornea in association with neovascularization into the lesion. Here, we report a case of isolated nonvascularized corneal epithelial dysplasia surrounded by normal corneal epithelium with immune histochemical finding of ocular surface tissues cytokeratins, for example, keratin 13 and keratin 12. Case Presentation. A 76-year-old man consulted us for visual disturbance with localized opacification of the corneal epithelium in his left eye. His visual acuity was 20/20 and 20/200 in his right and left eye, respectively. Slit lamp examination showed a whitish plaque-like lesion at the center of his left corneal epithelium. No vascular invasion to the lesion was found. The lesion was surgically removed and subjected to histopathological examination and diagnosed as epithelial dysplasia. Amyloidosis was excluded by direct fast scarlet 4BS (DFS) staining. Immunohistochemistry showed that the dysplastic epithelial cells express keratin 13 and vimentin, but not keratin 12, indicating that the neoplastic epithelial cells lacked corneal-type epithelium differentiation. Conclusions. The lesion was diagnosed as nonvascularized epithelial dysplasia of ocular surface. Etiology of the lesion is not known. PMID:27042371

  4. Cell volume regulation in epithelial physiology and cancer

    PubMed Central

    Pedersen, Stine F.; Hoffmann, Else K.; Novak, Ivana

    2013-01-01

    The physiological function of epithelia is transport of ions, nutrients, and fluid either in secretory or absorptive direction. All of these processes are closely related to cell volume changes, which are thus an integrated part of epithelial function. Transepithelial transport and cell volume regulation both rely on the spatially and temporally coordinated function of ion channels and transporters. In healthy epithelia, specific ion channels/transporters localize to the luminal and basolateral membranes, contributing to functional epithelial polarity. In pathophysiological processes such as cancer, transepithelial and cell volume regulatory ion transport are dys-regulated. Furthermore, epithelial architecture and coordinated ion transport function are lost, cell survival/death balance is altered, and new interactions with the stroma arise, all contributing to drug resistance. Since altered expression of ion transporters and channels is now recognized as one of the hallmarks of cancer, it is timely to consider this especially for epithelia. Epithelial cells are highly proliferative and epithelial cancers, carcinomas, account for about 90% of all cancers. In this review we will focus on ion transporters and channels with key physiological functions in epithelia and known roles in the development of cancer in these tissues. Their roles in cell survival, cell cycle progression, and development of drug resistance in epithelial cancers will be discussed. PMID:24009588

  5. Microfluidic approaches for epithelial cell layer culture and characterisation

    PubMed Central

    Thuenauer, Roland; Rodriguez-Boulan, Enrique; Römer, Winfried

    2014-01-01

    In higher eukaryotes, epithelial cell layers line most body cavities and form selective barriers that regulate the exchange of solutes between compartments. In order to fulfil these functions, the cells assume a polarised architecture and maintain two distinct plasma membrane domains, the apical domain facing the lumen and the basolateral domain facing other cells and the extracellular matrix. Microfluidic biochips offer the unique opportunity to establish novel in vitro models of epithelia in which the in vivo microenvironment of epithelial cells is precisely reconstituted. In addition, analytical tools to monitor biologically relevant parameters can be directly integrated on-chip. In this review we summarise recently developed biochip designs for culturing epithelial cell layers. Since endothelial cell layers, which line blood vessels, have similar barrier functions and polar organisation as epithelial cell layers, we also discuss biochips for culturing endothelial cell layers. Furthermore, we review approaches to integrate tools to analyse and manipulate epithelia and endothelia in microfluidic biochips, including methods to perform electrical impedance spectroscopy, methods to detect substances undergoing trans-epithelial transport via fluorescence, spectrophotometry, and mass spectrometry, techniques to mechanically stimulate cells via stretching and fluid flow-induced shear stress, and methods to carry out high-resolution imaging of vesicular trafficking with light microscopy. Taken together, this versatile microfluidic toolbox enables novel experimental approaches to characterise epithelial monolayers. PMID:24668405

  6. Microfluidic approaches for epithelial cell layer culture and characterisation.

    PubMed

    Thuenauer, Roland; Rodriguez-Boulan, Enrique; Römer, Winfried

    2014-07-01

    In higher eukaryotes, epithelial cell layers line most body cavities and form selective barriers that regulate the exchange of solutes between compartments. In order to fulfil these functions, the cells assume a polarised architecture and maintain two distinct plasma membrane domains, the apical domain facing the lumen and the basolateral domain facing other cells and the extracellular matrix. Microfluidic biochips offer the unique opportunity to establish novel in vitro models of epithelia in which the in vivo microenvironment of epithelial cells is precisely reconstituted. In addition, analytical tools to monitor biologically relevant parameters can be directly integrated on-chip. In this review we summarise recently developed biochip designs for culturing epithelial cell layers. Since endothelial cell layers, which line blood vessels, have similar barrier functions and polar organisation as epithelial cell layers, we also discuss biochips for culturing endothelial cell layers. Furthermore, we review approaches to integrate tools to analyse and manipulate epithelia and endothelia in microfluidic biochips; including methods to perform electrical impedance spectroscopy; methods to detect substances undergoing trans-epithelial transport via fluorescence, spectrophotometry, and mass spectrometry; techniques to mechanically stimulate cells via stretching and fluid flow-induced shear stress; and methods to carry out high-resolution imaging of vesicular trafficking using light microscopy. Taken together, this versatile microfluidic toolbox enables novel experimental approaches to characterise epithelial monolayers. PMID:24668405

  7. Diversity of Epithelial Stem Cell Types in Adult Lung

    PubMed Central

    Li, Feng; He, Jinxi; Wei, Jun; Cho, William C.; Liu, Xiaoming

    2015-01-01

    Lung is a complex organ lined with epithelial cells. In order to maintain its homeostasis and normal functions following injuries caused by varied extraneous and intraneous insults, such as inhaled environmental pollutants and overwhelming inflammatory responses, the respiratory epithelium normally undergoes regenerations by the proliferation and differentiation of region-specific epithelial stem/progenitor cells that resided in distinct niches along the airway tree. The importance of local epithelial stem cell niches in the specification of lung stem/progenitor cells has been recently identified. Studies using cell differentiating and lineage tracing assays, in vitro and/or ex vivo models, and genetically engineered mice have suggested that these local epithelial stem/progenitor cells within spatially distinct regions along the pulmonary tree contribute to the injury repair of epithelium adjacent to their respective niches. This paper reviews recent findings in the identification and isolation of region-specific epithelial stem/progenitor cells and local niches along the airway tree and the potential link of epithelial stem cells for the development of lung cancer. PMID:25810726

  8. Boundary crossing in epithelial wound healing

    PubMed Central

    Fong, Eileen; Tzlil, Shelly; Tirrell, David A.

    2010-01-01

    The processes of wound healing and collective cell migration have been studied for decades. Intensive research has been devoted to understanding the mechanisms involved in wound healing, but the role of cell-substrate interactions is still not thoroughly understood. Here we probe the role of cell-substrate interactions by examining in vitro the healing of monolayers of human corneal epithelial (HCE) cells cultured on artificial extracellular matrix (aECM) proteins. We find that the rate of wound healing is dependent on the concentration of fibronectin-derived (RGD) cell-adhesion ligands in the aECM substrate. The wound closure rate varies nearly sixfold on the substrates examined, despite the fact that the rates of migration and proliferation of individual cells show little sensitivity to the RGD concentration (which varies 40-fold). To explain this apparent contradiction, we study collective migration by means of a dynamic Monte Carlo simulation. The cells in the simulation spread, retract, and proliferate with probabilities obtained from a simple phenomenological model. The results indicate that the overall wound closure rate is determined primarily by the rate at which cells cross the boundary between the aECM protein and the matrix deposited under the cell sheet. PMID:20974917

  9. Stochastic Terminal Dynamics in Epithelial Cell Intercalation

    NASA Astrophysics Data System (ADS)

    Eule, Stephan; Metzger, Jakob; Reichl, Lars; Kong, Deqing; Zhang, Yujun; Grosshans, Joerg; Wolf, Fred

    2015-03-01

    We found that the constriction of epithelial cell contacts during intercalation in germ band extension in Drosophila embryos follows intriguingly simple quantitative laws. The mean contact length < L > follows < L > (t) ~(T - t) α , where T is the finite collapse time; the time dependent variance of contact length is proportional to the square of the mean; finally the time dependent probability density of the contact lengths remains close to Gaussian during the entire process. These observations suggest that the dynamics of contact collapse can be captured by a stochastic differential equation analytically tractable in small noise approximation. Here, we present such a model, providing an effective description of the non-equilibrium statistical mechanics of contact collapse. All model parameters are fixed by measurements of time dependent mean and variance of contact lengths. The model predicts the contact length covariance function that we obtain in closed form. The contact length covariance function closely matches experimental observations suggesting that the model well captures the dynamics of contact collapse.

  10. Sepsis-associated AKI: epithelial cell dysfunction.

    PubMed

    Emlet, David R; Shaw, Andrew D; Kellum, John A

    2015-01-01

    Acute kidney injury (AKI) occurs frequently in critically ill patients with sepsis, in whom it doubles the mortality rate and half of the survivors suffer permanent kidney damage or chronic kidney disease. Failure in the development of viable therapies has prompted studies to better elucidate the cellular and molecular etiologies of AKI, which have generated novel theories and paradigms for the mechanisms of this disease. These studies have shown multifaceted origins and elements of AKI that, in addition to/in lieu of ischemia, include the generation of damage-associated molecular patterns and pathogen-associated molecular patterns, the inflammatory response, humoral and cellular immune activation, perturbation of microvascular flow and oxidative stress, bioenergetic alterations, cell-cycle alterations, and cellular de-differentiation/re-differentiation. It is becoming clear that a major etiologic effector of all these inputs is the renal tubule epithelial cell (RTEC). This review discusses these elements and their effects on RTECs, and reviews the current hypotheses of how these effects may determine the fate of RTECs during sepsis-induced AKI. PMID:25795502

  11. Epithelial sodium channel modulates platelet collagen activation.

    PubMed

    Cerecedo, Doris; Martínez-Vieyra, Ivette; Alonso-Rangel, Lea; Benítez-Cardoza, Claudia; Ortega, Arturo

    2014-03-01

    Activated platelets adhere to the exposed subendothelial extracellular matrix and undergo a rapid cytoskeletal rearrangement resulting in shape change and release of their intracellular dense and alpha granule contents to avoid hemorrhage. A central step in this process is the elevation of the intracellular Ca(2+) concentration through its release from intracellular stores and on throughout its influx from the extracellular space. The Epithelial sodium channel (ENaC) is a highly selective Na(+) channel involved in mechanosensation, nociception, fluid volume homeostasis, and control of arterial blood pressure. The present study describes the expression, distribution, and participation of ENaC in platelet migration and granule secretion using pharmacological inhibition with amiloride. Our biochemical and confocal analysis in suspended and adhered platelets suggests that ENaC is associated with Intermediate filaments (IF) and with Dystrophin-associated proteins (DAP) via α-syntrophin and β-dystroglycan. Migration assays, quantification of soluble P-selectin, and serotonin release suggest that ENaC is dispensable for migration and alpha and dense granule secretion, whereas Na(+) influx through this channel is fundamental for platelet collagen activation. PMID:24679405

  12. Prostasin: An Epithelial Sodium Channel Regulator.

    PubMed

    Aggarwal, Shakti; Dabla, Pradeep K; Arora, Sarika

    2013-01-01

    Prostasin is a glycophosphatidylinositol-anchored protein which is found in prostate gland, kidney, bronchi, colon, liver, lung, pancreas, and salivary glands. It is a serine protease with trypsin-like substrate specificity which was first purified from seminal fluid in 1994. In the last decade, its diverse roles in various biological and physiological processes have been elucidated. Many studies done to date suggest that prostasin is one of several membrane peptidases regulating epithelial sodium channels in mammals. A comprehensive literature search was conducted from the websites of Pubmed Central, the US National Library of Medicine's digital archive of life sciences literature and the National Library of Medicine. The data was also assessed from journals and books that published relevant articles in this field. Understanding the mechanism by which prostasin and its inhibitors regulate sodium channels has provided a new insight into the treatment of hypertension and some other diseases like cystic fibrosis. Prostasin plays an important role in epidermal growth factor receptor (EGFR) signal modulation. Extracellular proteases have been implicated in tumor metastasis and local tissue invasion because of their ability to degrade extracellular matrices. PMID:26317012

  13. Tweak induces mammary epithelial branching morphogenesis.

    PubMed

    Michaelson, Jennifer S; Cho, Sandy; Browning, Beth; Zheng, Timothy S; Lincecum, John M; Wang, Monica Z; Hsu, Yen-Ming; Burkly, Linda C

    2005-04-14

    Members of the tumor necrosis factor (TNF) superfamily regulate cell survival and proliferation and have been implicated in cancer. Tweak (TNF-related weak inducer of apoptosis) has pleiotropic biological functions including proapoptotic, proangiogenic and proinflammatory activities. We explored a role for Tweak in mammary gland transformation using a three-dimensional model culture system. Tweak stimulates a branching morphogenic phenotype, similar to that induced by pro-oncogenic factors, in Eph4 mammary epithelial cells cultured in matrigel. Increased proliferation and invasiveness are observed, with a concomitant inhibition of functional differentiation. Levels of matrix metalloproteinase-9 (MMP-9) are significantly increased following Tweak treatment. Notably, MMP inhibitors are sufficient to block the branching phenotype induced by Tweak. The capacity to promote proliferation, inhibit differentiation and induce invasion suggests a role for Tweak in mammary gland tumorigenesis. Consistent with this, we have observed elevated protein levels of the Tweak receptor, Fn14, in human breast tumor cell lines and xenograft models as well as in primary human breast tumors. Together, our results suggest that the Tweak/Fn14 pathway may be protumorigenic in human breast cancer. PMID:15735761

  14. Periderm prevents pathological epithelial adhesions during embryogenesis

    PubMed Central

    Richardson, Rebecca J.; Hammond, Nigel L.; Coulombe, Pierre A.; Saloranta, Carola; Nousiainen, Heidi O.; Salonen, Riitta; Berry, Andrew; Hanley, Neil; Headon, Denis; Karikoski, Riitta; Dixon, Michael J.

    2014-01-01

    Appropriate development of stratified, squamous, keratinizing epithelia, such as the epidermis and oral epithelia, generates an outer protective permeability barrier that prevents water loss, entry of toxins, and microbial invasion. During embryogenesis, the immature ectoderm initially consists of a single layer of undifferentiated, cuboidal epithelial cells that stratifies to produce an outer layer of flattened periderm cells of unknown function. Here, we determined that periderm cells form in a distinct pattern early in embryogenesis, exhibit highly polarized expression of adhesion complexes, and are shed from the outer surface of the embryo late in development. Mice carrying loss-of-function mutations in the genes encoding IFN regulatory factor 6 (IRF6), IκB kinase-α (IKKα), and stratifin (SFN) exhibit abnormal epidermal development, and we determined that mutant animals exhibit dysfunctional periderm formation, resulting in abnormal intracellular adhesions. Furthermore, tissue from a fetus with cocoon syndrome, a lethal disorder that results from a nonsense mutation in IKKA, revealed an absence of periderm. Together, these data indicate that periderm plays a transient but fundamental role during embryogenesis by acting as a protective barrier that prevents pathological adhesion between immature, adhesion-competent epithelia. Furthermore, this study suggests that failure of periderm formation underlies a series of devastating birth defects, including popliteal pterygium syndrome, cocoon syndrome, and Bartsocas-Papas syndrome. PMID:25133425

  15. Laser barometer

    SciTech Connect

    Abercrombie, K.R.; Shiels, D.; Rash, T.

    1998-04-01

    This paper describes an invention of a pressure measuring instrument which uses laser radiation to sense the pressure in an enclosed environment by means of measuring the change in refractive index of a gas - which is pressure dependent.

  16. Laser fusion

    SciTech Connect

    Smit, W.A.; Boskma, P.

    1980-12-01

    Unrestricted laser fusion offers nations an opportunity to circumvent arms control agreements and develop thermonuclear weapons. Early laser weapons research sought a clean radiation-free bomb to replace the fission bomb, but this was deceptive because a fission bomb was needed to trigger the fusion reaction and additional radioactivity was induced by generating fast neutrons. As laser-implosion experiments focused on weapons physics, simulating weapons effects, and applications for new weapons, the military interest shifted from developing a laser-ignited hydrogen bomb to more sophisticated weapons and civilian applications for power generation. Civilian and military research now overlap, making it possible for several countries to continue weapons activities and permitting proliferation of nuclear weapons. These countries are reluctant to include inertial confinement fusion research in the Non-Proliferation Treaty. 16 references. (DCK)

  17. Laser Research

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Eastman Kodak Company, Rochester, New York is a broad-based firm which produces photographic apparatus and supplies, fibers, chemicals and vitamin concentrates. Much of the company's research and development effort is devoted to photographic science and imaging technology, including laser technology. Eastman Kodak is using a COSMIC computer program called LACOMA in the analysis of laser optical systems and camera design studies. The company reports that use of the program has provided development time savings and reduced computer service fees.

  18. Laser Technology

    NASA Technical Reports Server (NTRS)

    1989-01-01

    Amoco Laser Company, a subsidiary of Amoco Corporation, has developed microlasers for the commercial market based on a JPL concept for optical communications over interplanetary distances. Lasers emit narrow, intense beams of light or other radiation. The beams transmit communication signals, drill, cut or melt materials or remove diseased body tissue. The microlasers cover a broad portion of the spectrum, and performance is improved significantly. Current applications include medical instrumentation, color separation equipment, telecommunications, etc.

  19. Photodynamic therapy in the treatment of epithelial potentially malignant disorders of the mouth: advantages and disadvantages

    NASA Astrophysics Data System (ADS)

    Gaimari, G.; Russo, C.; Palaia, G.; Tenore, G.; Del Vecchio, A.; Romeo, U.

    2016-03-01

    Introduction: Leukoplakia is a potentially malignant epithelial lesion with carcinomatous percentages transformation comprehended between 1% and 7% for the homogeneous forms and from 4% to 15% for the non-homogeneous ones. Their removal can be performed by scalpel or laser surgery (excision or vaporization). Photodynamic therapy (PDT) is a bloodless treatment option, based on the involvement of three elements: light, photosensitizer and oxygen. When the molecules of the photosensitizer are activated by a low power laser, energy is transferred to molecular oxygen creating highly reactive radicals of oxygen, that have a cytotoxic effect on target cells. Aim of the study: According to several studies in Literature, it has been decided to evaluate through an initial clinical trial, the efficacy of PDT using topical aminolevulinic acid (5-ALA) activated by a laser diode (λ = 635 nm) to treat potentially oral malignant lesions and to illustrate the advantages and disadvantages derived from the use of this technique. Materials and Methods: Five patients, affected by oral leukoplakia (OL) and oral verrucous leukoplakia (OVL) on the mucosal cheeks, labial commissure, fornix and retromolar areas, have been treated using the PDT. Irradiation time with Diode laser: 1000s. Irradiation mode: Scanning. 5 cycles of 3 minute + final cycle of 100 seconds. Each cycle has been interrupted by pauses of 3 minutes. Results and conclusion: PDT results to be effective in the treatment of OL, especially on OVL. In fact, OVL, due to its irregularity, has got an area of increased retention for the gel that is more difficult to be removed by salivary flow. This could explain the better results obtained in this case rather than in those ones of OL. Furthermore, the advantages have been represented by: less invasivity, high sensitivity for altered tissues, minimal scar tissue, less side effects and no pain during and after operation. In contrast to this, the disadvantages were: longer treatment

  20. Laser optomechanics.

    PubMed

    Yang, Weijian; Gerke, Stephen Adair; Ng, Kar Wei; Rao, Yi; Chase, Christopher; Chang-Hasnain, Connie J

    2015-01-01

    Cavity optomechanics explores the interaction between optical field and mechanical motion. So far, this interaction has relied on the detuning between a passive optical resonator and an external pump laser. Here, we report a new scheme with mutual coupling between a mechanical oscillator supporting the mirror of a laser and the optical field generated by the laser itself. The optically active cavity greatly enhances the light-matter energy transfer. In this work, we use an electrically-pumped vertical-cavity surface-emitting laser (VCSEL) with an ultra-light-weight (130 pg) high-contrast-grating (HCG) mirror, whose reflectivity spectrum is designed to facilitate strong optomechanical coupling, to demonstrate optomechanically-induced regenerative oscillation of the laser optomechanical cavity. We observe >550 nm self-oscillation amplitude of the micromechanical oscillator, two to three orders of magnitude larger than typical, and correspondingly a 23 nm laser wavelength sweep. In addition to its immediate applications as a high-speed wavelength-swept source, this scheme also offers a new approach for integrated on-chip sensors. PMID:26333804

  1. Laser Angioplasty

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The principal method of dealing with coronary artery blockage is bypass surgery. A non-surgical alternative available to some patients is balloon angioplasty. For several years, medical researchers have been exploring another alternative that would help a wider circle of patients than the balloon treatment and entail less risk than bypass surgery. A research group is on the verge of an exciting development: laser angioplasty with a 'cool' type of laser, called an excimer laser, that does not damage blood vessel walls and offers non-surgical cleansing of clogged arteries with extraordinary precision. The system is the Dymer 200+ Excimer Laser Angioplasty System, developed by Advanced Intraventional Systems. Used in human clinical tests since 1987, the system is the first fully integrated 'cool' laser capable of generating the requisite laser energy and delivering the energy to target arteries. Thirteen research hospitals in the U.S. have purchased Dymer 200+ systems and used them in clinical trials in 121 peripheral and 555 coronary artery cases. The success rate in opening blocked coronary arteries is 85 percent, with fewer complications than in balloon angioplasty. Food and Drug Administration approval for the system is hoped for in the latter part of 1990. * Advanced Intraventional Systems became Spectranetics in 1994 and discontinued the product.

  2. Laser optomechanics

    NASA Astrophysics Data System (ADS)

    Yang, Weijian; Adair Gerke, Stephen; Wei Ng, Kar; Rao, Yi; Chase, Christopher; Chang-Hasnain, Connie J.

    2015-09-01

    Cavity optomechanics explores the interaction between optical field and mechanical motion. So far, this interaction has relied on the detuning between a passive optical resonator and an external pump laser. Here, we report a new scheme with mutual coupling between a mechanical oscillator supporting the mirror of a laser and the optical field generated by the laser itself. The optically active cavity greatly enhances the light-matter energy transfer. In this work, we use an electrically-pumped vertical-cavity surface-emitting laser (VCSEL) with an ultra-light-weight (130 pg) high-contrast-grating (HCG) mirror, whose reflectivity spectrum is designed to facilitate strong optomechanical coupling, to demonstrate optomechanically-induced regenerative oscillation of the laser optomechanical cavity. We observe >550 nm self-oscillation amplitude of the micromechanical oscillator, two to three orders of magnitude larger than typical, and correspondingly a 23 nm laser wavelength sweep. In addition to its immediate applications as a high-speed wavelength-swept source, this scheme also offers a new approach for integrated on-chip sensors.

  3. Laser optomechanics

    PubMed Central

    Yang, Weijian; Adair Gerke, Stephen; Wei Ng, Kar; Rao, Yi; Chase, Christopher; Chang-Hasnain, Connie J.

    2015-01-01

    Cavity optomechanics explores the interaction between optical field and mechanical motion. So far, this interaction has relied on the detuning between a passive optical resonator and an external pump laser. Here, we report a new scheme with mutual coupling between a mechanical oscillator supporting the mirror of a laser and the optical field generated by the laser itself. The optically active cavity greatly enhances the light-matter energy transfer. In this work, we use an electrically-pumped vertical-cavity surface-emitting laser (VCSEL) with an ultra-light-weight (130 pg) high-contrast-grating (HCG) mirror, whose reflectivity spectrum is designed to facilitate strong optomechanical coupling, to demonstrate optomechanically-induced regenerative oscillation of the laser optomechanical cavity. We observe >550 nm self-oscillation amplitude of the micromechanical oscillator, two to three orders of magnitude larger than typical, and correspondingly a 23 nm laser wavelength sweep. In addition to its immediate applications as a high-speed wavelength-swept source, this scheme also offers a new approach for integrated on-chip sensors. PMID:26333804

  4. Porphyromonas gingivalis Fimbriae Bind to Cytokeratin of Epithelial Cells

    PubMed Central

    Sojar, Hakimuddin T.; Sharma, Ashu; Genco, Robert J.

    2002-01-01

    The adherence of Porphyromonas gingivalis to host cells is likely a prerequisite step in the pathogenesis of P. gingivalis-induced periodontal disease. P. gingivalis binds to and invades epithelial cells, and fimbriae are shown to be involved in this process. Little is known regarding epithelial receptor(s) involved in binding of P. gingivalis fimbriae. Using an overlay assay with purified P. gingivalis fimbriae as a probe, two major epithelial cell proteins with masses of 50 and 40 kDa were identified by immunoblotting with fimbria-specific antibodies. Iodinated purified fimbriae also bound to the same two epithelial cell proteins. An affinity chromatography technique was utilized to isolate and purify the epithelial components to which P. gingivalis fimbriae bind. Purified fimbriae were coupled to CNBr-activated Sepharose-4B, and the solubilized epithelial cell extract proteins bound to the immobilized fimbriae were isolated from the column. A major 50-kDa component and a minor 40-kDa component were purified and could be digested with trypsin, suggesting that they were proteins. These affinity-eluted 50- and 40-kDa proteins were then subjected to amino-terminal sequencing, and no sequence could be determined, suggesting that these proteins have blocked amino-terminal residues. CNBr digestion of the 50-kDa component resulted in an internal sequence homologous to that of Keratin I molecules. Further evidence that P. gingivalis fimbriae bind to cytokeratin molecule(s) comes from studies showing that multicytokeratin rabbit polyclonal antibodies cross-react with the affinity-purified 50-kDa epithelial cell surface component. Also, binding of purified P. gingivalis fimbriae to epithelial components can be inhibited in an overlay assay by multicytokeratin rabbit polyclonal antibodies. Furthermore, we showed that biotinylated purified fimbriae bind to purified human epidermal keratin in an overlay assay. These studies suggest that the surface-accessible epithelial

  5. Epithelial deletion of podoplanin is dispensable for re-epithelialization of skin wounds.

    PubMed

    Baars, Sebastian; Bauer, Christine; Szabowski, Sibylle; Hartenstein, Bettina; Angel, Peter

    2015-10-01

    The mucin-like transmembrane protein podoplanin (PDPN) is prominently represented in tumor-associated gene expression signatures of numerous types of cancer including squamous cell carcinoma, and gain-of-function and knockdown approaches in tissue culture strongly suggested an important role of PDPN in cell proliferation, migration and adhesion. PDPN is absent during epidermal homeostasis but is highly expressed in basal keratinocytes during cutaneous wound healing. Enhanced motility of immortalized keratinocytes upon ectopic PDPN overexpression argues for wound healing defects upon podoplanin deficiency in keratinocytes; however, in vivo data that unequivocally define the impact of PDPN by functional studies in a physiologically relevant system are still missing. Here, we have applied an in vivo loss-of-function approach by generating a novel transgenic mouse line with keratinocyte-specific podoplanin deficiency. Performing cutaneous full-thickness excisional wounds to examine re-epithelialization capacity, unexpectedly, no defects were observed in wound healing properties of mutant mice. Similarly, PDPN-deficient primary keratinocytes showed no impairment in migration, adhesion or proliferation. Thus, PDPN function is not rate-limiting for re-epithelialization but may be functionally compensated by an as yet unknown protein. Our data also call for in vivo functional studies on PDPN in settings of skin tumor development and progression to clarify PDPN's role in skin pathology. PMID:26121181

  6. Laser pointer induced macular damage: case report and mini review.

    PubMed

    Turaka, Kiran; Bryan, J Shepard; Gordon, Alan J; Reddy, Rahul; Kwong, Henry M; Sell, Clive H

    2012-06-01

    To report laser pointer induced damage to retina and choroid and briefly review literature. A case report of a 13-year old Caucasian boy developed blurry central vision and central scotoma in right eye (OD). He was exposed for one minute to class IIIA green laser pointer of 650 nm wavelength and 5 mW power. Clinical examination showed a grayish lesion in foveal region. Ancillary testing revealed disruption of the retinal pigment epithelial (RPE) layer in foveal region and indocyanine green angiography demonstrated evidence of choroidal hypofluorescence suggestive of choroidal infarction in OD. Visual acuity improved from 20/100 to 20/60 in one day and he was treated with tapering doses of oral prednisolone (40 mg) for 3 weeks. Laser pointer with a power of >5 mW caused damage to RPE in the macula. Children should not be given laser pointers as toys especially those with label of danger instructions. PMID:22466425

  7. Claudin immunolocalization in neonatal mouse epithelial tissues.

    PubMed

    Troy, Tammy-Claire; Arabzadeh, Azadeh; Yerlikaya, Seda; Turksen, Kursad

    2007-11-01

    Emerging evidence supports the notion that claudins (Cldns) are dynamically regulated under normal conditions to respond to the selective permeability requirements of various tissues, and that their expression is developmentally controlled. We describe the localization of those Cldns that we have previously demonstrated to be functionally important in epidermal differentiation and the formation of the epidermal permeability barrier, e.g., Cldn1, Cldn6, Cldn11, and Cldn18, and the presence of Cldn3 and Cldn5 in various neonatal mouse epithelia including the epidermis, nail, oral mucosa, tongue, and stomach. Cldn1 is localized in the differentiated and/or undifferentiated compartments of the epidermis and nail and in the dorsal surface of the tongue and glandular compartment of the stomach but is absent from the oral mucosa and the keratinized compartment of the stomach. Cldn3 is present in the basal cells of the nail matrix and both compartments of the murine stomach but not in the epidermis, oral mucosa, or tongue. Cldn5 is found in the glandular compartment of the stomach but not in the epidermis, nail unit, oral mucosa, forestomach, and tongue. Cldn6, Cldn11, and Cldn18 occur in the differentiating suprabasal compartment of the epidermis, nail, and oral mucosa and in the dorsal and ventral surfaces of the tongue and the keratinized squamous epithelium of the stomach. The simple columnar epithelium of the glandular stomach stains for Cldn18 and reveals a non-membranous pattern for Cldn6 and Cldn11 expression. Our results demonstrate differential Cldn protein profiles in various epithelial tissues and their differentiation stages. Although the molecular mechanisms regulating Cldn expression are unknown, elucidation of their differential localization patterns in tissues with diverse permeability requirements should provide a better understanding of the role of tight junctions in tissue function. PMID:17828607

  8. Clinical and pathological aspects of epithelial hyperplasia.

    PubMed

    Gîrtan, Mihaela; Stăniceanu, Florica; Zurac, Sabina; Laba, Elisabeta; Forna, Norina

    2008-01-01

    In many cases, the oral health status indicates the general status of the body. 90% of the disorders of the body also manifest at the level of the oral cavity, which means that the dentist can draw the attention of a certain health problem. Diabetes mellitus is associated with a high prevalence of the lesions of the oral mucous, especially lichen planus, recurrent aphthous stomatitis or oral candidiasis. We present here a case of diabetes mellitus with hyperplasic lesion at the level of the inferior vestibule, extended to the right jugal mucosa. The lesion appeared pursuant to the application of removable prosthetics. The biopsy specimen was examined using normal and special staining (HE Hematoxiline - eosine, Van Gieson VG) and immunohistochemistry (IHC). In the HE stain, an epithelial hyperplasia was noticed as a result of the proliferation of the basal cells, associated with hyperkeratosis (parakeratosis or orthokeratosis). A moderated inflammatory limphoplasmocitary infiltrate, composed by lymphocytes and plasma cells, was present within the hyperplasic chorion. The immunohistochemical reactions revealed Ki-67 positive nuclei in the basal and suprabasal strata (indicating an increased proliferating activity); rare p53 positive nuclei in the basal stratum (indicating a suppressive action on the cell proliferation); CD3/CD8 positive cells in the inflammatory infiltrate (indicating an important number of T suppressor lymphocytes in the inflammatory infiltrate). In conclusion, diabetes mellitus is a disease which frequently determines major modifications at the level of the oral cavity. Interdisciplinary collaboration between the pathologist and the dentist is necessary for adequate diagnosis and successful treatment. PMID:20201276

  9. Sonic Hedgehog regulates thymic epithelial cell differentiation

    PubMed Central

    Saldaña, José Ignacio; Solanki, Anisha; Lau, Ching-In; Sahni, Hemant; Ross, Susan; Furmanski, Anna L.; Ono, Masahiro; Holländer, Georg; Crompton, Tessa

    2016-01-01

    Sonic Hedgehog (Shh) is expressed in the thymus, where it regulates T cell development. Here we investigated the influence of Shh on thymic epithelial cell (TEC) development. Components of the Hedgehog (Hh) signalling pathway were expressed by TEC, and use of a Gli Binding Site-green fluorescence protein (GFP) transgenic reporter mouse demonstrated active Hh-dependent transcription in TEC in the foetal and adult thymus. Analysis of Shh-deficient foetal thymus organ cultures (FTOC) showed that Shh is required for normal TEC differentiation. Shh-deficient foetal thymus contained fewer TEC than wild type (WT), the proportion of medullary TEC was reduced relative to cortical TEC, and cell surface expression of MHC Class II molecules was increased on both cortical and medullary TEC populations. In contrast, the Gli3-deficient thymus, which shows increased Hh-dependent transcription in thymic stroma, had increased numbers of TEC, but decreased cell surface expression of MHC Class II molecules on both cortical and medullary TEC. Neutralisation of endogenous Hh proteins in WT FTOC led to a reduction in TEC numbers, and in the proportion of mature Aire-expressing medullary TEC, but an increase in cell surface expression of MHC Class II molecules on medullary TEC. Likewise, conditional deletion of Shh from TEC in the adult thymus resulted in alterations in TEC differentiation and consequent changes in T cell development. TEC numbers, and the proportion of mature Aire-expressing medullary TEC were reduced, and cell surface expression of MHC Class II molecules on medullary TEC was increased. Differentiation of mature CD4 and CD8 single positive thymocytes was increased, demonstrating the regulatory role of Shh production by TEC on T cell development. Treatment of human thymus explants with recombinant Shh or neutralising anti-Shh antibody indicated that the Hedgehog pathway is also involved in regulation of differentiation from DP to mature SP T cells in the human thymus. PMID

  10. Epithelial Na(+) channels are regulated by flow.

    PubMed

    Satlin, L M; Sheng, S; Woda, C B; Kleyman, T R

    2001-06-01

    Na(+) absorption in the renal cortical collecting duct (CCD) is mediated by apical epithelial Na(+) channels (ENaCs). The CCD is subject to continuous variations in intraluminal flow rate that we speculate alters hydrostatic pressure, membrane stretch, and shear stress. Although ENaCs share limited sequence homology with putative mechanosensitive ion channels in Caenorhabditis elegans, controversy exists as to whether ENaCs are regulated by biomechanical forces. We examined the effect of varying the rate of fluid flow on whole cell Na(+) currents (I(Na)) in oocytes expressing mouse alpha,beta,gamma-ENaC (mENaC) and on net Na(+) absorption in microperfused rabbit CCDs. Oocytes injected with mENaC but not water responded to the initiation of superfusate flow (to 4-6 ml/min) with a reversible threefold stimulation of I(Na) without a change in reversal potential. The increase in I(Na) was variable among oocytes. CCDs responded to a threefold increase in rate of luminal flow with a twofold increase in the rate of net Na(+) absorption. An increase in luminal viscosity achieved by addition of 5% dextran to the luminal perfusate did not alter the rate of net Na(+) absorption, suggesting that shear stress does not influence Na(+) transport in the CCD. In sum, our data suggest that flow stimulation of ENaC activity and Na(+) absorption is mediated by an increase in hydrostatic pressure and/or membrane stretch. We propose that intraluminal flow rate may be an important regulator of channel activity in the CCD. PMID:11352841

  11. Sonic Hedgehog regulates thymic epithelial cell differentiation.

    PubMed

    Saldaña, José Ignacio; Solanki, Anisha; Lau, Ching-In; Sahni, Hemant; Ross, Susan; Furmanski, Anna L; Ono, Masahiro; Holländer, Georg; Crompton, Tessa

    2016-04-01

    Sonic Hedgehog (Shh) is expressed in the thymus, where it regulates T cell development. Here we investigated the influence of Shh on thymic epithelial cell (TEC) development. Components of the Hedgehog (Hh) signalling pathway were expressed by TEC, and use of a Gli Binding Site-green fluorescence protein (GFP) transgenic reporter mouse demonstrated active Hh-dependent transcription in TEC in the foetal and adult thymus. Analysis of Shh-deficient foetal thymus organ cultures (FTOC) showed that Shh is required for normal TEC differentiation. Shh-deficient foetal thymus contained fewer TEC than wild type (WT), the proportion of medullary TEC was reduced relative to cortical TEC, and cell surface expression of MHC Class II molecules was increased on both cortical and medullary TEC populations. In contrast, the Gli3-deficient thymus, which shows increased Hh-dependent transcription in thymic stroma, had increased numbers of TEC, but decreased cell surface expression of MHC Class II molecules on both cortical and medullary TEC. Neutralisation of endogenous Hh proteins in WT FTOC led to a reduction in TEC numbers, and in the proportion of mature Aire-expressing medullary TEC, but an increase in cell surface expression of MHC Class II molecules on medullary TEC. Likewise, conditional deletion of Shh from TEC in the adult thymus resulted in alterations in TEC differentiation and consequent changes in T cell development. TEC numbers, and the proportion of mature Aire-expressing medullary TEC were reduced, and cell surface expression of MHC Class II molecules on medullary TEC was increased. Differentiation of mature CD4 and CD8 single positive thymocytes was increased, demonstrating the regulatory role of Shh production by TEC on T cell development. Treatment of human thymus explants with recombinant Shh or neutralising anti-Shh antibody indicated that the Hedgehog pathway is also involved in regulation of differentiation from DP to mature SP T cells in the human thymus. PMID

  12. Epithelial injury and repair in airways diseases.

    PubMed

    Grainge, Christopher L; Davies, Donna E

    2013-12-01

    Asthma is a common chronic disease characterized by variable respiratory distress with underlying airway inflammation and airflow obstruction. The incidence of asthma has risen inexorably over the past 50 years, suggesting that environmental factors are important in its etiology. All inhaled environmental stimuli interact with the lung at the respiratory epithelium, and it is a testament to the effectiveness of the airway innate defenses that the majority of inhaled substances are cleared without the need to elicit an inflammatory response. However, once this barrier is breached, effective communication with immune and inflammatory cells is required to protect the internal milieu of the lung. In asthma, the respiratory epithelium is known to be structurally and functionally abnormal. Structurally, the epithelium shows evidence of damage and has more mucus-producing cells than normal airways. Functionally, the airway epithelial barrier can be more permeable and more sensitive to oxidants and show a deficient innate immune response to respiratory virus infection compared with that in normal individuals. The potential of a susceptible epithelium and the underlying mesenchyme to create a microenvironment that enables deviation of immune and inflammatory responses to external stimuli may be crucial in the development and progression of asthma. In this review, we consider three important groups of environmental stimuli on the epithelium in asthma: oxidants, such as environmental pollution and acetaminophen; viruses, including rhinovirus; and agents that cause barrier disruption, such as house dust mite allergens. The pathology associated with each stimulus is considered, and potential future treatments arising from research on their effects are presented. PMID:24297122

  13. LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis

    PubMed Central

    Sartaj, Rachel; Chee, Ru‐ik; Yang, Jing; Wan, Pengxia; Liu, Aihong; Guaiquil, Victor; Fuchs, Elaine

    2016-01-01

    Abstract The cornea requires constant epithelial renewal to maintain clarity for appropriate vision. A subset of stem cells residing at the limbus is primarily responsible for maintaining corneal epithelium homeostasis. Trauma and disease may lead to stem cell deficiency and therapeutic targeting to replenish the stemness capacity has been stalled by the lack of reliable corneal epithelial stem cell markers. Here we identified the location of Lhx2 in mice (mLhx2) cornea and conjunctival tissue using an Lhx2eGFP reporter model and in human tissues (hLHX2). Lhx2 localized to the basal cells of central cornea, the conjunctiva and the entire limbal epithelium in humans and mice. To ascribe a functional role we generated Lhx2 conditional knockout (cKO) mice and the phenotypic effects in corneas were analyzed by slit lamp microscopy, in cell‐based assays and in a model of corneal epithelium debridement. Immunodetection on corneal sections were used to visualize conjunctivalization, a sign of limbal barrier failure. Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification. Cell based assays showed that Lhx2cKO derived corneal epithelial cells have a significantly lower capacity to form colonies over time and delayed wound‐healing recovery when compared to wildtype cells. Repeated corneal epithelial wounding resulted in decreased re‐epithelialization and multiple cornea lesions in Lhx2cKO mice compared to normal recovery seen in wildtype mice. We conclude that Lhx2 is required for maintenance of the corneal epithelial cell compartment and the limbal barrier. Stem Cells 2016;34:493–503 PMID:26661907

  14. Induction of apoptosis in oral epithelial cells by Candida albicans.

    PubMed

    Villar, C Cunha; Chukwuedum Aniemeke, J; Zhao, X-R; Huynh-Ba, G

    2012-12-01

    During infection, interactions between Candida albicans and oral epithelial cells result in oral epithelial cell death. This is clinically manifested by the development of oral mucosal ulcerations generally associated with discomfort. In vitro studies have shown that C. albicans induces early apoptotic alterations in oral epithelial cells; however, these studies have also shown that treatment of infected cells with caspase inhibitors does not prevent their death. The reasons for these contradictory results are unknown and it is still not clear if C. albicans stimulates oral epithelial signaling pathways that promote apoptotic cell death. Activation of specific death pathways in response to microbial organisms plays an essential role in modulating the pathogenesis of a variety of infectious diseases. The aim of this study was to (i) characterize C. albicans-induced apoptotic morphological alterations in oral epithelial cells, and (ii) investigate the activation of apoptotic signaling pathways and expression of apoptotic genes during infection. Candida albicans induced early apoptotic changes in over 50% of oral epithelial cells. However, only 15% of those showed mid-late apoptotic alterations. At the molecular level, C. albicans caused a loss of the mitochondrial transmembrane potential and translocation of mitochondrial cytochrome c. Caspase-3/9 activities increased only during the first hours of infection. Moreover, poly[ADP ribose] polymerase 1 was cleaved into apoptotic and necrotic-like fragments. Finally, five anti-apoptotic genes were significantly upregulated and two pro-apoptotic genes were downregulated during infection. Altogether, these findings indicate that epithelial apoptotic pathways are activated in response to C. albicans, but fail to progress and promote apoptotic cell death. PMID:23134609

  15. Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis

    PubMed Central

    Jolly, Mohit Kumar; Boareto, Marcelo; Huang, Bin; Jia, Dongya; Lu, Mingyang; Ben-Jacob, Eshel; Onuchic, José N.; Levine, Herbert

    2015-01-01

    Transitions between epithelial and mesenchymal phenotypes – the epithelial to ­mesenchymal transition (EMT) and its reverse the mesenchymal to epithelial transition (MET) – are hallmarks of cancer metastasis. While transitioning between the epithelial and mesenchymal phenotypes, cells can also attain a hybrid epithelial/mesenchymal (E/M) (i.e., partial or intermediate EMT) phenotype. Cells in this phenotype have mixed epithelial (e.g., adhesion) and mesenchymal (e.g., migration) properties, thereby allowing them to move collectively as clusters. If these clusters reach the bloodstream intact, they can give rise to clusters of circulating tumor cells (CTCs), as have often been seen experimentally. Here, we review the operating principles of the core regulatory network for EMT/MET that acts as a “three-way” switch giving rise to three distinct phenotypes – E, M and hybrid E/M – and present a theoretical framework that can elucidate the role of many other players in regulating epithelial plasticity. Furthermore, we highlight recent studies on partial EMT and its association with drug resistance and tumor-initiating potential; and discuss how cell–cell communication between cells in a partial EMT phenotype can enable the formation of clusters of CTCs. These clusters can be more apoptosis-resistant and have more tumor-initiating potential than singly moving CTCs with a wholly mesenchymal (complete EMT) phenotype. Also, more such clusters can be formed under inflammatory conditions that are often generated by various therapies. Finally, we discuss the multiple advantages that the partial EMT or hybrid E/M phenotype have as compared to a complete EMT phenotype and argue that these collectively migrating cells are the primary “bad actors” of metastasis. PMID:26258068

  16. Control of Francisella tularensis Intracellular Growth by Pulmonary Epithelial Cells

    PubMed Central

    Maggio, Savannah; Takeda, Kazuyo; Stark, Felicity; Meierovics, Anda I.; Yabe, Idalia; Cowley, Siobhan C.

    2015-01-01

    The virulence of F. tularensis is often associated with its ability to grow in macrophages, although recent studies show that Francisella proliferates in multiple host cell types, including pulmonary epithelial cells. Thus far little is known about the requirements for killing of F. tularensis in the non-macrophage host cell types that support replication of this organism. Here we sought to address this question through the use of a murine lung epithelial cell line (TC-1 cells). Our data show that combinations of the cytokines IFN-γ, TNF, and IL-17A activated murine pulmonary epithelial cells to inhibit the intracellular growth of the F. tularensis Live Vaccine Strain (LVS) and the highly virulent F. tularensis Schu S4 strain. Although paired combinations of IFN-γ, TNF, and IL-17A all significantly controlled LVS growth, simultaneous treatment with all three cytokines had the greatest effect on LVS growth inhibition. In contrast, Schu S4 was more resistant to cytokine-induced growth effects, exhibiting significant growth inhibition only in response to all three cytokines. Since one of the main antimicrobial mechanisms of activated macrophages is the release of reactive nitrogen intermediates (RNI) via the activity of iNOS, we investigated the role of RNI and iNOS in Francisella growth control by pulmonary epithelial cells. NOS2 gene expression was significantly up-regulated in infected, cytokine-treated pulmonary epithelial cells in a manner that correlated with LVS and Schu S4 growth control. Treatment of LVS-infected cells with an iNOS inhibitor significantly reversed LVS killing in cytokine-treated cultures. Further, we found that mouse pulmonary epithelial cells produced iNOS during in vivo respiratory LVS infection. Overall, these data demonstrate that lung epithelial cells produce iNOS both in vitro and in vivo, and can inhibit Francisella intracellular growth via reactive nitrogen intermediates. PMID:26379269

  17. LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis.

    PubMed

    Sartaj, Rachel; Chee, Ru-ik; Yang, Jing; Wan, Pengxia; Liu, Aihong; Guaiquil, Victor; Fuchs, Elaine; Rosenblatt, Mark I

    2016-02-01

    The cornea requires constant epithelial renewal to maintain clarity for appropriate vision. A subset of stem cells residing at the limbus is primarily responsible for maintaining corneal epithelium homeostasis. Trauma and disease may lead to stem cell deficiency and therapeutic targeting to replenish the stemness capacity has been stalled by the lack of reliable corneal epithelial stem cell markers. Here we identified the location of Lhx2 in mice (mLhx2) cornea and conjunctival tissue using an Lhx2eGFP reporter model and in human tissues (hLHX2). Lhx2 localized to the basal cells of central cornea, the conjunctiva and the entire limbal epithelium in humans and mice. To ascribe a functional role we generated Lhx2 conditional knockout (cKO) mice and the phenotypic effects in corneas were analyzed by slit lamp microscopy, in cell-based assays and in a model of corneal epithelium debridement. Immunodetection on corneal sections were used to visualize conjunctivalization, a sign of limbal barrier failure. Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification. Cell based assays showed that Lhx2cKO derived corneal epithelial cells have a significantly lower capacity to form colonies over time and delayed wound-healing recovery when compared to wildtype cells. Repeated corneal epithelial wounding resulted in decreased re-epithelialization and multiple cornea lesions in Lhx2cKO mice compared to normal recovery seen in wildtype mice. We conclude that Lhx2 is required for maintenance of the corneal epithelial cell compartment and the limbal barrier. PMID:26661907

  18. Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

    SciTech Connect

    Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole

    1999-02-01

    The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

  19. Probiotics promote endocytic allergen degradation in gut epithelial cells

    SciTech Connect

    Song, Chun-Hua; Liu, Zhi-Qiang; Huang, Shelly; Zheng, Peng-Yuan; Yang, Ping-Chang

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Knockdown of A20 compromised the epithelial barrier function. Black-Right-Pointing-Pointer The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Black-Right-Pointing-Pointer Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. Black-Right-Pointing-Pointer Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

  20. The Epithelial Cell in Lung Health and Emphysema Pathogenesis

    PubMed Central

    Mercer, Becky A.; Lemaître, Vincent; Powell, Charles A.; D’Armiento, Jeanine

    2009-01-01

    Cigarette smoking is the primary cause of the irreversible lung disease emphysema. Historically, inflammatory cells such as macrophages and neutrophils have been studied for their role in emphysema pathology. However, recent studies indicate that the lung epithelium is an active participant in emphysema pathogenesis and plays a critical role in the lung’s response to cigarette smoke. Tobacco smoke increases protease production and alters cytokine expression in isolated epithelial cells, suggesting that these cells respond potently even in the absence of a complete inflammatory program. Tobacco smoke also acts as an immunosuppressant, reducing the defense function of airway epithelial cells and enhancing colonization of the lower airways. Thus, the paradigm that emphysema is strictly an inflammatory-cell based disease is shifting to consider the involvement of resident epithelial cells. Here we review the role of epithelial cells in lung development and emphysema. To better understand tobacco-epithelial interactions we performed microarray analyses of RNA from human airway epithelial cells exposed to smoke extract for 24 hours. These studies identified differential regulation of 425 genes involved in diverse biological processes, such as apoptosis, immune function, cell cycle, signal transduction, proliferation, and antioxidants. Some of these genes, including VEGF, glutathione peroxidase, IL-13 receptor, and cytochrome P450, have been previously reported to be altered in the lungs of smokers. Others, such as pirin, cathepsin L, STAT1, and BMP2, are shown here for the first time to have a potential role in smoke-associated injury. These data broaden our understanding of the importance of epithelial cells in lung health and cigarette smoke-induced emphysema. PMID:19662102

  1. Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

    SciTech Connect

    Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S.; Bissell, M.J.

    1997-10-13

    Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

  2. Laser therapy for cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...

  3. Tunable solid state lasers

    SciTech Connect

    Hammerling, R.; Budgor, A.B.; Pinto, A.

    1985-01-01

    This book presents the papers given at a conference on solid state lasers. Topics considered at the conference included transition-metal-doped lasers, line-narrowed alexandrite lasers, NASA specification, meteorological lidars, laser materials spectroscopy, laser pumped single pass gain, vibronic laser materials growth, crystal growth methods, vibronic laser theory, cross-fertilization through interdisciplinary fields, and laser action of color centers in diamonds.

  4. Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis.

    PubMed

    Igietseme, Joseph U; Omosun, Yusuf; Stuchlik, Olga; Reed, Matthew S; Partin, James; He, Qing; Joseph, Kahaliah; Ellerson, Debra; Bollweg, Brigid; George, Zenas; Eko, Francis O; Bandea, Claudiu; Liu, Hsi; Yang, Genyan; Shieh, Wun-Ju; Pohl, Jan; Karem, Kevin; Black, Carolyn M

    2015-01-01

    Chlamydia trachomatis genital infection in women causes serious adverse reproductive complications, and is a strong co-factor for human papilloma virus (HPV)-associated cervical epithelial carcinoma. We tested the hypothesis that Chlamydia induces epithelial-mesenchyme transition (EMT) involving T cell-derived TNF-alpha signaling, caspase activation, cleavage inactivation of dicer and dysregulation of micro-RNA (miRNA) in the reproductive epithelium; the pathologic process of EMT causes fibrosis and fertility-related epithelial dysfunction, and also provides the co-factor function for HPV-related cervical epithelial carcinoma. Using a combination of microarrays, immunohistochemistry and proteomics, we showed that chlamydia altered the expression of crucial miRNAs that control EMT, fibrosis and tumorigenesis; specifically, miR-15a, miR-29b, miR-382 and MiR-429 that maintain epithelial integrity were down-regulated, while miR-9, mi-R-19a, miR-22 and miR-205 that promote EMT, fibrosis and tumorigenesis were up-regulated. Chlamydia induced EMT in vitro and in vivo, marked by the suppression of normal epithelial cell markers especially E-cadherin but up-regulation of mesenchymal markers of pathological EMT, including T-cadherin, MMP9, and fibronectin. Also, Chlamydia upregulated pro-EMT regulators, including the zinc finger E-box binding homeobox protein, ZEB1, Snail1/2, and thrombospondin1 (Thbs1), but down-regulated anti-EMT and fertility promoting proteins (i.e., the major gap junction protein connexin 43 (Cx43), Mets1, Add1Scarb1 and MARCKSL1). T cell-derived TNF-alpha signaling was required for chlamydial-induced infertility and caspase inhibitors prevented both infertility and EMT. Thus, chlamydial-induced T cell-derived TNF-alpha activated caspases that inactivated dicer, causing alteration in the expression of reproductive epithelial miRNAs and induction of EMT. EMT causes epithelial malfunction, fibrosis, infertility, and the enhancement of tumorigenesis of HPV

  5. Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis

    PubMed Central

    Igietseme, Joseph U.; Omosun, Yusuf; Stuchlik, Olga; Reed, Matthew S.; Partin, James; He, Qing; Joseph, Kahaliah; Ellerson, Debra; Bollweg, Brigid; George, Zenas; Eko, Francis O.; Bandea, Claudiu; Liu, Hsi; Yang, Genyan; Shieh, Wun-Ju; Pohl, Jan; Karem, Kevin; Black, Carolyn M.

    2015-01-01

    Chlamydia trachomatis genital infection in women causes serious adverse reproductive complications, and is a strong co-factor for human papilloma virus (HPV)-associated cervical epithelial carcinoma. We tested the hypothesis that Chlamydia induces epithelial-mesenchyme transition (EMT) involving T cell-derived TNF-alpha signaling, caspase activation, cleavage inactivation of dicer and dysregulation of micro-RNA (miRNA) in the reproductive epithelium; the pathologic process of EMT causes fibrosis and fertility-related epithelial dysfunction, and also provides the co-factor function for HPV-related cervical epithelial carcinoma. Using a combination of microarrays, immunohistochemistry and proteomics, we showed that chlamydia altered the expression of crucial miRNAs that control EMT, fibrosis and tumorigenesis; specifically, miR-15a, miR-29b, miR-382 and MiR-429 that maintain epithelial integrity were down-regulated, while miR-9, mi-R-19a, miR-22 and miR-205 that promote EMT, fibrosis and tumorigenesis were up-regulated. Chlamydia induced EMT in vitro and in vivo, marked by the suppression of normal epithelial cell markers especially E-cadherin but up-regulation of mesenchymal markers of pathological EMT, including T-cadherin, MMP9, and fibronectin. Also, Chlamydia upregulated pro-EMT regulators, including the zinc finger E-box binding homeobox protein, ZEB1, Snail1/2, and thrombospondin1 (Thbs1), but down-regulated anti-EMT and fertility promoting proteins (i.e., the major gap junction protein connexin 43 (Cx43), Mets1, Add1Scarb1 and MARCKSL1). T cell-derived TNF-alpha signaling was required for chlamydial-induced infertility and caspase inhibitors prevented both infertility and EMT. Thus, chlamydial-induced T cell-derived TNF-alpha activated caspases that inactivated dicer, causing alteration in the expression of reproductive epithelial miRNAs and induction of EMT. EMT causes epithelial malfunction, fibrosis, infertility, and the enhancement of tumorigenesis of HPV

  6. Sources of the monochromatic aberrations induced in human eyes after laser refractive surgery

    NASA Astrophysics Data System (ADS)

    Porter, Jason

    Laser in-situ keratomileusis (LASIK) procedures correct the eye's defocus and astigmatism but also introduce higher order monochromatic aberrations. Little is known about the origins of these induced aberrations. The advent of wavefront sensor technology has made it possible to measure accurately and quickly the aberrations of normal and postoperative LASIK eyes. The goal of this thesis was to exploit this technology to better understand some of the potential mechanisms by which aberrations could be introduced during LASIK. A first step towards investigating these sources was to characterize the aberration changes in post-LASIK eyes. Higher order rms wavefront error increased after conventional and customized LASIK surgery. On average, spherical aberration approximately doubled, and significant changes in vertical and horizontal coma were observed. We examined two sources of postoperative aberrations: the creation of a microkeratome flap and the subsequent laser ablation. Higher order rms increased slightly and there was a wide variation in the response of individual Zernike modes after cutting a flap. The majority of induced spherical aberration was due to the laser ablation and not the flap-cut. Aberrations are also induced by static and dynamic decentrations of the patient's pupil. We found that ablations were typically decentered in the superotemporal direction due to shifts in pupil center location between aberration measurement (dilated) and surgical (undilated) conditions in customized LASIK eyes. There was a weak correlation between the horizontal coma theoretically induced by this offset and that measured postoperatively. Finally, dynamic eye movements during the procedure induce higher order aberrations. We found that the most problematic decentrations during LASIK are relatively slow drifts in eye position. An eye-tracking system with a 2-Hz closed-loop bandwidth could compensate for most eye movements during LASIK. One solution for reducing the

  7. Epithelial internalization of superparamagnetic nanoparticles and response to external magnetic field.

    PubMed

    Dormer, Kenneth; Seeney, Charles; Lewelling, Kevin; Lian, Guoda; Gibson, Donald; Johnson, Matthew

    2005-05-01

    Superparamagnetic magnetite nanoparticles (MNP) coated with silica were synthesized and chronically implanted into the middle ear epithelial tissues of a guinea pig model (n=16) for the generation of force by an external magnetic field. In vivo limitations of biocompatibility include particle morphology, size distribution, composition and mode of internalization. Synthesis of MNP was performed using a modified precipitation technique and they were characterized by transmission electron microscopy, X-ray diffractometry and energy dispersive spectroscopy, which verified size distribution, composition and silica encapsulation. The mechanism for internalizing 16+/-2.3 nm diameter MNP was likely endocytosis, enhanced by magnetically force. Using sterile technique, middle ear epithelia of tympanic membrane or ossicles was exposed and a suspension of particles with fluoroscein isothiocyanate (FITC) label applied to the surface. A rare earth, NdFeBo magnet (0.35 T) placed under the animal, was used to pull the MNP into the tissue. After 8 days, following euthanasia, tissues were harvested and confocal scanning laser interferometry was used to verify intracellular MNP. Displacements of the osscicular chain in response to an external sinusoidal electromagnetic field were also measured using laser Doppler interferometry. We showed for the first time a physiologically relevant, biomechanical function, produced by MNP responding to a magnetic field. PMID:15576180

  8. Ovarian yolk sac tumors in older women arising from epithelial ovarian tumors or with no detectable epithelial component.

    PubMed

    Roth, Lawrence M; Talerman, Aleksander; Levy, Tally; Sukmanov, Oleg; Czernobilsky, Bernard

    2011-09-01

    Yolk sac tumor (YST) occurs rarely in older women, either in association with a variety of ovarian epithelial tumors or, considerably less often, without an identifiable epithelial precursor. The patients often have elevated serum levels of α-fetoprotein that roughly correlate with the amount of the YST component. In postmenopausal women with an ovarian mass and elevated serum levels of α-fetoprotein, a tumor of this type should be suspected. Endometrioid carcinoma is the most common putative precursor, and the tumor is often associated with an endometriotic cyst; however, malignant Müllerian mixed tumor and mucinous neoplasms have also been reported as precursors. We report 4 cases of YST in postmenopausal women. Of the 3 cases with an identified epithelial component, 1 was serous carcinoma, another was clear cell adenocarcinoma, and the third was an admixture of endometrioid and clear cell adenocarcinoma arising from an endometriotic cyst. Although a precursor epithelial ovarian neoplasm, typically a malignancy (somatic carcinoma), is usually identified, no precursor neoplasm was observed in 1 of our cases and in 5 cases from the literature. We believe that YSTs in older women, whether or not an epithelial component is detected histologically, constitute a single entity that is distinct from YSTs in younger patients and should be treated aggressively. Neoplasms with a YST component in older women are less responsive to the chemotherapy currently used for ovarian germ cell tumors; therefore, adjuvant therapy should include platinum-based chemotherapy designed to treat both epithelial ovarian cancer and germ cell tumors. Of the 24 reported cases, including our own, 17 died of neoplasms within 25 months and another was living with disease at 2 months. However, 2 more recent patients treated aggressively with platinum-based chemotherapy designed to treat both epithelial and germ cell tumor components with stage 1 disease are living and have been disease free >1

  9. Downregulation of miR-153 contributes to epithelial-mesenchymal transition and tumor metastasis in human epithelial cancer.

    PubMed

    Xu, Qin; Sun, Qiang; Zhang, Jianjun; Yu, Jingshuang; Chen, Wantao; Zhang, Zhiyuan

    2013-03-01

    The epithelial-mesenchymal transition (EMT) is a crucial step in epithelial cancer invasion and metastasis. The aims of this study were to investigate and validate unidentified micro RNAs (miRNAs) that regulate EMT and to reveal their clinical relevance in epithelial cancer patients. By applying miRNA array screening in a natural epithelial-mesenchymal phenotype cell line pair and in a transforming growth factor β-induced EMT cell model, we found miR-153 was markedly downregulated in the cells that underwent an EMT. A close association was confirmed between inhibition of miR-153 and the EMT phenotype, as well as the invasive ability of epithelial cancer cells. Ectopic expression of miR-153 in mesenchymal-like cells resulted in an epithelial morphology change with decreased cellular invasive ability. On the contrary, transfection of a miR-153 inhibitor in epithelial-like cells led to a mesenchymal phenotype change. In vivo ectopic expression of miR-153 significantly inhibited tumor cell metastasis formation. Data from the dual-luciferase reporter gene assay showed, for the first time, that SNAI1 and ZEB2 were direct targets of miR-153. Inverse correlations were also observed between miR-153 and SNA1 and ZEB2 levels in oral cancer patients' samples. Furthermore, low expression level of miR-153 was found to be significantly related to metastasis and poor prognosis in oral cancer patients. These data demonstrate that miR-153 is a novel regulator of EMT by targeting SNAI1 and ZEB2 and indicate its potential therapeutic value for reducing cancer metastasis. PMID:23188671

  10. Differentiation of porcine mesenchymal stem cells into epithelial cells as a potential therapeutic application to facilitate epithelial regeneration.

    PubMed

    Kokubun, Kelsey; Pankajakshan, Divya; Kim, Min-Jung; Agrawal, Devendra K

    2016-02-01

    Epithelial denudation is one of the characteristics of chronic asthma. To restore its functions, the airway epithelium has to rapidly repair the injuries and regenerate its structure and integrity. Mesenchymal stem cells (MSCs) have the ability to differentiate into many cell lineages. However, the differentiation of MSCs into epithelial cells has not been fully studied. Here, we examined the differentiation of MSCs into epithelial cells using three different media compositions with various growth supplementations. The MSCs were isolated from porcine bone marrow by density gradient centrifugation. The isolated MSCs were CD11(-) CD34(-) CD45(-) CD44(+) CD90(+) and CD105(+) by immunostaining and flow cytometry. MSCs were stimulated with EpiGRO (Millipore), BEpiCM (ScienCell) and AECGM (PromoCell) media for 5 and 10 days, and epithelial differentiation was assessed by qPCR (keratin 14, 18 and EpCAM), fluorometry (cytokeratin 7-8, cytokeratin 14-15-16-19 and EpCAM), western blot analysis (pancytokeratin, EpCAM) and flow cytometry (cytokeratin 7-8, cytokeratin 14-15-16-19 and EpCAM). The functional marker MUC1 was also assessed after 10 days of air-liquid interface (ALI) culture in optimized media. Cells cultured in BEpiCM containing fibroblast growth factor and prostaglandin E2 showed the highest expression of the epithelial markers: CK7-8 (85.90%); CK-14-15-16-19 (10.14%); and EpCAM (64.61%). The cells also expressed functional marker MUC1 after ALI culture. The differentiated MSCs when cultured in BEpiCM medium ex vivo in a bioreactor on a decellularized trachea for 10 days retained the epithelial-like phenotype. In conclusion, porcine bone marrow-derived MSCs demonstrate commitment to the epithelial lineage and might be a potential therapy for facilitating the repair of denuded airway epithelium. PMID:23696537

  11. Mechanobiology in Lung Epithelial Cells: Measurements, Perturbations, and Responses

    PubMed Central

    Waters, Christopher M.; Roan, Esra; Navajas, Daniel

    2015-01-01

    Epithelial cells of the lung are located at the interface between the environment and the organism and serve many important functions including barrier protection, fluid balance, clearance of particulate, initiation of immune responses, mucus and surfactant production, and repair following injury. Because of the complex structure of the lung and its cyclic deformation during the respiratory cycle, epithelial cells are exposed to continuously varying levels of mechanical stresses. While normal lung function is maintained under these conditions, changes in mechanical stresses can have profound effects on the function of epithelial cells and therefore the function of the organ. In this review, we will describe the types of stresses and strains in the lungs, how these are transmitted, and how these may vary in human disease or animal models. Many approaches have been developed to better understand how cells sense and respond to mechanical stresses, and we will discuss these approaches and how they have been used to study lung epithelial cells in culture. Understanding how cells sense and respond to changes in mechanical stresses will contribute to our understanding of the role of lung epithelial cells during normal function and development and how their function may change in diseases such as acute lung injury, asthma, emphysema, and fibrosis. PMID:23728969

  12. Intracellular mediators of JAM-A–dependent epithelial barrier function

    PubMed Central

    Monteiro, Ana C.; Parkos, Charles A.

    2012-01-01

    JAM-A is a critical signaling component of the apical junctional complex, a structure composed of several transmembrane and scaffold molecules that controls the passage of nutrients and solutes across epithelial surfaces. Observations from JAM-A–deficient epithelial cells and JAM-A knockout animals indicate that JAM-A is an important regulator of epithelial paracellular permeability, however the mechanism(s) linking JAM-A to barrier function are not understood. This review highlights recent findings relevant to JAM-A–mediated regulation of epithelial permeability, focusing on the role of upstream and downstream signaling candidates. We draw on what is known about proteins reported to associate with JAM-A in other pathways and on known modulators of barrier function to propose candidate effectors that may mediate JAM-A regulation of epithelial paracellular permeability. Further investigation of pathways highlighted in this review may provide ideas for novel therapeutics that target debilitating conditions associated with barrier dysfunction, such as inflammatory bowel disease. PMID:22671597

  13. Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis

    PubMed Central

    Liu, Weicheng; Chen, Yunzi; Golan, Maya Aharoni; Annunziata, Maria L.; Du, Jie; Dougherty, Urszula; Kong, Juan; Musch, Mark; Huang, Yong; Pekow, Joel; Zheng, Changqing; Bissonnette, Marc; Hanauer, Stephen B.; Li, Yan Chun

    2013-01-01

    The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn’s disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4+CD45RBhi T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null mice from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-κB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent of nonepithelial immune VDR actions. PMID:23945234

  14. Phototoxic aptamers selectively enter and kill epithelial cancer cells

    PubMed Central

    Ferreira, Cátia S. M.; Cheung, Melissa C.; Missailidis, Sotiris; Bisland, Stuart; Gariépy, Jean

    2009-01-01

    The majority of cancers arise from malignant epithelial cells. We report the design of synthetic oligonucleotides (aptamers) that are only internalized by epithelial cancer cells and can be precisely activated by light to kill such cells. Specifically, phototoxic DNA aptamers were selected to bind to unique short O-glycan-peptide signatures on the surface of breast, colon, lung, ovarian and pancreatic cancer cells. These surface antigens are not present on normal epithelial cells but are internalized and routed through endosomal and Golgi compartments by cancer cells, thus providing a focused mechanism for their intracellular delivery. When modified at their 5′ end with the photodynamic therapy agent chlorin e6 and delivered to epithelial cancer cells, these aptamers exhibited a remarkable enhancement (>500-fold increase) in toxicity upon light activation, compared to the drug alone and were not cytotoxic towards cell types lacking such O-glycan-peptide markers. Our findings suggest that these synthetic oligonucleotide aptamers can serve as delivery vehicles in precisely routing cytotoxic cargoes to and into epithelial cancer cells. PMID:19103663

  15. The syncytial nature of epithelial cells in the thymic cortex.

    PubMed Central

    Kendall, M D

    1986-01-01

    The epithelial cells of the cortex of human and rodent thymus glands were examined by light and electron microscopy, and the intracellular membrane potentials measured from the subcapsular, cortical and medullary regions. In the human thymus cortex, there is a highly correlated age-independent relationship (r = 0.78) between the distance in micron from one adjacent Type 2/3 epithelial nucleus to another, and the number of thymocytes between them. In rodent glands that had undergone some degree of involution due to hypoxia simulating an altitude of 17 000 feet or following the injection of phenylhydrazine, Type 2/3 epithelial cells were often found to be bi- or multinucleated. Electrophysiological studies of 10 mouse thymus lobes using 0.2 micron tipped electrodes showed that there were highly significant differences (P less than 0.0001) between the intracellular membrane potentials of the subcapsular zone, the cortex and the medulla. When dyes were injected intracellularly (through 0.5 micron tipped electrodes) into individual epithelial cells, methylene blue remained within the cytoplasm, but procion yellow passed in 30 minutes into the nuclei of all the epithelial cells of the cortex but not those of the subcapsular zone, nor the medulla. This indicates that the cortex must be a functional syncytium and it differs in this respect from the rest of the gland. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:3319999

  16. Parvalbumin in cortical epithelial cells of the pigeon thymus

    PubMed Central

    ATOJI, YASURO; YAMAMOTO, YOSHIO; SUZUKI, YOSHITAKA

    2000-01-01

    We examined the distribution of parvalbumin in the pigeon thymus by light and electron microscopic immunohistochemistry. Tissues were also examined by conventional electron microscopy to determine the ultrastructure of immunoreactive cells. Parvalbumin immunoreaction was located in epithelial cells of the cortex, which formed dense mesh-like structures. Parvalbumin-positive epithelial cells were classified into 2 types. The first comprised elongated cells. In these, the nucleus was spindle-shaped, oval, or triangular, with a slightly irregular contour and contained rich heterochromatin peripherally. The cytoplasm was pale and processes extended laterally or ramified among the surrounding thymocytes. This type of cell formed the majority of immunoreactive cells. The other cell type consisted of polygonal epithelial cells. The nucleus was oval with deep indentations. Euchromatin occupied a large part of the nucleus. The cytoplasm contained numerous cell organelles compared with the elongated type, in particular, electron-dense vacuoles of various sizes and often bundles of tonofilaments. Both types of epithelial cell were interconnected by desmosomes. No secretory granules were found in the cytoplasm of elongated or polygonal cells. These results indicate the presence of heterogeneous group of parvalbumin-immunoreactive epithelial cells and suggest the likelihood of different functional roles for parvalbumin in the pigeon thymus. PMID:10853953

  17. Interferons Mediate Terminal Differentiation of Human Cortical Thymic Epithelial Cells

    PubMed Central

    Vidalain, Pierre-Olivier; Laine, David; Zaffran, Yona; Azocar, Olga; Servet-Delprat, Christine; Wild, T. Fabian; Rabourdin-Combe, Chantal; Valentin, Hélène

    2002-01-01

    In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-β) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-β induction. Finally, we demonstrated that recombinant IFN-α, IFN-β, or IFN-γ was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections. PMID:12050353

  18. Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function

    PubMed Central

    Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A.; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M.; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin

    2012-01-01

    The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness. PMID:23027535

  19. Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers.

    PubMed

    Bergstralh, Dan T; Lovegrove, Holly E; St Johnston, Daniel

    2015-11-01

    Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium. Here we test this assumption in three types of Drosophila epithelium; the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these tissues reorients mitotic spindles, resulting in one daughter cell being born outside the epithelial layer. Live imaging reveals that these misplaced cells reintegrate into the tissue. Reducing the levels of the lateral homophilic adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise to extra-epithelial cells, whereas disruption of adherens junctions has no effect. Thus, the reinsertion of misplaced cells seems to be driven by lateral adhesion, which pulls cells born outside the epithelial layer back into it. Our findings reveal a robust mechanism that protects epithelia against the consequences of misoriented divisions. PMID:26414404

  20. Plexins function in epithelial repair in both Drosophila and zebrafish

    PubMed Central

    Yoo, Sa Kan; Pascoe, Heath G.; Pereira, Telmo; Kondo, Shu; Jacinto, Antonio; Zhang, Xuewu; Hariharan, Iswar K.

    2016-01-01

    In most multicellular organisms, homeostasis is contingent upon maintaining epithelial integrity. When unanticipated insults breach epithelial barriers, dormant programmes of tissue repair are immediately activated. However, many of the mechanisms that repair damaged epithelia remain poorly characterized. Here we describe a role for Plexin A (PlexA), a protein with particularly well-characterized roles in axonal pathfinding, in the healing of damaged epithelia in Drosophila. Semaphorins, which are PlexA ligands, also regulate tissue repair. We show that Drosophila PlexA has GAP activity for the Rap1 GTPase, which is known to regulate the stability of adherens junctions. Our observations suggest that the inhibition of Rap1 activity by PlexA in damaged Drosophila epithelia allows epithelial remodelling, thus facilitating wound repair. We also demonstrate a role for Plexin A1, a zebrafish orthologue of Drosophila PlexA, in epithelial repair in zebrafish tail fins. Thus, plexins function in epithelial wound healing in diverse taxa. PMID:27452696

  1. Epithelial expression of interleukin-37b in inflammatory bowel disease.

    PubMed

    Imaeda, H; Takahashi, K; Fujimoto, T; Kasumi, E; Ban, H; Bamba, S; Sonoda, H; Shimizu, T; Fujiyama, Y; Andoh, A

    2013-06-01

    Interleukin (IL)-37 is a member of the IL-1 cytokine family. We investigated IL-37b expression in the inflamed mucosa of inflammatory bowel disease (IBD) patients. Furthermore, we analysed IL-37b expression in human colonic epithelial cells. The human colonic epithelial cell line T84 and human colonic subepithelial myofibroblasts (SEMFs) were used. IL-37b expression in the IBD mucosa was evaluated by immunohistochemistry. IL-37b mRNA and protein expression were determined by real time-polymerase chain reaction (PCR) and Western blotting, respectively. IL-37b was not detected in the normal colonic mucosa. In the inflamed mucosa of IBD patients, epithelial IL-37b expression was increased markedly. In ulcerative colitis (UC) and Crohn's disease (CD) patients, IL-37b expression was enhanced in the affected mucosa. In the intestinal epithelial cell line T84, the expression of IL-37b mRNA and protein was enhanced by tumour necrosis factor (TNF)-α. This IL-37b induction by TNF-α was mediated by nuclear factor (NF)-κB and activator protein (AP)-1 activation. Furthermore, IL-37b inhibited TNF-α-induced interferon-γ-inducible protein (IP)-10 expression significantly in human colonic SEMFs. Epithelial IL-37b expression was increased in IBD patients, especially UC patients. IL-37b may be involved in the pathophysiology of IBD as an anti-inflammatory cytokine and an inhibitor of both innate and acquired immune responses. PMID:23600829

  2. The assembly and maintenance of epithelial junctions in C. elegans

    PubMed Central

    Lynch, Allison M.; Hardin, Jeff

    2010-01-01

    The epithelial tissues of the C. elegans embryo provide a “minimalist” system for examining phylogenetically conserved proteins that function in epithelial polarity and cell-cell adhesion in a multicellular organism. In this review, we provide an overview of three major molecular complexes at the apical surface of epithelial cells in the C. elegans embryo: the cadherin-catenin complex, the more basal DLG-1/AJM-1 complex, and the apical membrane domain, which shares similarities with the subapical complex in Drosophila and the PAR/aPKC complex in vertebrates. We discuss how the assembly of these complexes contributes to epithelial polarity and adhesion, proteins that act as effectors and/or regulators of each subdomain, and how these complexes functionally interact during embryonic morphogenesis. Although much remains to be clarified, significant progress has been made in recent years to clarify the role of these protein complexes in epithelial morphogenesis, and suggests that C. elegans will continue to be a fruitful system in which to elucidate functional roles for these proteins in a living embryo. PMID:19273138

  3. Non-coding RNAs in epithelial immunity to Cryptosporidium infection

    PubMed Central

    Zhou, Rui; Feng, Yaoyu; Chen, Xian-Ming

    2015-01-01

    SUMMARY Cryptosporidium spp. is a protozoan parasite that infects the gastrointestinal epithelium and causes diarrhoeal disease worldwide. It is one of the most common pathogens responsible for moderate to severe diarrhoea in children younger than 2 years. Because of the ‘minimally invasive’ nature of Cryptosporidium infection, mucosal epithelial cells are critical to the host’s anti-Cryptosporidium immunity. Gastrointestinal epithelial cells not only provide the first and most rapid defence against Cryptosporidium infection, they also mobilize immune effector cells to the infection site to activate adaptive immunity. Recent advances in genomic research have revealed the existence of a large number of non-protein-coding RNA transcripts, so called non-coding RNAs (ncRNAs), in mammalian cells. Some ncRNAs may be key regulators for diverse biological functions, including innate immune responses. Specifically, ncRNAs may modulate epithelial immune responses at every step of the innate immune network following Cryptosporidium infection, including production of antimicrobial molecules, expression of cytokines/chemokines, release of epithelial cell-derived exosomes, and feedback regulation of immune homoeostasis. This review briefly summarizes the current science on ncRNA regulation of innate immunity to Cryptosporidium, with a focus on microRNA-associated epithelial immune responses. PMID:24828969

  4. Epithelial impedance analysis in experimentally induced colon cancer.

    PubMed Central

    Davies, R J; Joseph, R; Kaplan, D; Juncosa, R D; Pempinello, C; Asbun, H; Sedwitz, M M

    1987-01-01

    Epithelial impedance analysis was used to measure the alterations in resistance of the large bowel in a murine model of large bowel cancer. The technique was able to resolve the epithelial resistance from the total resistance of the bowel wall. A progressive decrease in resistance of the bowel epithelium occurs during carcinogenesis induced with dimethyhydrazine. About a 21% decrease in epithelial resistance from 22.0 +/- 1.3 omega.cm-2 to 17.5 +/- 1.1 omega cm-2 (p less than 0.025) was observed after 20 wk of carcinogen administration. The sensitivity of the technique in detecting altered epithelial resistance in premalignant bowel mucosa was improved by examining the impedance profile in a sodium-free Ringer's solution where the epithelium of control colons had a resistance of 24.4 +/- 1.8 omega.cm-2 compared with 19.0 +/- 1.1 omega.cm-2 (p less than 0.02) in colons from animals treated for only 4 wk with the carcinogen. Epithelial impedance analysis would seem to be a sensitive technique capable of identifying changes in the electrical properties or the large bowel early in disease states. PMID:3427187

  5. Porphyromonas gingivalis invades oral epithelial cells in vitro.

    PubMed

    Sandros, J; Papapanou, P; Dahlén, G

    1993-05-01

    The aim of the present study was to analyze the adhesive and invasive potential of a number of P. gingivalis strains, in an in vitro system utilizing cultures of human oral epithelial cells (KB cell line, ATCC CCL 17). P. gingivalis strains W50 and FDC 381 (laboratory strains) and OMGS 1738, 1743 and 1439 (clinical isolates) as well as E. coli strain HB 101 (non-adhering, non-invasive control) were used. Adherence was assessed by means of scintillation counting and light microscopy, after incubation of radiolabelled bacteria with epithelial cells. In the invasion assay, monolayers were infected with the P. gingivalis and E. coli strains and further incubated with an antibiotic mixture (metronidazole 0.1 mg/ml and gentamicin 0.5 mg/ml). Invasion was evaluated by (i) assessing presence of bacteria surviving the antibiotic treatment, and (ii) electron microscopy. All P. gingivalis strains adhered to and entered into the oral epithelial cells. After 3 hours of incubation, bacteria were frequently identified intracellularly by means of electron microscopy. The cellular membranes, encapsulating the microorganisms in early stages of the invasive process, appeared later to disintegrate. The presence of coated pits on the epithelial cell surfaces suggested that internalization of P. gingivalis was associated with receptor-mediated endocytosis (RME). Formation of outer membrane vesicles (blebs) by intracellular bacteria indicated that internalized P. gingivalis was able to retain its viability. E. coli strain HB 101 neither adhered to nor invaded epithelial cells. PMID:8388449

  6. Lingual Epithelial Stem Cells and Organoid Culture of Them

    PubMed Central

    Hisha, Hiroko; Tanaka, Toshihiro; Ueno, Hiroo

    2016-01-01

    As tongue cancer is one of the major malignant cancers in the world, understanding the mechanism of maintenance of lingual epithelial tissue, which is known to be the origin of tongue cancer, is unquestionably important. However, the actual stem cells that are responsible for the long-term maintenance of the lingual epithelium have not been identified. Moreover, a simple and convenient culture method for lingual epithelial stem cells has not yet been established. Recently, we have shown that Bmi1-positive cells, residing at the second or third layer of the epithelial cell layer at the base of the interpapillary pit (IPP), were slow-cycling and could supply keratinized epithelial cells for over one year, indicating that Bmi1-positive cells are long-term lingual epithelial stem cells. In addition, we have developed a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Here, we discuss current progress in the identification of lingual stem cells and future applications of the lingual culture system for studying the regulatory mechanisms of the lingual epithelium and for regenerative medicine. PMID:26828484

  7. Neuroprotective therapy for argon-laser-induced retinal injury

    NASA Astrophysics Data System (ADS)

    Belkin, Michael; Rosner, Mordechai; Solberg, Yoram; Turetz, Yosef

    1999-06-01

    Laser photocoagulation treatment of the central retina is often complicated by an immediate side effect of visual impairment, caused by the unavoidable laser-induced destruction of the normal tissue lying adjacent to the lesion and not affected directly by the laser beam. Furthermore, accidental laser injuries are at present untreatable. A neuroprotective therapy for salvaging the normal tissue might enhance the benefit obtained from treatment and allow safe perifoveal photocoagulation. We have developed a rat model for studying the efficacy of putative neuroprotective compounds in ameliorating laser-induced retinal damage. Four compounds were evaluated: the corticosteroid methylprednisolone, the glutamate-receptor blocker MK-801, the anti-oxidant enzyme superoxide dismutase, and the calcim-overload antagonist flunarizine. The study was carried out in two steps: in the first, the histopathological development of retinal laser injuries was studied. Argon laser lesions were inflicted in the retinas of 18 pigmented rats. The animals were sacrificed after 3, 20 or 60 days and their retinal lesions were evaluated under the light microscope. The laser injury mainly involved the outer layers of the retina, where it destroyed significant numbers of photoreceptor cells. Over time, evidence of two major histopathological processes was observed: traction of adjacent nomral retinal cells into the central area of the lesion forming an internal retinal bulging, and a retinal pigmented epithelial proliferative reaction associated with subretinal neovascularization and invations of the retinal lesion site by phagocytes. The neuroprotective effects of each of the four compounds were verified in a second step of the study. For each drug tested, 12 rats were irradiated wtih argon laser inflictions: six of them received the tested agent while the other six were treated with the corresponding vehicle. Twenty days after laser expsoure, the rats were sacrificed and their lesions were

  8. 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

  9. Regulated Mucin Secretion from Airway Epithelial Cells

    PubMed Central

    Adler, Kenneth B.; Tuvim, Michael J.; Dickey, Burton F.

    2013-01-01

    Secretory epithelial cells of the proximal airways synthesize and secrete gel-forming polymeric mucins. The secreted mucins adsorb water to form mucus that is propelled by neighboring ciliated cells, providing a mobile barrier which removes inhaled particles and pathogens from the lungs. Several features of the intracellular trafficking of mucins make the airway secretory cell an interesting comparator for the cell biology of regulated exocytosis. Polymeric mucins are exceedingly large molecules (up to 3 × 106 Da per monomer) whose folding and initial polymerization in the ER requires the protein disulfide isomerase Agr2. In the Golgi, mucins further polymerize to form chains and possibly branched networks comprising more than 20 monomers. The large size of mucin polymers imposes constraints on their packaging into transport vesicles along the secretory pathway. Sugar side chains account for >70% of the mass of mucins, and their attachment to the protein core by O-glycosylation occurs in the Golgi. Mature polymeric mucins are stored in large secretory granules ∼1 μm in diameter. These are translocated to the apical membrane to be positioned for exocytosis by cooperative interactions among myristoylated alanine-rich C kinase substrate, cysteine string protein, heat shock protein 70, and the cytoskeleton. Mucin granules undergo exocytic fusion with the plasma membrane at a low basal rate and a high stimulated rate. Both rates are mediated by a regulated exocytic mechanism as indicated by phenotypes in both basal and stimulated secretion in mice lacking Munc13-2, a sensor of the second messengers calcium and diacylglycerol (DAG). Basal secretion is induced by low levels of activation of P2Y2 purinergic and A3 adenosine receptors by extracellular ATP released in paracrine fashion and its metabolite adenosine. Stimulated secretion is induced by high levels of the same ligands, and possibly by inflammatory mediators as well. Activated receptors are coupled to

  10. Excimer lasers

    NASA Technical Reports Server (NTRS)

    Palmer, A. J.; Hess, L. D.; Stephens, R. R.

    1976-01-01

    A theoretical and experimental investigation into the possibility of achieving CW discharge pumped excimer laser oscillation is reported. Detailed theoretical modeling of capillary discharge pumping of the XeF and KXe and K2 excimer systems was carried out which predicted the required discharge parameters for reaching laser threshold on these systems. Capillary discharge pumping of the XeF excimer system was investigated experimentally. The experiments revealed a lower excimer level population density than predicted theoretically by about an order of magnitude. The experiments also revealed a fluorine consumption problem in the discharge in agreement with theory.

  11. Airborne laser

    NASA Astrophysics Data System (ADS)

    Lamberson, Steven E.

    2002-06-01

    The US Air Force Airborne Laser (ABL) is an airborne, megawatt-class laser system with a state-of-the-art atmospheric compensation system to destroy enemy ballistic missiles at long ranges. This system will provide both deterrence and defense against the use of such weapons during conflicts. This paper provides an overview of the ABL weapon system including: the notional operational concept, the development approach and schedule, the overall aircraft configuration, the technologies being incorporated in the ABL, and the risk reduction approach being utilized to ensure program success.

  12. Laser Resonator

    NASA Technical Reports Server (NTRS)

    Harper, L. L. (Inventor)

    1983-01-01

    An optical resonator cavity configuration has a unitary mirror with oppositely directed convex and concave reflective surfaces disposed into one fold and concertedly reversing both ends of a beam propagating from a laser rod disposed between two total internal reflection prisms. The optical components are rigidly positioned with perpendicularly crossed virtual rooflines by a compact optical bed. The rooflines of the internal reflection prisms, are arranged perpendicularly to the axis of the laser beam and to the optical axes of the optical resonator components.

  13. Laser barometer

    DOEpatents

    Abercrombie, Kevin R.; Shiels, David; Rash, Tim

    2001-02-06

    A pressure measuring instrument that utilizes the change of the refractive index of a gas as a function of pressure and the coherent nature of a laser light to determine the barometric pressure within an environment. As the gas pressure in a closed environment varies, the index of refraction of the gas changes. The amount of change is a function of the gas pressure. By illuminating the gas with a laser light source, causing the wavelength of the light to change, pressure can be quantified by measuring the shift in fringes (alternating light and dark bands produced when coherent light is mixed) in an interferometer.

  14. Reversible Femtosecond Laser-Assisted Myopia Correction: A Non-Human Primate Study of Lenticule Re-Implantation after Refractive Lenticule Extraction

    PubMed Central

    Chaurasia, Shyam S.; Lee, Wing S.; Tan, Donald T.; Mehta, Jodhbir S.

    2013-01-01

    LASIK (laser-assisted in situ keratomileusis) is a common laser refractive procedure for myopia and astigmatism, involving permanent removal of anterior corneal stromal tissue by excimer ablation beneath a hinged flap. Correction of refractive error is achieved by the resulting change in the curvature of the cornea and is limited by central corneal thickness, as a thin residual stromal bed may result in biomechanical instability of the cornea. A recently developed alternative to LASIK called Refractive Lenticule Extraction (ReLEx) utilizes solely a femtosecond laser (FSL) to incise an intrastromal refractive lenticule (RL), which results in reshaping the corneal curvature and correcting the myopia and/or astigmatism. As the RL is extracted intact in the ReLEx, we hypothesized that it could be cryopreserved and re-implanted at a later date to restore corneal stromal volume, in the event of keratectasia, making ReLEx a potentially reversible procedure, unlike LASIK. In this study, we re-implanted cryopreserved RLs in a non-human primate model of ReLEx. Mild intrastromal haze, noted during the first 2 weeks after re-implantation, subsided after 8 weeks. Refractive parameters including corneal thickness, anterior curvature and refractive error indices were restored to near pre-operative values after the re-implantation. Immunohistochemistry revealed no myofibroblast formation or abnormal collagen type I expression after 8 weeks, and a significant attenuation of fibronectin and tenascin expression from week 8 to 16 after re-implantation. In addition, keratocyte re-population could be found along the implanted RL interfaces. Our findings suggest that RL cryopreservation and re-implantation after ReLEx appears feasible, suggesting the possibility of potential reversibility of the procedure, and possible future uses of RLs in treating other corneal disorders and refractive errors. PMID:23826194

  15. Epithelial-Mesenchymal Transition (EMT) gene variants and Epithelial Ovarian Cancer (EOC) risk

    PubMed Central

    Amankwah, Ernest K.; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chen, Zhihua; Chen, Y. Ann; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N.; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Ian; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Thomsen, Lotte; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vierkant, Robert A.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E.; Berchuck, Andrew; Schildkraut, Joellen M.; Ramus, Susan J.; Goode, Ellen L.; Monteiro, Alvaro N.A.; Gayther, Simon A.; Narod, Steven A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2016-01-01

    Introduction Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to EOC risk have been based on small sample sizes and none have sought replication in an independent population. Methods We screened 1254 SNPs in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (p<0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A p-value <0.05 and a false discovery rate (FDR) <0.2 was considered statistically significant. Results In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (OR=1.16, 95%CI=1.07–1.25, p=0.0003, FDR=0.19), while F8 rs7053448 (OR=1.69, 95%CI=1.27–2.24, p=0.0003, FDR=0.12), F8 rs7058826 (OR=1.69, 95%CI=1.27–2.24, p=0.0003, FDR=0.12), and CAPN13 rs1983383 (OR=0.79, 95%CI=0.69–0.90, p=0.0005, FDR=0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. Conclusion These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC. PMID:26399219

  16. Mesenchymal stroma: primary determinant and therapeutic target for epithelial cancer

    PubMed Central

    Goruppi, Sandro; Dotto, G. Paolo

    2013-01-01

    Multifocal and recurrent epithelial tumors, originating from either dormant or de novo cancer cells, are major causes of morbidity and mortality. The age-dependent increase of cancer incidence has long been assumed to result from the sequential accumulation of cancer driving or facilitating mutations with induction of cellular senescence as a protective mechanism. However, recent evidence suggests that the initiation and development of epithelial cancer results from a close interplay with its altered tissue microenvironment, with chronic inflammation, stromal senescence, autophagy, and activation of cancer associated fibroblasts (CAFs) playing possible primary roles. We will discuss recent progress in these areas, and highlight how this understanding may be used for devising novel preventive and therapeutic approaches to the epithelial cancer problem. PMID:24074947

  17. Salivary epithelial cells: an unassuming target site for gene therapeutics

    PubMed Central

    Perez, Paola; Rowzee, Anne M.; Zheng, Changyu; Adriaansen, Janik; Baum, Bruce J.

    2010-01-01

    Salivary glands are classical exocrine glands whose external secretions result in the production of saliva. However, in addition to the secretion of exocrine proteins, salivary epithelial cells are also capable of secreting proteins internally, into the bloodstream. This brief review examines the potential for using salivary epithelial cells as a target site for in situ gene transfer, with an ultimate goal of producing therapeutic proteins for treating both systemic and upper gastrointestinal tract disorders. The review discusses the protein secretory pathways reported to be present in salivary epithelial cells, the viral gene transfer vectors shown useful for transducing these cells, model transgenic secretory proteins examined, and some clinical conditions that might benefit from such salivary gland gene transfer. PMID:20219693

  18. Testing gene therapy vectors in human primary nasal epithelial cultures

    PubMed Central

    Cao, Huibi; Ouyang, Hong; Ip, Wan; Du, Kai; Duan, Wenming; Avolio, Julie; Wu, Jing; Duan, Cathleen; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Hu, Jim; Moraes, Theo J

    2015-01-01

    Cystic fibrosis (CF) results from mutations in the CF transmembrane conductance regulator (CFTR) gene, which codes for a chloride/bicarbonate channel in the apical epithelial membranes. CFTR dysfunction results in a multisystem disease including the development of life limiting lung disease. The possibility of a cure for CF by replacing defective CFTR has led to different approaches for CF gene therapy; all of which ultimately have to be tested in preclinical model systems. Primary human nasal epithelial cultures (HNECs) derived from nasal turbinate brushing were used to test the efficiency of a helper-dependent adenoviral (HD-Ad) vector expressing CFTR. HD-Ad-CFTR transduction resulted in functional expression of CFTR at the apical membrane in nasal epithelial cells obtained from CF patients. These results suggest that HNECs can be used for preclinical testing of gene therapy vectors in CF. PMID:26730394

  19. Effects of ethanol on an intestinal epithelial cell line

    SciTech Connect

    Nano, J.L.; Cefai, D.; Rampal, P. )

    1990-02-01

    The effect of exposure of an intestinal epithelial cell line to various concentrations of ethanol (217 mM (1%) to 652 mM (3%)) during 24, 48, and 72 hr was investigated in vitro using a rat intestinal epithelial cell line (IRD 98). Incubation of these cells in the presence of ethanol significantly decreased cell growth. This inhibition was accompanied by a strong increase in cellular protein. Stimulation of specific disaccharidases, gamma-glutamyl transferase, and aminopeptidase activities by ethanol was dose- and time-dependent. Ethanol induces a change in the relative proportions of the different lipid classes synthesized; triglycerides, fatty acids, and cholesterol esters were preferentially synthethysed. Our findings show that cell lines are good models for investigation of the effects of ethanol, and that alcohol considerably modifies the functions of intestinal epithelial cells.

  20. Wound repair: role of immune–epithelial interactions

    PubMed Central

    Leoni, G; Neumann, P-A; Sumagin, R; Denning, TL; Nusrat, A

    2016-01-01

    The epithelium serves as a highly selective barrier at mucosal surfaces. Upon injury, epithelial wound closure is orchestrated by a series of events that emanate from the epithelium itself as well as by the temporal recruitment of immune cells into the wound bed. Epithelial cells adjoining the wound flatten out, migrate, and proliferate to rapidly cover denuded surfaces and re-establish mucosal homeostasis. This process is highly regulated by proteins and lipids, proresolving mediators such as Annexin A1 protein and resolvins released into the epithelial milieu by the epithelium itself and infiltrating innate immune cells including neutrophils and macrophages. Failure to achieve these finely tuned processes is observed in chronic inflammatory diseases that are associated with non-healing wounds. An improved understanding of mechanisms that mediate repair is important in the development of therapeutics aimed to promote mucosal wound repair. PMID:26174765

  1. Cyfip1 is a putative invasion suppressor in epithelial cancers

    PubMed Central

    Silva, Jose M.; Ezhkova, Elena; Silva, Javier; Heart, Stephen; Castillo, Mireia; Campos, Yolanda; Castro, Veronica; Bonilla, Felix; Cordon-Cardo, Carlos; Muthuswamy, Senthil K.; Powers, Scott; Fuchs, Elaine; Hannon, Gregory J.

    2009-01-01

    Summary Identification of bona fide tumor suppressors is often challenging because of the large number of alterations present in most human cancers. To evaluate candidates present within regions recurrently deleted in human cancers we coupled high-resolution genomic analysis with a two-stage genetic study using RNA interference (RNAi). We found that Cyfip1, a subunit of the WAVE complex, which regulates cytoskeletal dynamics, is commonly deleted in human epithelial cancers. Reduced expression of Cyfip1 is commonly observed during invasion of epithelial tumors and it associated with poor prognosis in same tumor types. Silencing of Cyfip1 disturbed normal epithelial morphogenesis in vitro and cooperated with oncogenic Ras to produce invasive carcinomas in vivo. Mechanistically, we have linked alterations in WAVE-regulated actin dynamics with impaired cell-cell adhesion and cell-ECM interactions. Thus, we propose Cyfip1 as an invasion suppressor gene. PMID:19524508

  2. Morphological appearances of human lens epithelial cells in culture.

    PubMed

    Power, W; Neylan, D; Collum, L

    1993-01-01

    A system for culturing human lens epithelial cells in the laboratory was developed. The morphological appearances of the cells was studied using phase contrast, scanning and transmission electron microscopy. Cell marker studies using monoclonal antibodies to cytokeratin, vimentin and epithelial membrane antigen were also performed. There was a marked increase in cell size as a function of time in culture. After 3 to 4 weeks cells showed early signs of ageing. By 6 to 8 weeks the majority of the cells had become very irregular in shape and demonstrated irregularities of the plasma membrane and intra-cytoplasmic vacuole formation. The cells stained strongly for vimentin and epithelial membrane antigen. Staining with cytokeratin was somewhat weaker. This culture technique provides us with a suitable model for studying the growth behavior of these cells. PMID:7512459

  3. Development of human epithelial cell systems for radiation risk assessment

    NASA Technical Reports Server (NTRS)

    Yang, C. H.; Craise, L. M.

    1994-01-01

    The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-Linear Energy Transfer (LET) radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic tranformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

  4. Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling

    PubMed Central

    Baum, Buzz

    2011-01-01

    The epithelial cadherin (E-cadherin)–catenin complex binds to cytoskeletal components and regulatory and signaling molecules to form a mature adherens junction (AJ). This dynamic structure physically connects neighboring epithelial cells, couples intercellular adhesive contacts to the cytoskeleton, and helps define each cell’s apical–basal axis. Together these activities coordinate the form, polarity, and function of all cells in an epithelium. Several molecules regulate AJ formation and integrity, including Rho family GTPases and Par polarity proteins. However, only recently, with the development of live-cell imaging, has the extent to which E-cadherin is actively turned over at junctions begun to be appreciated. This turnover contributes to junction formation and to the maintenance of epithelial integrity during tissue homeostasis and remodeling. PMID:21422226

  5. Hydraulic fracture and resilience of epithelial monolayers under stretch

    NASA Astrophysics Data System (ADS)

    Arroyo, Marino; Lucantonio, Alessandro; Noselli, Giovanni; Casares, Laura; Desimone, Antonio; Trepat, Xavier

    Epithelial monolayers are very simple and prevalent tissues. Their functions include delimiting distinct physicochemical containers and protecting us from pathogens. Epithelial fracture disrupts the mechanical integrity of this barrier, and hence compromises these functions. Here, we show that in addition to the conventional fracture resulting from excessive tissue tension, epithelia can hydraulically fracture under stretch as a result of the poroelastic nature of the matrix. We will provide experimental evidence of this counterintuitive mechanism of fracture, in which cracks appear under compression. Intriguingly, unlike tensional fracture, which is localized and catastrophic, hydraulic epithelial fracture is distributed and reversible. We will also describe the active mechanisms responsible for crack healing, and the physical principles by which the poroelastic matrix contributes to this resilient behavior.

  6. Role of autophagy in the regulation of epithelial cell junctions.

    PubMed

    Nighot, Prashant; Ma, Thomas

    2016-01-01

    Autophagy is a cell survival mechanism by which bulk cytoplasmic material, including soluble macromolecules and organelles, is targeted for lysosomal degradation. The role of autophagy in diverse cellular processes such as metabolic stress, neurodegeneration, cancer, aging, immunity, and inflammatory diseases is being increasingly recognized. Epithelial cell junctions play an integral role in the cell homeostasis via physical binding, regulating paracellular pathways, integrating extracellular cues into intracellular signaling, and cell-cell communication. Recent data indicates that cell junction composition is very dynamic. The junctional protein complexes are actively regulated in response to various intra- and extra-cellular clues by intracellular trafficking and degradation pathways. This review discusses the recent and emerging information on how autophagy regulates various epithelial cell junctions. The knowledge of autophagy regulation of epithelial junctions will provide further rationale for targeting autophagy in a wide variety of human disease conditions. PMID:27583189

  7. TGF-β induced epithelial-mesenchymal transition modeling

    NASA Astrophysics Data System (ADS)

    Xenitidis, P.; Seimenis, I.; Kakolyris, S.; Adamopoulos, A.

    2015-09-01

    Epithelial cells may undergo a process called epithelial to mesenchymal transition (EMT). During EMT, cells lose their epithelial characteristics and acquire a migratory ability. Transforming growth factor-beta (TGF-β) signaling is considered to play an important role in EMT by regulating a set of genes through a gene regulatory network (GRN). This work aims at TGF-β induced EMT GRN modeling using publicly available experimental data (gene expression microarray data). The time-series network identification (TSNI) algorithm was used for inferring the EMT GRN. Receiver operating characteristic (ROC) and precision-recall (P-R) curves were constructed and the areas under them were used for evaluating the algorithm performance regarding network inference.

  8. The inflammatory network: bridging senescent stroma and epithelial tumorigenesis

    PubMed Central

    Shan, Weiwei; Yang, Gong; Liu, Jinsong

    2010-01-01

    Cellular senescence or cellular aging, defined by permanent cell cycle arrest, is well known for its evolutionary advantage in protecting the organism from developing cancer; however, it is also acknowledged that aged stromal cells can significantly expedite epithelial tumorigenesis, although exactly how they function to augment tumor formation remains elusive. Recent evidence suggests that this tumor-promoting effect is likely mediated by diffusible pro-inflammatory molecules synthesized and released by senescent stromal fibroblasts, acting in a paracrine fashion on adjacent tumor epithelium. Mobilization of the inflammatory network by senescent fibroblasts has bifurcated roles on the epithelial and stromal compartments, converging on the promotion of epithelial tumorigenesis. A thorough understanding of the regulatory mechanisms underlying these events may lead to improved approaches in cancer treatment. PMID:19273333

  9. Mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling

    PubMed Central

    Sennett, Rachel; Rendl, Michael

    2012-01-01

    Embryonic hair follicle induction and formation are regulated by mesenchymal-epithelial interactions between specialized dermal cells and epidermal stem cells that switch to a hair fate. Similarly, during postnatal hair growth, communication between mesenchymal dermal papilla cells and surrounding epithelial matrix cells coordinates hair shaft production. Adult hair follicle regeneration in the hair cycle again is thought to be controlled by activating signals originating from the mesenchymal compartment and acting on hair follicle stem cells. Although many signaling pathways are implicated in hair follicle formation and growth, the precise nature, timing, and intersection of these inductive and regulatory signals remains elusive. The goal of this review is to summarize our current understanding and to discuss recent new insights into mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling. PMID:22960356

  10. Modeling Stromal-Epithelial Interactions in Disease Progression

    PubMed Central

    Strand, Douglas W.; Hayward, Simon W.

    2014-01-01

    The role of tumor stroma in progression to malignancy has become the subject of intense experimental and clinical interest. The stromal compartment of organs is composed of all the non-epithelial cell types and maintains the proper architecture and nutrient levels required for epithelial and, ultimately, organ function. The composition of the reactive stroma surrounding tumors is vastly different from normal stromal tissue. Stromal phenotype can be correlated with, and predictive of, disease recurrence. In addition, the stroma is now seen as a legitimate target for therapeutic intervention. Although much has been learned about the role of the stromal compartment in development and disease in recent years, a number of key questions remain. Here we review how some of these questions are beginning to be addressed using new models of stromal-epithelial interaction. PMID:20587339

  11. Testing gene therapy vectors in human primary nasal epithelial cultures.

    PubMed

    Cao, Huibi; Ouyang, Hong; Ip, Wan; Du, Kai; Duan, Wenming; Avolio, Julie; Wu, Jing; Duan, Cathleen; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Hu, Jim; Moraes, Theo J

    2015-01-01

    Cystic fibrosis (CF) results from mutations in the CF transmembrane conductance regulator (CFTR) gene, which codes for a chloride/bicarbonate channel in the apical epithelial membranes. CFTR dysfunction results in a multisystem disease including the development of life limiting lung disease. The possibility of a cure for CF by replacing defective CFTR has led to different approaches for CF gene therapy; all of which ultimately have to be tested in preclinical model systems. Primary human nasal epithelial cultures (HNECs) derived from nasal turbinate brushing were used to test the efficiency of a helper-dependent adenoviral (HD-Ad) vector expressing CFTR. HD-Ad-CFTR transduction resulted in functional expression of CFTR at the apical membrane in nasal epithelial cells obtained from CF patients. These results suggest that HNECs can be used for preclinical testing of gene therapy vectors in CF. PMID:26730394

  12. [Epithelial cell in intestinal homeostasis and inflammatory bowel diseases].

    PubMed

    Zouiten-Mekki, Lilia; Serghini, Meriem; Fekih, Monia; Kallel, Lamia; Matri, Samira; Ben Mustapha, Nadia; Boubaker, Jalel; Filali, Azza

    2013-12-01

    Crohn's disease (CD) and ulcerative colitis (UC) are the principal inflammatory bowel diseases (IBD) which physiopathology is currently poorly elucidated. During these diseases, the participation of the epithelial cell in the installation and the perpetuation of the intestinal inflammation is now clearly implicated. In fact, the intestinal epithelium located at the interface between the internal environment and the intestinal luminal, is key to the homeostatic regulation of the intestinal barrier. This barrier can schematically be regarded as being three barriers in one: a physical, chemical and immune barrier. The barrier function of epithelial cell can be altered by various mechanisms as occurs in IBD. The goal of this article is to review the literature on the role of the epithelial cell in intestinal homeostasis and its implication in the IBD. PMID:24356146

  13. Downregulation of miR-205 in migrating epithelial tongue facilitates skin wound re-epithelialization by derepressing ITGA5.

    PubMed

    Wang, Tao; Zhao, Na; Long, Shuang; Ge, Lan; Wang, Aiping; Sun, Huiqin; Ran, Xinze; Zou, Zhongmin; Wang, Junping; Su, Yongping

    2016-08-01

    Keratinocyte migration is essential for re-epithelialization during skin wound healing, but the molecular mechanisms regulating this cellular response remain to be completely clarified. Here we show that keratinocyte-specific miR-205 is significantly downregulated in the leading edge of the migrating epithelial tongue after skin injury in mice. In HaCaT keratinocytes, miR-205 could be downregulated by TGF-β1 stimulation. And similar to the effect of TGF-β1, miR-205 knockdown could promote keratinocyte migration in wound scratch model in vitro. Furthermore, topical inhibition of miR-205 by administrating Pluronic gel containing antagomir-205 could accelerate re-epithelialization in mouse skin wound model in vivo. Moreover, we identified integrin alpha 5 (ITGA5) as one key functional miR-205 target in the re-epithelialization process and epidermal downregulation of miR-205 may desilence ITGA5 to promote keratinocyte migration. And knockdown of ITGA5 would abolish the pro-migratory effects of miR-205 inhibition in vitro. What's more, we found dysregulation of miR-205 and its target ITGA5 in epidermis of clinical chronic wound samples with persistence of high level miR-205 and absence of ITGA5. Our findings indicate that downregulation of miR-205 in the leading migrating keratinocytes is critical for re-epithelialization and miR-205 may be a potential therapeutic target for chronic wounds. PMID:27169579

  14. Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells

    PubMed Central

    Zhang, Shiwu; Mercado-Uribe, Imelda; Sood, Anil; Bast, Robert C.; Liu, Jinsong

    2016-01-01

    Stromal cells are generally considered to be derived primarily from the host's normal mesenchymal stromal cells or bone marrow. However, the origins of stromal cells have been quite controversial. To determine the role of polyploidy in tumor development, we examined the fate of normal mullerian epithelial cells during the immortalization and transformation process by tracing the expression of SV40 large T antigen. Here we show that immortalized or HRAS-transformed mullerian epithelial cells contain a subpopulation of polyploid giant cells that grow as multicellular spheroids expressing hematopoietic markers in response to treatment with CoCl2. The immortalized or transformed epithelial cells can transdifferentiate into stromal cells when transplanted into nude mice. Immunofluorescent staining revealed expression of stem cell factors OCT4, Nanog, and SOX-2 in spheroid, whereas expression of embryonic stem cell marker SSEA1 was increased in HRAS-transformed cells compared with their immortalized isogenic counterparts. These results suggest that normal mullerian epithelial cells are intrinsically highly plastic, via the formation of polyploid giant cells and activation of embryonic stem-like program, which work together to promote the coevolution of neoplastic epithelial cells and multiple lineage stromal cells. PMID:27382431

  15. AMP-18 Targets p21 to Maintain Epithelial Homeostasis

    PubMed Central

    Chen, Peili; Li, Yan Chun; Toback, F. Gary

    2015-01-01

    Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD. PMID:25919700

  16. Anoctamin 1 dysregulation alters bronchial epithelial repair in cystic fibrosis.

    PubMed

    Ruffin, Manon; Voland, Mélanie; Marie, Solenne; Bonora, Monique; Blanchard, Elise; Blouquit-Laye, Sabine; Naline, Emmanuel; Puyo, Philippe; Le Rouzic, Philippe; Guillot, Loic; Corvol, Harriet; Clement, Annick; Tabary, Olivier

    2013-12-01

    Cystic fibrosis (CF) airway epithelium is constantly subjected to injury events due to chronic infection and inflammation. Moreover, abnormalities in CF airway epithelium repair have been described and contribute to the lung function decline seen in CF patients. In the last past years, it has been proposed that anoctamin 1 (ANO1), a Ca(2+)-activated Cl(-) channel, might offset the CFTR deficiency but this protein has not been characterized in CF airways. Interestingly, recent evidence indicates a role for ANO1 in cell proliferation and tumor growth. Our aims were to study non-CF and CF bronchial epithelial repair and to determine whether ANO1 is involved in airway epithelial repair. Here, we showed, with human bronchial epithelial cell lines and primary cells, that both cell proliferation and migration during epithelial repair are delayed in CF compared to non-CF cells. We then demonstrated that ANO1 Cl(-) channel activity was significantly decreased in CF versus non-CF cells. To explain this decreased Cl(-) channel activity in CF context, we compared ANO1 expression in non-CF vs. CF bronchial epithelial cell lines and primary cells, in lung explants from wild-type vs. F508del mice and non-CF vs. CF patients. In all these models, ANO1 expression was markedly lower in CF compared to non-CF. Finally, we established that ANO1 inhibition or overexpression was associated respectively with decreases and increases in cell proliferation and migration. In summary, our study demonstrates involvement of ANO1 decreased activity and expression in abnormal CF airway epithelial repair and suggests that ANO1 correction may improve this process. PMID:24080196

  17. Simulated Reflux Decreases Vocal Fold Epithelial Barrier Resistance

    PubMed Central

    Erickson, Elizabeth; Sivasankar, Mahalakshmi

    2010-01-01

    Objectives/Hypothesis The vocal fold epithelium provides a barrier to the entry of inhaled and systemic challenges. However, the location of the epithelium makes it vulnerable to damage. Past research suggests, but does not directly demonstrate, that exposure to gastric reflux adversely affects the function of the epithelial barrier. Understanding the nature of reflux-induced epithelial barrier dysfunction is necessary to better recognize the mechanisms for vocal fold susceptibility to this disease. Therefore, we examined the effects of physiologically relevant reflux challenges on vocal fold transepithelial resistance and gross epithelial and subepithelial appearance. Study Design Ex vivo, mixed design with between-group and repeated-measures analyses. Methods Healthy, native porcine vocal folds (N = 52) were exposed to physiologically relevant acidic pepsin, acid-only, or pepsin-only challenges and examined with electrophysiology and light microscopy. For all challenges, vocal folds exposed to a neutral pH served as control. Results Acidic pepsin and acid-only challenges, but not pepsin-only or control challenges significantly reduced transepithelial resistance within 30 minutes. Reductions in transepithelial resistance were irreversible. Challenge exposure produced minimal gross changes in vocal fold epithelial or subepithelial appearance as evidenced by light microscopy. Conclusions These findings demonstrate that acidic environments characteristic of gastric reflux compromise epithelial barrier function without gross structural changes. In healthy, native vocal folds, reductions in transepithelial resistance could reflect reflux-related epithelial disruption. These results might guide the development of pharmacologic and therapeutic recommendations for patients with reflux, such as continued acid-suppression therapy and patient antireflux behavioral education. PMID:20564752

  18. N-acetylcysteine inhibits alveolar epithelial-mesenchymal transition

    PubMed Central

    Felton, V. M.; Borok, Z.

    2009-01-01

    The ability of transforming growth factor-β1 (TGF-β1) to induce epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AEC) in vitro and in vivo, together with the demonstration of EMT in biopsies of idiopathic pulmonary fibrosis (IPF) patients, suggests a role for TGF-β1-induced EMT in disease pathogenesis. We investigated the effects of N-acetylcysteine (NAC) on TGF-β1-induced EMT in a rat epithelial cell line (RLE-6TN) and in primary rat alveolar epithelial cells (AEC). RLE-6TN cells exposed to TGF-β1 for 5 days underwent EMT as evidenced by acquisition of a fibroblast-like morphology, downregulation of the epithelial-specific protein zonula occludens-1, and induction of the mesenchymal-specific proteins α-smooth muscle actin (α-SMA) and vimentin. These changes were inhibited by NAC, which also prevented Smad3 phosphorylation. Similarly, primary alveolar epithelial type II cells exposed to TGF-β1 also underwent EMT that was prevented by NAC. TGF-β1 decreased cellular GSH levels by 50–80%, whereas NAC restored them to ∼150% of those found in TGF-β1-treated cells. Treatment with glutathione monoethyl ester similarly prevented an increase in mesenchymal marker expression. Consistent with its role as an antioxidant and cellular redox stabilizer, NAC dramatically reduced intracellular reactive oxygen species production in the presence of TGF-β1. Finally, inhibition of intracellular ROS generation during TGF-β1 treatment prevented alveolar EMT, but treatment with H2O2 alone did not induce EMT. We conclude that NAC prevents EMT in AEC in vitro, at least in part through replenishment of intracellular GSH stores and limitation of TGF-β1-induced intracellular ROS generation. We speculate that beneficial effects of NAC on pulmonary function in IPF may be mediated by inhibitory effects on alveolar EMT. PMID:19648289

  19. N-acetylcysteine inhibits alveolar epithelial-mesenchymal transition.

    PubMed

    Felton, V M; Borok, Z; Willis, B C

    2009-11-01

    The ability of transforming growth factor-beta1 (TGF-beta1) to induce epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AEC) in vitro and in vivo, together with the demonstration of EMT in biopsies of idiopathic pulmonary fibrosis (IPF) patients, suggests a role for TGF-beta1-induced EMT in disease pathogenesis. We investigated the effects of N-acetylcysteine (NAC) on TGF-beta1-induced EMT in a rat epithelial cell line (RLE-6TN) and in primary rat alveolar epithelial cells (AEC). RLE-6TN cells exposed to TGF-beta1 for 5 days underwent EMT as evidenced by acquisition of a fibroblast-like morphology, downregulation of the epithelial-specific protein zonula occludens-1, and induction of the mesenchymal-specific proteins alpha-smooth muscle actin (alpha-SMA) and vimentin. These changes were inhibited by NAC, which also prevented Smad3 phosphorylation. Similarly, primary alveolar epithelial type II cells exposed to TGF-beta1 also underwent EMT that was prevented by NAC. TGF-beta1 decreased cellular GSH levels by 50-80%, whereas NAC restored them to approximately 150% of those found in TGF-beta1-treated cells. Treatment with glutathione monoethyl ester similarly prevented an increase in mesenchymal marker expression. Consistent with its role as an antioxidant and cellular redox stabilizer, NAC dramatically reduced intracellular reactive oxygen species production in the presence of TGF-beta1. Finally, inhibition of intracellular ROS generation during TGF-beta1 treatment prevented alveolar EMT, but treatment with H2O2 alone did not induce EMT. We conclude that NAC prevents EMT in AEC in vitro, at least in part through replenishment of intracellular GSH stores and limitation of TGF-beta1-induced intracellular ROS generation. We speculate that beneficial effects of NAC on pulmonary function in IPF may be mediated by inhibitory effects on alveolar EMT. PMID:19648289

  20. Plasmolipin—a new player in endocytosis and epithelial development

    PubMed Central

    Le Guelte, Armelle; Macara, Ian G

    2015-01-01

    Polarized vesicle sorting is essential not only for epithelial cell function but also for cell polarization and tissue morphogenesis. Endocytosis is a key determinant of the surface abundance of plasma membrane proteins and is highly regulated. In an important recent paper, Rodríguez-Fraticelli et al (4) identify a new player in apical endocytosis—a previously uncharacterized protein called Plasmolipin. They report not only its mechanism of action through binding to an epsin, but also highlight an essential role in regulating Notch signaling, which controls epithelial differentiation. PMID:25825384

  1. Epithelial cell cultures from normal and cancerous human tissues.

    PubMed

    Owens, R B; Smith, H S; Nelson-Rees, W A; Springer, E L

    1976-04-01

    Thirty epithelial cell strains were isolated from human carcinomas and normal epithelial tissues by collagenase digestion and selective removal of fibroblasts with trypsin-Versene. Most strains were obtained from metastatic carcinomas or epithelia of the urinary and intestinal tracts. The success rate for growth of both neoplastic and normal tissues (excluding skin) was 38%. Six of these strains showed gross morphologic and chromosome changes typical of malignant cells. Nine resembled normal epithelium. The other 15 exhibited some degree of morphologic change from normal. PMID:176412

  2. Solid and papillary epithelial neoplasm of the pancreas

    SciTech Connect

    Friedman, A.C.; Lichtenstein, J.E.; Fishman, E.K.; Oertel, J.E.; Dachman, A.H.; Siegelman, S.S.

    1985-02-01

    Solid and papillary epithelial neoplasm of the pancreas is an uncommon low grade malignant tumor histologically distinct from the usual ductal adenocarcinoma and amenable to cure by surgical excision. It tends to occur in black women in their second or third decade of life and has often been misclassified as nonfunctional islet cell tumor or as cystadenoma or cystadenocarcinoma. Twelve cases were reviewed. Sonography and CT of solid and pipillary epithelial neoplasms depict a well-demarcated mass that can be solid, mixed cystic and solid, or largely cystic. The radiologic appearance is dependent on the maintenance of the integrity of the neoplasm versus the extent of retrogressive changes that have occurred.

  3. Effect of freezing on lens epithelial cell growth.

    PubMed

    Fukaya, Y; Hara, T; Hara, T; Iwata, S

    1988-05-01

    The effect of freezing on the growth of rat lens epithelial cells was studied in vitro. We found that 80% of the lens epithelial cells died after freezing at -45 degrees C for two hours and that the surviving cells could grow with the addition of growth factors or when placed on a sheet of type 4 collagen, but not when placed on a plain plastic culture dish. These results suggest that the surviving cells are at the Go phase of the cell cycle and that type 4 collagen or growth factors can initiate cell division. PMID:3294380

  4. Flow Cytometry Analysis of Thymic Epithelial Cells and Their Subpopulations.

    PubMed

    Ohigashi, Izumi; Takahama, Yousuke

    2016-01-01

    The parenchyma of the thymus is compartmentalized into the cortex and the medulla, which are constructed by cortical thymic epithelial cells (cortical TECs, cTECs) and medullary thymic epithelial cells (mTECs), respectively. cTECs and mTECs essentially and differentially regulate the development and repertoire selection of T cells. Consequently, the biology of T cell development and selection includes the study of TECs in addition to the study of developing T cells and other hematopoietic cells including dendritic cells. In this chapter, we describe the methods for flow cytometric analysis and sorting of TECs and their subpopulations, including cTECs and mTECs. PMID:26294398

  5. Airway Epithelial miRNA Expression Is Altered in Asthma

    PubMed Central

    Solberg, Owen D.; Ostrin, Edwin J.; Love, Michael I.; Peng, Jeffrey C.; Bhakta, Nirav R.; Nguyen, Christine; Solon, Margaret; Nguyen, Cindy; Barczak, Andrea J.; Zlock, Lorna T.; Blagev, Denitza P.; Finkbeiner, Walter E.; Ansel, K. Mark; Arron, Joseph R.; Erle, David J.

    2012-01-01

    Rationale: Changes in airway epithelial cell differentiation, driven in part by IL-13, are important in asthma. Micro-RNAs (miRNAs) regulate cell differentiation in many systems and could contribute to epithelial abnormalities in asthma. Objectives: To determine whether airway epithelial miRNA expression is altered in asthma and identify IL-13–regulated miRNAs. Methods: We used miRNA microarrays to analyze bronchial epithelial brushings from 16 steroid-naive subjects with asthma before and after inhaled corticosteroids, 19 steroid-using subjects with asthma, and 12 healthy control subjects, and the effects of IL-13 and corticosteroids on cultured bronchial epithelial cells. We used quantitative polymerase chain reaction to confirm selected microarray results. Measurements and Main Results: Most (12 of 16) steroid-naive subjects with asthma had a markedly abnormal pattern of bronchial epithelial miRNA expression by microarray analysis. Compared with control subjects, 217 miRNAs were differentially expressed in steroid-naive subjects with asthma and 200 in steroid-using subjects with asthma (false discovery rate < 0.05). Treatment with inhaled corticosteroids had modest effects on miRNA expression in steroid-naive asthma, inducing a statistically significant (false discovery rate < 0.05) change for only nine miRNAs. qPCR analysis confirmed differential expression of 22 miRNAs that were highly differentially expressed by microarrays. IL-13 stimulation recapitulated changes in many differentially expressed miRNAs, including four members of the miR-34/449 family, and these changes in miR-34/449 family members were resistant to corticosteroids. Conclusions: Dramatic alterations of airway epithelial cell miRNA levels are a common feature of asthma. These alterations are only modestly corrected by inhaled corticosteroids. IL-13 effects may account for some of these alterations, including repression of miR-34/449 family members that have established roles in airway

  6. First Identification of a Triple Corneal Dystrophy Association: Keratoconus, Epithelial Basement Membrane Corneal Dystrophy and Fuchs’ Endothelial Corneal Dystrophy

    PubMed Central

    Mazzotta, Cosimo; Traversi, Claudio; Raiskup, Frederik; Rizzo, Caterina Lo; Renieri, Alessandra

    2014-01-01

    Purpose To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC), epithelial basement membrane corneal dystrophy (EBMCD) and Fuchs’ endothelial corneal dystrophy (FECD). Methods A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing. Results Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman's layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1. Conclusion This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy. PMID:25408666

  7. Laser Cladding

    NASA Astrophysics Data System (ADS)

    Lepski, Dietrich; Brückner, Frank

    Laser cladding is a modern technology whose uses include, for example, the creation of protective coatings to reduce wear and corrosion on engine parts and tools. The aircraft and automotive industries are examples of industries in which it is much used. This account considers the theory of a number of aspects of the process in detail. The first to be studied is the interaction of the laser beam directly with the powder that is being deposited; the effects of gravity, beam shadowing, and particle heating are investigated. This is followed by a discussion of the mechanisms by which the particles adhere to the surface of the work piece and are absorbed into it. In order to understand the process, a study of the melt pool and the associated temperature distribution is necessary; it is then possible to infer the final bead geometry. An inevitable consequence of a thermal process such as laser cladding is the induced thermal stress and resulting distortion of the work piece. The fundamentals are discussed, a numerical model presented and in addition a simple heuristic model is given. The use of induction-assisted laser cladding as a means of preventing the formation of cracks is discussed.

  8. Excimer lasers

    NASA Technical Reports Server (NTRS)

    Palmer, A. J.; Hess, L. D.; Stephens, R. R.; Pepper, D. M.

    1977-01-01

    The results of a two-year investigation into the possibility of developing continuous wave excimer lasers are reported. The program included the evaluation and selection of candidate molecular systems and discharge pumping techniques. The K Ar/K2 excimer dimer molecules and the xenon fluoride excimer molecule were selected for study; each used a transverse and capillary discharges pumping technique. Experimental and theoretical studies of each of the two discharge techniques applied to each of the two molecular systems are reported. Discharge stability and fluorine consumption were found to be the principle impediments to extending the XeF excimer laser into the continuous wave regime. Potassium vapor handling problems were the principal difficulty in achieving laser action on the K Ar/K2 system. Of the four molecular systems and pumping techniques explored, the capillary discharge pumped K Ar/K2 system appears to be the most likely candidate for demonstrating continuous wave excimer laser action primarily because of its predicted lower pumping threshold and a demonstrated discharge stability advantage.

  9. Laser iridotomy.

    PubMed

    Perkins, E S

    1970-06-01

    A ruby laser has been used to produce a permeable lesion in the iris to establish a communication between the anterior and posterior chambers. In a preliminary study in nine patients the technique gave satisfactory results in the prophylactic treatment of four cases of incipient closed-angle glaucoma and of two cases of iris bombé following uveitis. PMID:5526615

  10. Laser altimeter

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of a laser altimeter for use in the Apollo Lunar Orbital Experiments mission is discussed. The altimeter provides precise measurement of an Apollo vehicle above the lunar surface from an orbit of 40 to 80 nautical miles. The technical characteristics of the altimeter are described. Management of the altimeter development program is analyzed.

  11. Laser capture.

    PubMed

    Potter, S Steven; Brunskill, Eric W

    2012-01-01

    This chapter describes detailed methods used for laser capture microdissection (LCM) of discrete subpopulations of cells. Topics covered include preparing tissue blocks, cryostat sectioning, processing slides, performing the LCM, and purification of RNA from LCM samples. Notes describe the fine points of each operation, which can often mean the difference between success and failure. PMID:22639264

  12. Alix-mediated assembly of the actomyosin–tight junction polarity complex preserves epithelial polarity and epithelial barrier

    PubMed Central

    Campos, Yvan; Qiu, Xiaohui; Gomero, Elida; Wakefield, Randall; Horner, Linda; Brutkowski, Wojciech; Han, Young-Goo; Solecki, David; Frase, Sharon; Bongiovanni, Antonella; d'Azzo, Alessandra

    2016-01-01

    Maintenance of epithelial cell polarity and epithelial barrier relies on the spatial organization of the actin cytoskeleton and proper positioning/assembly of intercellular junctions. However, how these processes are regulated is poorly understood. Here we reveal a key role for the multifunctional protein Alix in both processes. In a knockout mouse model of Alix, we identified overt structural changes in the epithelium of the choroid plexus and in the ependyma, such as asymmetrical cell shape and size, misplacement and abnormal beating of cilia, blebbing of the microvilli. These defects culminate in excessive cell extrusion, enlargement of the lateral ventricles and hydrocephalus. Mechanistically, we find that by interacting with F-actin, the Par complex and ZO-1, Alix ensures the formation and maintenance of the apically restricted actomyosin–tight junction complex. We propose that in this capacity Alix plays a role in the establishment of apical–basal polarity and in the maintenance of the epithelial barrier. PMID:27336173

  13. Alix-mediated assembly of the actomyosin-tight junction polarity complex preserves epithelial polarity and epithelial barrier.

    PubMed

    Campos, Yvan; Qiu, Xiaohui; Gomero, Elida; Wakefield, Randall; Horner, Linda; Brutkowski, Wojciech; Han, Young-Goo; Solecki, David; Frase, Sharon; Bongiovanni, Antonella; d'Azzo, Alessandra

    2016-01-01

    Maintenance of epithelial cell polarity and epithelial barrier relies on the spatial organization of the actin cytoskeleton and proper positioning/assembly of intercellular junctions. However, how these processes are regulated is poorly understood. Here we reveal a key role for the multifunctional protein Alix in both processes. In a knockout mouse model of Alix, we identified overt structural changes in the epithelium of the choroid plexus and in the ependyma, such as asymmetrical cell shape and size, misplacement and abnormal beating of cilia, blebbing of the microvilli. These defects culminate in excessive cell extrusion, enlargement of the lateral ventricles and hydrocephalus. Mechanistically, we find that by interacting with F-actin, the Par complex and ZO-1, Alix ensures the formation and maintenance of the apically restricted actomyosin-tight junction complex. We propose that in this capacity Alix plays a role in the establishment of apical-basal polarity and in the maintenance of the epithelial barrier. PMID:27336173

  14. Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair.

    PubMed

    Xia, Jingjing; Swiercz, Jakub M; Bañón-Rodríguez, Inmaculada; Matković, Ivana; Federico, Giuseppina; Sun, Tianliang; Franz, Timo; Brakebusch, Cord H; Kumanogoh, Atsushi; Friedel, Roland H; Martín-Belmonte, Fernando; Gröne, Hermann-Josef; Offermanns, Stefan; Worzfeld, Thomas

    2015-05-01

    Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central regulatory mechanism of mitotic spindle orientation necessary for the alignment of epithelial cell divisions with the epithelial plane. PMID:25892012

  15. Modulation of Candida albicans attachment to human epithelial cells by bacteria and carbohydrates.

    PubMed Central

    Centeno, A; Davis, C P; Cohen, M S; Warren, M M

    1983-01-01

    The effects of carbohydrates (mannose and dextrose). Escherichia coli 07KL. and Klebsiella pneumoniae on Candida albicans attachment to epithelial cells was studied. Dextrose had no effect on yeast attachment to epithelial cells. Conversely, mannose significantly decreased both yeast and piliated bacterial attachment (E. coli 07KL, heavily piliated K. pneumoniae) whereas having no effect on nonpiliated K. pneumoniae attachment to epithelial cells. The number of yeasts attaching to epithelial cells was enhanced by preincubation of epithelial cells with piliated strains of bacteria, whereas preincubation with nonpiliated strains of bacteria had no effect on yeast attachment. Scanning electron microscopy showed that piliated bacteria and yeasts were juxtaposed on the epithelial cell surface. These data suggest that certain piliated strains of bacteria can enhance C. albicans attachment to epithelial cells and that type 1 pili of bacteria can be a factor in the enhanced attachment of C. albicans to epithelial cells. Images PMID:6132878

  16. KLF4 transcriptionally activates non-canonical WNT5A to control epithelial stratification

    PubMed Central

    Tetreault, Marie-Pier; Weinblatt, Daniel; Shaverdashvili, Khvaramze; Yang, Yizeng; Katz, Jonathan P.

    2016-01-01

    Epithelial differentiation and stratification are essential for normal homeostasis, and disruption of these processes leads to both injury and cancer. The zinc-finger transciption factor KLF4 is a key driver of epithelial differentiation, yet the mechanisms and targets by which KLF4 controls differentiation are not well understood. Here, we define WNT5A, a non-canonical Wnt ligand implicated in epithelial differentiation, repair, and cancer, as a direct transcriptional target that is activated by KLF4 in squamous epithelial cells. Further, we demonstrate functionally that WNT5A mediates KLF4 control of epithelial differentiation and stratification, as treatment of keratinocytes with WNT5A rescues defective epithelial stratification resulting from KLF4 loss. Finally, we show that the small GTPase CDC42 is regulated by KLF4 in a WNT5A dependent manner. As such, we delineate a novel pathway for epithelial differentiation and stratification and define potential therapeutic targets for epithelial diseases. PMID:27184424

  17. *Iron accumulation in bronchial epithelial cells is dependent on concurrent sodium transport

    EPA Science Inventory

    Airway epithelial cells prevent damaging effects of extracellular iron by taking up the metal and sequestering it within intracellular ferritin. Epithelial iron transport is associated with transcellular movement of other cations including changes in the expression or activity of...

  18. Nanowire Lasers

    NASA Astrophysics Data System (ADS)

    Couteau, C.; Larrue, A.; Wilhelm, C.; Soci, C.

    2015-05-01

    We review principles and trends in the use of semiconductor nanowires as gain media for stimulated emission and lasing. Semiconductor nanowires have recently been widely studied for use in integrated optoelectronic devices, such as light-emitting diodes (LEDs), solar cells, and transistors. Intensive research has also been conducted in the use of nanowires for subwavelength laser systems that take advantage of their quasione- dimensional (1D) nature, flexibility in material choice and combination, and intrinsic optoelectronic properties. First, we provide an overview on using quasi-1D nanowire systems to realize subwavelength lasers with efficient, directional, and low-threshold emission. We then describe the state of the art for nanowire lasers in terms of materials, geometry, andwavelength tunability.Next,we present the basics of lasing in semiconductor nanowires, define the key parameters for stimulated emission, and introduce the properties of nanowires. We then review advanced nanowire laser designs from the literature. Finally, we present interesting perspectives for low-threshold nanoscale light sources and optical interconnects. We intend to illustrate the potential of nanolasers inmany applications, such as nanophotonic devices that integrate electronics and photonics for next-generation optoelectronic devices. For instance, these building blocks for nanoscale photonics can be used for data storage and biomedical applications when coupled to on-chip characterization tools. These nanoscale monochromatic laser light sources promise breakthroughs in nanophotonics, as they can operate at room temperature, can potentially be electrically driven, and can yield a better understanding of intrinsic nanomaterial properties and surface-state effects in lowdimensional semiconductor systems.

  19. Protective effect of Ac-SDKP on alveolar epithelial cells through inhibition of EMT via TGF-β1/ROCK1 pathway in silicosis in rat.

    PubMed

    Deng, Haijing; Xu, Hong; Zhang, Xianghong; Sun, Yue; Wang, Ruimin; Brann, Darrell; Yang, Fang

    2016-03-01

    The epithelial-mesenchymal transition (EMT) is a critical stage during the development of silicosis fibrosis. In the current study, we hypothesized that the anti-fibrotic tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) may exert its anti-fibrotic effects via activation of the TGF-β1/ROCK1 pathway, leading to inhibition of EMT. To address this hypothesis, we first examined the effect of Ac-SDKP upon EMT using an in vivo rat silicosis model, as well as in an in vitro model of TGF-β1-induced EMT. Confocal laser scanning microscopy was used to examine colocalization of surfactant protein A (SP-A), fibroblast specific protein-1 (FSP-1) and α-smooth muscle actin (α-SMA) in vivo. Western blot analysis was used to examine for changes in the protein levels of E-cadherin (E-cad) and SP-A (epithelial cell markers), vimentin (mesenchymal cell marker), α-SMA (active myofibroblast marker), and collagen I and III in both in vivo and in vitro experiments. Secondly, we utilized Western blot analysis and confocal laser scanning microscopy to examine the protein expression of TGF-β1 and ROCK1 in in vivo and in vitro studies. The results revealed that Ac-SDKP treatment prevented increases in the expression of mesenchymal markers as well as TGF-β1, ROCK1, collagen I and III. Furthermore, Ac-SDKP treatment prevented decreases in the expression of epithelial cell markers in both in vivo and in vitro experiments. Based on the results, we conclude that Ac-SDKP inhibits the transition of epithelial cell-myofibroblast in silicosis via activation of the TGF-β1/ROCK1 signaling pathway, which may serve as a novel mechanism by which it exerts its anti-fibrosis properties. PMID:26785300

  20. Burkholderia pseudomallei Biofilm Promotes Adhesion, Internalization and Stimulates Proinflammatory Cytokines in Human Epithelial A549 Cells

    PubMed Central

    Kunyanee, Chanikarn; Kamjumphol, Watcharaporn; Taweechaisupapong, Suwimol; Kanthawong, Sakawrat; Wongwajana, Suwin; Wongratanacheewin, Surasak; Hahnvajanawong, Chariya

    2016-01-01

    Burkholderia pseudomallei is a Gram-negative bacterium that causes melioidosis. Inhalational exposure leading to pulmonary melioidosis is the most common clinical manifestation with significant mortality. However, the role of B. pseudomallei biofilm phenotype during bacterial-host interaction remains unclear. We hypothesize that biofilm phenotype may play a role in such interactions. In this study, B. pseudomallei H777 (biofilm wild type), B. pseudomallei M10 (biofilm mutant) and B. pseudomallei C17 (biofilm-complemented) strains were used to assess the contribution of biofilm to adhesion to human lung epithelial cells (A549), intracellular interactions, apoptosis/necrosis and impact on proinflammatory responses. Confocal laser scanning microscopy demonstrated that B. pseudomallei H777 and C17 produced biofilm, whereas M10 did not. To determine the role of biofilm in host interaction, we assessed the ability of each of the three strains to interact with the A549 cells at MOI 10. Strain H777 exhibited higher levels of attachment and invasion compared to strain M10 (p < 0.05). In addition, the biofilm-complemented strain, C17 exhibited restored bacterial invasion ability. Flow cytometry combined with a double-staining assay using annexin V and propidium iodide revealed significantly higher numbers of early apoptotic and late apoptotic A549 cells when these were infected with strain H777 (1.52%) and C17 (1.43%) compared to strain M10 (0.85%) (p < 0.05). Strains H777 and C17 were able to stimulate significant secretion of IL-6 and IL-8 compared with the biofilm mutant (p < 0.05). Together, these findings demonstrated the role of biofilm-associated phenotypes of B. pseudomallei in cellular pathogenesis of human lung epithelial cells with respect to initial attachment and invasion, apoptosis and proinflammatory responses. PMID:27529172

  1. [Primary thinning and de-epithelialization of microsurgical transplants from the lateral thigh].

    PubMed

    Wolff, K D; Plath, T; Frege, J; Hoffmeister, B

    2000-03-01

    To expand the indicational spectrum of the myocutaneous vastus lateralis flap, which is often too voluminous for intraoral application, we performed extreme, primary thinning of the fat and muscle component of this microsurgical transplant in 14 patients. After subfascial localization of the 0.5- to 1.0-mm-thick perforating vessel, it is exposed through the fascia and muscles up to its exit from the descending branch of the lateral circumflex femoral artery. After isolating the perforating vessel, it is no longer necessary to include parts of the vastus lateralis muscle in the flap. The fatty tissue of the remaining epifascial fat component is completely removed except for a ca. 1- to 2-cm-wide cuff of fatty tissue and fascia around the perforating vessel. When performing this primary radical removal of the subcutaneous fatty tissue, care should be taken not to injure the deep subdermal vascular plexus. In addition to the thinning procedure, de-epithelialization of the skin was performed using scalpel blade dissection (five patients) or carbon dioxide laser (6 W, five patients). This thinning technique was used for covering ten intraoral and four extraoral defects and enabled the raising of skin flaps with a thickness of 3-5 mm even in obese patients. The vessel pedicle length of thinned flaps was between 12 and 16 cm; flap size varied between 4 x 5 and 9 x 15 cm, and the donor sites were directly closed. In one case, there was a partial necrosis (20%), but the remaining flaps healed without complications. On the intraoral flaps, a thin, smooth and pliable surface developed after re-epithelialization within 3-6 weeks. The described method expands the application possibilities of the myocutaneous vastus lateralis flap for a large number of intraoral and flat defects with minimal donor-site morbidity. PMID:10851881

  2. Lipid and protein distribution in epithelial cells assessed with confocal microscopy

    NASA Astrophysics Data System (ADS)

    Peterson, Kajsa H.; Randen, Michael; Hays, Richard M.; Magnusson, Karl-Eric

    1992-06-01

    Confocal laser scanning microscopy, image processing, and volume visualization were used to characterize the 3-D distribution of lectin receptors, lipid probes, and actin cytoskeleton in epithelial cells. Small intestine-like cells were grown on glass or filter supports and apically labelled with different fluorescent lipid and lectin probes. The restriction of the probes by the tight junctions was studied in living cells. Series of confocal x-y sections were transferred to an image processing system for analysis. The fluorescence intensity within a specified area of all x-y sections was plotted as a function of the vertical position of the sections. The curve inclination was used to describe the degree of restriction to the probes. It was found that lectins were more confined to the apical part than the lipids, which showed varying degree of redistribution to the basolateral membrane. Volume rendering, and specifically animated sequences with varying viewpoint and opacity mapping, were used to visualize the structure of actin cytoskeleton and distribution of lipid and lectin probes. In toad bladder epithelial cells, actin was labelled before and after treatment with the antidiuretic hormone vasopressin. The hormone-induced redistribution of actin in the apical and lateral portion of the cells was measured on x-z scanned images. Ratios of apical-to-lateral intensity were calculated. It was found that the decrease in the ratios after vasopressin treatment was around 30%. The decrease was due to loss of actin apically. This is supposed to facilitate apical fusion of vesicles containing the water-channel forming proteins, being important in water homeostasis.

  3. Ac-SDKP suppresses epithelial-mesenchymal transition in A549 cells via HSP27 signaling.

    PubMed

    Deng, Haijing; Yang, Fang; Xu, Hong; Sun, Yue; Xue, Xinxin; Du, Shipu; Wang, Xiaojun; Li, Shifeng; Liu, Yan; Wang, Ruimin

    2014-08-01

    The synthetic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has been shown to be a modulator of molecular aspects of the fibrosis pathway. This study reveals that Ac-SDKP exerts an anti-fibrotic effect on human type II alveolar epithelial cells (A549), which are a source of myofibroblasts once exposed to TGF-β1, by decreasing the expression of heat shock protein 27 (HSP27). We used A549 cells in vitro to detect morphological evidence of epithelial-mesenchymal transition (EMT) by phase-contrast microscopy. Immunocytochemical and western blot analysis determined the distributions of cytokeratin 8 (CK8), α-smooth muscle actin (α-SMA), and SNAI1. Confocal laser scanning microscopy revealed a colocalization of HSP27 and SNAI1 on TGF-β1-induced A549 cells. These results also demonstrated that A549 cells became spindle-like when exposed to TGF-β1. Coincident with these morphological changes, expression levels of CK8 and E-cad decreased, while those of vimentin and α-SMA increased. This process was accompanied by increases in levels of HSP27, SNAI1, and type I and type III collagen. In vitro transfection experiments demonstrated that the inhibition of HSP27 in cultured A549 cells could decrease the expression of SNAI1 and α-SMA while increasing the expression of E-cad. A noticeable reduction in collagen types I and III was also evident. Our results found that Ac-SDKP inhibited the transition of cultured A549 cells to myofibroblasts and attenuated collagen synthesis through modulating the expression of HSP27. PMID:24998956

  4. CXCL9 Regulates TGF-β1 induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells

    PubMed Central

    O’Beirne, Sarah L; Walsh, Sinead M; Fabre, Aurélie; Reviriego, Carlota; Worrell, Julie C; Counihan, Ian P; Lumsden, Robert V; Cramton-Barnes, Jennifer; Belperio, John A.; Donnelly, Seamas C; Boylan, Denise; Marchal-Somme, Joëlle; Kane, Rosemary; Keane, Michael P

    2016-01-01

    Epithelial to mesenchymal transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells. Coexpression of the epithelial maker thyroid transcription factor-1, and mesenchymal marker α-smooth muscle actin and CXCR3 expression was examined by immunohistochemical staining of IPF surgical lung biopsies. Epithelial and mesenchymal marker expression was examined by quantitative real-time PCR, Western blotting, and immunofluorescence in human alveolar epithelial (A549) cells treated with TGF-β1 and CXCL9, whilst Smad2, Smad3, and Smad7 expression and cellular localization examined by Western blotting. We found that significantly more cells were undergoing EMT in fibrotic versus normal areas of lung in IPF surgical lung biopsy samples. CXCR3 was expressed by type II pneumocytes and fibroblasts in fibrotic areas in close proximity to cells undergoing EMT. In vitro, CXCL9 abrogated TGF-β1 induced EMT. A decrease in TGF-β1 induced phosphorylation of Smad2 and Smad3 occurred with CXCL9 treatment. This was associated with increased shuttling of Smad7 from the nucleus to the cytoplasm where it inhibits Smad phosphorylation. This suggests a role for EMT in the pathogenesis of IPF and provides a novel mechanism for the inhibitory effects of CXCL9 on TGF-β1 induced EMT. PMID:26268659

  5. Comparison of laser phacovaporization using the Er:YAG and the Er:YSGG laser

    NASA Astrophysics Data System (ADS)

    Gailitis, Raymond P.; Patterson, Scott W.; Samuels, Mark A.; Hagen, Kerry B.; Ren, Qiushi; Waring, George O., III

    1992-08-01

    Future advances in cataract surgery aim to remove the crystalline lens through a small opening such that the capsular bag, once devoid of lens epithelial cells, may be refilled with a clear polymer which may exhibit the elastic properties of a young lens and restore accommodation. Several different lasers are currently being investigated for laser cataract surgery including the excimer, pulsed visible and short infrared, and mid infrared lasers. Taking advantage of the strong water absorption peak at 2.94 micrometers , we have investigated the laser tissue interaction of the Er:YAG (2.94 micrometers ) and Er:YSGG (2.79 micrometers ) which have water absorption coefficients of 13,000 cm-1 and 7,000 cm-1, respectively. We have devised a delivery system which measures the ablation time versus radiant energy through a known thickness on a lens nucleus in free air for these two wavelengths. The current presentation compares the ablation rates versus radiant exposure of these two lasers in human lens nuclei. We also show the histopathology from ablated lenses of these two different wavelengths at different radiant exposures. Integration with fiberoptics and clinical applications is discussed.

  6. Dissecting cellular biomechanics with a laser

    NASA Astrophysics Data System (ADS)

    Hutson, M. Shane

    2011-10-01

    The biological tissues of a developing organism are built and reshaped by the mechanical behavior of individual cells. We probe the relevant cellular mechanics in vivo using laser-microsurgery -- both qualitatively, to assess whether removal of specific cells alters the dynamics of tissue reshaping, and quantitatively, to measure sub-cellular mechanical properties and stresses. I will detail two quantitative microsurgical measurements. The first uses a laser to drill a sub-cellular hole in a sheet of cells. The subsequent retraction of surrounding cells allows one to infer the local mechanical stress. The second uses a laser to isolate a single cell from the rest of a cell sheet. Isolation is accomplished on a microsecond time scale by holographically shaping a single laser pulse. The subsequent retraction (or expansion) of the isolated cell allows one to separate and quantify the effects of internal and external stresses in the determination of cell shape. I will discuss application of these techniques to the time-dependent biomechanics of epithelial tissues during early fruit fly embryogenesis -- specifically during the processes of germband retraction and dorsal closure.

  7. Femtosecond laser versus mechanical microkeratome-assisted flap creation for LASIK: a prospective, randomized, paired-eye study

    PubMed Central

    Pajic, Bojan; Vastardis, Iraklis; Pajic-Eggspuehler, Brigitte; Gatzioufas, Zisis; Hafezi, Farhad

    2014-01-01

    Purpose To compare a femtosecond laser with a microkeratome for flap creation during laser in situ keratomileusis (LASIK) in terms of flap thickness predictability and visual outcomes. Patients and methods This was a prospective, randomized, masked, paired-eye study. Forty-four patients (34 females) who received bilateral LASIK were included. Patients were stratified by ocular dominance, and they then underwent randomization of flap creation using the femtosecond laser on one eye and undergoing the microkeratome procedure on the other one. The visual outcome differences between the corrected distance visual acuity (CDVA) at baseline and the uncorrected distance visual acuity (UDVA) on the first day postoperatively were set as the efficiency index for both groups. All visual acuity outcome results and the deviation of flap thickness were evaluated. P-values <0.05 were considered statistically significant. Results The index of efficiency regarding the postoperative visual outcomes in the microkeratome group was lower (P<0.0001). This result was correlated with the difference between intended and achieved flap thickness (P=0.038; r=0.28), and a negative relationship in the regression analysis was confirmed (P<0.04; R2=0.1428). The UDVA in the microkeratome group improved significantly by the end of the first month (P<0.0271) in comparison to the baseline CDVA. The deviation between intended and postoperative flap thickness using either optical coherence pachymetry or Heidelberg Retinal Tomography II confocal microscopy was statistically significant (paired t-test; P<0.001) between the groups. The flap thickness deviation in the microkeratome group was higher. In the femtosecond laser group, the efficiency index was stable postoperatively (P=0.64) The UDVA improved significantly by the end of the first postoperative week (P=0.0043) in comparison to the baseline CDVA. Six months after surgery, improvement in the UDVA was significant in both groups (all P<0.001; one way

  8. Valacyclovir for the prevention of recurrent herpes simplex virus eye disease after excimer laser photokeratectomy.

    PubMed Central

    Asbell, P A

    2000-01-01

    PURPOSE: A variety of factors have been reported as inducing the reactivation of latent herpes simplex virus (HSV), among them stress, trauma, and UV radiation. Excimer laser photorefractive keratectomy (PRK) is a surgical procedure utilizing a 193 nm ultraviolet light to alter the curvature of the cornea and hence correct vision. Reactivation of ocular herpes simplex keratitis following such excimer laser PRK has been reported. All published cases of HSV reactivation following excimer laser treatment in humans are reviewed. The present study evaluates whether stress, trauma of the corneal de-epithelialization prior to the laser, or the excimer laser treatment itself to the stromal bed induces this ocular reactivation of the latent HSV, and whether a systemic antiviral agent, valacyclovir, would prevent such laser PRK-induced reactivation of the HSV. METHODS: Forty-three normal 1.5- to 2.5-kg New Zealand white rabbits were infected on the surface of the cornea with HSV-1, strain RE. The animals were monitored until resolution, and then all animals were divided into 5 treatment groups: (1) de-epithelialization only, intraperitoneal (i.p.) saline for 14 days; (2) de-epithelialization plus laser, i.p. saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day i.p. for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day i.p. for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day i.p. for 14 days. Animals were evaluated in a masked fashion by clinical examination biweekly and viral cultures biweekly through day 28. RESULTS: The reactivation rates were as follows: group 1, 0%; group 2, 67%; group 3, 50%; group 4, 17%; and group 5, 0%. Viral titers were negative in animals that had no reactivation but persistently positive in those that had reactivation (day 6 through day 28). CONCLUSIONS: Excimer laser (193 nm) treatment can trigger reactivation of ocular herpes disease (67%) and viral

  9. Laser weapons. II - Strategic laser weapons

    NASA Astrophysics Data System (ADS)

    Hecht, J.

    1982-07-01

    Potential strategic missions for laser weapons, particularly those involving space-based lasers, are discussed. The functions of space-based lasers and the history of their conceptual development are summarized, and the problems of implementing such systems, including the building of a suitable laser and power source, and resolving the problem of optics, are discussed. Ongoing development programs are described, and the contrasting views of the necessity and usefulness of strategic laser systems are set forth.

  10. CCL20, (gamma)(delta) T cells, and IL-22 in corneal epithelial healing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6 (+) IL-17(+) gamma delta T cells migrate into the epithelium. Gamma delta T-cell-deficient (TCRd(-/-)) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mR...

  11. Circulating progenitor epithelial cells traffic via CXCR4/CXCL12 in response to airway injury.

    PubMed

    Gomperts, Brigitte N; Belperio, John A; Rao, P Nagesh; Randell, Scott H; Fishbein, Michael C; Burdick, Marie D; Strieter, Robert M

    2006-02-01

    Recipient airway epithelial cells are found in human sex-mismatched lung transplants, implying that circulating progenitor epithelial cells contribute to the repair of the airway epithelium. Markers of circulating progenitor epithelial cells and mechanisms for their trafficking remain to be elucidated. We demonstrate that a population of progenitor epithelial cells exists in the bone marrow and the circulation of mice that is positive for the early epithelial marker cytokeratin 5 (CK5) and the chemokine receptor CXCR4. We used a mouse model of sex-mismatched tracheal transplantation and found that CK5+ circulating progenitor epithelial cells contribute to re-epithelialization of the airway and re-establishment of the pseudostratified epithelium. The presence of CXCL12 in tracheal transplants provided a mechanism for CXCR4+ circulating progenitor epithelial cell recruitment to the airway. Depletion of CXCL12 resulted in the epithelium defaulting to squamous metaplasia, which was derived solely from the resident tissue progenitor epithelial cells. Our findings demonstrate that CK5+CXCR4+ cells are markers of circulating progenitor epithelial cells in the bone marrow and circulation and that CXCR4/CXCL12-mediated recruitment of circulating progenitor epithelial cells is necessary for the re-establishment of a normal pseudostratified epithelium after airway injury. These findings support a novel paradigm for the development of squamous metaplasia of the airway epithelium and for developing therapeutic strategies for circulating progenitor epithelial cells in airway diseases. PMID:16424223

  12. Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

    ClinicalTrials.gov

    2013-04-11

    Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Ovarian Epithelial Cancer; Stage III Borderline Ovarian Surface Epithelial-stromal Tumor; Stage III Ovarian Epithelial Cancer; Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor; Stage IV Ovarian Epithelial Cancer

  13. Paracrine CCL20 loop induces epithelial-mesenchymal transition in breast epithelial cells.

    PubMed

    Marsigliante, S; Vetrugno, C; Muscella, A

    2016-07-01

    We previously found that CCL20 induced primarily cultured healthy breast cell proliferation and migration. The objective of this study was to investigate the hypothesis that CCL20 modulated the epithelial-mesenchymal transition (EMT) of primarily cultured healthy breast epithelial cells and the angiogenesis in areas adjacent to the tumor. Key results showed that CCL20 (a) down-regulated E-cadherin and ZO-1; (b) up-regulated N-cadherin, vimentin, and Snail expressions; (c) increased mRNA and secretion of VEGF and (d) increased angiogenic micro vessel sprouting. Thus, the signal transduction pathways evoked by CCL20 were investigated. We showed that NF-kB p65 down-regulation (by small interfering RNA, siRNA) reversed CCL20-induced Snail and blocked the up-regulation of vimentin and N-cadherin mRNAs. Furthermore, PI3K/AKT inhibition (by LY294002) completely blocked CCL20-induced Snail and NF-kB activation. Inhibition of JNK1/2 (by SP60125) or PKC-α (by siRNA) or src (by PP1) blocked NF-kB activation and Snail expression suggesting that these kinases are all upstream of NF-kB/Snail. Inhibition of mTOR (by rapamycin) abolished the effects of CCL20 on N-cadherin and vimentin protein synthesis. Furthermore, siRNA of PKC-δ inhibited the phosphorylation of CCL20-induced mTOR and S6, increased vimentin and N-cadherin expressions and, finally, blocked the CCL20 induced-EMT. CCL20 increased mRNA and secretion of VEGF by healthy breast cells by using PKC-α, src, Akt, NF-kB, and Snail signalling. In summary, tumor cells signal to the surrounding healthy cells through CCL20 inducing the modulation of the expression of molecules involved in EMT and promoting angiogenesis directly and indirectly through the secretion of VEGF, a major contributor to angiogenesis. © 2015 Wiley Periodicals, Inc. PMID:26154142

  14. TTC7A mutations disrupt intestinal epithelial apicobasal polarity

    PubMed Central

    Bigorgne, Amélie E.; Farin, Henner F.; Lemoine, Roxane; Mahlaoui, Nizar; Lambert, Nathalie; Gil, Marine; Schulz, Ansgar; Philippet, Pierre; Schlesser, Patrick; Abrahamsen, Tore G.; Oymar, Knut; Davies, E. Graham; Ellingsen, Christian Lycke; Leteurtre, Emmanuelle; Moreau-Massart, Brigitte; Berrebi, Dominique; Bole-Feysot, Christine; Nischke, Patrick; Brousse, Nicole; Fischer, Alain; Clevers, Hans; de Saint Basile, Geneviève

    2013-01-01

    Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients. All patients displayed a profound, generalized lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients also had profound disruption of the epithelial barrier along the entire gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we identified 10 mutations in tetratricopeptide repeat domain–7A (TTC7A), all of which potentially abrogate TTC7A expression. Intestinal organoid cultures from patient biopsies displayed an inversion of apicobasal polarity of the epithelial cells that was normalized by pharmacological inhibition of Rho kinase. Our data indicate that TTC7A deficiency results in increased Rho kinase activity, which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development. PMID:24292712

  15. Characteristics and EGFP expression of porcine mammary gland epithelial cells.

    PubMed

    Zheng, Yue-Mao; He, Xiao-Ying

    2010-12-01

    The aims of this study were to establish a porcine mammary gland epithelial (PMGE) cell line, and to determine if these PMGE cells could be maintained long-term in culture by continuous subculturing following transfection with a reporter gene, enhanced green fluorescence protein (EGFP). Primary culture of PMGE cells was achieved by outgrowth of migrating cells from the fragments of the mammary gland tissue of a lactating pig. The passage sixteen PMGE cells were transfected with EGFP gene using lipofection. The expression of Cell keratins of epithelial cells in PMGE cells was tested by immunofluorescence. Βeta-Casein gene mRNA was tested for PMGE cells by RT-PCR. The results showed that PMGE cells could form dome-like structure which looked like nipple, and the cells contained different cell types. The expression of Cell keratins demonstrated the property of epithelial cells, and the PMGE cells could express transcript encoding a Βeta-Casein protein. EGFP gene was successfully transferred into the PMGE cells, and the transfected cells could be maintained long-term in culture by continuous subculturing. In conclusion, we have established a EGFP gene transfected porcine mammary gland epithelial (ET-PMGE) cell line. PMID:20400167

  16. Airway epithelial cell response to human metapneumovirus infection

    SciTech Connect

    Bao, X.; Liu, T.; Spetch, L.; Kolli, D.; Garofalo, R.P.; Casola, A.

    2007-11-10

    Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections (LRTIs) in infants, elderly and immunocompromised patients. In this study, we show that hMPV can infect in a similar manner epithelial cells representative of different tracts of the airways. hMPV-induced expression of chemokines IL-8 and RANTES in primary small alveolar epithelial cells (SAE) and in a human alveolar type II-like epithelial cell line (A549) was similar, suggesting that A549 cells can be used as a model to study lower airway epithelial cell responses to hMPV infection. A549 secreted a variety of CXC and CC chemokines, cytokines and type I interferons, following hMPV infection. hMPV was also a strong inducer of transcription factors belonging to nuclear factor (NF)-{kappa}B, interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) families, which are known to orchestrate the expression of inflammatory and immunomodulatory mediators.

  17. 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

  18. Temporal Monitoring of Differentiated Human Airway Epithelial Cells Using Microfluidics

    PubMed Central

    Blume, Cornelia; Reale, Riccardo; Held, Marie; Millar, Timothy M.; Collins, Jane E.; Davies, Donna E.; Morgan, Hywel; Swindle, Emily J.

    2015-01-01

    The airway epithelium is exposed to a variety of harmful agents during breathing and appropriate cellular responses are essential to maintain tissue homeostasis. Recent evidence has highlighted the contribution of epithelial barrier dysfunction in the development of many chronic respiratory diseases. Despite intense research efforts, the responses of the airway barrier to environmental agents are not fully understood, mainly due to lack of suitable in vitro models that recapitulate the complex in vivo situation accurately. Using an interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the airway epithelium, incorporating fully differentiated primary human airway epithelial cells at the air-liquid interface and a basolateral microfluidic supply of nutrients simulating the interstitial flow observed in vivo. Through combination of the microfluidic culture system with an automated fraction collector the kinetics of cellular responses by the airway epithelium to environmental agents can be analysed at the early phases for the first time and with much higher sensitivity compared to common static in vitro models. Following exposure of primary differentiated epithelial cells to pollen we show that CXCL8/IL–8 release is detectable within the first 2h and peaks at 4–6h under microfluidic conditions, a response which was not observed in conventional static culture conditions. Such a microfluidic culture model is likely to have utility for high resolution temporal profiling of toxicological and pharmacological responses of the airway epithelial barrier, as well as for studies of disease mechanisms. PMID:26436734

  19. Regulation and pathophysiological role of