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Sample records for human tracheal gland

  1. Lubiprostone stimulates secretion from tracheal submucosal glands of sheep, pigs, and humans.

    PubMed

    Joo, N S; Wine, J J; Cuthbert, A W

    2009-05-01

    Lubiprostone, a putative ClC-2 chloride channel opener, has been investigated for its effects on airway epithelia (tracheas). Lubiprostone is shown to increase submucosal gland secretion in pigs, sheep, and humans and to increase short-circuit current (SCC) in the surface epithelium of pigs and sheep. Use of appropriate blocking agents and ion-substitution experiments shows anion secretion is the driving force for fluid formation in both glands and surface epithelium. From SCC concentration-response relations, it is shown that for apical lubiprostone K(d) = 10.5 nM with a Hill slope of 1.08, suggesting a single type of binding site and, from the speed of the response, close to the apical surface, confirmed the rapid blockade by Cd ions. Responses to lubiprostone were reversible and repeatable, responses being significantly larger with ventral compared with dorsal epithelium. Submucosal gland secretion rates following basolateral lubiprostone were, respectively, 0.2, 0.5, and 0.8 nl gl(-1) min(-1) in humans, sheep, and pigs. These rates dwarf any contribution surface secretion adds to the accumulation of surface liquid under the influence of lubiprostone. Lubiprostone stimulated gland secretion in two out of four human cystic fibrosis (CF) tissues and in two of three disease controls, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (COPD/IPF), but in neither type of tissue was the increase significant. Lubiprostone was able to increase gland secretion rates in normal human tissue in the continuing presence of a high forskolin concentration. Lubiprostone had no spasmogenic activity on trachealis muscle, making it a potential agent for increasing airway secretion that may have therapeutic utility.

  2. Cultures of human tracheal gland cells of mucous or serous phenotype

    PubMed Central

    Finkbeiner, Walter E.; Zlock, Lorna T.; Mehdi, Irum

    2009-01-01

    There are two main epithelial cell types in the secretory tubules of mammalian glands: serous and mucous. The former is believed to secrete predominantly water and antimicrobials, the latter mucins. Primary cultures of human airway gland epithelium have been available for almost 20 yr, but they are poorly differentiated and lack clear features of either serous or mucous cells. In this study, by varying growth supports and media, we have produced cultures from human airway glands that in terms of their ultrastructure and secretory products resemble either mucous or serous cells. Of four types of porous-bottomed insert tested, polycarbonate filters (Transwells) most strongly promoted the mucous phenotype. Coupled with the addition of epidermal growth factor (EGF), this growth support produced “mucous” cells that contained the large electron-lucent granules characteristic of native mucous cells, but lacked the small electron-dense granules characteristic of serous cells. Furthermore, they showed high levels of mucin secretion and low levels of release of lactoferrin and lysozyme (markers of native serous cells). By contrast, growth on polyethylene terephthalate filters (Cyclopore) in medium lacking EGF produced “serous” cells in which small electron-dense granules replaced the electron-lucent ones, and the cells had high levels of lactoferrin and lysozyme but low levels of mucins. Measurements of transepithelial resistance and short-circuit current showed that both “serous” and “mucous” cell cultures possessed tight junctions, had become polarized, and were actively secreting Cl. PMID:19998060

  3. Neuropeptides degranulate serous cells of ferret tracheal glands

    SciTech Connect

    Gashi, A.A.; Borson, D.B.; Finkbeiner, W.E.; Nadel, J.A.; Basbaum, C.B.

    1986-08-01

    To determine whether serous or mucous cells in tracheal submucosal glands respond to the neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP). The authors studied the peptide-induced changes in gland cell morphology accompanying release of TVSO4-labeled macromolecules from tracheal explants of ferrets. Explants were labeled for 1 h in medium containing TVSO4 and washed for 3.5 additional hours. Base-line secretion in the absence of drugs declined between 1.5 and 3.5 h after the pulse. Between 2.5 and 3.5 h, the average percent change in counts per minute recovered per sample period was not significantly different from zero. Substance P and VIP added 4 h after labeling each increased greatly the release of TVSO4-labeled macromolecules above base line. Bethanechol, a muscarinic-cholinergic agonist, increased secretion by an average of 142% above base line. Light and electron microscopy of the control tissues showed glands with narrow lumens and numerous secretory granules. Glands treated with SP or VIP had enlarged lumens and the serous cells were markedly degranulated. These phenomena were documented by morphometry and suggest that SP and VIP cause secretion from glands at least partially by stimulating exocytosis from serous cells.

  4. Vasoactive intestinal peptide stimulates tracheal submucosal gland secretion in ferret

    SciTech Connect

    Peatfield, A.C.; Barnes, P.J.; Bratcher, C.; Nadel, J.A.; Davis, B.

    1983-07-01

    We studied the effect of vasoactive intestinal peptide (VIP) on the output of 35S-labeled macromolecules from ferret tracheal explants either placed in beakers or suspended in modified Ussing chambers. In Ussing chamber experiments, the radiolabel precursor, sodium (35S)sulfate, and all drugs were placed on the submucosal side of the tissue. Washings were collected at 30-min intervals from the luminal side and were dialyzed to remove unbound 35S, leaving radiolabeled macromolecules. Vasoactive intestinal peptide at 3 X 10(-7) M stimulated bound 35S output by a mean of + 252.6% (n . 14). The VIP response was dose-dependent with a near maximal response and a half maximal response at approximately 10(-6) M and 10(-8), M, respectively. The VIP effect was not inhibited by a mixture of tetrodotoxin, atropine, I-propranolol, and phentolamine. Vasoactive intestinal peptide had no effect on the electrical properties of the of the tissues. We conclude that VIP stimulates output of sulfated-macromolecules from ferret tracheal submucosal glands without stimulating ion transport. Our studies also suggest that VIP acts on submucosal glands via specific VIP receptors. Vasoactive intestinal peptide has been shown to increase intracellular levels of cyclic AMP, and we suggest that this may be the mechanism for its effect on the output of macromolecules. This mechanism may be important in the neural regulation of submucosal gland secretion.

  5. Postnatal development of tracheal surface epithelium and submucosal glands in the ferret.

    PubMed

    Leigh, M W; Gambling, T M; Carson, J L; Collier, A M; Wood, R E; Boat, T F

    1986-01-01

    We explored the usefulness of the postnatal ferret as a model for early developmental events in the large airways, using light and scanning electron microscopy. In the first 28 postnatal days, ferret tracheal surface epithelium and glands undergo dramatic growth and development. Tracheal surface area increases 8-fold. At birth, ciliated cells are sparse (9.4 +/- 1.2% of total epithelial cells). A significant increase in ciliated cells is observed at weekly intervals and by day 28 the ciliated cell is the predominant cell type (54.2 +/- 2.8% of total epithelial cells). Secretory cells decrease from 66.4 +/- 1.0% at birth to 22.2 +/- 2.8% of total epithelial cells. Histochemical staining of the granules of the epithelial secretory cells changes from predominantly non-acidic (staining with PAS but not Alcian blue) to predominantly acidic (staining also with Alcian blue). During the same time interval, tracheal glands develop from intraepithelial cellular aggregates devoid of secretory granules at birth into complex, submucosal tubuloacinar structures composed predominantly of cells containing non-acidic secretory granules at 28 days. Therefore, infant ferrets offer an opportunity to examine the structural and functional components of the mucociliary clearance mechanism at developmental stages which occur prenatally in many laboratory animals and in humans.

  6. Mucus secretion by single tracheal submucosal glands from normal and cystic fibrosis transmembrane conductance regulator knockout mice

    PubMed Central

    Ianowski, Juan P; Choi, Jae Young; Wine, Jeffrey J; Hanrahan, John W

    2007-01-01

    Submucosal glands line the cartilaginous airways and produce most of the antimicrobial mucus that keeps the airways sterile. The glands are defective in cystic fibrosis (CF), but how this impacts airway health remains uncertain. Although most CF mouse strains exhibit mild airway defects, those with the C57Bl/6 genetic background have increased airway pathology and susceptibility to Pseudomonas. Thus, they offer the possibility of studying whether, and if so how, abnormal submucosal gland function contributes to CF airway disease. We used optical methods to study fluid secretion by individual glands in tracheas from normal, wild-type (WT) mice and from cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice (Cftrm1UNC/Cftrm1UNC; CF mice). Glands from WT mice qualitatively resembled those in humans by responding to carbachol and vasoactive intestinal peptide (VIP), although the relative rates of VIP- and forskolin-stimulated secretion were much lower in mice than in large mammals. The pharmacology of mouse gland secretion was also similar to that in humans; adding bumetanide or replacement of HCO3− by Hepes reduced the carbachol response by ∼50%, and this inhibition increased to 80% when both manoeuvres were performed simultaneously. It is important to note that glands from CFTR knockout mice responded to carbachol but did not secrete when exposed to VIP or forskolin, as has been shown previously for glands from CF patients. Tracheal glands from WT and CF mice both had robust secretory responses to electrical field stimulation that were blocked by tetrodotoxin. It is interesting that local irritation of the mucosa using chili pepper oil elicited secretion from WT glands but did not stimulate glands from CF mice. These results clarify the mechanisms of murine submucosal gland secretion and reveal a novel defect in local regulation of glands lacking CFTR which may also compromise airway defence in CF patients. PMID:17204498

  7. Viscoelastic Properties of Human Tracheal Tissues.

    PubMed

    Safshekan, Farzaneh; Tafazzoli-Shadpour, Mohammad; Abdouss, Majid; Shadmehr, Mohammad B

    2017-01-01

    The physiological performance of trachea is highly dependent on its mechanical behavior, and therefore, the mechanical properties of its components. Mechanical characterization of trachea is key to succeed in new treatments such as tissue engineering, which requires the utilization of scaffolds which are mechanically compatible with the native human trachea. In this study, after isolating human trachea samples from brain-dead cases and proper storage, we assessed the viscoelastic properties of tracheal cartilage, smooth muscle, and connective tissue based on stress relaxation tests (at 5% and 10% strains for cartilage and 20%, 30%, and 40% for smooth muscle and connective tissue). After investigation of viscoelastic linearity, constitutive models including Prony series for linear viscoelasticity and quasi-linear viscoelastic, modified superposition, and Schapery models for nonlinear viscoelasticity were fitted to the experimental data to find the best model for each tissue. We also investigated the effect of age on the viscoelastic behavior of tracheal tissues. Based on the results, all three tissues exhibited a (nonsignificant) decrease in relaxation rate with increasing the strain, indicating viscoelastic nonlinearity which was most evident for cartilage and with the least effect for connective tissue. The three-term Prony model was selected for describing the linear viscoelasticity. Among different models, the modified superposition model was best able to capture the relaxation behavior of the three tracheal components. We observed a general (but not significant) stiffening of tracheal cartilage and connective tissue with aging. No change in the stress relaxation percentage with aging was observed. The results of this study may be useful in the design and fabrication of tracheal tissue engineering scaffolds.

  8. Characterization of muscarinic receptors on isolated swine tracheal submucosal gland cells

    SciTech Connect

    Yang, C.M.; Dwyer, T.M.; Farley, J.M.

    1986-03-05

    Muscarinic receptors play an important role in the regulation of tracheobronchial secretion. Tracheal epithelium was cut into small pieces (approx.10 mm/sup 2/) and dissociated using collagenase in HEPES-Ringer solution at 37/sup 0/C. After dissociation the glands cells were isolated by discontinuous Percoll density gradient centrifugation. Submucosal gland cells concentrated above the layers with densities of 1.084 and 1.057 g/ml after centrifugation at x 500 g for 10 min at 15/sup 0/C. Cell viability was > 95% as determined by exclusion of trypan blue. Over 98% of the isolated cells were identified by periodic acid Schiff staining method to be gland cells. Muscarinic receptors on intact gland cells were characterized using the binding of specific muscarinic antagonist (/sup 3/H)quinuclidinyl benzilate ((/sup 3/H)QNB) binding. Scatchard plot analysis of saturation isotherms, showed that the maximal receptor density (B/sub max/) and dissociation constant (K/sub D/) were 7400 +/- 200 sites/cell and 100 +/- 20 pM, respectively (n = 3). These two parameters were less than those from cat tracheal gland cells, B/sub max/ = 42,000 sites/cell and K/sub D/ = 200 pM. In conclusion, this study provided a useful method to isolate tracheal gland cells and characterized the presence of muscarinic receptors on isolated intact cells.

  9. Effects of ozone on the cholinergic secretory responsiveness of ferret tracheal glands

    SciTech Connect

    McBride, R.K.; Oberdoerster, G.; Marin, M.G. )

    1991-06-01

    Oxidant air pollutants exacerbate several pulmonary diseases. Inhalation of ozone has been shown to induce airway smooth muscle hyperresponsiveness. Oxidant injury could also affect airway secretory mechanisms. The authors postulated that oxidant exposure would alter the glycoconjugate secretory function of airway submucosal glands. To test this hypothesis they examined the effects of in vivo ozone exposure on the in vitro secretory responsiveness of ferret tracheal glands. Ferrets were exposed to 1 ppm ozone, 24 hr/day for 3 or 7 days. Following exposure, glandular explants, denuded of surface epithelial cells, were prepared and incubated in medium containing 3H-glucosamine for 18 hr. Basal secretion of labeled glycoconjugates was significantly increased 31% following 3 days of ozone exposure (P less than or equal to 0.05) and remained elevated 11% after 7 days of exposure compared to the air-exposed group. After 3 or 7 days of exposure to ozone, tracheal gland responsiveness to carbachol was increased as indicated by significantly lower EC50 values (log molar concentration) of -6.43 {plus minus} 0.04 (n = 6) and -6.50 {plus minus} 0.11 (n = 5), respectively; compared to -6.20 {plus minus} 0.08 (n = 6) for the air-exposed group. There was no difference in carbachol EC50 values for air and 7-day ozone-exposed animals treated with dexamethasone. Dexamethasone did not attenuate the ozone-induced increase in basal secretion. Tracheal gland responsiveness to {alpha}- or {beta}-adrenergic agonists was not changed by oxidant exposure. These experiments suggest that oxidant injury not only increases basal secretion of respiratory glycoconjugates but also increases tracheal gland sensitivity to a cholinergic agonist.

  10. Effect of tobacco smoke exposure on rat tracheal submucosal glands: an ultrastructural study.

    PubMed Central

    Lewis, D J; Jakins, P R

    1981-01-01

    The ultrastructural appearance of rat tracheal submucosal glands after exposure to tobacco smoke for up to two years is described. Within the mucous cells many of the rough endoplasmic reticulum cisternae were grossly dilated with an accumulation of amorphous, electron-lucent material. The Golgi zones were prominent, and the secretion granules often contained dense cores, and appeared to have coalesced. Histochemically, increased amounts of sulphated mucus were present in exposed rats. Serous, ciliated, and myoepithelial cells were unaffected by smoke exposure. Images PMID:7314036

  11. An Apical-Membrane Chloride Channel in Human Tracheal Epithelium

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.

    1986-06-01

    The mechanism of chloride transport by airway epithelia has been of substantial interest because airway and sweat gland-duct epithelia are chloride-impermeable in cystic fibrosis. The decreased chloride permeability prevents normal secretion by the airway epithelium, thereby interfering with mucociliary clearance and contributing to the morbidity and mortality of the disease. Because chloride secretion depends on and is regulated by chloride conductance in the apical cell membrane, the patch-clamp technique was used to directly examine single-channel currents in primary cultures of human tracheal epithelium. The cells contained an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches. The channel was also blocked by analogs of carboxylic acid that decrease apical chloride conductance in intact epithelia. When attached to the cell, the channel was activated by isoproterenol, although the channel was also observed to open spontaneously. However, in some cases, the channel was only observed after the patch was excised from the cell. These results suggest that this channel is responsible for the apical chloride conductance in airway epithelia.

  12. Human Lacrimal Gland Gene Expression

    PubMed Central

    Aakalu, Vinay Kumar; Parameswaran, Sowmya; Maienschein-Cline, Mark; Bahroos, Neil; Shah, Dhara; Ali, Marwan; Krishnakumar, Subramanian

    2017-01-01

    Background The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development. Methods We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix ® gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium. Results The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described. Conclusions Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas. PMID:28081151

  13. Endothelin-1 inhibits pre-stimulated tracheal submucosal gland secretion and epithelial albumin transport.

    PubMed Central

    Yurdakos, E.; Webber, S. E.

    1991-01-01

    1. Endothelin-1 potently contracts smooth muscle, including that in the airways. However, its effect on airway mucosal function has not so far been studied. 2. We have used the ferret whole trachea in vitro to examine the effect of endothelin-1 on tracheal smooth muscle tone, transepithelial potential difference (p.d.), submucosal gland secretion (including lysozyme secretion from serous cells) and active epithelial albumin transport. In addition we have examined the effects of endothelin on submucosal gland secretion and albumin transport pre-stimulated with the muscarinic agonist methacholine and the alpha-adrenoceptor agonist phenylephrine. The effects of the Ca2+ channel blocker nifedipine on the responses to endothelin have also been assessed. 3. Endothelin (0.1-100 nM) produced concentration-dependent increases in intraluminal tracheal pressure indicating smooth muscle contraction, and in the negativity of the transepithelial p.d. These effects were partially inhibited by nifedipine (10 microM). 4. Endothelin (0.01-100 nM) had no significant effect on baseline rates of mucus, lysozyme or albumin outputs, but produced concentration-dependent reductions in maintained methacholine- and phenylephrine-induced mucus, lysozyme and albumin outputs. In general endothelin was more potent against methacholine-induced effects. All of the concentration-response curves for endothelin were shallow and some appeared to be biphasic, suggesting the possibility of more than one mechanism of action of endothelin. 5. The effects of endothelin (at concentrations greater than 1 nM) on phenylephrine-induced mucus volume, lysozyme and albumin outputs were significantly inhibited by nifedipine. Similarly the effect of endothelin (greater than 1 nM) on methacholine-induced mucus volume and albumin outputs (but not lysozyme output) was attenuated by nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1810592

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

    PubMed

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

    2015-10-01

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

  15. Characterization of human pineal gland proteome.

    PubMed

    Yelamanchi, Soujanya D; Kumar, Manish; Madugundu, Anil K; Gopalakrishnan, Lathika; Dey, Gourav; Chavan, Sandip; Sathe, Gajanan; Mathur, Premendu P; Gowda, Harsha; Mahadevan, Anita; Shankar, Susarla K; Prasad, T S Keshava

    2016-11-15

    The pineal gland is a neuroendocrine gland located at the center of the brain. It is known to regulate various physiological functions in the body through secretion of the neurohormone melatonin. Comprehensive characterization of the human pineal gland proteome has not been undertaken to date. We employed a high-resolution mass spectrometry-based approach to characterize the proteome of the human pineal gland. A total of 5874 proteins were identified from the human pineal gland in this study. Of these, 5820 proteins were identified from the human pineal gland for the first time. Interestingly, 1136 proteins from the human pineal gland were found to contain a signal peptide domain, which indicates the secretory nature of these proteins. An unbiased global proteomic profile of this biomedically important organ should benefit molecular research to unravel the role of the pineal gland in neuropsychiatric and neurodegenerative diseases.

  16. Pirenzepine block of ACh-induced mucus secretion in tracheal submucosal gland cells

    SciTech Connect

    Farley, J.M.; Dwyer, T.M. )

    1991-01-01

    Muscarinic stimulation of mucus secretion, as measured by the release of ({sup 3}H)glycoprotein, was studied in explants from the tracheal epithelium of weanling swine. The mucus glycoprotein secretion was transient, ceasing within the first 10 min of a continuous exposure to 100 {mu}M ACh. Increasing the solutions' osmotic pressure did not alter basal mucus glycoprotein secretion. Mucus glycoprotein secretion was inhibited by 2-10 {mu}M PZP, indicting that the M{sub 3} muscarinic receptors mediate cholinergic stimulation of mucus production.

  17. Muscarinic receptors: evidence for a nonuniform distribution in tracheal smooth muscle and exocrine glands

    SciTech Connect

    Basbaum, C.B.; Grillo, M.A.; Widdicombe, J.H.

    1984-02-01

    Muscarinic receptor distribution in smooth muscle, exocrine glands, and epithelium of the ferret trachea was determined using (3H)propylbenzilylcholine mustard ((3H)PrBCM) binding and autoradiography. Specific, atropine-sensitive (3H)PrBCM binding was quantified autoradiographically in the trachealis muscle (approximately 21 binding sites/microns2), surface epithelium (approximately 6 binding sites/microns2), and submucosal glands (approximately 5 binding sites/microns2). Serous and mucous cells in the glands did not differ in receptor density. Binding sites on gland and epithelial cells were associated with basolateral membranes. In the trachealis muscle, a gradient in receptor density was observed, with outer layers of muscle containing 3 to 10 times more receptors per unit area than inner layers. Receptor distribution in both glands and muscle paralleled the distribution of cholinergic axons. However, at the light microscope level, there was no evidence for the presence of receptor ''hot spots'' related to the position of individual axons. The parallelism in the distribution of axons and receptors suggests the possibility of neural control of the genesis and/or maintenance of receptor distribution in these tissues.

  18. Humanization of the mouse mammary gland.

    PubMed

    Wronski, A; Arendt, L M; Kuperwasser, Charlotte

    2015-01-01

    Although mouse models have provided invaluable information on the mechanisms of mammary gland development, anatomical and developmental differences between human and mice limit full understanding of this fundamental process. Humanization of the mouse mammary gland by injecting immortalized human breast stromal cells into the cleared murine mammary fat pad enables the growth and development of human mammary epithelial cells or tissue. This facilitates the characterization of human mammary gland development or tumorigenesis by utilizing the mouse mammary fat pad. Here we describe the process of isolating human mammary stromal and epithelial cells as well as their introduction into the mammary fat pads of immunocompromised mice.

  19. Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells.

    PubMed

    Yasuda, H; Yamaya, M; Sasaki, T; Inoue, D; Nakayama, K; Yamada, M; Asada, M; Yoshida, M; Suzuki, T; Nishimura, H; Sasaki, H

    2006-07-01

    The aim of the study was to examine the effects of a mucolytic drug, carbocisteine, on rhinovirus (RV) infection in the airways. Human tracheal epithelial cells were infected with a major-group RV, RV14. RV14 infection increased virus titres and the cytokine content of supernatants. Carbocisteine reduced supernatant virus titres, the amount of RV14 RNA in cells, cell susceptibility to RV infection and supernatant cytokine concentrations, including interleukin (IL)-6 and IL-8, after RV14 infection. Carbocisteine reduced the expression of mRNA encoding intercellular adhesion molecule (ICAM)-1, the receptor for the major group of RVs. It also reduced the supernatant concentration of a soluble form of ICAM-1, the number and fluorescence intensity of acidic endosomes in the cells before RV infection, and nuclear factor-kappaB activation by RV14. Carbocisteine also reduced the supernatant virus titres of the minor group RV, RV2, although carbocisteine did not reduce the expression of mRNA encoding a low density lipoprotein receptor, the receptor for RV2. These results suggest that carbocisteine inhibits rhinovirus 2 infection by blocking rhinovirus RNA entry into the endosomes, and inhibits rhinovirus 14 infection by the same mechanism as well as by reducing intercellular adhesion molecule-1 levels. Carbocisteine may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.

  20. Goblet Cell Glycoprotein and Tracheal Gland Hypertrophy in Rat Airways: The Effect of Tobacco Smoke with or without the Anti-Inflammatory Agent Phenylmethyloxadiazole

    PubMed Central

    Jones, R.; Bolduc, P.; Reid, L.

    1973-01-01

    A quantitative analysis has been made of tracheal gland size and of histochemical changes occurring in goblet cells of the respiratory epithelium, in rats exposed either to tobacco smoke alone or to tobacco smoke with phenylmethyloxadiazole (PMO). Exposure to tobacco smoke alone causes an increase in goblet cell number with a shift from the production of neutral to acid glycoprotein, mainly sialidase resistant sialomucin but some sialidase sensitive sialomucin and sulphomucin. Acid glycoprotein, and each of its types, appears first at the cell apex. The addition of PMO to the tobacco protects against the increase in goblet cell number but gives no protection against the shift from neutral to acid glycoprotein and causes a larger secretory mass within the goblet cell. In the tracheal gland exposure to smoke from either tobacco alone or tobacco with PMO causes a significant increase in cell size and acinar diameter and a lesser increase in lumen diameter. There is also an increase in the thickness of the gland and its depth. Each of these gland changes is more pronounced in those animals receiving PMO with the tobacco. PMID:4121724

  1. Morphogenesis of the human lacrimal gland

    PubMed Central

    de la Cuadra-Blanco, C; Peces-Peña, M D; Mérida-Velasco, J R

    2003-01-01

    The aim of this study was to determine the main stages of the lacrimal gland's developmental process in humans and to establish its precise morphogenetic timetable. Its onset is generally assumed to take place at O'Rahilly's stage 21, arising from an epithelial thickening of the superior extreme of the temporary conjunctival fornix. However, the present study points to a prior stage in the process: the presence of epithelial–mesenchymal changes in embryos at O'Rahilly's stage 19. The study was performed using light microscopy on serial sections of 37 human specimens: 23 embryos and 14 fetuses ranging from 15 to 137 mm crown–rump length (7–116 weeks of development). Three stages in lacrimal gland morphogenesis were identified: (1) the presumptive glandular stage, O'Rahilly's stages 19–20, characterized by a thickening of the superior fornix epithelium together with surrounding mesenchymal condensation; (2) the bud stage, generally assumed to be the first manifestation of glandular origin, characterized initially by the appearance of nodular formations in the region of the superior conjunctival fornix and concluding with the appearance of lumina within the epithelial buds; and (3) the glandular maturity stage, weeks 9–16, the period in which the gland begins to take on the morphology of adulthood. PMID:14635806

  2. Proteomic analysis of human meibomian gland secretions

    PubMed Central

    Tsai, P S; Evans, J E; Green, K M; Sullivan, R M; Schaumberg, D A; Richards, S M; Dana, M R; Sullivan, D A

    2006-01-01

    Background/aim Human tears contain hundreds of proteins that may exert a significant influence on tear film stability, ocular surface integrity, and visual function. The authors hypothesise that many of these proteins originate from the meibomian gland. This study's aim was to begin to develop the proteomic methodology to permit the testing of their hypothesis. Methods Meibomian gland secretions were collected from the lower eyelids of adult volunteers and placed in a chloroform‐methanol mixture. Samples were partitioned in a biphasic system and non‐lipid phase materials were reduced, alkylated, and trypsin digested to obtain peptides for protein identification. This peptide mixture was separated by µ‐capillary reverse phase chromatography and the effluent examined by nano‐electrospray MS and data dependent MS/MS. SEQUEST software was used to identify proteins from the MS/MS spectra. Results The methodological approach to date has permitted the identification of more than 90 proteins in human meibomian gland secretions. Proteins include the α2‐macroglobulin receptor, IgA α chain, farnesoid X activated receptor, interferon regulatory factor 3, lacritin precursor, lactotransferrin, lipocalin 1, lysozyme C precursor, potential phospholipid transporting ATPase IK, seven transmembrane helix receptor (also termed somatostatin receptor type 4), testes development related NYD‐SP21 (also termed high affinity IgE receptor β subunit), and TrkC tyrosine kinase. Conclusions These findings indicate that the meibomian gland secretes a number of proteins into the tear film. It is quite possible that these proteins contribute to the dynamics of the tear film in both health and disease. PMID:16488965

  3. The human meibomian gland epithelial cell line as a model to study meibomian gland dysfunction.

    PubMed

    Hampel, Ulrike; Garreis, Fabian

    2017-10-01

    The meibomian gland dysfunction (MGD) is the leading cause of dry eye disease (DED) throughout the world. The investigation of MGD lacks suitable in vivo and in vitro models. In 2010 a human meibomian gland epithelial cell line (HMGEC) was established, so far the only available meibomian gland cell line. The characterization of HMGEC is of major importance to clarify its suitability for studying the meibomian gland (patho)physiology in vitro. The current culture protocol and new concepts of HMGEC culture will be compared. Hormones are believed to be a key factor in meibomian gland dysfunction thus HMGEC responsiveness to hormone stimulation is crucial to elucidate the hormonal influence on the meibomian gland. This review will summarize current findings about HMGEC and discuss its role in the meibomian gland dysfunction research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Proteomic Analysis of Pure Human Airway Gland Mucus Reveals a Large Component of Protective Proteins

    PubMed Central

    Joo, Nam Soo; Evans, Idil Apak T.; Cho, Hyung-Ju; Park, Il-Ho; Engelhardt, John F.; Wine, Jeffrey J.

    2015-01-01

    Airway submucosal glands contribute to innate immunity and protect the lungs by secreting mucus, which is required for mucociliary clearance and which also contains antimicrobial, anti-inflammatory, anti-proteolytic and anti-oxidant proteins. We stimulated glands in tracheal trimmings from three lung donors and collected droplets of uncontaminated mucus as they formed at the gland orifices under an oil layer. We analyzed the mucus using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analysis identified 5486 peptides and 441 proteins from across the 3 samples (269–319 proteins per subject). We focused on 269 proteins common to at least 2 0f 3 subjects, of which 102 (38%) had protective or innate immunity functions. While many of these have long been known to play such roles, for many others their cellular protective functions have only recently been appreciated in addition to their well-studied biologic functions (e.g. annexins, apolipoproteins, gelsolin, hemoglobin, histones, keratins, and lumican). A minority of the identified proteins are known to be secreted via conventional exocytosis, suggesting that glandular secretion occurs via multiple mechanisms. Two of the observed protective proteins, major vault protein and prohibitin, have not been observed in fluid from human epithelial cultures or in fluid from nasal or bronchoalveolar lavage. Further proteomic analysis of pure gland mucus may help clarify how healthy airways maintain a sterile environment. PMID:25706550

  5. Anatomy and Histology of Rodent and Human Major Salivary Glands

    PubMed Central

    Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

    2012-01-01

    Major salivary glands of both humans and rodents consist of three pairs of macroscopic glands: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638–1686), Thomas Wharton (1614–1673), and Caspar Bartholin (1655–1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands. The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands. PMID:23209333

  6. [Development of the human adrenal glands].

    PubMed

    Folligan, K; Bouvier, R; Targe, F; Morel, Y; Trouillas, J

    2005-09-01

    The human adrenal is an endocrine gland located at the superior part of the kidney. Composed of the adrenal cortex of mesoblastic origin and the adrenal medulla of neuroectoblastic origin, the human fetal adrenal grows considerably during the first three months of development. From 12 to 18 weeks of development (WD), the weight of the adrenals increases seven-fold. The gland's weight doubles from 18 to 28 WD and from 28 to 36 WD. At birth, the two adrenals weigh on average 10 g. At the 8th week, two zones are individualized in the adrenal cortex: the definitive zone and the fetal inner zone. At the second trimester, according to ultrastructural and biochemical studies, a third zone, called the transition zone, is individualized between the definitive zone and the fetal inner zone. The definitive zone persists, but the origin of the three zones (glomerular, fascicular and reticular) of adult adrenal cortex is not known. The fetal inner zone regresses from the 5th month of gestation and disappears totally one year after birth. At the 8th week, the immature neuroblasts migrate to the definitive zone, then to the fetal inner zone to compose the adrenal medulla, which develops essentially after birth and during the first year. Before the 10th week, the human fetal adrenal is able to produce steroid hormones, in particular dehydroepiandrosterone sulfate (DHEA-S); the secretion of cortisol remains discussed. The development of the human fetal adrenal is complex and is under the control of hormones (ACTH, LH and betaHCG), growth factors (ACTH essentially) and transcription factors (essentially SF1 and DAX-1). Knowledge of morphological and molecular phenomena of this development permits to understand the pathophisiology of congenital adrenal deficiencies.

  7. First robotic tracheal intubations in humans using the Kepler intubation system.

    PubMed

    Hemmerling, T M; Taddei, R; Wehbe, M; Zaouter, C; Cyr, S; Morse, J

    2012-06-01

    Intubation is one of the most important anaesthetic skills. We developed a robotic intubation system (Kepler intubation system, KIS) for oral tracheal intubation. In this pilot study, 12 patients were enrolled after approval of the local Ethics board and written informed consent. The KIS consists of four main components: a ThrustMaster T.Flight Hotas X joystick (Guillemot Inc., New York, NY, USA), a JACO robotic arm (Kinova Rehab, Montreal, QC, Canada), a Pentax AWS video laryngoscope (Ambu A/S, Ballerup, Denmark), and a software control system. The joystick allows simulation of the wrist or arm movements of a human operator. The success rate of intubation and intubation times were measured. Eleven men and one woman aged 66 yr were included in this study. Intubation was successful in all but one patient using KIS at a total time of [median (inter-quartile range; range)] 93 (87, 109; 76, 153) s; in one patient, fogging of the video laryngoscope prevented intubation using KIS. We present the first human testing of a robotic intubation system for oral tracheal intubation. The success rate was high at 91%. Future studies are needed to assess the performance and safety of such a system.

  8. Measurement of human surfactant protein-B turnover in vivo from tracheal aspirates using targeted proteomics.

    PubMed

    Tomazela, Daniela M; Patterson, Bruce W; Hanson, Elizabeth; Spence, Kimberly L; Kanion, Tiffany B; Salinger, David H; Vicini, Paolo; Barret, Hugh; Heins, Hillary B; Cole, F Sessions; Hamvas, Aaron; MacCoss, Michael J

    2010-03-15

    We describe a method to measure protein synthesis and catabolism in humans without prior purification and use the method to measure the turnover of surfactant protein-B (SP-B). SP-B, a lung-specific, hydrophobic protein essential for fetal-neonatal respiratory transition, is present in only picomolar quantities in tracheal aspirate samples and difficult to isolate for dynamic turnover studies using traditional in vivo tracer techniques. Using infusion of [5,5,5-(2)H(3)] leucine and a targeted proteomics method, we measured both the quantity and kinetics of SP-B tryptic peptides in tracheal aspirate samples of symptomatic newborn infants. The fractional synthetic rate (FSR) of SP-B measured using the most abundant proteolytic fragment, a 10 amino acid peptide from the carboxy-terminus of proSP-B (SPTGEWLPR), from the circulating leucine pool was 0.035 +/- 0.005 h(-1), and the fractional catabolic rate was 0.044 +/- 0.003 h(-1). This technique permits high-throughput and sensitive measurement of turnover of low abundance proteins with minimal sample preparation.

  9. Measurement of human surfactant protein-B turnover in vivo from tracheal aspirates using targeted proteomics

    PubMed Central

    Tomazela, Daniela; Patterson, Bruce W.; Hanson, Elizabeth; Spence, Kimberly L.; Kanion, Tiffany B.; Salinger, David H.; Vicini, Paolo; Barret, Hugh; Heins, Hillary B.; Cole, F. Sessions; Hamvas, Aaron; MacCoss, Michael J.

    2010-01-01

    We describe a method to measure protein synthesis and catabolism in humans without prior purification and use the method to measure the turnover of surfactant protein-B (SP-B). SP-B, a lung-specific, hydrophobic protein essential for fetal-neonatal respiratory transition, is present in only picomolar quantities in tracheal aspirate samples and difficult to isolate for dynamic turnover studies using traditional in vivo tracer techniques. Using infusion of [5,5,5-2H3] leucine and a targeted proteomics method, we measured both the quantity and kinetics of SP-B tryptic peptides in tracheal aspirate samples of symptomatic newborn infants. The fractional synthetic rate (FSR) of SP-B measured using the most abundant proteolytic fragment, a 10 amino acid peptide from the carboxy-terminus of proSP-B (SPTGEWLPR), from the circulating leucine pool was 0.035±0.005 hr−1 and fractional catabolic rate was 0.044±0.003 hr−1. This technique permits high-throughput, sensitive measurement of turnover of low abundance proteins with minimal sample preparation. PMID:20178338

  10. Dynamic OCT of sweat glands of human finger tip

    NASA Astrophysics Data System (ADS)

    Haruna, Masamitsu; Ueda, Yoshihiro; Ohmi, Masato; Fuji, Toshie

    2006-02-01

    Dynamic optical coherence tomography (OCT) is demonstrated for dynamic study of sweat glands of human finger tip using the all-optical-fiber imaging system. Stress-induced and physical activation of sweat glands can be observed clearly in time-sequential OCT images. The method for image data acquisition is presented as well as the experimental results.

  11. Human eccrine sweat gland cells can reconstitute a stratified epidermis.

    PubMed

    Biedermann, Thomas; Pontiggia, Luca; Böttcher-Haberzeth, Sophie; Tharakan, Sasha; Braziulis, Erik; Schiestl, Clemens; Meuli, Martin; Reichmann, Ernst

    2010-08-01

    Eccrine sweat glands are generally considered to be a possible epidermal stem cell source. Here we compared the multilayered epithelia formed by epidermal keratinocytes and those formed by eccrine sweat gland cells. We demonstrated both in vitro and in vivo the capability of human eccrine sweat gland cells to form a stratified interfollicular epidermis substitute on collagen hydrogels. This is substantiated by the following findings: (1) a stratified epidermis consisting of 10-12 cell layers is formed by sweat gland cells; (2) a distinct stratum corneum develops and is maintained after transplantation onto immuno-incompetent rats; (3) proteins such as filaggrin, loricrin, involucrin, envoplakin, periplakin, and transglutaminases I and III match with the pattern of the normal human skin; (4) junctional complexes and hemidesmosomes are readily and regularly established; (5) cell proliferation in the basal layer reaches homeostatic levels; (6) the sweat gland-derived epidermis is anchored by hemidesmosomes within a well-developed basal lamina; and (7) palmo-plantar or mucosal markers are not expressed in the sweat gland-derived epidermis. These data suggest that human eccrine sweat glands are an additional source of keratinocytes that can generate a stratified epidermis. Our findings raise the question of the extent to which the human skin is repaired and/or permanently renewed by eccrine sweat gland cells.

  12. 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

  13. Gene Expression in Human Accessory Lacrimal Glands of Wolfring

    PubMed Central

    Ubels, John L.; Gipson, Ilene K.; Spurr-Michaud, Sandra J.; Tisdale, Ann S.; Van Dyken, Rachel E.; Hatton, Mark P.

    2012-01-01

    Purpose. The accessory lacrimal glands are assumed to contribute to the production of tear fluid, but little is known about their function. The goal of this study was to conduct an analysis of gene expression by glands of Wolfring that would provide a more complete picture of the function of these glands. Methods. Glands of Wolfring were isolated from frozen sections of human eyelids by laser microdissection. RNA was extracted from the cells and hybridized to gene expression arrays. The expression of several of the major genes was confirmed by immunohistochemistry. Results. Of the 24 most highly expressed genes, 9 were of direct relevance to lacrimal function. These included lysozyme, lactoferrin, tear lipocalin, and lacritin. The glands of Wolfring are enriched in genes related to protein synthesis, targeting, and secretion, and a large number of genes for proteins with antimicrobial activity were detected. Ion channels and transporters, carbonic anhydrase, and aquaporins were abundantly expressed. Genes for control of lacrimal function, including cholinergic, adrenergic, vasoactive intestinal polypeptide, purinergic, androgen, and prolactin receptors were also expressed in gland of Wolfring. Conclusions. The data suggest that the function of glands of Wolfring is similar to that of main lacrimal glands and are consistent with secretion electrolytes, fluid, and protein under nervous and hormonal control. Since these glands secrete directly onto the ocular surface, their location may allow rapid response to exogenous stimuli and makes them readily accessible to topical drugs. PMID:22956620

  14. Distribution of Tight Junction Proteins in Adult Human Salivary Glands

    PubMed Central

    Maria, Ola M.; Kim, Jung-Wan Martin; Gerstenhaber, Jonathan A.; Baum, Bruce J.; Tran, Simon D.

    2008-01-01

    Tight junctions (TJs) are an essential structure of fluid-secreting cells, such as those in salivary glands. Three major families of integral membrane proteins have been identified as components of the TJ: claudins, occludin, and junctional adhesion molecules (JAMs), plus the cytosolic protein zonula occludens (ZO). We have been working to develop an orally implantable artificial salivary gland that would be suitable for treating patients lacking salivary parenchymal tissue. To date, little is known about the distribution of TJ proteins in adult human salivary cells and thus what key molecular components might be desirable for the cellular component of an artificial salivary gland device. Therefore, the aim of this study was to determine the distribution of TJ proteins in human salivary glands. Salivary gland samples were obtained from 10 patients. Frozen and formalin-fixed paraffin-embedded sections were stained using IHC methods. Claudin-1 was expressed in ductal, endothelial, and ∼25% of serous cells. Claudins-2, -3, and -4 and JAM-A were expressed in both ductal and acinar cells, whereas claudin-5 was expressed only in endothelial cells. Occludin and ZO-1 were expressed in acinar, ductal, and endothelial cells. These results provide new information on TJ proteins in two major human salivary glands and should serve as a reference for future studies to assess the presence of appropriate TJ proteins in a tissue-engineered human salivary gland. (J Histochem Cytochem 56:1093–1098, 2008) PMID:18765838

  15. Orthotopic tracheal transplantation using human bronchus: an original xenotransplant model of obliterative airway disorder.

    PubMed

    Guihaire, Julien; Itagaki, Ryo; Stubbendorff, Mandy; Hua, Xiaoqin; Deuse, Tobias; Ullrich, Sebastian; Fadel, Elie; Dorfmüller, Peter; Robbins, Robert C; Reichenspurner, Hermann; Schumacher, Udo; Schrepfer, Sonja

    2016-12-01

    Bronchiolitis obliterans syndrome (BOS) is a main cause of allograft dysfunction and mortality after lung transplantation (LTx). A better understanding of BOS pathogenesis is needed to overcome this treatment-refractory complication. Orthotopic tracheal transplantation using human bronchus was performed in Brown Norway (BN) and nude (RNU) rats. Allografts were recovered in both strains at Day 7 (BN7 , n = 6; RNU7 , n = 7) or Day 28 (BN28 , n = 6; RNU28 , n = 6). Immune response of the host against the bronchial graft was assessed. Human samples from BOS patients were used to compare with the histological features of the animal model. Obstruction of the allograft lumen associated with significant infiltration of CD3+ and CD68+ cells was observed in the BN group on Day 28. Immune response from type 1 T-helper cells against the tracheal xenograft was higher in BN animals compared to nude animals on Days 7 and 28 (P < 0.001 and P = 0.035). Xenoreactive antibodies were significantly higher at Day 7 (IgM) and Day 28 (IgG) in the BN group compared to RNU (respectively, 37.6 ± 6.5 vs. 5.8 ± 0.7 mean fluorescence, P = 0.039; and 22.4 ± 3.8 vs. 6.9 ± 1.6 mean fluorescence, P = 0.011). Immunocompetent animals showed a higher infiltration of S100A4+ cells inside the bronchial wall after 28 days, associated with cartilage damage ranging from invasion to complete destruction. In vitro expression of S100A4 by human fibroblasts was higher when stimulated by mononuclear cells (MNCs) from BN rats than from RNU (2.9 ± 0.1 vs. 2.4 ± 0.1 mean fluorescence intensity, P = 0.005). Similarly, S100A4 was highly expressed in response to human MNCs compared to stimulation by T-cell-depleted human MNCs (4.3 ± 0.2 vs. 2.7 ± 0.1 mean fluorescence intensity, P < 0.001). Obliterative bronchiolitis has been induced in a new xenotransplant model in which chronic airway obstruction was associated with immune activation against the xenograft. Cartilage infiltration by S100A4+ cells might be

  16. Frequency of varicella zoster virus DNA in human adrenal glands.

    PubMed

    Badani, Hussain; White, Teresa; Schulick, Nicole; Raeburn, Christopher D; Topkaya, Ibrahim; Gilden, Don; Nagel, Maria A

    2016-06-01

    Varicella zoster virus (VZV) becomes latent in ganglionic neurons derived from neural crest cells. Because the adrenal gland also contains medullary chromaffin cells of neural crest origin, we examined human adrenal glands and medullary chromaffin cell tumors (pheochromocytomas) for VZV and herpes simplex virus type 1 (HSV-1). We found VZV, but not HSV-1, DNA in 4/63 (6 %) normal adrenal glands. No VZV transcripts or antigens were detected in the 4 VZV DNA-positive samples. No VZV or HSV-1 DNA was found in 21 pheochromocytomas.

  17. Neurotransmitter Influence on Human Meibomian Gland Epithelial Cells

    PubMed Central

    Kam, Wendy R.

    2011-01-01

    Purpose. A striking characteristic of the human meibomian gland is its rich sensory, sympathetic, and parasympathetic innervation, yet the functional relevance of these nerve fibers remains unknown. Acting on the hypothesis that neurotransmitters are released in the vicinity of the gland, act on glandular receptors, and influence the production, secretion, and/or delivery of meibomian gland secretions to the ocular surface, the goal in this study was to begin to determine whether neurotransmitters influence the meibomian gland. Methods. Immortalized human meibomian gland epithelial (SLHMG) cells were examined for the presence of vasoactive intestinal peptide (VIP) and muscarinic acetylcholine (mACh) receptor transcripts and proteins. Cells were also exposed to VIP, carbachol, forskolin, and/or 3-isobutyl-1-methylxanthine (IBMX) to determine whether these agents, alone or in combination, modulate the adenylyl cyclase pathway, the accumulation of intracellular free calcium ([Ca2+]i), or cell proliferation. Results. Results demonstrate that SLHMG cells transcribe and translate VIP and mACh receptors; VIP, with either IBMX or forskolin, activates the adenylyl cyclase pathway, and the effect of VIP and forskolin together is synergistic; both VIP and carbachol increase intracellular [Ca2+] in SLHMG cells; and VIP with forskolin stimulates SLHMG cell proliferation. Conclusions. This study shows that parasympathetic neurotransmitters and their agonists influence the function of human meibomian gland epithelial cells. It remains to be determined whether this action alters the production, secretion, and/or delivery of meibum to the ocular surface. PMID:21969302

  18. Characterization of human tracheal epithelial cells transformed by an origin-defective simian virus 40.

    PubMed Central

    Gruenert, D C; Basbaum, C B; Welsh, M J; Li, M; Finkbeiner, W E; Nadel, J A

    1988-01-01

    To facilitate understanding of the mechanisms underlying pulmonary diseases, including lung cancer and cystic fibrosis, we have transformed and characterized cultures of human tracheal epithelial cells. Cells were transfected by calcium phosphate precipitation with a plasmid containing a replication-defective simian virus 40 (SV40) genome. Colonies of cells with enhanced growth potential were isolated and analyzed for transformation- and epithelial-specific characteristics. Precrisis cells were observed to express the SV40 large tumor antigen, produce cytokeratins, have microvilli, and form tight junctions. After crisis, cells continued to express the SV40 large tumor antigen as well as epithelial-specific cytokeratins and to display the apical membrane microvilli. Apical membrane Cl channels were opened in postcrisis cells exposed to 50 microM forskolin. These channels showed electrical properties similar to those observed in primary cultures. The postcrisis cells have been in culture for greater than 250 generations and are potentially "immortal." In addition to providing a useful in vitro model for the study of ion transport by human airway epithelial cells, the cells can be used to examine stages of neoplastic progression. Images PMID:2457904

  19. Anatomy and histology of rodent and human major salivary glands: -overview of the Japan salivary gland society-sponsored workshop-.

    PubMed

    Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

    2012-10-31

    MAJOR SALIVARY GLANDS OF BOTH HUMANS AND RODENTS CONSIST OF THREE PAIRS OF MACROSCOPIC GLANDS: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638-1686), Thomas Wharton (1614-1673), and Caspar Bartholin (1655-1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands.The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands.

  20. Increased TGF-β: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

    PubMed

    Vuckovic, Aline; Herber-Jonat, Susanne; Flemmer, Andreas W; Ruehl, Ina M; Votino, Carmela; Segers, Valérie; Benachi, Alexandra; Martinovic, Jelena; Nowakowska, Dorota; Dzieniecka, Monika; Jani, Jacques C

    2016-02-15

    Survivors of severe congenital diaphragmatic hernia (CDH) present significant respiratory morbidity despite lung growth induced by fetal tracheal occlusion (TO). We hypothesized that the underlying mechanisms would involve changes in lung extracellular matrix and dysregulated transforming growth factor (TGF)-β pathway, a key player in lung development and repair. Pulmonary expression of TGF-β signaling components, downstream effectors, and extracellular matrix targets were evaluated in CDH neonates who died between birth and the first few weeks of life after prenatal conservative management or TO, and in rabbit pups that were prenatally randomized for surgical CDH and TO vs. sham operation. Before tissue harvesting, lung tissue mechanics in rabbits was measured using the constant-phase model during the first 30 min of life. Human CDH and control fetal lungs were also collected from midterm onwards. Human and experimental CDH did not affect TGF-β/Smad2/3 expression and activity. In human and rabbit CDH lungs, TO upregulated TGF-β transcripts. Analysis of downstream pathways indicated increased Rho-associated kinases to the detriment of Smad2/3 activation. After TO, subtle accumulation of collagen and α-smooth muscle actin within alveolar walls was detected in rabbit pups and human CDH lungs with short-term mechanical ventilation. Despite TO-induced lung growth, mediocre lung tissue mechanics in the rabbit model was associated with increased transcription of extracellular matrix components. These results suggest that prenatal TO increases TGF-β/Rho kinase pathway, myofibroblast differentiation, and matrix deposition in neonatal rabbit and human CDH lungs. Whether this might influence postnatal development of sustainably ventilated lungs remains to be determined. Copyright © 2016 the American Physiological Society.

  1. Culture, Immortalization, and Characterization of Human Meibomian Gland Epithelial Cells

    PubMed Central

    Liu, Shaohui; Hatton, Mark P.; Khandelwal, Payal

    2010-01-01

    Purpose. Meibomian gland epithelial cells are essential in maintaining the health and integrity of the ocular surface. However, very little is known about their physiological regulation. In this study, the cellular control mechanisms were explored, first to establish a defined culture system for the maintenance of primary epithelial cells from human meibomian glands and, second, to immortalize these cells, thereby developing a preclinical model that could be used to identify factors that regulate cell activity. Methods. Human meibomian glands were removed from lid segments after surgery, enzymatically digested, and dissociated. Isolated epithelial cells were cultured in media with or without serum and/or 3T3 feeder layers. To attempt immortalization, the cells were exposed to retroviral human telomerase reverse transcriptase (hTERT) and/or SV40 large T antigen cDNA vectors, and antibiotic-resistant cells were selected, expanded, and subcultured. Analyses for possible biomarkers, cell proliferation and differentiation, lipid-related enzyme gene expression, and the cellular response to androgen were performed with biochemical, histologic, and molecular biological techniques. Results. It was possible to isolate viable human meibomian gland epithelial cells and to culture them in serum-free medium. These cells proliferated, survived through at least the fifth passage, and contained neutral lipids. Infection with hTERT immortalized these cells, which accumulated neutral lipids during differentiation, expressed multiple genes for lipogenic enzymes, responded to androgen, and continued to proliferate. Conclusions. The results show that human meibomian gland epithelial cells may be isolated, cultured, and immortalized. PMID:20335607

  2. l-carbocisteine inhibits respiratory syncytial virus infection in human tracheal epithelial cells.

    PubMed

    Asada, Masanori; Yoshida, Motoki; Hatachi, Yukimasa; Sasaki, Takahiko; Yasuda, Hiroyasu; Deng, Xue; Nishimura, Hidekazu; Kubo, Hiroshi; Nagatomi, Ryoichi; Yamaya, Mutsuo

    2012-01-15

    To examine the effects of l-carbocisteine on airway infection with respiratory syncytial (RS) virus, human tracheal epithelial cells were pretreated with l-carbocisteine and infected with RS virus. Viral titer, virus RNA, and pro-inflammatory cytokine secretion, including interleukin (IL)-1 and IL-6, increased with time after infection. l-carbocisteine reduced the viral titer in the supernatant fluids, the amount of RS virus RNA, RS virus infection susceptibility, and the concentration of pro-inflammatory cytokines induced by virus infection. l-carbocisteine reduced the expression of intercellular adhesion molecule (ICAM)-1, an RS virus receptor, on the cells. However, l-carbocisteine had no effects on the expression of heparan sulfate, a glycosaminoglycan that binds to the RS virus attachment protein, or on the amount of intracellular activated-RhoA, isoform A of the Ras-homologous family, that binds to the RS virus fusion protein. These findings suggest that l-carbocisteine may inhibit RS virus infection by reducing the expression of ICAM-1. It may also modulate airway inflammation during RS virus infection.

  3. Ambroxol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells.

    PubMed

    Yamaya, Mutsuo; Nishimura, Hidekazu; Nadine, Lusamba Kalonji; Ota, Chiharu; Kubo, Hiroshi; Nagatomi, Ryoichi

    2014-04-01

    The mucolytic drug ambroxol hydrochloride reduces the production of pro-inflammatory cytokines and the frequency of exacerbation in patients with chronic obstructive pulmonary disease (COPD). However, the inhibitory effects of ambroxol on rhinovirus infection, the major cause of COPD exacerbations, have not been studied. We examined the effects of ambroxol on type 14 rhinovirus (RV14) infection, a major RV group, in primary cultures of human tracheal epithelial cells. RV14 infection increased virus titers and cytokine content in the supernatants and RV14 RNA in the cells. Ambroxol (100 nM) reduced RV14 titers and cytokine concentrations of interleukin (IL)-1β, IL-6 and IL-8 in the supernatants and RV14 RNA in the cells after RV14 infection, in addition to reducing susceptibility to RV14 infection. Ambroxol also reduced the expression of intercellular adhesion molecule-1 (ICAM-1), the receptor for RV14, and the number of acidic endosomes from which RV14 RNA enters the cytoplasm. In addition, ambroxol reduced the activation of the transcription factor nuclear factor kappa B (NF-κB) in the nucleus. These results suggest that ambroxol inhibits RV14 infection partly by reducing ICAM-1 and acidic endosomes via the inhibition of NF-κB activation. Ambroxol may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.

  4. 21 CFR 868.5730 - Tracheal tube.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tracheal tube. 868.5730 Section 868.5730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5730 Tracheal tube. (a) Identification. A tracheal tube is...

  5. 21 CFR 868.5730 - Tracheal tube.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tracheal tube. 868.5730 Section 868.5730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5730 Tracheal tube. (a) Identification. A tracheal tube is...

  6. 21 CFR 868.5730 - Tracheal tube.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tracheal tube. 868.5730 Section 868.5730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5730 Tracheal tube. (a) Identification. A tracheal tube is...

  7. 21 CFR 868.5730 - Tracheal tube.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tracheal tube. 868.5730 Section 868.5730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5730 Tracheal tube. (a) Identification. A tracheal tube is...

  8. 21 CFR 868.5730 - Tracheal tube.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tracheal tube. 868.5730 Section 868.5730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5730 Tracheal tube. (a) Identification. A tracheal tube is...

  9. Rabies viral antigen in human tongues and salivary glands.

    PubMed

    Li, Z; Feng, Z; Ye, H

    1995-10-01

    Lingual and major salivary tissue samples from three cases of rabies were stained with the immunoperoxidase (ABC) technique. All tissue blocks had been embedded in paraffin 4-10 years before. The first antibody used was monoclonal antirabies nucleocapsin (N) mouse antibody (HAM). Four out of five pieces of tongue from two cases showed a large amount of granular staining indicating rabies antigen (RVAg) inside serous glandular cells, terminal nerves, muscle cells and covering epithelial cells including taste cells. In the tissue probes from the third case only minimal granular staining was found, probably due to complete absence of the serous gland. In contrast to the tongue, only a little weakly reacting material was found in 4 out of 9 probes of salivary gland, either in acini or in nerve fibres. The amount of RVAg is evidently much greater in the human tongue than in major salivary glands, whereas major salivary glands from infected dogs, foxes and skunks reportedly contain much RVAg. As the human tongue's serous gland appears to be a preferred location for RVAg, it may be a source of oral infection.

  10. Changes in Gene Expression in Human Meibomian Gland Dysfunction

    PubMed Central

    Liu, Shaohui; Richards, Stephen M.; Lo, Kristine; Hatton, Mark; Fay, Aaron

    2011-01-01

    Purpose. Meibomian gland dysfunction (MGD) may be the leading cause of dry eye syndrome throughout the world. However, the precise mechanism(s) underlying the pathogenesis of this disease is unclear. This study was conducted to identify meibomian gland genes that may promote the development and/or progression of human MGD. Methods. Lid tissues were obtained from male and female MGD patients and age-matched controls after eyelid surgeries (e.g., to correct entropion or ectropion). Meibomian glands were isolated and processed for RNA extraction and the analysis of gene expression. Results. The results show that MGD is associated with significant alterations in the expression of almost 400 genes in the human meibomian gland. The levels of 197 transcripts, including those encoding various small proline-rich proteins and S100 calcium-binding proteins, are significantly increased, whereas the expression of 194 genes, such as claudin 3 and cell adhesion molecule 1, is significantly decreased. These changes, which cannot be accounted for by sex differences, are accompanied by alterations in many gene ontologies (e.g., keratinization, cell cycle, and DNA repair). The findings also show that the human meibomian gland contains several highly expressed genes that are distinct from those in an adjacent tissue (i.e., conjunctival epithelium). Conclusions. The results demonstrate that MGD is accompanied by multiple changes in gene expression in the meibomian gland. The nature of these alterations, including the upregulation of genes encoding small proline-rich proteins and S100 calcium-binding proteins, suggest that keratinization plays an important role in the pathogenesis of MGD. PMID:21372006

  11. Precursors of hexoneogenesis within the human mammary gland

    USDA-ARS?s Scientific Manuscript database

    The human mammary gland is capable of de novo synthesis of glucose and galactose (hexoneogenesis); however, the carbon source is incompletely understood. In this study, we investigated the role of acetate, glutamine, lactate and glycerol as potential carbon sources for hexoneogenesis. Healthy breast...

  12. Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands.

    PubMed

    Jeong, Jaemin; Baek, Hyunjung; Kim, Yoon-Ju; Choi, Youngwook; Lee, Heekyung; Lee, Eunju; Kim, Eun Sook; Hah, Jeong Hun; Kwon, Tack-Kyun; Choi, Ik Joon; Kwon, Heechung

    2013-11-15

    Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue-specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cell surface antigen markers, such as CD44, CD49f, CD90 and CD105, but not the hematopoietic stem cell markers, CD34 and CD45, and that were able to undergo adipogenic, osteogenic and chondrogenic differentiation. In addition, hSGSCs were differentiated into amylase-expressing cells by using a two-step differentiation method. Transplantation of hSGSCs to radiation-damaged rat salivary glands rescued hyposalivation and body weight loss, restored acinar and duct cell structure, and decreased the amount of apoptotic cells. These data suggest that the isolated hSGSCs, which may have characteristics of mesenchymal-like stem cells, could be used as a cell therapy agent for the damaged salivary gland.

  13. Anatomy of the human mammary gland: Current status of knowledge.

    PubMed

    Hassiotou, Foteini; Geddes, Donna

    2013-01-01

    Mammary glands are unique to mammals, with the specific function of synthesizing, secreting, and delivering milk to the newborn. Given this function, it is only during a pregnancy/lactation cycle that the gland reaches a mature developmental state via hormonal influences at the cellular level that effect drastic modifications in the micro- and macro-anatomy of the gland, resulting in remodeling of the gland into a milk-secretory organ. Pubertal and post-pubertal development of the breast in females aids in preparing it to assume a functional state during pregnancy and lactation. Remarkably, this organ has the capacity to regress to a resting state upon cessation of lactation, and then undergo the same cycle of expansion and regression again in subsequent pregnancies during reproductive life. This plasticity suggests tight hormonal regulation, which is paramount for the normal function of the gland. This review presents the current status of knowledge of the normal macro- and micro-anatomy of the human mammary gland and the distinct changes it undergoes during the key developmental stages that characterize it, from embryonic life through to post-menopausal age. In addition, it discusses recent advances in our understanding of the normal function of the breast during lactation, with special reference to breastmilk, its composition, and how it can be utilized as a tool to advance knowledge on normal and aberrant breast development and function. Finally, anatomical and molecular traits associated with aberrant expansion of the breast are discussed to set the basis for future comparisons that may illuminate the origin of breast cancer.

  14. Replication of Oral BK Virus in Human Salivary Gland Cells

    PubMed Central

    Burger-Calderon, Raquel; Madden, Victoria; Hallett, Ryan A.; Gingerich, Aaron D.; Nickeleit, Volker

    2014-01-01

    BK polyomavirus (BKPyV) is the most common viral pathogen among allograft patients. Increasing evidence links BKPyV to the human oral compartment and to HIV-associated salivary gland disease (HIVSGD). To date, few studies have analyzed orally derived BKPyV. This study aimed to characterize BKPyV isolated from throat wash (TW) samples from HIVSGD patients. The replication potential of HIVSGD-derived clinical isolates HIVSGD-1 and HIVSGD-2, both containing the noncoding control region (NCCR) architecture OPQPQQS, were assessed and compared to urine-derived virus. The BKPyV isolates displayed significant variation in replication potential. Whole-genome alignment of the two isolates revealed three nucleotide differences that were analyzed for a potential effect on the viral life cycle. Analysis revealed a negligible difference in NCCR promoter activity despite sequence variation and emphasized the importance of functional T antigen (Tag) for efficient replication. HIVSGD-1 encoded full-length Tag, underwent productive infection in both human salivary gland cells and kidney cells, and expressed viral DNA and Tag protein. Additionally, HIVSGD-1 generated DNase-resistant particles and by far surpassed the replication potential of the kidney-derived isolate in HSG cells. HIVSGD-2 encoded a truncated form of Tag and replicated much less efficiently. Quantitation of infectious virus, via the fluorescent forming unit assay, suggested that HIVSGD BKPyV had preferential tropism for salivary gland cells over kidney cells. Similarly, the results suggested that kidney-derived virus had preferential tropism for kidney cells over salivary gland cells. Evidence of HIVSGD-derived BKPyV oral tropism and adept viral replication in human salivary gland cells corroborated the potential link between HIVSGD pathogenesis and BKPyV. PMID:24173219

  15. Analysis of tracheal noise of forced human expiration according to clinical experimental data

    NASA Astrophysics Data System (ADS)

    Korenbaum, V. I.; Pochekutova, I. A.

    2004-09-01

    The analysis of tracheal noise of forced expiration is one of the promising methods for the diagnosis of bronchial patency disorders, which are a sign of such widespread diseases as bronchial asthma and chronic obstructive bronchitis. The aim of this study is the verification and refinement of the acoustic model of forced expiration (Korenbaum et al., 1998) on the basis of a statistical analysis of clinical experimental data. A sample of 127 volunteers (from 18 to 74 years old) is used as an experimental statistical model: 34 persons suffering from bronchial asthma, 21 persons suffering from chronic obstructive bronchitis, 29 healthy persons, and 43 persons liable to developing the aforementioned diseases. The following parameters are analyzed: the total duration of noise of forced expiration at the trachea, the duration of wheeze of forced expiration with frequencies from 400 to 600 Hz, and the presence of narrowband high-frequency (over 600 700 Hz) spectral components at the end of forced expiration and during the whole expiration process. Reliable differences in the parameters of tracheal noise are revealed in the groups under study. The high prognostic value (a sensitivity of 89% and a specificity of 86%) of the parameters of tracheal noise of forced expiration, which were suggested a priori as the diagnostic parameters on the basis of the acoustic model (Korenbaum et al., 1998), indirectly confirms the adequacy of this model. The biomechanical-pathophysiological interpretation of the occurrence of acoustic deviations in the experimental sample groups provides an opportunity to relate the parameters of tracheal noise of forced expiration to the degree of mechanical nonuniformity of the lungs.

  16. Expression of steroidogenic enzymes in human sebaceous glands.

    PubMed

    Inoue, Takayoshi; Miki, Yasuhiro; Kakuo, Shingo; Hachiya, Akira; Kitahara, Takashi; Aiba, Setsuya; Zouboulis, Christos C; Sasano, Hironobu

    2014-09-01

    Androgens are well known to influence sebum synthesis and secretion. Various factors related to androgen biosynthesis are expressed in human sebaceous glands. In this study, immunohistochemical analysis of human skin specimens from 43 subjects indicated that various androgen-producing and -metabolizing enzymes were functionally localized to sebocytes accumulating lipid droplets and that the exclusive expression of 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2 (HSD17B2)) in sebaceous glands was negatively correlated with that of peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), which also significantly changed in an age-dependent manner. We also demonstrated that the changes of 17β-HSD2 expression in human immortalized sebocytes (SZ95) influenced the expressions of sebogenesis-related factors. In addition, the overexpression of 17β-HSD2 in SZ95 significantly increased the androstenedione production and markedly decreased the amounts of testosterone and dihydrotestosterone when DHEA was added externally. On the other hand, the phosphorylation of mammalian target of rapamycin, which is well known to induce sebum secretion and the onset and/or aggravation of acne, was increased by the addition of testosterone in the presence of IGF1 in hamster sebocytes. These results all indicated that local androgen biosynthesis and metabolism in human sebaceous glands could play a pivotal role in sebum synthesis and secretion. © 2014 Society for Endocrinology.

  17. [Generation of transgenic mice expressing human lysozyme in mammary gland].

    PubMed

    Yan, Hua; Li, Guo-cai; Sun, Huai-chang

    2005-10-01

    To evaluate the feasibility of generating animal mammary gland bioreactors expressing human lysozyme (hLYZ). The recombinant vector p205C3-hLYZ, as a result of connecting the hLYZ cDNA with the mammry gland expression vector p205C3, was used to generate transfer genic mice by microinjection. A total of 136 F0 mice were obtained, of which 7 (2 females and 5 males) and 4 (1 females and 3 males) were found to contain the transfer-gene by PCR and Southern blotting respectively. The results of Western blotting indicated that the expressed protein had the same molecular weight as that of normal hLYZ. From the F1 generation on, the mice mated only with their brothers or sisters and a colony of F7 transgenic mice was obtained. Among the offspring, the female transgenic mice maintained and expressed the transfer-gene stably with an expression level as high as 750 mg/L. The expressed protein had strong tissue specificity, and in addition to the mammary glands, some degree of ectropic expression in the spleens and intestines of the transgenic mice was confirmed by dot blotting assay. These data indicate that the mice mammary gland bioreactors expressing hLYZ have been successfully generated.

  18. Engineered cartilaginous tubes for tracheal tissue replacement via self-assembly and fusion of human mesenchymal stem cell constructs

    PubMed Central

    Dikina, Anna D.; Strobel, Hannah A.; Lai, Bradley P.; Rolle, Marsha W.; Alsberg, Eben

    2015-01-01

    There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted in a small animal model for airway defects. The modular, bottom up approach used to grow stem cell-based cartilaginous tubes in this report is a promising platform to engineer complex organs (e.g., trachea), with control over tissue size and geometry, and has the potential to be used to generate autologous tissue implants for human clinical applications. PMID:25818451

  19. Engineered cartilaginous tubes for tracheal tissue replacement via self-assembly and fusion of human mesenchymal stem cell constructs.

    PubMed

    Dikina, Anna D; Strobel, Hannah A; Lai, Bradley P; Rolle, Marsha W; Alsberg, Eben

    2015-06-01

    There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted into a small animal model for airway defects. The modular, bottom up approach used to grow stem cell-based cartilaginous tubes in this report is a promising platform to engineer complex organs (e.g., trachea), with control over tissue size and geometry, and has the potential to be used to generate autologous tissue implants for human clinical applications.

  20. The pineal gland - Its possible roles in human reproduction

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Wurtman, Richard J.

    1988-01-01

    The paper discusses the role of the pineal gland in controlling mammalian reproduction, with particular attention given to the role of melatonin in polyestrus mammals, like humans and laboratory rodents. Evidence is cited indicating the influence of melatonin production and blood content on the age of puberty, the timing of the ovulatory cycle, gonadal steriodogenesis, and patterns of reproductive behavior. It is suggested that abnormal patterns of melatonin might be associated with amenorrhea, anovulation, unexplained infertility, premature menopause, and habitual abortions.

  1. The pineal gland - Its possible roles in human reproduction

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Wurtman, Richard J.

    1988-01-01

    The paper discusses the role of the pineal gland in controlling mammalian reproduction, with particular attention given to the role of melatonin in polyestrus mammals, like humans and laboratory rodents. Evidence is cited indicating the influence of melatonin production and blood content on the age of puberty, the timing of the ovulatory cycle, gonadal steriodogenesis, and patterns of reproductive behavior. It is suggested that abnormal patterns of melatonin might be associated with amenorrhea, anovulation, unexplained infertility, premature menopause, and habitual abortions.

  2. Neuropeptide Y in the adult and fetal human pineal gland.

    PubMed

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  3. TGFβ signaling regulates lipogenesis in human sebaceous glands cells

    PubMed Central

    2013-01-01

    Background Sebaceous glands are components of the skin essential for its normal lubrication by the production of sebum. This contributes to skin health and more importantly is crucial for the skin barrier function. A mechanistic understanding of sebaceous gland cells growth and differentiation has lagged behind that for keratinocytes, partly because of a lack of an in vitro model that can be used for experimental manipulation. Methods We have developed an in vitro culture model to isolate and grow primary human sebocytes without transformation that display functional characteristics of sebocytes. We used this novel method to probe the effect of Transforming Growth Factor β (TGFβ) signaling on sebocyte differentiation, by examining the expression of genes involved in lipogenesis upon treatment with TGFβ1. We also repressed TGFβ signaling through knockdown of the TGFβ Receptor II to address if the effect of TGFβ activation is mediated via canonical Smad signal transduction. Results We find that activation of the TGFβ signaling pathway is necessary and sufficient for maintaining sebocytes in an undifferentiated state. The presence of TGFβ ligand triggered decreased expression in genes required for the production of characteristics sebaceous lipids and for sebocyte differentiation such as FADS2 and PPARγ, thereby decreasing lipid accumulation through the TGFβ RII-Smad2 dependent pathway. Conclusion TGFβ signaling plays an essential role in sebaceous gland regulation by maintaining sebocytes in an undifferentiated state. This data was generated using a novel method for human sebocyte culture, which is likely to prove generally useful in investigations of sebaceous gland growth and differentiation. These findings open a new paradigm in human skin biology with important implications for skin therapies. PMID:23343495

  4. Pituitary gland and sella turcica in human trisomy 18 fetuses.

    PubMed

    Kjaer, I; Keeling, J W; Reintoft, I; Hjalgrim, H; Nolting, D; Fischer Hansen, B

    1998-02-26

    The purpose of this study was to elucidate the phenotypic conditions in the sella turcica/pituitary gland complex in human trisomy 18 fetuses. Fourteen human fetuses with gestational ages from 12 to 39 weeks were included in the study. Normal fetuses at corresponding ages were used as controls. Whole body and special radiographic examination was undertaken before the midsagittal cranial base block, including the pituitary gland, was excised and analyzed histologically and immunohistochemically (keratin wide spectrum [KWS], thyroid-stimulating hormone [TSH], and neurophysin [Nph]). In all trisomy 18 fetuses, TSH-positive adenopituitary tissue was present in the sella and in greater or lesser amounts pharyngeally. The neurohypophysis was Nph-positive and located normally in the sella turcica. The adenohypophyseal tissue reacted either KWS-faint or KWS-negative, whereas KWS-positive reaction occurs in normal fetuses. This circumstance might suggest an altered cytoskeletal structure of the surface ectoderm in the pituitary placode in trisomy 18. The sella turcica was malformed in all the fetuses. Very broad craniopharyngeal canals were observed in some of the fetuses. Because endocrine disorders occur in many congenital malformations, it is essential in future studies to chart the sella turcica/pituitary gland region systematically in different genotypes.

  5. Drosophila awd, the homolog of human nm23, regulates FGF receptor levels and functions synergistically with shi/dynamin during tracheal development.

    PubMed

    Dammai, Vincent; Adryan, Boris; Lavenburg, Kim R; Hsu, Tien

    2003-11-15

    Human nm23 has been implicated in suppression of metastasis in various cancers, but the underlying mechanism of such activity has not been fully understood. Using Drosophila tracheal system as a genetic model, we examined the function of the Drosophila homolog of nm23, the awd gene, in cell migration. We show that loss of Drosophila awd results in dysregulated tracheal cell motility. This phenotype can be suppressed by reducing the dosage of the chemotactic FGF receptor (FGFR) homolog, breathless (btl), indicating that btl and awd are functionally antagonists. In addition, mutants of shi/dynamin show similar tracheal phenotypes as in awd and exacerbate those in awd mutant, suggesting defects in vesicle-mediated turnover of FGFR in the awd mutant. Consistent with this, Btl-GFP chimera expressed from a cognate btl promoter-driven system accumulate at high levels on tracheal cell membrane of awd mutants as well as in awd RNA duplex-treated cultured cells. Thus, we propose that awd regulates tracheal cell motility by modulating the FGFR levels, through a dynamin-mediated pathway.

  6. Isolation and characterization of sweat gland myoepithelial cells from human skin.

    PubMed

    Kurata, Ryuichiro; Futaki, Sugiko; Nakano, Itsuko; Tanemura, Atsushi; Murota, Hiroyuki; Katayama, Ichiro; Sekiguchi, Kiyotoshi

    2014-01-01

    Stem cells routinely maintain the main epidermal components, i.e. the interfollicular epidermis, hair follicles, and sweat glands. Human sweat glands present throughout the body are glandular exocrine organs that mainly play a role in thermoregulation by sweating. Emerging evidence points to the presence of stem cells in sweat glands, but it remains unclear whether such stem cells exist in human sweat glands. Here, we attempted to gather evidence for stem cells in human sweat glands, which would be characterized by self-renewal ability and multipotency. First, we explored human sweat gland cells for expression of stem cell markers. CD29 and Notch, epidermal stem cell markers, were found to reside among α-smooth muscle actin-positive myoepithelial cells in human sweat glands. Next, sweat gland myoepithelial cells were isolated from human skin as a CD29(hi)CD49f (hi) subpopulation. The myoepithelial cell-enriched CD29(hi)CD49f (hi) subpopulation possessed the ability to differentiate into sweat gland luminal cells in sphere-forming assays. Furthermore, CD29(hi)CD49f (hi) subpopulation-derived sphere-forming cells exhibited long-term proliferative potential upon multiple passaging, indicating that the CD29(hi)CD49f (hi) myoepithelial subpopulation includes stem cells with self-renewal ability. These findings provide evidence that human sweat gland myoepithelial cells contain stem cells that possess both self-renewal ability and multipotency to differentiate into sweat glands.

  7. Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum

    PubMed Central

    Choi, Eunyoung; Roland, Joseph T.; Barlow, Brittney J.; O’Neal, Ryan; Rich, Amy E.; Nam, Ki Taek; Shi, Chanjuan; Goldenring, James R.

    2014-01-01

    Objective The glands of the stomach body and antral mucosa contain a complex compendium of cell lineages. In lower mammals, the distribution of oxyntic glands and antral glands define the anatomical regions within the stomach. We examined in detail the distribution of the full range of cell lineages within the human stomach. Design We determined the distribution of gastric gland cell lineages with specific immunocytochemical markers in entire stomach specimens from three non-obese organ donors. Results The anatomical body and antrum of the human stomach were defined by the presence of ghrelin and gastrin cells, respectively. Concentrations of somatostatin cells were observed in the proximal stomach. Parietal cells were seen in all glands of the body of stomach as well as in over 50% of antral glands. MIST1-expressing chief cells were predominantly observed in the body, although individual glands of the antrum also showed MIST1-expressing chief cells. While classically-described antral glands were observed with gastrin cells and deep antral mucous cells without any parietal cells, we also observed a substantial population of mixed-type glands containing both parietal cells and G cells throughout the antrum. Conclusions Enteroendocrine cells show distinct patterns of localization in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations. PMID:24488499

  8. Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands.

    PubMed

    Pringle, Sarah; Maimets, Martti; van der Zwaag, Marianne; Stokman, Monique A; van Gosliga, Djoke; Zwart, Erik; Witjes, Max J H; de Haan, Gerald; van Os, Ronald; Coppes, Rob P

    2016-03-01

    Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment, and functional restoration in a xenotransplantation model. Indeed, transplanted human salisphere-derived cells restored saliva production and greatly improved the regenerative potential of irradiated SGs. Further selection for c-Kit expression enriched for cells with enhanced regenerative potencies. Interestingly, interaction of transplanted cells with the recipient SG may also be involved in functional recovery. Thus, we show for the first time that salispheres cultured from human SGs contain stem/progenitor cells capable of self-renewal and differentiation and rescue of saliva production. Our study underpins the therapeutic promise of salisphere cell therapy for the treatment of xerostomia.

  9. Human eccrine sweat gland epithelial cultures express ductal characteristics.

    PubMed Central

    Brayden, D J; Cuthbert, A W; Lee, C M

    1988-01-01

    1. Isolated human eccrine sweat glands were cultured in vitro. Cells were harvested and plated onto permeable supports to form confluent cell sheets, area 0.2 cm2. These were used to study the electrogenic transepithelial transport of ions by measurement of short-circuit current (SCC). Epithelial sheets had a basal SCC of 5.89 +/- 0.62 microA cm-2 (n = 33) and a transepithelial resistance of 74.1 +/- 5.6 omega cm2 (n = 33). The transepithelial potential difference varied between -0.2 and -1.8 mV with a mean value of -0.71 +/- 0.09 mV (n = 33). 2. The basal current was abolished by addition of 10 microM-amiloride to the apical bathing solution. The concentration of amiloride which inhibited basal SCC by 50% (EC50) was 0.4 microM. Cultures prepared from the secretory coil of sweat glands, rather than from whole glands, were similarly sensitive to amiloride (EC50 = 0.8 microM). 3. Lysylbradykinin (LBK), carbachol, isoprenaline, prostaglandin E2 (PGE2) and A23187 all increased SCC in cultures from whole glands. LBK responses were obtained with basolateral and not with apical application. Furthermore LBK actions were not substantially altered by cyclo-oxygenase inhibition but showed marked desensitization upon repeated application. Sheet cultures prepared from sweat gland coils also showed SCC responses to both carbachol and LBK. Forskolin, an activator of adenylate cyclase, did not alter SCC in either type of preparation. 4. Replacement of chloride and of chloride and bicarbonate in the bathing solution did not cause attenuation of the responses to LBK or carbachol in whole-gland sheet cultures. Furthermore responses were unaffected by piretanide or acetazolamide. These results were taken to indicate that anion secretion was not the basis for the SCC responses. 5. Responses to LBK and carbachol were significantly reduced by amiloride (10 microM), this effect being reversible. No responses to LBK or carbachol were seen when N-methyl-D-glucamine (NMDG) was used to

  10. Acute lung injury after tracheal instillation of acidified soya-based or Enfalac formula or human breast milk in rabbits.

    PubMed

    Chin, C; Lerman, J; Endo, J

    1999-03-01

    The aim of this study was to compare the severity of the acute lung injury after tracheal instillation of acidified soya-based or Enfalac infant formula, or human breast milk (HBM) in anesthetized rabbits. Alveolar-arterial oxygen tension gradient (A-aDO2) and dynamic compliance were measured before (baseline) and hourly for four hours after tracheal instillation of 0.8 ml x kg(-1) soya-based or Enfalac infant formula or HBM (all acidified to pH 1.8 with hydrochloric acid) or no fluid (control) in 24 anesthetized and tracheotomized adult rabbits. The A-aDO2, the difference between alveolar and arterial oxygen tensions, was corrected for barometric pressure and carbon dioxide tension. Dynamic compliance was the ratio of the expired tidal volume to the peak inspiratory airway pressure, normalized to body weight. Baseline A-aDO2 and dynamic compliance were similar among the four groups. In the control rabbits, A-aDO2 remained unchanged throughout the four hours, whereas mean A-aDO2 increased 180 mm Hg in the soya-based group (P < 0.0025) and 350 and 275 mm Hg in the Enfalac and HBM groups respectively (P < 0.0002). The order of the A-aDO2 post-instillation was Enfalac approximately/= HBM > soya > control (P < 0.0002). Dynamic compliance decreased 10-12% in the control rabbits during the four post-instillation measurements compared with baseline (P < 0.033), decreased 20% in the soya-based group (P < 0.0002) and 40-50% in the Enfalac and HBM groups (P < 0.0002). The severity of the acute lung injury after intratracheal instillation of infant feeds in a volume of 0.8 ml x kg(-1) and at pH 1.8 in rabbits depends in part, on the type of feed: Enfalac approximately/= HBM > soya > control.

  11. Morphological study of tracheal shape in donkeys with and without tracheal obstruction.

    PubMed

    Powell, R J; du Toit, N; Burden, F A; Dixon, P M

    2010-03-01

    There is limited information on the gross tracheal morphology of donkeys with or without tracheal abnormalities. To: 1) examine the morphology of tracheas of donkeys with and without clinical and/or post mortem evidence of tracheal obstruction; 2) record the cross-sectional dimensions and shapes of tracheal rings at fixed sites; and 3) document prevalence, sites and characteristics of detected tracheal abnormalities. The tracheas of 75, predominantly aged (median age 30 years, range 7-48 years) donkeys that died or were subjected to euthanasia on humane grounds were examined. Five had severe dyspnoea due to tracheal obstruction (with intercurrent lung disease in 3), while 7 had post mortem evidence of severe tracheal airway obstruction. Every 5th tracheal ring was dissected free and the inner and outer vertical and transverse dimensions and cross sectional areas were measured. Each dissected ring was photographed and the shape of the trachea was classified as normal or, in one of 6 abnormal grades, according to the type and degree of structural abnormality present. The tracheas had a mean of 43 (range 34-50) tracheal rings that tended to be more oval in shape in the distal cervical region. Only 31.2% of rings examined had a circular to oval shape. Dorso-ventral flattening was present in 0.9% of tracheal rings, dorsal ligament separation in 24.4%, slight cartilage deformity in 26.0%, moderate cartilage deformity in 10.4%, marked cartilage deformity in 1.9% and miscellaneous other abnormalities in 4.9% of tracheal rings. The 12 donkeys with ante or post mortem evidence of tracheal obstruction had significantly increased tracheal abnormality grade in comparison to the remaining donkeys. Structural tracheal abnormalities are present in most old donkeys, but generally do not cause clinical problems in these sedentary animals unless intercurrent pulmonary disease is present.

  12. 21 CFR 878.3720 - Tracheal prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tracheal prosthesis. 878.3720 Section 878.3720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3720 Tracheal prosthesis....

  13. 21 CFR 878.3720 - Tracheal prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tracheal prosthesis. 878.3720 Section 878.3720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3720 Tracheal prosthesis....

  14. 21 CFR 878.3720 - Tracheal prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tracheal prosthesis. 878.3720 Section 878.3720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3720 Tracheal prosthesis....

  15. 21 CFR 878.3720 - Tracheal prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tracheal prosthesis. 878.3720 Section 878.3720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3720 Tracheal prosthesis....

  16. 21 CFR 878.3720 - Tracheal prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tracheal prosthesis. 878.3720 Section 878.3720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3720 Tracheal prosthesis....

  17. Clarification of the terminology of the major human salivary glands: acinus and alveolus are not synonymous.

    PubMed

    Gilloteaux, Jacques; Afolayan, Adebowale

    2014-08-01

    Discrepancies in the terminology of the major human salivary glands often appear in anatomical textbooks and tend to adversely affect student's learning experience in Microscopic Anatomy. The main culprit is the inconsistent description of the morphology of these glands secretory end pieces where "acinus" and "alveolus" are used interchangeably. The correct terminology originated from Malpighi (1687), repeated by Kölliker (1854), but over the years has been misinterpreted by prominent authors as a result of the nature of specimen preparation. This commentary is based on etymology, current standard light microscopy, research studies and consultation with experts. The overall objective of this publication is to recommend that textbooks should endeavour to modify the relevant descriptions about this terminology in their future editions. The most appropriate terminology for the major human salivary glands would be: (1) the parotid gland, entirely serous, should be called compound acinar glands; (2) the submandibular glands are mixed glands; their serous components are compound acinar while some of the mucinous areas are tubular with serous, crescents or demilunes, as acinar end pieces hence they should be named compound tubuloacinar glands; (3) the sublingual glands, mainly mucous glands with tubular shape, with small acinar end pieces that are serous crescents thence they should be called compound tubuloacinar glands.

  18. Eccrine Sweat Glands are Major Contributors to Reepithelialization of Human Wounds

    PubMed Central

    Rittié, Laure; Sachs, Dana L.; Orringer, Jeffrey S.; Voorhees, John J.; Fisher, Gary J.

    2014-01-01

    Eccrine sweat glands are skin-associated epithelial structures (appendages) that are unique to some primates including humans and are absent in the skin of most laboratory animals including rodents, rabbits, and pigs. On the basis of the known importance of other skin appendages (hair follicles, apocrine glands, and sebaceous glands) for wound repair in model animals, the present study was designed to assess the role of eccrine glands in the repair of wounded human skin. Partial-thickness wounds were generated on healthy human forearms, and epidermal repair was studied in skin biopsy samples obtained at precise times during the first week after wounding. Wound reepithelialization was assessed using immunohistochemistry and computer-assisted 3-dimensional reconstruction of in vivo wounded skin samples. Our data demonstrate a key role for eccrine sweat glands in reconstituting the epidermis after wounding in humans. More specifically, i) eccrine sweat glands generate keratinocyte outgrowths that ultimately form new epidermis; ii) eccrine sweat glands are the most abundant appendages in human skin, outnumbering hair follicles by a factor close to 3; and iii) the rate of expansion of keratinocyte outgrowths from eccrine sweat glands parallels the rate of reepithelialization. This novel appreciation of the unique importance of eccrine sweat glands for epidermal repair may be exploited to improve our approaches to understanding and treating human wounds. PMID:23159944

  19. Eccrine sweat glands are major contributors to reepithelialization of human wounds.

    PubMed

    Rittié, Laure; Sachs, Dana L; Orringer, Jeffrey S; Voorhees, John J; Fisher, Gary J

    2013-01-01

    Eccrine sweat glands are skin-associated epithelial structures (appendages) that are unique to some primates including humans and are absent in the skin of most laboratory animals including rodents, rabbits, and pigs. On the basis of the known importance of other skin appendages (hair follicles, apocrine glands, and sebaceous glands) for wound repair in model animals, the present study was designed to assess the role of eccrine glands in the repair of wounded human skin. Partial-thickness wounds were generated on healthy human forearms, and epidermal repair was studied in skin biopsy samples obtained at precise times during the first week after wounding. Wound reepithelialization was assessed using immunohistochemistry and computer-assisted 3-dimensional reconstruction of in vivo wounded skin samples. Our data demonstrate a key role for eccrine sweat glands in reconstituting the epidermis after wounding in humans. More specifically, (i) eccrine sweat glands generate keratinocyte outgrowths that ultimately form new epidermis; (ii) eccrine sweat glands are the most abundant appendages in human skin, outnumbering hair follicles by a factor close to 3; and (iii) the rate of expansion of keratinocyte outgrowths from eccrine sweat glands parallels the rate of reepithelialization. This novel appreciation of the unique importance of eccrine sweat glands for epidermal repair may be exploited to improve our approaches to understanding and treating human wounds.

  20. Evaluations of thyme extract effects in human normal bronchial and tracheal epithelial cell lines and in human lung cancer cell line.

    PubMed

    Oliviero, Marinelli; Romilde, Iannarelli; Beatrice, Morelli Maria; Matteo, Valisi; Giovanna, Nicotra; Consuelo, Amantini; Claudio, Cardinali; Giorgio, Santoni; Filippo, Maggi; Massimo, Nabissi

    2016-08-25

    Thyme (Thymus vulgaris) is used traditionally to prepare herbal remedies possessing expectorant, mucolytic, antitussive and antispasmodic properties. The aim of the present study was to investigate the effects of a standardized hydroalcoholic extract of thyme on primary human airway (bronchial/tracheal) epithelial cell lines in a model of lung inflammation induced by LPS. In addition, the effects of thyme extract on human lung cancer cell line (H460) were analysed. Thyme extract showed significant anti-inflammatory properties by reducing the NF-κB p65 and NF-κB p52 transcription factors protein levels followed by the decrease of pro-inflammatory cytokines (IL-1 beta and IL-8), and Muc5ac secretion in human normal bronchial and tracheal epithelial cells. Moreover, the extract showed cytotoxic effects on H460 cancer cells, modulated the release of IL-1 beta, IL-8 and down-regulated NF-κB p65 and NF-κB p52 proteins. Taken together, these results substantiated the traditional uses of thyme in the treatment of respiratory diseases. Thyme extract might be an effective treatment of chronic diseases based on inflammatory processes when hypersecretion of mucus overwhelms the ciliary clearance and obstructs airways, causing morbidity and mortality. Moreover thyme extract, evaluated in H460 lung cancer cell line, demonstrated to induce cell cytotoxicity in addition to reduce inflammatory cell signals.

  1. Dynamic OCT of mentally stress-induced sweating in sweat glands of the human finger tip

    NASA Astrophysics Data System (ADS)

    Ohmi, Masato; Ueda, Yoshihiro; Haruna, Masamitsu

    2007-02-01

    We demonstrate in-vivo imaging of sweat glands of human finger tip using the dynamic optical coherence tomography (OCT). Mentally-stress-induced sweating in sweat glands of human finger tip can be observed clearly in time-sequential OCT images. In the experiment, a sweat pore opened clearly on the skin surface according to a stimulus of sound.

  2. Human Parotid Gland Alpha-Amylase Secretion as a Function of Chronic Hyperbaric Exposure

    DTIC Science & Technology

    1979-01-01

    parotid ...Pullman, WA 99163 Gilman, S. C, G. J. Fischer, R. J. Biersner, R. D. Thornton, and D. A. Miller. 1979. Human parotid gland alpha-amylase secretion...as a function of chronic hyperbaric exposure. Undersea Biomed. Res. 6(3):303-307.—Secretion of a-amylase by the human parotid gland increased

  3. Comparison of proliferating cells between human adult and fetal eccrine sweat glands.

    PubMed

    Li, Hai-Hong; Fu, Xiao-Bing; Zhang, Lei; Zhou, Gang

    2008-04-01

    Studies of sweat glands had demonstrated that there were degenerating cells and proliferating cells in the eccrine sweat glands. To compare the differences in the proliferating cells between human adult and fetal eccrine sweat glands, immunostaining of proliferating-associated proliferating cell nuclear antigen (PCNA) and Ki67 nuclear antigen (Ki67) was performed, and the location and the percentage of the positive staining cells were analyzed. The results showed that a few cells of the secretory and ductal portion in both the adult and fetal eccrine sweat glands stained positive with Ki67 and PCNA. The labeling index of PCNA in adult eccrine sweat glands was 34.71 +/- 8.37%, while that in the fetal was 62.72 +/- 6.54%. The labeling index of PCNA in fetal eccrine sweat glands was higher than that in adult. Myoepithelial cells were negative staining with anti-PCNA antibody in adult eccrine sweat glands, while in the fetal a few myoepithelial cells were positive staining. Labeling index of Ki67 in adult eccrine sweat glands was similar to that in the fetal, ranging from 0.5 to 4.3%. Myoepithelial cells of the adult and fetal eccrine sweat glands both were negative staining with anti-Ki67 antibody. We concluded that the myoepithelial cells had proliferating ability only in fetal eccrine sweat glands, and that the proliferating ability of fetal eccrine sweat glands was stronger than that of the adult.

  4. THE ULTRASTRUCTURE AND HISTOPHYSIOLOGY OF HUMAN ECCRINE SWEAT GLANDS

    PubMed Central

    Munger, Bryce L.

    1961-01-01

    The electron microscopy of human eccrine sweat glands has been studied before and after stimulation by pilocarpine iontophoresis. The identity of the dark and clear cells in the secretory segment as defined by Montagna et al. (23) was determined by studying serial sections, thin for electron microscopy and thick for light microscopy. Cells with numerous apical secretory vacuoles are termed mucoid (dark) cells, since these vacuoles stain positively for acid mucopolysaccharide. Clear cells are intimately associated with intercellular canaliculi. The "cuticular border" of surface cells of the duct is a condensation of tonofilaments and granules. Numerous mitochondria are concentrated in basal cells of the duct. The presence of mucoid cells in the secretory segment may bear on the interpretation of the pathologic findings in the disease cystic fibrosis of the pancreas, and suggests that this disease may be due to a basic disorder of mucopolysaccharide production. The possible roles of the various cellular components in the elaboration of sweat are discussed. PMID:14477206

  5. Weight gain increases human aromatase expression in mammary gland.

    PubMed

    Chen, Dong; Zhao, Hong; Coon, John S; Ono, Masanori; Pearson, Elizabeth K; Bulun, Serdar E

    2012-05-15

    Adulthood weight gain predicts estrogen receptor-positive breast cancer. Because local estrogen excess in the breast likely contributes to cancer development, and aromatase is the key enzyme in estrogen biosynthesis, we investigated the role of local aromatase expression in weight gain-associated breast cancer risk in a humanized aromatase (Arom(hum)) mouse model containing the coding region and the 5'-regulatory region of the human aromatase gene. Compared with littermates on normal chow, female Arom(hum) mice on a high fat diet gained more weight, and had a larger mammary gland mass with elevated total human aromatase mRNA levels via promoters I.4 and II associated with increased levels of their regulators TNFα and C/EBPβ. There was no difference in total human aromatase mRNA levels in gonadal white adipose tissue. Our data suggest that diet-induced weight gain preferentially stimulates local aromatase expression in the breast, which may lead to local estrogen excess and breast cancer risk.

  6. Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum.

    PubMed

    Choi, Eunyoung; Roland, Joseph T; Barlow, Brittney J; O'Neal, Ryan; Rich, Amy E; Nam, Ki Taek; Shi, Chanjuan; Goldenring, James R

    2014-11-01

    The glands of the stomach body and antral mucosa contain a complex compendium of cell lineages. In lower mammals, the distribution of oxyntic glands and antral glands define the anatomical regions within the stomach. We examined in detail the distribution of the full range of cell lineages within the human stomach. We determined the distribution of gastric gland cell lineages with specific immunocytochemical markers in entire stomach specimens from three non-obese organ donors. The anatomical body and antrum of the human stomach were defined by the presence of ghrelin and gastrin cells, respectively. Concentrations of somatostatin cells were observed in the proximal stomach. Parietal cells were seen in all glands of the body of the stomach as well as in over 50% of antral glands. MIST1 expressing chief cells were predominantly observed in the body although individual glands of the antrum also showed MIST1 expressing chief cells. While classically described antral glands were observed with gastrin cells and deep antral mucous cells without any parietal cells, we also observed a substantial population of mixed type glands containing both parietal cells and G cells throughout the antrum. Enteroendocrine cells show distinct patterns of localisation in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Overview of Human Salivary Glands: Highlights of Morphology and Developing Processes.

    PubMed

    de Paula, Fernanda; Teshima, Tathyane Harumi Nakajima; Hsieh, Ricardo; Souza, Milena Monteiro; Nico, Marcello Menta Simonsen; Lourenco, Silvia Vanessa

    2017-02-13

    Salivary glands are essential organs that produce and secrete saliva to the oral cavity. During gland morphogenesis, many developmental processes involve a series of coordinated movements and reciprocal interactions between the epithelium and mesenchyme that generate the ductal system and the secretory units. Recent studies have shown new findings about salivary gland development, particularly regarding lumen formation and expansion, with the involvement of apoptosis and cell polarization, respectively. Moreover, it has been observed that human minor salivary glands start forming earlier than previously published and that distinct apoptotic mediators can trigger duct lumen opening in humans. This review summarizes updated morphological and cellular features of human salivary glands and also explores new aspects of the human developmental process. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc.

  8. Immunohistochemical study of oestrogen receptors in 351 human thyroid glands.

    PubMed

    Tavangar, S M; Monajemzadeh, M; Larijani, B; Haghpanah, V

    2007-08-01

    It is well recognised that the pathogenesis of thyroid diseases is complex and different factors such as genetic factors, iodine deficiency, sex, age, radiation therapy in childhood, growth stimulating antibodies, and other epithelial growth factors can influence them. Epidemiological features of thyroid tumours and experimental evidence suggest that female sex hormones may exert effects on the thyroid gland and its neoplasms. This possibility was addressed by investigating the expression of oestrogen receptor protein in 351 thyroid lesions. The tissues from 351 human thyroid glands comprising 130 nodular goitres and 221 neoplastic lesions were used for the present immunohistochemical assessment of oestrogen receptor expression. Incidence of oestrogen receptor positive cases were 24 percent (31/130) for nodular goitres, 22 percent (8/37) for follicular adenomas, 11 percent (2/18) for follicular carcinomas, 31 percent (37/119) for papillary carcinomas, zero percent (0/35) for medullary carcinomas and zero percent (0/12) for undifferentiated carcinomas. The incidence of oestrogen receptor positivity, which is compatible with other studies, is higher in well-differentiated thyroid lesions. The incidence of oestrogen receptor reactivity does not significantly differ between females and males of different age groups and it does not correlate with lymph node status, and vascular and capsular invasions. The relatively high proportion of oestrogen receptor positivity in goitres, follicular adenomas and papillary carcinomas, compared with its reactivity in other thyroid neoplasms, and contrasted against normal thyroid tissue, suggests that the incidence of oestrogen receptor reactivity tends to increase with better differentiation of thyroid lesions. This finding may have clinical relevance.

  9. Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process

    PubMed Central

    Choi, Jae Young; Khansaheb, Monal; Joo, Nam Soo; Krouse, Mauri E.; Robbins, Robert C.; Weill, David; Wine, Jeffrey J.

    2009-01-01

    Chronic bacterial airway infections are the major cause of mortality in cystic fibrosis (CF). Normal airway defenses include reflex stimulation of submucosal gland mucus secretion by sensory neurons that release substance P (SubP). CFTR is an anion channel involved in fluid secretion and mutated in CF; the role of CFTR in secretions stimulated by SubP is unknown. We used optical methods to measure SubP-mediated secretion from human submucosal glands in lung transplant tissue. Glands from control but not CF subjects responded to mucosal chili oil. Similarly, serosal SubP stimulated secretion in more than 60% of control glands but only 4% of CF glands. Secretion triggered by SubP was synergistic with vasoactive intestinal peptide and/or forskolin but not with carbachol; synergy was absent in CF glands. Pig glands demonstrated a nearly 10-fold greater response to SubP. In 10 of 11 control glands isolated by fine dissection, SubP caused cell volume loss, lumen expansion, and mucus flow, but in 3 of 4 CF glands, it induced lumen narrowing. Thus, in CF, the reduced ability of mucosal irritants to stimulate airway gland secretion via SubP may be another factor that predisposes the airways to infections. PMID:19381016

  10. Expression of the gene encoding growth hormone in the human mammary gland

    SciTech Connect

    Mol, J.A.; Misdorp, W.; Rijnberk, A.

    1995-10-01

    Progestins cause a syndrome of growth hormone (GH) excess and enhanced mammary tumorigenesis in the dog. This has been regarded as being specific for the dog. Recently we reported that progestin-induced GH excess originates from foci of hyperplastic ductular epithelium of the mammary gland in the dog. In the present report we demonstrate by reverse-transcriptase PCR and immunohistochemistry that a main factor involved in tissue growth, i.e. GH, is also expressed in normal and neoplastic human mammary glands. The gene expressed in the human mammary gland proved to be identical to the gene encoding GH in the pituitary gland. The role of progesterone in the GH expression of the human mammary gland needs, however, to be proven. It is hypothesized that this locally produced hGH may play a pathogenetic role in breast cancer. 21 refs., 2 figs., 1 tab.

  11. The human adrenal gland proteome defined by transcriptomics and antibody-based profiling.

    PubMed

    Bergman, Julia; Botling, Johan; Fagerberg, Linn; Hallström, Björn M; Djureinovic, Dijana; Uhlén, Mathias; Pontén, Fredrik

    2016-11-30

    The adrenal gland is a composite endocrine organ with vital functions that include the synthesis and release of glucocorticoids and catecholamines. To define the molecular landscape that underlies the specific functions of the adrenal gland, we combined a genome-wide transcriptomics approach based on mRNA sequencing of human tissues with immunohistochemistry-based protein profiling on tissue microarrays. Approximately two-thirds of all putative protein coding genes were expressed in the adrenal gland and the analysis identified 253 genes with an elevated pattern of expression in the adrenal gland, with only 37 genes showing a markedly higher expression level (>5-fold) in the adrenal gland compared to 31 other normal human tissue types analyzed. The analyses allowed for an assessment of the relative expression levels for well-known proteins involved in adrenal gland function, but also identified previously poorly characterized proteins in the adrenal cortex, such as FERM domain containing 5 (FRMD5) and protein NOV homolog (NOV). In summary, we provide a global analysis of the adrenal gland transcriptome and proteome, with a comprehensive list of genes with elevated expression in the adrenal gland and spatial information with examples of protein expression patterns for corresponding proteins. These genes and proteins constitute important starting points for an improved understanding of the normal function and pathophysiology of the adrenal glands.

  12. Lrig1 Expression in Human Sebaceous Gland Tumors

    PubMed Central

    Pünchera, Jöri; Barnes, Laurent; Kaya, Gürkan

    2016-01-01

    Background Sebaceous glands contribute significantly to the barrier functions of the skin. However, little is known about their homeostasis and tumorigenesis. Recently, increased expression of stem cell marker Lrig1 has been reported in sebaceous carcinoma-like tumors of K14ΔNLef1 transgenic mice. In this study, we analyzed the Lrig1 expression in human sebaceous tumors. Methods Twenty-eight formalin-fixed paraffin-embedded sebaceous tumor specimens (7 sebaceous hyperplasias, 7 sebaceous adenomas, 10 sebaceomas and 4 sebaceous carcinomas) were stained with anti-Lrig1, anti-CD44v3 and anti-Ki67 antibody. Results Four (100%) sebaceous carcinomas, 8 (80%) sebaceomas, 3 (43%) sebaceous adenomas and no sebaceous hyperplasia showed Lrig1 overexpression. Discussion and Conclusion Lrig1 is a known tumor suppressor gene and is usually considered to be an indicator of poorly aggressive tumors. In human sebaceous tumors, the stronger Lrig1 staining in sebaceous carcinoma compared to other sebaceous tumors might be a feature of an advanced stage in tumorigenesis and a bad prognosis. In our study, 100% of sebaceous carcinomas revealed Lrig1 overexpression. We propose that Lrig1 may be used as a possible new marker of poorly differentiated sebaceous carcinoma. PMID:27504445

  13. Precursors of hexoneogenesis within the human mammary gland.

    PubMed

    Mohammad, Mahmoud A; Maningat, Patricia; Sunehag, Agneta L; Haymond, Morey W

    2015-04-15

    The human mammary gland is capable of de novo synthesis of glucose and galactose (hexoneogenesis); however, the carbon source is incompletely understood. In this study, we investigated the role of acetate, glutamine, lactate and glycerol as potential carbon sources for hexoneogenesis. Healthy breastfeeding women were studied following a 24-h fast on two occasions separated by 1-3 wk. Five women were infused with [U-¹³C]lactate or [1,2-¹³C₂]glutamine and five women with [U-¹³C]glycerol or [1,2-¹³C₂]acetate. Enrichments of ¹³C in plasma and milk substrates were analyzed using GC-MS. Infusion of labeled lactate, glycerol, glutamine, and acetate resulted in plasma glucose being 22.0±3.7, 11.2±1.0, 2.5±0.5, and 1.3±0.2% labeled, respectively. Lactate, glutamine, or acetate did not contribute to milk glucose or galactose (0-2%). In milk, ¹³C-free glycerol enrichment was one-fourth that in plasma but free glycerol concentration in milk was fourfold higher than in plasma. Using [U-¹³C]glycerol and by accounting for tracer dilution, glycerol alone contributed to 10±2 and 69±11% of the hexoneogenesis of milk glucose and galactose, respectively. During [U-¹³C]glycerol infusion, the ratio of M₃ enrichment on 4-6 carbons/M₃ on 1-3 carbons of galactose was higher (P<0.05, 1.22±0.05) than those of glucose in plasma (1.05±0.03) and milk (1.07±0.02). Reanalysis of samples from a previous study involving [U-¹³C]glucose infusion alone suggested labeling a portion of galactose consistent with pentose phosphate pathway (PPP) activity. We conclude that, although lactate contributed significantly to gluconeogenesis, glycerol alone provides the vast majority of substrate for hexoneogenesis. The relative contribution of the PPP vs. the reversal Embden-Meyerhof pathway to hexoneogenesis within the human mammary gland remains to be determined.

  14. Structure and function of human sweat glands studied with histochemistry and cytochemistry.

    PubMed

    Saga, Kenji

    2002-01-01

    The basic structure and the physiological function of human sweat glands were reviewed. Histochemical and cytochemical techniques greatly contributed the elucidation of the ionic mechanism of sweat secretion. X-ray microanalysis using freeze-dried cryosections clarified the level of Na, K, and Cl in each secretory cell of the human sweat gland. Enzyme cytochemistry, immunohistochemistry and autoradiography elucidated the localization of Na,K-ATPase. These data supported the idea that human eccrine sweat is produced by the model of N-K-2Cl cotransport. Cationic colloidal gold localizes anionic sites on histological sections. Human eccrine and apocrine sweat glands showed completely different localization and enzyme sensitivity of anionic sites studied with cationic gold. Human sweat glands have many immunohistochemical markers. Some of them are specific to apocrine sweat glands, although many of them stain both eccrine and apocrine sweat glands. Histochemical techniques, especially immunohistochemistry using a confocal laser scanning microscope and in situ hybridization, will further clarify the relationship of the structure and function in human sweat glands.

  15. [Age-dependent morphology of human pineal gland: supravital study].

    PubMed

    Ivanov, S V

    2007-01-01

    On the base of analysis of 5784 events of diagnostic magnetic-resonance tomography studies of the head of patients in radio diagnosis departments the database is formed. Only events (n=411) without cerebral, oncology, endocrine and other pathology are taken in database. The material was grouped to time and date of the study, sex and age in accordance with generally accepted categorization. Maximum linear sizes of pineal gland and hypophysis cerebri in sagittal, axial and coronar projection were measured in all events; volumes of the organs were calculated on the formula of a ball. It is defined that the volume of pineal gland increases from birth till 17-21 year age, gradually falls till the second mature age and is getting stable in old age. The normative factors of the volume of pineal gland and hypophysis cerebri for 8 age groups are determined. "Brain sand" and false cysts in pineal gland can be observed in all age groups. The petrification degree of pineal gland, as of computer tomography, varies from 30 to 277 ed. HV. For the factor of pineal gland volume and factor of cysts frequency in pineal gland a puberty "collapse" is typical, mainly in men.

  16. Three-dimensional culture and identification of human eccrine sweat glands in matrigel basement membrane matrix.

    PubMed

    Li, Haihong; Chen, Lu; Zhang, Mingjun; Tang, Shijie; Fu, Xiaobing

    2013-12-01

    Interactions between the extracellular matrix (ECM) and epithelial cells are necessary for the proper organization and function of the epithelium. In the present study, we show that human eccrine sweat gland epithelial cells cultured in matrigel, a representation of ECM components, constitute a good model for studying three-dimensional reconstruction, wound repair and regeneration and differentiation of the human eccrine sweat gland. In matrigel, epithelial cells from the human eccrine sweat gland form tubular-like structures and then the tubular-like structures coil into sphere-like shapes that structurally resemble human eccrine sweat glands in vivo. One sphere-like shape can be linked to another sphere-like shape or to a cell monolayer via tubular-like structures. Hematoxylin and eosin staining has revealed that the tubular-like structures have a single layer or stratified epithelial cells located peripherally and a lumen at the center, similar to the secretory part or duct part, respectively, of the eccrine sweat gland in sections of skin tissue. Immunohistochemical analysis of the cultures has demonstrated that the cells express CK7, CK19, epithelial membrane antigen and actin. Thus, matrigel promotes the organization and differentiation of epithelial cells from the human eccrine sweat gland into eccrine sweat gland tissues.

  17. Growth patterns for acervuli in human pineal gland

    PubMed Central

    Kim, Jinkyung; Kim, Hyun-Wook; Chang, Soeun; Kim, Jee Woong; Je, Jung Ho; Rhyu, Im Joo

    2012-01-01

    Acervuli are calcified concretions in the pineal gland (PG). Particularly interesting are their incidence and size, which are believed to affect neurological disorders and many physiological functions of PG such as regulating circadian rhythm. Despite long investigations for a century, detailed growth mechanism of acervuli has yet to be studied. Here we study the growth morphology of acervuli in human PGs by a direct visualization in 3-dimension (3-D) using a synchrotron X-ray imaging method. For an entire PG, non-aggregated acervuli show Gaussian distribution in size with 47±28 µm. The 3-D volume rendered images of acervuli reveal that the bumpy surfaces developed by lamination result in the mulberry-like structure. In addition, coalescence of multiple acervuli leads to large-scale lamination on the whole aggregate. We suggest a novel hypothesis on the growth patterns of acervuli by their nucleation density (Nd): i) mulberry-like structure at low Nd, and ii) large-scale lamination on an aggregate at high Nd. PMID:23248747

  18. Matrigel-induced tubular morphogenesis of human eccrine sweat gland epithelial cells.

    PubMed

    Lei, Xia; Liu, Bo; Wu, Jinjin; Lu, Yuangang; Yang, Yadong

    2011-09-01

    Human eccrine sweat glands are tubule-structured glands of the skin that are vital in thermoregulation, secretion, and excretion of water and electrolytes. A study of tubular morphogenesis in vitro would facilitate the development of a tissue engineering model for eccrine sweat glands and other tubule-structured glands. Matrigel, a basement membrane matrix, has been shown to promote differentiation and morphogenesis of many different cell types, including tubular cells. This study investigated the growth, differentiation, and tubular morphogenesis of human eccrine sweat gland epithelial cells cultured in Matrigel. Human eccrine gland epithelial cells were isolated and cultured in vitro. The cell growth in Matrigel was evidenced by the formation of cell clusters, which were observed under an inverted microscope. The internal structure of the cell clusters was further investigated by hematoxylin-eosin (HE) staining and confocal laser scanning microscopy (CLSM) of propidium iodide-stained nuclei. The results demonstrated that although on a plastic surface or in a collagen gel the cells could not form tubular structures, they formed tubular structures when cultured in Matrigel. Consequently, we conclude that Matrigel can promote tubular morphogenesis of human eccrine sweat gland epithelial cells.

  19. A comparative study between mixed-type tumours from human salivary and canine mammary glands

    PubMed Central

    Genelhu, Marisa CLS; Cardoso, Sérgio V; Gobbi, Helenice; Cassali, Geovanni D

    2007-01-01

    Background In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours. Methods Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin. Results After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions. Conclusion There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations. PMID:18045453

  20. A comparative study between mixed-type tumours from human salivary and canine mammary glands.

    PubMed

    Genelhu, Marisa C L S; Cardoso, Sérgio V; Gobbi, Helenice; Cassali, Geovanni D

    2007-11-28

    In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours. Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, beta-catenin, and E-cadherin. After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions. There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations.

  1. Using tracheal segments for replacement of cervical oesophagus: an experimental study.

    PubMed

    Abbasidezfouli, Azizollah; Sharifi, Davood; Sasani, Farhang; Ansari, Damoon; Abarkar, Mohammad; Rahmanijoo, Nasrin; Abbasidezfouli, Golbahar; Sheikhy, Kambiz

    2012-03-01

    Segmental resection and anastomosis of oesophageal lesions are not performed as a routine clinical practice because of complications and associated problems, whereas tracheal resection and anastomosis are a routine clinical practice. In this experimental study, we resected a segment of cervical oesophagus and replaced it with a tracheal segment. In eight dogs (mixed races), weighing 20-30 kg, ageing 1-2 years, under general anaesthesia, through a cervical incision, 5 cm of cervical trachea was separated while preserving its attachments to surrounding fibroareolar tissues. Afterwards, 5 cm of the oesophagus was resected and replaced with a prepared segment of the trachea. Oral liquids were started at the first post-operative day; the animals were kept for 2 months and then euthanized. Quality of swallowing and voice were evaluated. After an autopsy, anastomoses were examined grossly and histopathologically. No complications occurred during surgery. Swallowing function and voice were normal in all eight dogs after the operation. No sign of aspiration was seen in clinical and radiographic examinations after starting oral diet. In autopsy examination, anastomoses were patent without narrowing or abnormal mucosal changes. Remarkable histopathological findings in replaced tracheal segments were squamous metaplasia, atrophy and degeneration of mucosal glands and degeneration of cartilages. Replacement of a segment of the oesophagus with an autogenous tracheal segment is a practical procedure with low complications and can probably be used for the treatment of cervical oesophageal lesions in human beings.

  2. Association of Oversized Tracheal Tubes and Cuff Overinsufflation With Postintubation Tracheal Ruptures

    PubMed Central

    Sudhoff, Tobias H.; Seidl, Rainer O.; Estel, Barbara

    2015-01-01

    Objectives Postintubation tracheal ruptures (PTR) are rare but cause severe complications. Our objective was to investigate the tracheal pattern of injury resulting from cuff inflation of the tracheal tube, to study the two main factors responsible for PTR (cuff overinsufflation and inapplicable tube sizes), and to explain the context, why small women are particularly susceptible to PTR. Methods Experimental study performed on 28 fresh human laryngotracheal specimens (16 males, 12 females) within 24 hours post autopsy. Artificial ventilation was simulated by using an underwater construction and a standard tracheal tube. Tube sizes were selected according to our previously published nomogram. Tracheal lesions were detected visually and tracheal diameters measured. The influence of body size, sex difference and appropriate tube size were investigated according to patient height. Results In all 28 cases, the typical tracheal lesion pattern was a longitudinal median rupture of the posterior trachea. Appropriate tube sizes according to body size caused PTR with significantly higher cuff pressure when compared with oversized tubes. An increased risk of PTR was found in shorter patients, when oversized tubes were used. Sex difference did not have any significant influence. Conclusion This experimental model provides information about tracheal patterns in PTR for the first time. The model confirms by experiment the observations of case series in PTR patients, and therefore emphasizes the importance of correct tube size selection according to patient height. This minimizes the risk of PTR, especially in shorter patients, who have an increased risk of PTR when oversized tubes are used. PMID:26622963

  3. Similarity of GATA-3 Expression between Rat and Human Mammary Glands.

    PubMed

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Tsubura, Airo

    2014-07-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans.

  4. Similarity of GATA-3 Expression between Rat and Human Mammary Glands

    PubMed Central

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Tsubura, Airo

    2014-01-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans. PMID:25352719

  5. PAR-2 receptor-induced effects on human eccrine sweat gland cells.

    PubMed

    L Bovell, Douglas; Kofler, Barbara; Lang, Roland

    2009-01-01

    Serine proteases can induce cell signaling by stimulating G-protein-coupled receptors, called proteinase-activated receptors (PAR's) on a variety of epithelial cells. While PAR-2, one such receptor, activates cell signaling in a secretory cell line derived from human sweat glands, there was no information on their presence and effects on intact sweat glands. PAR-2 presence and activation of eccrine sweat glands isolated from human skin samples was investigated using Western blot analysis, immunohistochemistry, electron microscopy (EM) and Ca(2+) imaging. Anti-human PAR-2 antibody demonstrated the presence of these receptors in eccrine sweat glands. EM showed that PAR-2 activation resulted in degranulation of secretory cells. Ca(2+) imaging using PAR-2 activators demonstrated a two phase increase in [Ca(2+)](i) which was dependent on extracellular Ca(2+) for the second phase, and that the response could be blocked by prior incubation with xestospongin, the IP(3) receptor blocker. The results demonstrated that PAR-2 receptors are present in human sweat gland secretory cells and that these receptors are functionally active and can induce changes associated with secretory events in eccrine glands.

  6. Parotid gland is the main source of human salivary epidermal growth factor

    SciTech Connect

    Thesleff, I.; Viinikka, L.; Saxen, L.; Lehtonen, E.; Perheentupa, J.

    1988-01-01

    To clarify the production of human epidermal growth factor (EGF) by different salivary glands, the authors measured its concentration by radioimmunoassay separately in whole saliva, in parotid gland (PG) saliva and in mixed submandibular (SMG) and sublingual gland (SLG) saliva. Also, they studied the presence of EGF in PG and SMG by immunohistochemistry. The mean concentrations of EDG in PG saliva was higher than in whole saliva, which in turn was higher than in mixed SMG + SLG saliva. No sex difference existed in any salivary gland EGF. Immunohistochemistry revealed EGF in the acinar cells of both PG and SMG, buy only in PG there were prominent EDG deposits in luminal spaces. Their data suggest that EDG is produced by both PG and SMG, but that more of it is secreted from the PG. This result is new and challenges the general view that human salivary EDG is mainly from SMG.

  7. Immunohistochemical evidence suggests intrinsic regulatory activity of human eccrine sweat glands

    PubMed Central

    ZANCANARO, CARLO; MERIGO, FLAVIA; CRESCIMANNO, CATERINA; ORLANDINI, SIMONETTA; OSCULATI, ANTONIO

    1999-01-01

    Immunohistochemistry of normal eccrine sweat glands was performed on paraffin sections of human skin. Immunoreactivity (ir) for neuron specific enolase, S100 protein (S100), regulatory peptides, nitric oxide synthase type I (NOS-I) and choline-acetyltransferase (ChAT) was found in small nerve bundles close to sweat glands. In the glands, secretory cells were labelled with anticytokeratin antibody. Using antibodies to S100, calcitonin gene-related peptide (CGRP) and substance P (SP) a specific distribution pattern was found in secretory cells. Granulated (dark) and parietal (clear) cells were immunopositive for CGRP, and S100 and SP, respectively. Immunoreactivity was diffuse in the cytoplasm for CGRP and S100, and peripheral for SP. Myoepithelial cells were not labelled. Electron microscopy revealed electron dense granules, probably containing peptide, in granulated cells. Using antibodies to NOS-I and ChAT, ir was exclusively found in myoepithelial cells. Immunoreactivity for the atrial natriuretic peptide was absent in sweat glands. These results provide evidence for the presence of both regulatory peptides involved in vasodilation and key enzymes for the synthesis of nitric oxide and acetylcholine in the secretory coil of human sweat glands. It is suggested that human sweat glands are capable of some intrinsic regulation in addition to that carried out by their nerve supply. PMID:10386780

  8. Development of a nude mouse model to study human sebaceous gland physiology and pathophysiology.

    PubMed Central

    Petersen, M J; Zone, J J; Krueger, G G

    1984-01-01

    Study of human sebaceous gland physiology and pathophysiology is limited by lack of an adequate animal model. This study was designed to develop an animal model using human face skin grafted onto the nude mouse to study human sebaceous glands. Full-thickness human face skin was grafted onto 60 adult male nude mice. 4 wk after grafting, androgens, which are known to stimulate sebaceous glands, were administered to test the system. Androgens were administered to 21 animals by implanted catheters that were filled with testosterone (T) or dihydrotestosterone (DHT). Empty catheters were implanted in 15 control animals. Graft biopsies and blood for androgen levels were obtained at time 1 (pre-catheter) and time 2 (26 d after catheter implantation). Three assessments were made on each biopsy: sebaceous gland volume, using an image analyzing computer; sebaceous cell size; and sebaceous gland labeling index. 29 mice completed the study through time 2. In the androgen-treated group, T levels (nanogram per milliliter) five times increased to 4.92 +/- 0.35, and DHT levels (nanogram per milliliter) increased 50 times to 16.70. In the androgen-treated group, sebaceous gland volume (micron 3 X 10(-3) increased from 896 +/- 194 to 3,233 +/- 754 (P less than 0.001), sebaceous cell area (micron 2) increased from 167 +/- 12 to 243 +/- 19 (P less than 0.001), and labeling index (percentage) increased from 2.7 +/- 0.7 to 6.4 +/- 0.9 (P less than 0.01). In the control group, sebaceous gland volume fell from 1,070 +/- 393 to 417 +/- 99 (NS), sebaceous cell size remained the same, and the labeling index fell from 5.1 +/- 1.9 to 3.2 +/- 1.1. After androgen administration, Halowax N-34, a known comedogen, or its vehicle, was applied to 15 grafts for 2-6 wk. Twice as many microcomedones were seen in the Halowax-treated grafts, compared with vehicle-treated grafts at the end of this time period. No visible comedones were produced. This study demonstrated that: (a) human sebaceous glands can

  9. Development of a nude mouse model to study human sebaceous gland physiology and pathophysiology.

    PubMed

    Petersen, M J; Zone, J J; Krueger, G G

    1984-10-01

    Study of human sebaceous gland physiology and pathophysiology is limited by lack of an adequate animal model. This study was designed to develop an animal model using human face skin grafted onto the nude mouse to study human sebaceous glands. Full-thickness human face skin was grafted onto 60 adult male nude mice. 4 wk after grafting, androgens, which are known to stimulate sebaceous glands, were administered to test the system. Androgens were administered to 21 animals by implanted catheters that were filled with testosterone (T) or dihydrotestosterone (DHT). Empty catheters were implanted in 15 control animals. Graft biopsies and blood for androgen levels were obtained at time 1 (pre-catheter) and time 2 (26 d after catheter implantation). Three assessments were made on each biopsy: sebaceous gland volume, using an image analyzing computer; sebaceous cell size; and sebaceous gland labeling index. 29 mice completed the study through time 2. In the androgen-treated group, T levels (nanogram per milliliter) five times increased to 4.92 +/- 0.35, and DHT levels (nanogram per milliliter) increased 50 times to 16.70. In the androgen-treated group, sebaceous gland volume (micron 3 X 10(-3) increased from 896 +/- 194 to 3,233 +/- 754 (P less than 0.001), sebaceous cell area (micron 2) increased from 167 +/- 12 to 243 +/- 19 (P less than 0.001), and labeling index (percentage) increased from 2.7 +/- 0.7 to 6.4 +/- 0.9 (P less than 0.01). In the control group, sebaceous gland volume fell from 1,070 +/- 393 to 417 +/- 99 (NS), sebaceous cell size remained the same, and the labeling index fell from 5.1 +/- 1.9 to 3.2 +/- 1.1. After androgen administration, Halowax N-34, a known comedogen, or its vehicle, was applied to 15 grafts for 2-6 wk. Twice as many microcomedones were seen in the Halowax-treated grafts, compared with vehicle-treated grafts at the end of this time period. No visible comedones were produced. This study demonstrated that: (a) human sebaceous glands can

  10. Effect of Growth Factors on the Proliferation and Gene Expression of Human Meibomian Gland Epithelial Cells

    PubMed Central

    Liu, Shaohui; Kam, Wendy R.; Ding, Juan; Hatton, Mark P.; Sullivan, David A.

    2013-01-01

    Purpose. We hypothesize that growth factors, including epidermal growth factor (EGF) and bovine pituitary extract (BPE), induce proliferation, but not differentiation (e.g., lipid accumulation), of human meibomian gland epithelial cells. We also hypothesize that these actions involve a significant upregulation of genes linked to cell cycle processes, and a significant downregulation of genes associated with differentiation. Our objective was to test these hypotheses. Methods. Immortalized human meibomian gland and conjunctival epithelial cells were cultured for varying time periods in the presence or absence of EGF, BPE, EGF + BPE, or serum, followed by cell counting, neutral lipid staining, or RNA isolation for molecular biological procedures. Results. Our studies show that growth factors stimulate a significant, time-dependent proliferation of human meibomian gland epithelial cells. These effects are associated with a significant upregulation of genes linked to cell cycle, DNA replication, ribosomes, and translation, and a significant decrease in those related to cell differentiation, tissue development, lipid metabolic processes, and peroxisome proliferator-activated receptor signaling. Serum-induced differentiation, but not growth factor-related proliferation, elicits a pronounced lipid accumulation in human meibomian gland epithelial cells. This lipogenic response is unique, and is not duplicated by human conjunctival epithelial cells. Conclusions. Our results demonstrate that EGF and BPE stimulate human meibomian gland epithelial cells to proliferate. Further, our findings show that action is associated with an upregulation of cell cycle and translation ontologies, and a downregulation of genetic pathways linked to differentiation and lipid biosynthesis. PMID:23493293

  11. Cidea control of lipid storage and secretion in mouse and human sebaceous glands.

    PubMed

    Zhang, Shasha; Shui, Guanghou; Wang, Guanqun; Wang, Chao; Sun, Shuhong; Zouboulis, Christos C; Xiao, Ran; Ye, Jing; Li, Wei; Li, Peng

    2014-05-01

    Sebaceous glands are skin appendages that secrete sebum onto hair follicles to lubricate the hair and maintain skin homeostasis. In this study, we demonstrated that Cidea is expressed at high levels in lipid-laden mature sebocytes and that Cidea deficiency led to dry hair and hair loss in aged mice. In addition, Cidea-deficient mice had markedly reduced levels of skin surface lipids, including triacylglycerides (TAGs) and wax diesters (WDEs), and these mice were defective in water repulsion and thermoregulation. Furthermore, we observed that Cidea-deficient sebocytes accumulated a large number of smaller-sized lipid droplets (LDs), whereas overexpression of Cidea in human SZ95 sebocytes resulted in increased lipid storage and the accumulation of large LDs. Importantly, Cidea was highly expressed in human sebaceous glands, and its expression levels were positively correlated with human sebum secretion. Our data revealed that Cidea is a crucial regulator of sebaceous gland lipid storage and sebum lipid secretion in mammals and humans.

  12. Isolation, culture and phenotypic characterization of human sweat gland epithelial cells.

    PubMed

    Gao, Yunhe; Li, Meiying; Zhang, Xueyan; Bai, Tingting; Chi, Guanfan; Liu, Jin Yu; Li, Yulin

    2014-10-01

    Sweat gland epithelial cells (SGECs) have been identified as essential for the regeneration of sweat glands and for the construction of skin substitutes containing skin appendages. Consequently, the isolation, culture and phenotypic characterization of SGECs are of paramount importance. In the present study study, human sweat glands were isolated by pipetting under a phase contrast microscope following digestion with collagenase type I. Subsequently, a microscopic organ culture technique was used for the primary culture of human SGECs, and the culture conditions were modified in order to achieve optimal cell growth status. Primary SGECs were identified based on their expression of markers specific for sweat glands, including carcinoembryonic antigen (CEA), CK7, CK8, CK14, CK15, CK18 and CK19. We explored the possible presence of stem cells in human sweat glands by detecting their expression of leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5). Primary SGECs achieved a good growth state when cultured under serum-free conditions. After one passage, the cells cultured in keratinocyte serum-free medium with 1% fetal bovine serum (FBS) still showed a prominent proliferative activity. Phenotypic analysis by immunofluorescence microscopy, reverse transcription-polymerase chain reaction (RT-PCR), and western blot analysis demonstrated the expression of sweat gland-specific markers, including CEA, CK7, CK8, CK14, CK15, CK18 and CK19. In addition, RT-PCR and immunochemistry detected the expression of LGR5. In comparison with traditional serum-containing conditions, serum-free culture provides the preferred culture conditions for human SGECs. LGR5 is a novel marker that identifies human sweat gland-derived stem cells.

  13. Electron microprobe analysis of human labial gland secretory granules in cystic fibrosis

    SciTech Connect

    Izutsu, K.; Johnson, D.; Schubert, M.; Wang, E.; Ramsey, B.; Tamarin, A.; Truelove, E.; Ensign, W.; Young, M.

    1985-06-01

    X-ray microanalysis of freeze-dried labial gland cryosections revealed that Na concentration was doubled and the Ca/S concentration ratio was decreased in secretory granules of labial glands from patients with cystic fibrosis (CF) when compared with glands from normal subjects. Other results suggested that the decrease in the Ca/S concentration ratio resulted from an increase in S concentration. These findings imply that mucous granules in labial saliva showed a CF-related increase in Na and S content, and such changes would be expected to affect the rheology of the mucus after exocytosis. In contrast with a previous study in human parotid glands, no evidence was found for CF-related changes in cytoplasmic or nuclear Na, K, and Ca concentrations. Significant elemental differences were found between secretory granules and nuclei and cytoplasm of control cells.

  14. Expression of Anti-apoptotic Protein BAG3 in Human Sebaceous Gland Carcinoma of the Eyelid.

    PubMed

    Yunoki, Tatsuya; Tabuchi, Yoshiaki; Hayashi, Atsushi

    2017-04-01

    Bcl-2-associated athanogene 3 (BAG3), a co-chaperone of heat shock protein 70 (HSP70), has been shown to play a role in anti-apoptosis of various malignant tumors. In this study, the expression of BAG3 was examined in human sebaceous gland carcinoma of the eyelid. The expression of BAG3 was evaluated by immunohistochemistry of surgical samples from 5 patients with sebaceous gland carcinoma in the eyelid. BAG3 was positive diffusely in the cytoplasm in all patients. The average positive rate of BAG3 was 73.0±26.0% in tumor cells of all patients. BAG3 was highly expressed in sebaceous gland carcinoma of the eyelid. BAG3 may play an important role in the pathogenesis and progression of sebaceous gland carcinoma of the eyelid. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

    PubMed

    Pivonello, Rosario; Waaijers, Marlijn; Kros, Johan M; Pivonello, Claudia; de Angelis, Cristina; Cozzolino, Alessia; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

    2017-08-01

    The dopamine D2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D2 receptor. D2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D2 receptors. D2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

  16. Differentiation of primary human submandibular gland cells cultured on basement membrane extract.

    PubMed

    Szlávik, Vanda; Szabó, Bálint; Vicsek, Tamás; Barabás, József; Bogdán, Sándor; Gresz, Veronika; Varga, Gábor; O'Connell, Brian; Vág, János

    2008-11-01

    There is no effective treatment for the loss of functional salivary tissue after irradiation for head and neck cancer or the autoimmune disease Sjögren's syndrome. One possible approach is the regeneration of salivary glands from stem cells. The present study aimed to investigate whether small pieces of human submandiblar gland tissue contain elements necessary for the reconstruction of salivary rudiments in vitro via acinar and ductal cell differentiation. Primary submandibular gland (primary total human salivary gland; PTHSG) cells were isolated from human tissue and cultured in vitro using a new method in which single cells form an expanding epithelial monolayer on plastic substrates. Differentiation, morphology, number, and organization of these cells were then followed on basement membrane extract (BME) using RNA quantitation (amylase, claudin-1 (CLN1), CLN3, kallikrein, vimentin), immunohistochemistry (amylase and occludin), viability assay, and videomicroscopy. On the surface of BME, PTHSG cells formed acinotubular structures within 24 h, did not proliferate, and stained for amylase. In cultures derived from half of the donors, the acinar markers amylase and CLN3 were upregulated. The PTHSG culture model suggests that human salivary gland may be capable of regeneration via reorganization and differentiation and that basement membrane components play a crucial role in the morphological and functional differentiation of salivary cells.

  17. Distribution and Size of Mucous Glands in the Ferret Tracheobronchial Tree

    PubMed Central

    HAJIGHASEMI-OSSAREH, MOHAMMAD; BORTHWELL, RACHEL M.; STEVENS, JEREMY E.; FINKBEINER, WALTER E.; WIDDICOMBE, JONATHAN H.

    2014-01-01

    A transgenic ferret model of cystic fibrosis has recently been generated. It is probable that malfunction of airway mucous glands contributes significantly to the airway pathology of this disease. The usefulness of the ferret model may therefore depend in part on how closely the airway glands of ferrets resemble those of humans. Here, we show that in the ferret trachea glands are commonest in its most ventral aspect and disappear about half way up the lateral walls; they are virtually absent from the dorsal membranous portion. Further, the aggregate volume of glands per unit mucosal surface declines progressively by about 60% between the larynx and the carina. The average frequency of glands openings for the ferret trachea as a whole is only about one-fifth that in humans (where gland openings are found at approximately the same frequency throughout the trachea). Glands in the ferret trachea are on average about one-third the size of those in the human. Therefore, the aggregate volume of tracheal glands (per unit mucosal surface area) in the ferret is only about 6% that in humans. As in other mammalian species, airway glands in the ferret disappear at an airway internal diameter of ~1 mm, corresponding approximately in this species to airway generation 6. PMID:24106034

  18. Distribution and size of mucous glands in the ferret tracheobronchial tree.

    PubMed

    Hajighasemi-Ossareh, Mohammad; Borthwell, Rachel M; Lachowicz-Scroggins, Marrah; Stevens, Jeremy E; Finkbeiner, Walter E; Widdicombe, Jonathan H

    2013-11-01

    A transgenic ferret model of cystic fibrosis has recently been generated. It is probable that malfunction of airway mucous glands contributes significantly to the airway pathology of this disease. The usefulness of the ferret model may therefore depend in part on how closely the airway glands of ferrets resemble those of humans. Here, we show that in the ferret trachea glands are commonest in its most ventral aspect and disappear about half way up the lateral walls; they are virtually absent from the dorsal membranous portion. Further, the aggregate volume of glands per unit mucosal surface declines progressively by about 60% between the larynx and the carina. The average frequency of glands openings for the ferret trachea as a whole is only about one-fifth that in humans (where gland openings are found at approximately the same frequency throughout the trachea). Glands in the ferret trachea are on average about one-third the size of those in the human. Therefore, the aggregate volume of tracheal glands (per unit mucosal surface area) in the ferret is only about 6% that in humans. As in other mammalian species, airway glands in the ferret disappear at an airway internal diameter of ∼1 mm, corresponding approximately in this species to airway generation 6. Copyright © 2013 Wiley Periodicals, Inc.

  19. Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells.

    PubMed

    Hirayama, Masatoshi; Ko, Shigeru B H; Kawakita, Tetsuya; Akiyama, Tomohiko; Goparaju, Sravan K; Soma, Atsumi; Nakatake, Yuhki; Sakota, Miki; Chikazawa-Nohtomi, Nana; Shimmura, Shigeto; Tsubota, Kazuo; Ko, Minoru S H

    2017-01-01

    Dry eye disease is the most prevalent pathological condition in aging eyes. One potential therapeutic strategy is the transplantation of lacrimal glands, generated in vitro from pluripotent stem cells such as human embryonic stem cells, into patients. One of the preceding requirements is a method to differentiate human embryonic stem cells into lacrimal gland epithelium cells. As the first step for this approach, this study aims to identify a set of transcription factors whose overexpression can promote the differentiation of human embryonic stem cells into lacrimal gland epithelium-like cells. We performed microarray analyses of lacrimal glands and lacrimal glands-related organs obtained from mouse embryos and adults, and identified transcription factors enriched in lacrimal gland epithelium cells. We then transfected synthetic messenger RNAs encoding human orthologues of these transcription factors into human embryonic stem cells and examined whether the human embryonic stem cells differentiate into lacrimal gland epithelium-like cells by assessing cell morphology and marker gene expression. The microarray analysis of lacrimal glands tissues identified 16 transcription factors that were enriched in lacrimal gland epithelium cells. We focused on three of the transcription factors, because they are expressed in other glands such as salivary glands and are also known to be involved in the development of lacrimal glands. We tested the overexpression of various combinations of the three transcription factors and PAX6, which is an indispensable gene for lacrimal glands development, in human embryonic stem cells. Combining PAX6, SIX1, and FOXC1 caused significant changes in morphology, i.e., elongated cell shape and increased expression (both RNAs and proteins) of epithelial markers such as cytokeratin15, branching morphogenesis markers such as BARX2, and lacrimal glands markers such as aquaporin5 and lactoferrin. We identified a set of transcription factors enriched in

  20. Cancer Secretome May Influence BSP and DSP Expression in Human Salivary Gland Cells.

    PubMed

    Hamilton, Samantha Lynn; Ferando, Blake; Eapen, Asha Sarah; Yu, Jennifer Chian; Joy, Anita Rose

    2017-03-01

    One of the biggest challenges in managing head and neck cancers, especially salivary gland cancers, is the identification of secreted biomarkers of the disease that can be evaluated noninvasively. A relevant source of enriched tumor markers could potentially be found in the tumor secretome. Although numerous studies have evaluated secretomes from various cancers, the influence of the cancer secretome derived from salivary gland cancers on the behavior of normal cells has not yet been elucidated. Our data indicate that secretome derived from salivary gland cancer cells can influence the expression of two potential biomarkers of oral cancer-namely, bone sialoprotein (BSP) and dentin sialoprotein (DSP)-in normal salivary gland cells. Using routine immunohistochemistry, immunofluorescence, and immunoblotting techniques, we demonstrate an enrichment of BSP and DSP in human salivary gland (HSG) cancer tissue, unique localizations of BSP and DSP in HSG cancer cells, and enriched expression of BSP and DSP in normal salivary gland cells exposed to a cancer secretome. The secretome domain of the cancer microenvironment could alter signaling cascades responsible for normal cell proliferation, migration, and invasion, thus enhancing cancer cell survival and the potential for cancer progression. The cancer secretome may be critical in maintaining and stimulating "cancer-ness," thus potentially promoting specific hallmarks of metastasis.

  1. Individual variations in structure and function of human eccrine sweat gland.

    PubMed

    Sato, K; Sato, F

    1983-08-01

    The mechanisms underlying variations in perspiration rate at the glandular level are still poorly understood. Human eccrine sweat glands were dissected from the back of 12 adults, cannulated, and stimulated in vitro with methacholine (Mch). The maximal sweat rate and pKA for Mch determined from the dose-response curve for each individual were compared with the anatomic dimensions of the isolated secretory tubules. There was significant correlation between Mch sensitivity (pKA) and the size of the sweat gland, sweat rate per gland, sweat rate per unit length of the secretory tubule, and sweat rate per unit glandular volume. The sweat glands from individuals judged to be poor sweaters exhibited smaller size, lower secretory activity both in vivo and in vitro, and decreased Mch sensitivity compared with glands from physically fit individuals. We conclude that the increased Mch sensitivity and glandular hypertrophy are the two important features of functionally active sweat glands and infer that these parameters could improve as a result of acclimatization to physical exercise and/or heat.

  2. Differential sorting of human parathyroid hormone after transduction of mouse and rat salivary glands.

    PubMed

    Adriaansen, J; Perez, P; Goldsmith, C M; Zheng, C; Baum, B J

    2008-10-01

    Gene transfer to salivary glands leads to abundant secretion of transgenic protein into either saliva or the bloodstream. This indicates significant clinical potential, depending on the route of sorting. The aim of this study was to probe the sorting characteristics of human parathyroid hormone (hPTH) in two animal models for salivary gland gene transfer. PTH is a key hormone regulating calcium levels in the blood. A recombinant serotype 5 adenoviral vector carrying the hPTH cDNA was administered to the submandibular glands of mice and rats. Two days after delivery, high levels of hPTH were found in the serum of mice, leading to elevated serum calcium levels. Only low amounts of hPTH were found in the saliva. Two days after vector infusion into rats, a massive secretion of hPTH was measured in saliva, with little secretion into serum. Confocal microscopy showed hPTH in the glands, localized basolaterally in mice and apically in rats. Submandibular gland transduction was effective and the produced hPTH was biologically active in vivo. Whereas hPTH sorted toward the basolateral side in mice, in rats hPTH was secreted mainly at the apical side. These results indicate that the interaction between hPTH and the cell sorting machinery is different between mouse and rat salivary glands. Detailed studies in these two species should result in a better understanding of cellular control of transgenic secretory protein sorting in this tissue.

  3. The Influence of 13-cis Retinoic Acid on Human Meibomian Gland Epithelial Cells

    PubMed Central

    Ding, Juan; Kam, Wendy R.; Dieckow, Julia; Sullivan, David A.

    2013-01-01

    Purpose. Meibomian gland dysfunction (MGD) is a primary cause of dry eye disease. One of the risk factors for MGD is exposure to 13-cis retinoic acid (13-cis RA), a metabolite of vitamin A. However, the mechanism is not well understood. We hypothesize that 13-cis RA inhibits cell proliferation, promotes cell death, alters gene and protein expressions, and attenuates cell survival pathways in human meibomian gland epithelial cells. Methods. To test our hypotheses, immortalized human meibomian gland epithelial cells were cultured with or without 13-cis RA for varying doses and time. Cell proliferation, cell death, gene expression, and proteins involved in proliferation/survival and inflammation were evaluated. Results. We found that 13-cis RA inhibited cell proliferation, induced cell death, and significantly altered the expression of 6726 genes, including those involved in cell proliferation, cell death, differentiation, keratinization, and inflammation, in human meibomian gland epithelial cells. Further, 13-cis RA also reduced the phosphorylation of Akt and increased the generation of interleukin-1β and matrix metallopeptidase 9. Conclusions. Exposure to 13-cis RA inhibits cell proliferation, increases cell death, alters gene expression, changes signaling pathways, and promotes inflammatory mediator and protease expression in meibomian gland epithelial cells. These effects may be responsible, at least in part, for the 13-cis RA–related induction of MGD. PMID:23722388

  4. Single Cell Clones Purified from Human Parotid Glands Display Features of Multipotent Epitheliomesenchymal Stem Cells

    PubMed Central

    Yi, TacGhee; Lee, Songyi; Choi, Nahyun; Shin, Hyun-Soo; Kim, Junghee; Lim, Jae-Yol

    2016-01-01

    A better understanding of the biology of tissue-resident stem cell populations is essential to development of therapeutic strategies for regeneration of damaged tissue. Here, we describe the isolation of glandular stem cells (GSCs) from a small biopsy specimen from human parotid glands. Single colony-forming unit-derived clonal cells were isolated through a modified subfractionation culture method, and their stem cell properties were examined. The isolated clonal cells exhibited both epithelial and mesenchymal stem cell (MSC)-like features, including differentiation potential and marker expression. The cells transiently displayed salivary progenitor phenotypes during salivary epithelial differentiation, suggesting that they may be putative multipotent GSCs rather than progenitor cells. Both epithelial and mesenchymal-expressing putative GSCs, LGR5+CD90+ cells, were found in vivo, mostly in inter-secretory units of human salivary glands. Following in vivo transplantation into irradiated salivary glands of mice, these cells were found to be engrafted around the secretory complexes, where they contributed to restoration of radiation-induced salivary hypofunction. These results showed that multipotent epitheliomesenchymal GSCs are present in glandular mesenchyme, and that isolation of homogenous GSC clones from human salivary glands may promote the precise understanding of biological function of bona fide GSCs, enabling their therapeutic application for salivary gland regeneration. PMID:27824146

  5. Epimorphin-induced differentiation of human umbilical cord mesenchymal stem cells into sweat gland cells.

    PubMed

    Tao, R; Sun, T-j; Han, Y-q; Xu, G; Liu, J; Han, Y-f

    2014-01-01

    Mesenchymal stem cells (MSCs) have the potential for multi-directional differentiation and can be induced to differentiate into sweat gland cells under certain conditions. Epimorphin (EPM) plays an important role in the promotion of epithelial cell morphogenesis; however, its effect on sweat gland-cell differentiation of MSCs remains unknown. The purpose of this study was to investigate how EPM regulates sweat gland cell differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs). hUCMSCs were labeled with 5-bromo-2-deoxyuridine (BrdU) before differentiation induction; were cultured in common culture medium, conditioned medium, or EPM-conditioned medium; and then induced to differentiate into sweat gland cells. Five days after induction, the expression rates of the sweat gland-cell antigens cytokeratin 14 (CK14), cytokeratin 19 (CK19), and carcinoembryonic antigen (CEA) in hUCMSCs were detected by flow cytometry, and the messenger ribonucleic acid (mRNA) and protein levels of CK14, CK19, and CEA were determined by reverse transcription polymerase chain reaction (RT-PCR) and western blot, respectively. hUCMSCs can be induced to differentiate into sweat gland cells in conditioned medium, and expression of CEA was detected by immunofluorescence assay. Flow cytometry results showed that the expression rate of the sweat gland-cell antigens CK14, CK19, and CEA in the conditioned medium were significantly lower than that in the EPM conditioned medium (p < 0.05). RT-PCR and western blot results showed that the mRNA and protein levels of CK14, CK19, and CEA in the conditioned medium were all significantly lower than that in the EPM-conditioned medium (p < 0.01). These results suggest that EPM can effectively induce the differentiation of hUCMSCs into sweat gland cells.

  6. Differential expression of dipeptidyl peptidase IV in human versus cynomolgus monkey skin eccrine sweat glands.

    PubMed

    Pantano, Serafino; Dubost, Valérie; Darribat, Katy; Couttet, Philippe; Grenet, Olivier; Busch, Steven; Moulin, Pierre

    2013-12-01

    Dipeptidyl peptidase IV (DPP4) is a peptidase whose inhibition is beneficial in Type II diabetes treatment. Several evidences suggest potential implication of DPP4 in skin disorders such as psoriasis, keloids and fibrotic skin diseases where its inhibition could also be beneficial. DPP4 expression in human skin was described mainly in dermal fibroblasts and a subset of keratinocytes in the basal layer. Of importance in the perspective of preclinical experimentation, DPP4 distribution in skin of non-human primate species has not been documented. This report evidences unexpected differences between a set of human and cynomolgus monkey skin samples revealing a major expression of DPP4 in eccrine sweat glands of cynomolgus monkeys but not in humans. This represents a unique distinctive feature compared to the conserved expression of dipeptidyl peptidases 8 and 9 and potential relevant DPP4 substrates such as neuropeptide Y (NPY) and receptors (NPY-receptor 1 and Neurokinin receptor). Finally the observation that cathepsin D, an unrelated protease, shows the opposite expression compared to DPP4 (present in human but not in cynomolgus monkey eccrine sweat glands) could indicate that human eccrine sweat glands evolved a divergent protease repertoire compared to non-human primates. These unexpected differences in the eccrine sweat glands protease repertoire will need to be confirmed extending the analysis to a major number of donors but could imply possible biochemical divergences, reflecting the functional evolution of the glands and the control of their activity. Our findings also demonstrate that non-human primates studies aiming at understanding DPP4 function in skin biology are not readily translatable to human.

  7. Morphology and morphometry of the human sublingual glands in mouth floor enlargements of edentulous patients

    PubMed Central

    de SÁ, Josiane Costa Rodrigues; TOLENTINO, Elen de Souza; AZEVEDO-ALANIS, Luciana Reis; IWAKI FILHO, Liogi; LARA, Vanessa Soares; DAMANTE, José Humberto

    2013-01-01

    Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. Objective The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. Material and Methods Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20) and edentulous cadavers (n=20). The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p<0.05). Results Acinar atrophy, duct-like structures, mononuclear infiltrates, replacement of parenchyma with fibrous/adipose tissue, mucous extravasation and oncocytosis were similar between the groups (p>0.05). Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043). The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05). Conclusion The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements. PMID:24473720

  8. Morphology and morphometry of the human sublingual glands in mouth floor enlargements of edentulous patients.

    PubMed

    Sá, Josiane Costa Rodrigues de; Tolentino, Elen de Souza; Azevedo-Alanis, Luciana Reis; Iwaki Filho, Liogi; Lara, Vanessa Soares; Damante, José Humberto

    2013-01-01

    Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20) and edentulous cadavers (n=20). The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p<0.05). Acinar atrophy, duct-like structures, mononuclear infiltrates, replacement of parenchyma with fibrous/adipose tissue, mucous extravasation and oncocytosis were similar between the groups (p>0.05). Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043). The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05). The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements.

  9. "Sebocytes' makeup": novel mechanisms and concepts in the physiology of the human sebaceous glands.

    PubMed

    Tóth, Balázs I; Oláh, Attila; Szöllosi, Attila G; Czifra, Gabriella; Bíró, Tamás

    2011-06-01

    The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this "mini-organ", the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development ("a living fossil with a past but no future"), and was thought to solely act as a producer of sebum, a lipid-enriched oily substance which protects our skin (and hence the body) against various insults. However, due to emerging research activities of the past two decades, it has now become evident that the sebaceous gland is not only a "passive" cutaneous "relic" to establish the physico-chemical barrier function of the skin against constant environmental challenges, but it rather functions as an "active" neuro-immuno-endocrine cutaneous organ. This review summarizes recent findings of sebaceous gland research by mainly focusing on newly discovered physiological functions, novel regulatory mechanisms, key events in the pathology of the gland, and future directions in both experimental and clinical dermatology.

  10. Estrogen receptors in human thyroid gland. An immunohistochemical study.

    PubMed

    Arain, Shoukat A; Shah, Munawar H; Meo, Sultan A; Jamal, Qamar

    2003-02-01

    Thyroid diseases affect women approximately 3 times more frequently than men. It has been suggested that the female sex steroids stimulate thyroid growth such as in the breast. Seventeen beta-estradiol, the major estrogen in the body acts via estrogen receptors (ER) present in the nucleus of the cell. The aim of the study is to determine the ER status in the thyroid gland tissues. Our study was based on immunohistochemical staining for ER. Fifty previously diagnosed cases of various thyroid lesions were selected from the Surgical Pathology Records of Pathology Department, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Center, Karachi, Pakistan between March and August 2000. The staining was performed on formalin-fixed paraffin embedded tissues using monoclonal anti-ER antibody (clone 1D5). Out of 50 cases, 8 were nodular goiter, 9 cases of adenoma, 19 papillary carcinoma, 10 follicular and 4 cases were of medullary carcinoma. Surrounding normal tissue was available in 25 (50%) cases, 4 non-neoplastic and 21 neoplastic lesions. Out of 50 cases, 10 (20%) were males and 40 (80%) were females, the youngest patient was a 14-year-old female and the eldest patient was a 56-year-old male. Despite the availability of normal thyroid tissue and a wide range of lesions, none of our cases showed positive staining. In contrary to many earlier reports by immunohistochemical method using monoclonal antibody (clone 1D5) on formalin-fixed paraffin-embedded thyroid tissues, the ER are not detectable. The effect of estrogen on thyroid gland may be indirect one.

  11. Glycoproteins of the carcinoembryonic antigen (CEA) family are expressed in sweat and sebaceous glands of human fetal and adult skin.

    PubMed

    Metze, D; Bhardwaj, R; Amann, U; Eades-Perner, A M; Neumaier, M; Wagener, C; Jantscheff, P; Grunert, F; Luger, T A

    1996-01-01

    The carcinoembryonic antigen (CEA) family comprises a group of glycoproteins including the classical CEA, nonspecific cross-reacting antigens (NCA), and biliary glycoprotein (BGP). CEA glycoproteins have been identified in many glandular and mucosal tissues. In view of their putative role in cell adhesion, protein sorting, and signal transduction, CEA glycoproteins are thought to be involved in embryogenesis, architectual integrity, and secretory mechanisms of glandular epithelia. Since there are few data available on the expression of CEA-like proteins in human skin, the aim of this study was to immunohistochemically specify and localize the CEA glycoproteins in cutaneous adult and fetal glands using a panel of well-characterized antibodies. The secretory parts of eccrine sweat glands expressed CEA, NCA-90, and BGP, whereas apocrine glands remained unreactive for CEA glycoproteins. The ductal epithelia of both eccrine and apocrine glands contained CEA and NCA-90. Sebaceous glands were stained for BGP only. Electron microscopy of sweat glands showed CEA glycoprotein expression in cytoplasmic organelles and on microvilli lining the ductal surface. In sebaceous glands, BGP were demonstrated in small vesicles and along the cell membranes of differentiating sebocytes. Fetal development of cutaneous glands was associated with early expression of CEA glycoproteins. Additionally, mice transgenic for human CEA were shown to express CEA in sweat glands. The overall distribution of CEA glycoproteins in cutaneous glands was consistent with that in epithelia of other glandular tissues.

  12. Left heart structures in human neonates with congenital diaphragmatic hernia and the effect of fetal endoscopic tracheal occlusion.

    PubMed

    Rocha, Luciane Alves da; Byrne, Francesca A; Keller, Roberta L; Miniati, Doug; Brook, Michael M; Silverman, Norman H; Moon-Grady, Anita J

    2014-01-01

    Small left heart structures are observed in fetuses with left-sided congenital diaphragmatic hernia (CDH). Fetoscopic tracheal occlusion (FETO) in mid-gestation promotes lung growth in fetuses with CDH, however cardiac effects of FETO are poorly described. We studied the effects of FETO on cardiac structure size at birth, hypothesizing that left heart structures would be larger in neonates who had undergone fetal intervention. We performed retrospective measurements of atrioventricular and semilunar valve and pulmonary artery diameters, ventricular lengths, left ventricular end-diastolic volume indexed (LVEDVi) to body surface area. 35 patients were studied (9 FETO, 26 controls). All fetuses had liver herniation and a lung-to-head ratio <1 at fetal presentation. At birth the intervention group had larger LVEDVi (16.8 vs. 12.76 ml/m(2), p < 0.05), LV length Z-score (-2.05 vs. -4, p < 0.01), LV:RV length ratio (1.43 vs. 1.04, p < 0.05), LPA diameter Z-score (+1.71 vs. -1.04, p < 0.05), and better growth of aortic valve (-2.18 FETO, -3.3 controls, p < 0.01). There was a trend toward higher LV output in the FETO group. Left heart structures and LPA were larger postnatally in patients with CDH who underwent FETO than in those who did not. Hemodynamic alterations are introduced with tracheal occlusion that are associated with alterations in ventricular loading and may influence growth. © 2013 S. Karger AG, Basel.

  13. Tracheal malignant melanoma: successful outcome with tracheal resection.

    PubMed

    Terra, Ricardo Mingarini; Minamoto, Helio; Junqueira, Jader J M; Falzoni, Roberto; Pêgo-Fernandes, Paulo Manuel; Jatene, Fabio Biscegli

    2008-07-01

    Primary tracheal malignant melanomas are uncommon neoplasms: only five cases have been reported. Different therapeutic approaches are described, with a short life expectancy observed. We report a case of a young woman with a primary tracheal malignant melanoma who underwent complete tracheal resection and is free of disease 4 years after surgical treatment.

  14. Salivary glands and human congenital cytomegalovirus infection: What happens in early fetal life?

    PubMed

    Gabrielli, Liliana; Bonasoni, Maria Paola; Chiereghin, Angela; Piccirilli, Giulia; Santini, Donatella; Pavia, Claudia; Turello, Gabriele; Squarzoni, Diego; Lazzarotto, Tiziana

    2017-02-01

    Salivary glands are a site of human cytomegalovirus (CMV) replication, latency, and persistence. Prolonged secretion of virus in saliva for months following a primary infection contribute to horizontal transmission. In order to better understand the early effects of CMV on salivary glands and the mechanisms of viral persistent replication, submandibular glands of six CMV congenitally infected fetuses at 21 weeks gestation were studied. Three fetuses at the same gestational age from CMV-seronegative women were compared as negative controls. Tissue viral load and the type of inflammatory infiltrate were evaluated. Moreover, development and branching of salivary glands, the number of myoepithelial cells, cellular proliferation, and expression of secretory proteins of the saliva (Gross Cystic Disease Fluid Protein-15 and lysozyme) were studied. A low viral load and rare CMV-positive cells associated with T CD8 cytotoxic lymphocytes were observed. Branching was impaired with a decrease in terminal acinar structures, the number of myoepithelial cells, and cellular proliferation were reduced. In addition, a compromised secretion of defense proteins involved in the oral humoral immunity was observed. These findings suggest that CMV may affect salivary glands, impairing structure development and secretion of defense proteins, probably responsible for the prolonged viral shedding in saliva. J. Med. Virol. 89:318-323, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Construction of a recombinant human FGF1 expression vector for mammary gland-specific expression in human breast cancer cells.

    PubMed

    Zhou, Yang; Ren, Linzhu; Zhu, Jianguo; Yan, Sen; Wang, Haijun; Song, Na; Li, Li; Ouyang, Hongsheng; Pang, Daxin

    2011-08-01

    Human Fibroblast growth factor 1 (FGF1) has been recognized as a valuable protein drug for the treatment of many diseases because of its multiple functions in regulating a variety of biological processes involved in embryonic development, cell growth and differentiation, morphogenesis, tissue repair, and others. The aim of this study was to develop an FGF1 mammary gland-specific expression vector to produce FGF1 on a large scale from transgenic cows to meet the demand for FGF1 in medical use. In this study, we generated an FGF1 mammary gland-specific expression vector and validated its function in human MCF-7 cells. This vector was shown to successfully express functional FGF1, thus potentially enabling the generation of transgenic cows to be used as mammary gland bioreactors.

  16. Calcification in the human choroid plexus, meningiomas and pineal gland.

    PubMed

    Alcolado, J C; Moore, I E; Weller, R O

    1986-01-01

    Calcification in the stroma of adult telencephalic choroid plexus was studied of 20 postmortem brains and one biopsy by light microscopy, transmission and scanning electron microscopy and compared with calcification in psammoma bodies in normal arachnoid, five spinal meningiomas and in calcospherites of six pineal glands. Fifteen fetal and newborn choroid plexuses were also examined by light microscopy. Calcium deposition was observed in the subepithelial regions of the adult choroid plexus, in the walls of blood vessels but was mostly seen in spherical psammoma bodies. Collagen whorls 20-60 microns in diameter and surrounded by arachnoid cells, were observed in the stroma of the choroid plexus; calcium, phosphorous and iron were deposited in the collagen whorls to form psammoma bodies. Matrix vesicles and spicules resembling hydroxyapatite were associated with the arachnoid cells surrounding the collagen whorls and with the collagen fibres within the whorls. The dense amorphous calcified core of each psammoma body was surrounded by an outer coating of entwined collagen fibres readily visible by scanning electron microscopy. Similar psammoma bodies were occasionally observed in normal arachnoid. Psammoma bodies in meningiomas resembled those in the choroid plexus stroma. Calcospherites in the pineal differed from psammoma bodies; they were lobulated, more irregular in shape and did not have a collagen base. The results of this study suggest that psammoma bodies in the choroid plexus, as in meningiomas, form by a process of dystrophic calcification associated with arachnoid cells and collagen fibres. The presence of iron in the choroid plexus psammoma bodies may be a result of haemorrhage into the stroma. The mechanism of calcification in pineal remains unclear.

  17. Primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy

    PubMed Central

    Abike, Faruk; Bingol, Banu; Temizkan, Osman; Dunder, Ilkkan; Kilic, Gokhan Sami; Cetin, Guven; Gundogdu, Cem

    2011-01-01

    Cancer complicates approximately 0.1% of all pregnancies. Primary tracheal carcinoma is one of very rarely seen tumors and the rate of its being seen makes up approximately % 0.2 of all tumors of respiratory tract. The patient, 28 years old, who has 28-weeks-pregnant, was diagnosed with primary tracheal adenocystic carcinoma. Patient was made operation as thoracotomy and tracheal tumor was removed at the 28th week of pregnancy. Patient was delivered with sectio abdominale at the 39th week of pregnancy. Primary tracheal adenocystic carcinoma is very rarely seen tumors and it is the first tracheal ACC with pregnancy case in literature to have been detected and surgically treated during pregnancy. We discussed primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy with literature. PMID:22066040

  18. Western blot confirmation of the H+/K+-ATPase proton pump in the human larynx and submandibular gland.

    PubMed

    Altman, Kenneth W; Kinoshita, Yayoi; Tan, Melin; Burstein, David; Radosevich, James A

    2011-11-01

    The authors have previously demonstrated the H(+)/K(+)-ATPase (proton pump) in human larynx and lung glands via immunohistochemistry (IHC). The present hypothesis is that the proton pump is expressed in other seromucinous glands of the digestive tract that can be confirmed by IHC and Western blot analysis. Prospective controlled tissue analysis study. Academic medical institution. Ten anonymous fresh-frozen donor specimens were obtained, comprising 3 submandibular glands, 4 larynges, and 3 normal stomach specimens for control. Submandibular gland sections were immunostained with 2 monoclonal antibodies selectively reactive with α or β subunits of the H(+)/K(+)-ATPase. Western blot analysis was performed on all specimens. Consistent IHC staining was observed in the submandibular gland specimens for both α and β subunits. Western blot analysis revealed very strong expression for the stomach at 100 kDa, corresponding to the α protein, and weak but notable banding for all larynx and submandibular gland specimens. Similar findings were noted for the 60- to 80-kDa glycosylated β subunit protein, as well as the 52-kDa β subunit precursor for all specimens. The H(+)/K(+)-ATPase (proton) pump is present in the human larynx and submandibular gland although in much lower concentrations than in the stomach. Proton pump involvement in human aerodigestive seromucinous glands may have a role in protecting mucosa from acid environments (local or systemic), explain heightened laryngeal sensitivity in those patients with laryngopharyngeal reflux, and be a site of action for proton pump inhibitor pharmacotherapy.

  19. Stem cells in the development and differentiation of the human adrenal glands.

    PubMed

    Terada, Tadashi

    2015-01-01

    There are no studies on stem cells (SCs) and development and differentiation (DD) of the human adrenal glands. The SCs in DD of the adrenal glands were herein investigated histochemically and immunohistochemically in 18 human embryonic adrenal glands at gestational week (GW) 7-40. At 7 GW, the adrenal glands were present, and at 7 GW, numerous embryonic SCs (ESCs) are seen to create the adrenal cortex. The ESCs were composed exclusively of small cells with hyperchromatic nuclei without nucleoli. The ESCs were positive for neural cell adhesion molecule, KIT, neuron-specific enolase, platelet-derived growth factor receptor-α, synaptophysin, and MET. They were negative for other SC antigens, including chromogranin, ErbB2, and bcl-2. They were also negative for lineage antigens, including cytokeratin (CK)7, CK8, CK18, and CK19, carcinoembryonic antigen, carbohydrate antigen 19-9, epithelial membrane antigen, HepPar1, mucin core apoprotein (MUC)1, MUC2, MUC5AC, and MUC6, and cluster differentiation (CD)3, CD45, CD20, CD34, and CD31. The Ki-67 labeling index (LI) was high (Ki-67 LI = around 20%). α-Fetoprotein was positive in the ESCs and adrenal cells. The ESC was first seen in the periphery of the adrenal cortex at 7-10 GW. The ESC migrates into the inner part of the adrenal cortex. Huge islands of ESC were present near the adrenal, and they appeared to provide the ESC of the adrenal. At 16 GW, adrenal medulla appeared, and the adrenal ESCs were present in the periphery or the cortex, in the cortical parenchyma, corticomedullary junctions, and in the medulla. The adrenal essential architecture was established around 20 GW; however, there were still ESCs. At term, there are a few ESCs. These data suggest that the adrenal glands were created by ESCs. © 2014 Wiley Periodicals, Inc.

  20. Presence of kisspeptin-like immunoreactivity in human adrenal glands and adrenal tumors.

    PubMed

    Takahashi, Kazuhiro; Shoji, Itaru; Shibasaki, Akiko; Kato, Ichiro; Hiraishi, Keisuke; Yamamoto, Hajime; Kaneko, Kiriko; Murakami, Osamu; Morimoto, Ryo; Satoh, Fumitoshi; Ito, Sadayoshi; Totsune, Kazuhito

    2010-05-01

    Kisspeptins are neuropeptides which activate the hypothalamo-pituitary gonadal axis and are considered to play important physiological roles in the reproduction. Kisspeptins have also been reported to stimulate the aldosterone secretion from the adrenal cortex. However, the expression of kisspeptins in human adrenal glands and adrenal tumors has not been clarified yet. We, therefore, studied the presence of kisspeptin-like immunoreactivity (LI) in human adrenal glands and adrenal tumors (adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas) by radioimmunoassay and immunocytochemistry. Kisspeptin-LI was detected in all the tissues examined; normal portions of adrenal glands (3.0 +/- 2.3 pmol/g wet weight, n = 21, mean +/- SD), aldosterone-producing adenomas (4.6 +/- 3.3 pmol/g wet weight, n = 10), cortisol-producing adenomas (2.7 +/- 1.4 pmol/g wet weight, n = 14), adrenocortical carcinomas (1.7 +/- 0.2 pmol/g wet weight, n = 4), and pheochromocytomas (1.8 +/- 0.8 pmol/g wet weight, n = 6). There was no significant difference in kisspeptin-LI levels among them. Immunocytochemistry showed positive kisspeptin-immunostaining in normal adrenal glands, with stronger immunostaining found in the medulla. Furthermore, positive kisspeptin-immunostaining was found in all types of adrenal tumors examined; adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas. The intensity of kisspeptin-immunostaining in these adrenal tumors was, however, not so strong as that in normal adrenal medulla. The present study has shown for the first time the presence of kisspeptin-LI in adrenal glands and adrenal tumors.

  1. Cidea Control of Lipid Storage and Secretion in Mouse and Human Sebaceous Glands

    PubMed Central

    Zhang, Shasha; Shui, Guanghou; Wang, Guanqun; Wang, Chao; Sun, Shuhong; Zouboulis, Christos C.; Xiao, Ran; Ye, Jing; Li, Wei

    2014-01-01

    Sebaceous glands are skin appendages that secrete sebum onto hair follicles to lubricate the hair and maintain skin homeostasis. In this study, we demonstrated that Cidea is expressed at high levels in lipid-laden mature sebocytes and that Cidea deficiency led to dry hair and hair loss in aged mice. In addition, Cidea-deficient mice had markedly reduced levels of skin surface lipids, including triacylglycerides (TAGs) and wax diesters (WDEs), and these mice were defective in water repulsion and thermoregulation. Furthermore, we observed that Cidea-deficient sebocytes accumulated a large number of smaller-sized lipid droplets (LDs), whereas overexpression of Cidea in human SZ95 sebocytes resulted in increased lipid storage and the accumulation of large LDs. Importantly, Cidea was highly expressed in human sebaceous glands, and its expression levels were positively correlated with human sebum secretion. Our data revealed that Cidea is a crucial regulator of sebaceous gland lipid storage and sebum lipid secretion in mammals and humans. PMID:24636991

  2. Effects of artificial tracheal fixation on tracheal epithelial regeneration and prevention of tracheal stenosis.

    PubMed

    Nakaegawa, Yuta; Nakamura, Ryosuke; Tada, Yasuhiro; Suzuki, Ryo; Takezawa, Toshiaki; Nakamura, Tatsuo; Omori, Koichi

    2017-06-01

    Tight fixation of the artificial trachea is important for epithelialization and tracheal stenosis. The authors have developed an artificial trachea and have used it for tracheal reconstruction. Although various studies on tracheal reconstruction have been conducted, no studies have examined the effect of artificial tracheal fixation on tracheal stenosis and regeneration. Therefore, the purpose of the present study was to evaluate the effect of artificial tracheal fixation. Preliminary animal experiment. Artificial tracheae were implanted into rabbits with partial tracheal defects. Tracheal stenosis and regeneration of the tracheal epithelium on the artificial tracheae were evaluated by endoscopic examination, scanning electron microscopic analysis, and histological examination. The artificial tracheae fixed to the tracheal defects were classified into three groups (0-point, 4-point, and 8-point) by the number of fixation points. At 14 and 28 days post-implantation, the luminal surface of the implantation area was mostly covered with epithelium in all fixation groups. However, a small amount of granulation tissue was observed in the 0-point fixation group at 14 days post-implantation. Moreover, tracheal stenosis did not occur in the 8-point fixation group, but stenosis was detected in the other groups.

  3. Effectiveness of skin absorption of tincture of I in blocking radioiodine from the human thyroid gland

    SciTech Connect

    Miller, K.L.; Coen, P.E.; White, W.J.; Hurst, W.J.; Achey, B.E.; Lang, C.M.

    1989-06-01

    Topical application of tincture of iodine (I) was found to be effective in blocking the thyroid uptake of orally administered /sup 131/I in humans. Abdominal skin application of tincture of I resulted in an approximately 82% reduction in the uptake of /sup 131/I by the thyroid gland. The effectiveness varied among individuals and may have depended on the quantity applied and on the application site. In each study group, elevated levels of serum I were observed.

  4. [Tracheal adenoid cystic carcinoma presenting as a thyroid tumor].

    PubMed

    Bahadir, Osman; Imamoğlu, Mehmet; Cobanoğlu, Umit; Korkmaz, Omer

    2006-01-01

    Primary tumors of the trachea are rare. Adenoid cystic carcinoma is the second most common tracheal malignancy and its symptoms are nonspecific. A 66-year-old woman presented with complaints of progressive dyspnea and cough of a two-week duration. She had received asthmatic treatment many times for the past four years. Physical examination revealed a large, firm, nontender, multilobular mass in the thyroid gland. Indirect laryngoscopic examination showed subglottic stenosis. On a plain cervical radiograph, there was narrowing of the tracheal lumen. Emergent tracheotomy was performed and a biopsy was taken from the mass. Histopathologic examination revealed adenoid cystic carcinoma, suggesting a thyroid mass with a tracheal origin. Despite medical treatment, the patient died in the fourth month.

  5. Three-Dimensional Human Bronchial-Tracheal Epithelial Tissue-Like Assemblies (TLAs) as Hosts for Severe Acute Respiratory Syndrome (SARS)-CoV Infection

    NASA Technical Reports Server (NTRS)

    Suderman, M. T.; McCarthy, M.; Mossell, E.; Watts, D. M.; Peters, C. J.; Shope, R.; Goodwin, T. J.

    2006-01-01

    A three-dimensional (3-D) tissue-like assembly (TLA) of human bronchial-tracheal mesenchymal (HBTC) cells with an overlay of human bronchial epithelial (BEAS-2B) cells was constructed using a NASA Bioreactor to survey the infectivity of SARS-CoV. This TLA was inoculated with a low passage number Urbani strain of SARS-CoV. At selected intervals over a 10-day period, media and cell aliquots of the 3-D TLA were harvested for viral titer assay and for light and electron microscopy examination. All viral titer assays were negative in both BEAS-2B two-dimensional monolayer and TLA. Light microscopy immunohistochemistry demonstrated antigen-antibody reactivity with anti-SARS-CoV polyclonal antibody to spike and nuclear proteins on cell membranes and cytoplasm. Coronavirus Group 2 cross-reactivity was demonstrated by positive reaction to anti-FIPV 1 and anti-FIPV 1 and 2 antibodies. TLA examination by transmission electron microscopy indicated increasing cytoplasmic vacuolation with numerous electron-dense bodies measuring 45 to 270 nm from days 4 through 10. There was no evidence of membrane blebbing, membrane duplication, or fragmentation of organelles in the TLAs. However, progressive disruption of endoplasmic reticulum was observed throughout the cells. Antibody response to SARS-CoV specific spike and nucleocapsid glycoproteins, cross-reactivity with FIPV antibodies, and the cytoplasmic pathology suggests this HBTE TLA model is permissive to SARS-CoV infection.

  6. Interaction of the tracheal tubules of Scutigera coleoptrata (Chilopoda, Notostigmophora) with glandular structures of the pericardial septum

    PubMed Central

    Hilken, Gero; Edgecombe, Gregory D.; Müller, Carsten H.G.; Sombke, Andy; Wirkner, Christian S.; Rosenberg, Jörg

    2015-01-01

    Abstract Notostigmophora (Scutigeromorpha) exhibit a special tracheal system compared to other Chilopoda. The unpaired spiracles are localized medially on the long tergites and open into a wide atrium from which hundreds of tracheal tubules originate and extend into the pericardial sinus. Previous investigators reported that the tracheal tubules float freely in the hemolymph. However, here we show for the first time that the tracheal tubules are anchored to a part of the pericardial septum. Another novel finding is this part of the pericardial septum is structured as an aggregated gland on the basis of its specialized epithelium being formed by hundreds of oligocellular glands. It remains unclear whether the pericardial septum has a differently structure in areas that lack a connection with tracheal tubules. The tracheal tubules come into direct contact with the canal cells of the glands that presumably secrete mucous substances covering the entire luminal cuticle of the tracheal tubules. Connections between tracheae and glands have not been observed in any other arthropods. PMID:26257546

  7. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    PubMed Central

    AZEVEDO-ALANIS, Luciana Reis; TOLENTINO, Elen de Souza; de ASSIS, Gerson Francisco; CESTARI, Tânia Mary; LARA, Vanessa Soares; DAMANTE, José Humberto

    2015-01-01

    Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated. Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death. Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years); II (31–60), and III (61–90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05). Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001). However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis. Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death. PMID:26537715

  8. Effect of skin temperature on the ion reabsorption capacity of sweat glands during exercise in humans.

    PubMed

    Shamsuddin, A K M; Kuwahara, T; Oue, A; Nomura, C; Koga, S; Inoue, Y; Kondo, N

    2005-07-01

    The effect of skin temperature on the ion reabsorption capacity of sweat glands during exercise in humans is unknown. In this study, eight healthy subjects performed a 60-min cycling exercise at a constant intensity (60% VO(2max)) under moderate (25 degrees C) and cool (15 degrees C) ambient temperatures at a constant relative humidity of 40%. The sweating rate (SR), index of sweat ion concentration (ISIC) by using sweat conductivity, esophageal temperature (Tes), mean skin temperature, and heart rate (HR) were measured continuously under both ambient temperatures. The SR and ISIC were significantly lower at the cool ambient temperature versus the moderate temperature. There were no significant differences in the changes in HR and esophageal temperature between these ambient temperature conditions, while the mean skin temperature was significantly lower at the cool ambient temperature by almost 3 degrees C (P < 0.05). The slopes of the relationships between Tes and the SR and ISIC were significantly lower and the thresholds of these relationships were significantly higher at the cool ambient temperature (P < 0.05). The ion reabsorption capacity of the sweat glands was significantly lower (P < 0.05) in a cool environment (0.21 +/- 0.04 vs. 0.52 +/- 0.06 mg/cm(2)/min at 15 and 25 degrees C, respectively) as evaluated using the relationships for SR and ISIC. The results suggest that the ion reabsorption capacity of the sweat glands is influenced by skin temperature during exercise in humans.

  9. Lectin binding pattern and proteoglycan distribution in human eccrine sweat glands.

    PubMed

    Sames, K; Moll, I; van Damme, E J; Peumans, W J; Schumacher, U

    1999-11-01

    The distribution pattern of glycoconjugates in human eccrine sweat glands has been studied by the binding of newly discovered lectins and by antibodies against a chondroitin sulphate proteoglycan and chondroitin sulphate glycosaminoglycans. Mannose-specific lectins labelled large intracellular granules, part of which could be extended cisternae of the endoplasmic reticulum or Golgi apparatus. In contrast, lectins specific for terminal mannose/glucose residues predominantly labelled basement membranes and the glycocalyx. Lectins recognizing terminal N-acetylgalactosamine groups left most parts of the glands unstained, but stained some dark cells intensely. These last cells were also intensively labelled by N-acetylglucosamine-specific and by fucose-specific lectins. Sialic acid residues were preferentially located in luminal borders of secretory coils. No terminal galactose residues were detected. All antibodies against chondroitin glycoconjugates stained large granules similar to those revealed by the mannose-specific lectins in the secretory cells. The basement membrane is only stained by the proteoglycan antibody and the chondroitin-6-sulphate antibody. Thus, a complex composition of glycoconjugates exists not only in matrix elements but also in the cells of eccrine glands of the human skin. A possible secretion of glycoconjugates is discussed.

  10. Examination of Duct Physiology in the Human Mammary Gland

    PubMed Central

    Mills, Dixie; Gomberawalla, Ameer; Gordon, Eva J.; Tondre, Julie; Nejad, Mitra; Nguyen, Tinh; Pogoda, Janice M.; Rao, Jianyu; Chatterton, Robert; Henning, Susanne; Love, Susan M.

    2016-01-01

    Background The human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit. Methods We examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data. Results We found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid. Conclusions Our results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas. PMID:27073976

  11. Tracheal replacement with an aortic autograft.

    PubMed

    Azorin, Jacques F; Bertin, Francois; Martinod, Emmanuel; Laskar, Marc

    2006-02-01

    Tracheal replacement after extensive resection remains a challenge for the thoracic surgeon. We propose an innovative solution: the use of an aortic autograft. After an experimental work on animals with aortic autografts and allografts [Martinod E, Seguin A, Pfeuty K, Fornes P, Kambouchner M, Azorin JF, Carpentier AF. Long-term evaluation of the replacement of the trachea with an autologous aortic graft. Ann Thorac Surg 2003;75(5):1572-8; Martinod E, Seguin A, Holder-Espinasse M, Kambouchner M, Duterque-Coquillaud M, Azorin JF, Carpentier AF. Tracheal regeneration following tracheal replacement with an allogenic aorta. Ann Thorac Surg 2005;79(3):942-8], we present the first human case of long tracheal replacement with an aortic autograft. In this case we replaced 7 cm of a tumoral trachea using an aortic infra-renal autograft supported by a silicone stent. The early postoperative course was uneventful. The stent was removed at three months. The patient died at six months from an acute pulmonary infection without any sign of anastomosis leakage or graft rupture. A new field of clinical study has to be investigated.

  12. Endoscopic laser reshaping of rabbit tracheal cartilage: preliminary investigations

    NASA Astrophysics Data System (ADS)

    Tsang, Walter; Lam, Anthony; Protsenko, Dmitry; Wong, Brian J.

    2005-04-01

    Background: Tracheal cartilage deformities due to trauma, prolonged endotracheal intubation or infection are difficult to correct. Current treatment options such as dilation, laser ablation, stent placement, and segmental resection are only temporary or carry significant risks. The objectives of this project were to design and test a laser activated endotracheal stent system that can actively modify the geometry of tracheal cartilage, leading to permanent retention of a new and desirable tracheal geometry. Methods: Ex vivo rabbit tracheal cartilage (simulating human neonate trachea) were irradiated with an Er: Glass laser, (λ= 1.54um, 0.5W-2.5W, 1 sec to 5 sec). Shape change and gross thermal injury were assessed visually to determine the best laser power parameters for reshaping. A rigid endoscopic telescope and hollow bronchoscope were used to record endoscopic images. The stent was constructed from nitinol wire, shaped into a zigzag configuration. An ex vivo testing apparatus was also constructed. Results: The best laser power parameter to produce shape change was 1 W for 6-7 seconds. At this setting, there was significant shape change with only minimal thermal injury to the tracheal mucosa, as assessed by visual inspection. The bronchoscopy system functioned adequately during testing in the ex vivo testing apparatus. Conclusion: We have successfully designed instrumentation and created the capability to endoscopically reshape tracheal cartilage in an ex vivo rabbit model. The results obtained in ex vivo tracheal cartilage indicated that reshaping using Er: Glass laser can be accomplished.

  13. Development of peptide-containing nerves in the human fetal prostate gland.

    PubMed Central

    Jen, P Y; Dixon, J S

    1995-01-01

    Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l

  14. Characterization of Angiogenesis and Lymphangiogenesis in Human Minor Salivary Glands with Sjögren's Syndrome.

    PubMed

    McCall, Andrew D; Baker, Olga J

    2015-05-01

    Angiogenesis has been proposed to play a role in the inflammation observed in Sjögren's Syndrome (SS). However, no studies have validated the degree of angiogenesis in salivary glands with SS. Therefore, the goal of this study was to determine the presence and localization of angiogenesis and lymphangiogenesis in salivary glands with SS. We used frozen tissue sections from human minor salivary glands (hMSG) with and without SS in our analyses. To investigate signs of angiogenesis, hMSG tissue lysates were used to detect levels of the pro-angiogenic protein vascular endothelial growth factor (VEGF) by western blot analyses. Additionally, we labeled blood vessels using antibodies specific to platelet endothelial cell adhesion molecule-1 (PECAM-1) and von Willebrand Factor (vWF) to determine blood vessel organization and volume fraction using fluorescence microscopy. Lymphatic vessel organization and volume fraction were determined using antibodies specific to lymphatic vessel endothelial hyaluronan receptor (LYVE-1). Our results suggest that expression levels of VEGF are decreased in hMSG with SS as compared with controls. Interestingly, there were no significant differences in blood or lymphatic vessel organization or volume fraction between hMSG with and without SS, suggesting that angiogenesis and lymphangiogenesis have little impact on the progression of SS. © The Author(s) 2015.

  15. Age-dependent increase of clusterin in the human pituitary gland.

    PubMed

    Ishikawa, Takaki; Zhu, Bao-Li; Li, Dong-Ri; Zhao, Dong; Michiue, Tomomi; Maeda, Hitoshi

    2006-01-01

    Clusterin is a glycoprotein known to play various physiological roles including complement activity, amyloid binding activity in Alzheimer disease, as well as binding with heat shock proteins and abnormal prions. The present study immunohistochemically investigated the expression of clusterin in the human pituitary gland in subjects of 10-88 years of age (n=173). Causes of death were blunt injury (n=35), sharp injury (n=15), poisoning (n=11), drowning (n=14), fire fatalities (n=28), asphyxiation (n=15), hypothermia (n=7), hyperthermia (n=3), and natural diseases (n=45). Clusterin was detected in mixed cell follicles and the anterior lobar parenchymal cells. The area occupied by cells positive for clusterin were measured, and the ratio to the whole area of the anterior lobe (% clusterin-positive cell area) was estimated. There was a good correlation between the age of the subjects in years and the % clusterin-positive cell area in the anterior lobe of the pituitary gland (r=0.736, P<0.01). Relationships between % clusterin-positive cell and gender, cause of death, and survival time were insignificant. These findings indicate an age-dependent accumulation of clusterin in the pituitary gland, which may be related to the aging of endocrine systems.

  16. Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells

    NASA Astrophysics Data System (ADS)

    Londei, Marco; Bottazzo, G. Franco; Feldmann, Marc

    1985-04-01

    The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

  17. Serum-Induced Keratinization Processes in an Immortalized Human Meibomian Gland Epithelial Cell Line

    PubMed Central

    Hampel, Ulrike; Schröder, Antje; Mitchell, Todd; Brown, Simon; Snikeris, Peta; Garreis, Fabian; Kunnen, Carolina; Willcox, Mark; Paulsen, Friedrich

    2015-01-01

    Purpose The aim of this study was to evaluate a human meibomian gland epithelial cell line (HMGEC) as a model for meibomian gland (patho)physiology in vitro. Methods HMGEC were cultured in the absence or presence of serum. Sudan III lipid staining, ultrastructural analysis and lipidomic analyses were performed. Impedance sensing, desmoplakin 1/2 mRNA and cytokeratin (CK) 1, 5, 6, 14 levels were evaluated. Serum containing medium supplemented with higher serum, glucose, an omega-3 lipid cocktail, eicosapentaenoic acid or sebomed medium were investigated for lipid accumulation and ultrastructural morphology. Results Lipid droplet accumulation in HMGEC was induced by serum containing media after 1 day, but decreased over time. Cultivation in serum induced desmosome and cytokeratin filament formation. Desmoplakin 1/2 gene levels were significantly upregulated after 1d of serum treatment. Furthermore, the normalized impedance increased significantly. Lipidome analysis revealed high levels of phospholipids (over 50%), but very low levels of wax ester and cholesteryl esters (under 1%). Stimulation with eicosapentaenoic acid increased lipid accumulation after one day. Conclusion Serum treatment of HMGEC caused lipid droplet formation to some extent but also induced keratinization. The cells did not produce typical meibum lipids under these growth conditions. HMGEC are well suited to study (hyper)keratinization processes of meibomian gland epithelial cells in vitro. PMID:26042605

  18. Human eccrine sweat gland cells turn into melanin-uptaking keratinocytes in dermo-epidermal skin substitutes.

    PubMed

    Böttcher-Haberzeth, Sophie; Biedermann, Thomas; Pontiggia, Luca; Braziulis, Erik; Schiestl, Clemens; Hendriks, Bart; Eichhoff, Ossia M; Widmer, Daniel S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

    2013-02-01

    Recently, Biedermann et al. (2010) have demonstrated that human eccrine sweat gland cells can develop a multilayered epidermis. The question still remains whether these cells can fulfill exclusive and very specific functional properties of epidermal keratinocytes, such as the incorporation of melanin, a feature absent in sweat gland cells. We added human melanocytes to eccrine sweat gland cells to let them develop into an epidermal analog in vivo. The interaction between melanocytes and sweat gland-derived keratinocytes was investigated. The following results were gained: (1) macroscopically, a pigmentation of the substitutes was seen 2-3 weeks after transplantation; (2) we confirmed the development of a multilayered, stratified epidermis with melanocytes distributed evenly throughout the basal layer; (3) melanocytic dendrites projected to suprabasal layers; and (4) melanin was observed to be integrated into former eccrine sweat gland cells. These skin substitutes were similar or equal to skin substitutes cultured from human epidermal keratinocytes. The only differences observed were a delay in pigmentation and less melanin uptake. These data suggest that eccrine sweat gland cells can form a functional epidermal melanin unit, thereby providing striking evidence that they can assume one of the most characteristic keratinocyte properties.

  19. Multielemental analysis of human thyroid glands using particle induced X-ray emission (PIXE)

    NASA Astrophysics Data System (ADS)

    Maeda, K.; Yokode, Y.; Sasa, Y.; Kusuyama, H.; Uda, M.

    1987-03-01

    PIXE spectroscopy has been applied to the analysis of human thyroid glands. Nontumor thyroid tissues taken from different patients showed almost the same composition which fell into the range of the data for normal thyroids given in the literature. On the other hand, a deficiency of iodine and iron was observed in all of the malignant and benign tumor tissues examined here. In some injured tissues considerable deviations of K and Ca from normal concentration levels were also recognized. This work demonstrates an important advantage of PIXE to analyze fugacious elements together with other elements simultaneously.

  20. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    PubMed

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

  1. Thermogenic and psychogenic recruitment of human eccrine sweat glands: Variations between glabrous and non-glabrous skin surfaces.

    PubMed

    Machado-Moreira, Christiano A; Taylor, Nigel A S

    2017-04-01

    Human eccrine sweat-gland recruitment and secretion rates were investigated from the glabrous (volar) and non-glabrous hand surfaces during psychogenic (mental arithmetic) and thermogenic stimuli (mild hyperthermia). It was hypothesised that these treatments would activate glands from both skin surfaces, with the non-thermal stimulus increasing secretion rates primarily by recruiting more sweat glands. Ten healthy men participated in two seated, resting trials in temperate conditions (25-26°C). Trials commenced under normothermic conditions during which the first psychogenic stress was applied. That was followed by passive heating (0.5°C mean body temperature elevation) and thermal clamping, with a second cognitive challenge then applied. Sudomotor activity was evaluated from both hands, with colourimetry used to identify activated sweat glands, skin conductance to determine the onset of precursor sweating and ventilated sweat capsules to measure rates of discharged sweating. From glandular activation and sweat rate data, sweat-gland outputs were derived. These psychogenic and thermogenic stimuli activated sweat glands from both the glabrous and non-glabrous skin surfaces, with the former dominating at the glabrous skin and the latter at the non-glabrous surface. Indeed, those stimuli individually accounted for ~90% of the site-specific maximal number of activated sweat glands observed when both stimuli were simultaneously applied. During the normothermic psychological stimulation, sweating from the glabrous surface was elevated via a 185% increase in the number of activated glands within the first 60s. The hypothetical mechanism for this response may involve the serial activation of additional eccrine sweat glands during the progressive evolution of psychogenic sweating.

  2. Influence of Omega 3 and 6 Fatty Acids on Human Meibomian Gland Epithelial Cells.

    PubMed

    Liu, Yang; Kam, Wendy R; Sullivan, David A

    2016-08-01

    Oral supplementation with omega 3 (ω-3) and/or 6 (ω-6) fatty acids (FAs) has been reported to alleviate the signs and symptoms of dry eye disease and to improve the expressibility and quality of meibum, in patients with meibomian gland dysfunction. We tested our hypothesis that these FA effects may reflect a direct FA action on human meibomian gland epithelial cells. Immortalized human meibomian gland epithelial cells (IHMGECs) were cultured with ω-3, ω-6, or both FAs together for up to 7 days in the presence or absence of serum. After FA exposure, cells were analyzed for lipid expression, lysosome content, and proliferative ability. Our research shows that ω-3 and ω-6 stimulate the accumulation of small neutral lipid-containing vesicles, but not lysosomes, in IHMGECs. This vesicular effect was associated with a 2.4- to 3.7-fold increase in the cellular content of triglycerides after ω-3 and ω-6 treatment, respectively. The combination of both FAs together also enhanced triglyceride levels. Of interest, culture of IHMGECs with ω-3 and azithromycin, a known inducer of IHMGEC differentiation, led to a significantly greater amount of total neutral lipids, relative to that found with azithromycin alone. Cellular exposure to the FAs did not alter the expression of free or esterified cholesterol, or phospholipids. Further, these FAs, alone or together, prevented the proliferation of IHMGECs in serum-free, but not serum-containing, media. Our findings support our hypothesis and demonstrate that ω-3 and ω-6 can act directly on IHMGECs to influence the quality and quantity of intracellular lipids.

  3. Dynamic analysis for mental sweating of a group of eccrin sweat glands on a human fingertip by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ohmi, Masato; Tanigawa, Motomu; Wada, Yuki; Haruna, Masamitsu

    2011-05-01

    OCT is highly potential for in vivo observation of human sweating dynamics which affects activity of the sympathetic nerve. In this paper, we demonstrate dynamic OCT analysis of mental sweating of a group of eccrin sweat glands. The sweating dynamics is tracked simultaneously for nineteen sweat glands by time-sequential piled-up en-face OCT images with the frame spacing of 3.3 sec. Strong non-uniformity is observed in mental sweating where the amount of excess sweat is different for each sweat gland although the sweat glands are adjacent to each other. The non-uniformity should be necessary to adjust as precisely the total amount of excess sweat as possible through the sympathetic nerve in response to strength of the stress.

  4. Lipopolysaccharide induces VCAM-1 expression and neutrophil adhesion to human tracheal smooth muscle cells: Involvement of Src/EGFR/PI3-K/Akt pathway

    SciTech Connect

    Lin, W.-N.; Luo, S.-F.; Wu, C.-B.; Lin, C.-C.; Yang, C.-M.

    2008-04-15

    In our previous study, LPS has been shown to induce vascular cell adhesion molecule-1(VCAM-1) expression through MAPKs and NF-{kappa}B in human tracheal smooth muscle cells (HTSMCs). In addition to these pathways, the non-receptor tyrosine kinases (Src), EGF receptor (EGFR), and phosphatidylinositol 3-kinase (PI3K) have been shown to be implicated in the expression of several inflammatory target proteins. Here, we reported that LPS-induced up-regulation of VCAM-1 enhanced the adhesion of neutrophils onto HTSMC monolayer, which was inhibited by LY294002 and wortmannin. LPS stimulated phosphorylation of protein tyrosine kinases including Src, PYK2, and EGFR, which were further confirmed using specific anti-phospho-Src, PYK2, or EGFR Ab, respectively, revealed by Western blotting. LPS-stimulated Src, PYK2, EGFR, and Akt phosphorylation and VCAM-1 expression were attenuated by the inhibitors of Src (PP1), EGFR (AG1478), PI3-K (LY294002 and wortmannin), and Akt (SH-5), respectively, or transfection with siRNAs of Src or Akt and shRNA of p110. LPS-induced VCAM-1 expression was also blocked by pretreatment with curcumin (a p300 inhibitor) or transfection with p300 siRNA. LPS-stimulated Akt activation translocated into nucleus and associated with p300 and VCAM-1 promoter region was further confirmed by immunofluorescence, immunoprecipitation, and chromatin immunoprecipitation assays. This association of Akt and p300 to VCAM-1 promoter was inhibited by pretreatment with PP1, AG1478, wortmannin, and SH-5. LPS-induced p300 activation enhanced VCAM-1 promoter activity and VCAM-1 mRNA expression. These results suggested that in HTSMCs, Akt phosphorylation mediated through transactivation of Src/PYK2/EGFR promoted the transcriptional p300 activity and eventually led to VCAM-1 expression induced by LPS.

  5. Endothelin-1 induces VCAM-1 expression-mediated inflammation via receptor tyrosine kinases and Elk/p300 in human tracheal smooth muscle cells.

    PubMed

    Lin, Chih-Chung; Lin, Wei-Ning; Hou, Wei-Chen; Hsiao, Li-Der; Yang, Chuen-Mao

    2015-08-01

    The elevated level of endothelin-1 (ET-1) has been detected in the bronchoalveolar lavage of patients with severe asthma, acute lung injury, acute respiratory distress syndrome, and sepsis. ET-1 may affect vessel tone together with lung physiology and pathology. Vascular cell adhesion molecule-1 (VCAM-1) is one kind of adhesion molecules participating in the process of polymorphonuclear leukocyte transmigration and regulating the occurrence and amplification of tissue inflammation. However, the molecular mechanisms underlying ET-1-mediated expression of VCAM-1 on human tracheal smooth muscle cells (HTSMCs) were largely unknown. Here we reported that ET-1 stimulated expression of VCAM-1 gene on HTSMCs, which was blocked by pretreatment with the inhibitors of ET receptors, Src, matrix metalloproteinases (MMPs), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), phosphatidylinositol 3-kinase (PI3K), AKT, MEK1/2, and p300, suggesting the participation of these signaling components in ET-1-regulated HTSMC responses. Furthermore, transfection with small-interfering RNA (siRNA) of Src, AKT, p42 mitogen-activated protein kinase (MAPK), or p300 downregulated the respective proteins and significantly attenuated ET-1-induced VCAM-1 expression. ET-1 also stimulated phosphorylation of Src, EGFR, PDGFR, AKT, p42/p44 MAPK, and Elk-1 and acetylation of histone H4 on HTSMCs. Immunoprecipitation assay showed the association between Elk-1 and p300 in the nucleus. Adhesion assay revealed that the adhesion of THP-1 to HTSMCs challenged with ET-1 was increased, which was attenuated by the inhibitors of ET receptors, Src, MMPs, EGFR, PDGFR, PI3K, AKT, p42/p44 MAPK, and p300. Taken together, these data suggested that ET-1 promotes occurrence and amplification of pathology-related airway inflammation via enhancing VCAM-1 expression in an ET receptor/Src/MMP/EGFR, PDGFR/PI3K/AKT/p42/p44 MAPK/Elk-1/p300 pathway in HTSMCs.

  6. Localization of carboxyl ester lipase in human pituitary gland and pituitary adenomas.

    PubMed

    La Rosa, Stefano; Vigetti, Davide; Placidi, Claudia; Finzi, Giovanna; Uccella, Silvia; Clerici, Moira; Bartolini, Barbara; Carnevali, Ileana; Losa, Marco; Capella, Carlo

    2010-10-01

    Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells.

  7. Immunological characterization of deglycosylated human and swine trachea and Cowper's gland mucin glycoproteins.

    PubMed

    Sangadala, S; Brewer, J M; Mendicino, J

    1991-04-01

    Antibodies were raised in rabbits against purified swine and human trachea and Cowper's gland mucin glycoproteins and their deglycosylated polypeptide chains. Three monospecific antibody fractions that recognize the carbohydrate, the deglycosylated or unglycosylated regions of the polypeptide chains in these glycoproteins, were isolated by immunoaffinity chromatography. The human and swine trachea mucin glycoproteins showed extensive immunological homology in both their carbohydrate and polypeptide chains. The carbohydrate chains and unglycosylated region of the polypeptide chain in Cowper's gland mucin glycoprotein showed little or no cross-reaction with comparable regions in respiratory mucin glycoproteins. However, the polypeptide chains in the deglycosylated regions of all three mucin glycoproteins showed extensive homology. Five bands with molecular masses ranging from 40 to 46 kDa that differed by a constant molecular mass of approximately 1.5 kDa were detected in hydrolysates of all of the polypeptide chains after treatment with S. aureus V8 protease. Monospecific antibodies to the deglycosylated region of these chains reacted with the peptides, whereas those directed against the unglycosylated region did not. The results suggest that these chains contain tandem repeating sequences of amino acids.

  8. Endocannabinoids regulate growth and survival of human eccrine sweat gland-derived epithelial cells.

    PubMed

    Czifra, Gabriella; Szöllősi, Attila G; Tóth, Balázs I; Demaude, Julien; Bouez, Charbel; Breton, Lionel; Bíró, Tamás

    2012-08-01

    The functional existence of the emerging endocannabinoid system (ECS), one of the new neuroendocrine players in cutaneous biology, is recently described in the human skin. In this study, using human eccrine sweat gland-derived immortalized NCL-SG3 model cells and a wide array of cellular and molecular assays, we investigated the effects of prototypic endocannabinoids (anandamide, 2-arachidonoylglycerol) on cellular functions. We show here that both endocannabinoids dose-dependently suppressed proliferation, induced apoptosis, altered expressions of various cytoskeleton proteins (e.g., cytokeratins), and upregulated lipid synthesis. Interestingly, as revealed by specific agonists and antagonists as well as by RNA interference, neither the metabotropic cannabinoid receptors (CB) nor the "ionotropic" CB transient receptor potential ion channels, expressed by these cells, mediated the cellular actions of the endocannabinoids. However, the endocannabinoids selectively activated the mitogen-activated protein kinase signaling pathway. Finally, other elements of the ECS (i.e., enzymes involved in the synthesis and degradation of endocannabinoids) were also identified on NCL-SG3 cells. These results collectively suggest that cannabinoids exert a profound regulatory role in the biology of the appendage. Therefore, from a therapeutic point of view, upregulation of endocannabinoid levels might help to manage certain sweat gland-derived disorders (e.g., tumors) characterized by unwanted growth.

  9. Immunocytochemical Localization of Sex Steroid Hormone Receptors in Normal Human Mammary Gland

    PubMed Central

    Li, Sijie; Han, Bing; Liu, Guojin; Li, Songyun; Ouellet, Johanne; Labrie, Fernand; Pelletier, Georges

    2010-01-01

    The sex steroids, estrogens, progesterone, and androgens, all play a role in mammary development and function. To precisely identify the sites of action of these steroids, we studied the localization of the estrogen receptor α (ERα) and ERβ, the progesterone receptor A (PRA) and PRB, and androgen receptors (AR) in the normal human mammary gland. Immunocytochemical localization of ERα, ERβ, PRA, PRB, and AR was performed with reduction mammoplasty specimens from premenopausal women. ERα, PRA, PRB, and AR were localized mostly to the inner layer of epithelial cells lining acini and intralobular ducts, as well as to myoepithelial cells scattered in the external layer of interlobular ducts. AR was also found in some stromal cells. ERβ staining was more widespread, resulting in epithelial and myoepithelial cells being labeled in acini and ducts as well as stromal cells. These results suggest that all sex steroids can directly act on epithelial cells to modulate development and function of the human mammary gland. Estrogens and androgens can also indirectly influence epithelial cell activity by an action on stromal cells. (J Histochem Cytochem 58:509–515, 2010) PMID:20026671

  10. Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours.

    PubMed

    Buslei, Rolf; Strissel, Pamela L; Henke, Christine; Schey, Regina; Lang, Nadine; Ruebner, Matthias; Stolt, Claus C; Fabry, Ben; Buchfelder, Michael; Strick, Reiner

    2015-02-01

    Adenohypophysis (AH) hormone-producing cells represent the origin of diverse groups of pituitary adenomas (PA). Deregulation of hypothalamic hormone receptors, growth factors and cAMP signalling have been implicated in the aetiology of PA. Endogenous retroviruses (ERVs) are derived from past exogenous retroviral infections and represent more than 8% of the human genome. Some ERV genes encode open reading frames and produce functional proteins, for example, the ERVW-1 envelope gene Syncytin-1, essential for placentogenesis, but also deregulated in human tumours. Data concerning ERV expression in the AH and related endocrine tumours are missing. Syncytin-1 protein was analysed in normal AH (n = 15) and compared with five PA subtypes (n = 117) by immunohistochemistry. Absolute gene expression of 20 ERV functional envelope genes and ERVW-5 gag was measured. PA tissues were examined for Syncytin-1 and the cAMP signalling marker phospho-CREB-Ser133 using immunohistochemistry. Isolated primary human PA cells were treated with different hormones. Murine embryonic and adult pituitary gland ERV expressions were compared with human AH. Syncytin-1 protein colocalized with corticotropic cells of AH. In contrast, all PA demonstrated significant Syncytin-1 protein overexpression, supporting deregulation. All other ERV genes showed significant up-regulations in different PA subtypes. Phospho-CREB-Ser133 and Syncytin-1 colocalized in PA cells. Cultivated primary PA cells with ACTH or CRH induced their respective receptors and ERV genes. Syncytin-A/-B, murine orthologues to human Syncytin-1/-2, localized to embryonic and adult pituitary glands demonstrating functional mammalian conservation. Deregulated ERV genes may contribute to PA development via cAMP signalling. © 2014 British Neuropathological Society.

  11. Adrenal glands

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002219.htm Adrenal glands To use the sharing features on this page, please enable JavaScript. The adrenal glands are two triangle-shaped glands. One gland is ...

  12. Basal epithelial cells of human prostate gland are not myoepithelial cells. A comparative immunohistochemical and ultrastructural study with the human salivary gland.

    PubMed Central

    Srigley, J. R.; Dardick, I.; Hartwick, R. W.; Klotz, L.

    1990-01-01

    The hypothesis that basal epithelial cells of the human prostate are of myoepithelial origin was investigated using immunohistochemical and ultrastructural methodologies. The immunohistologic analyses show significant phenotypic differences between prostatic basal cells and myoepithelial cells of the salivary gland. Although both cell types stain intensely with the 312C8-1 monoclonal antibody, only true myoepithelial cells demonstrated significant amounts of muscle-specific actin as decorated by the HHF35 monoclonal antibody. Furthermore, using double-labeling experiments, the prostatic basal cells were strongly decorated with a fluorescein-tagged basal cell-specific keratin but were negative with the rhodamine-tagged phalloidin, a chemical that binds specifically to actin microfilaments. Ultrastructural studies also showed an absence of thin microfilament bundles, dense bodies, and micropinocytotic vesicles in the prostatic basal cells. The current investigations show that the prostatic acini do not have a basal myoepithelium. Although some authors have suggested a stem cell role for prostatic basal cells, the weight of experimental work argues against this hypothesis. The exact role of the basal epithelial cells of the prostate is not known, although they may serve endocrine, paracrine, or other regulatory functions and may be involved in modulating signals between prostatic stroma and epithelium. Images Figure 3 Figure 1 Figure 2 Figure 4 PMID:1691595

  13. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases.

    PubMed

    Stehle, Jörg H; Saade, Anastasia; Rawashdeh, Oliver; Ackermann, Katrin; Jilg, Antje; Sebestény, Tamás; Maronde, Erik

    2011-08-01

    The human pineal gland is a neuroendocrine transducer that forms an integral part of the brain. Through the nocturnally elevated synthesis and release of the neurohormone melatonin, the pineal gland encodes and disseminates information on circadian time, thus coupling the outside world to the biochemical and physiological internal demands of the body. Approaches to better understand molecular details behind the rhythmic signalling in the human pineal gland are limited but implicitly warranted, as human chronobiological dysfunctions are often associated with alterations in melatonin synthesis. Current knowledge on melatonin synthesis in the human pineal gland is based on minimally invasive analyses, and by the comparison of signalling events between different vertebrate species, with emphasis put on data acquired in sheep and other primates. Together with investigations using autoptic pineal tissue, a remnant silhouette of premortem dynamics within the hormone's biosynthesis pathway can be constructed. The detected biochemical scenario behind the generation of dynamics in melatonin synthesis positions the human pineal gland surprisingly isolated. In this neuroendocrine brain structure, protein-protein interactions and nucleo-cytoplasmic protein shuttling indicate furthermore a novel twist in the molecular dynamics in the cells of this neuroendocrine brain structure. These findings have to be seen in the light that an impaired melatonin synthesis is observed in elderly and/or demented patients, in individuals affected by Alzheimer's disease, Smith-Magenis syndrome, autism spectrum disorder and sleep phase disorders. Already, recent advances in understanding signalling dynamics in the human pineal gland have significantly helped to counteract chronobiological dysfunctions through a proper restoration of the nocturnal melatonin surge.

  14. Differential distribution and expression of leptin and the functional leptin receptor in major salivary glands of humans.

    PubMed

    Bohlender, J; Rauh, M; Zenk, J; Gröschl, M

    2003-08-01

    Leptin plays a central role in the regulation of food intake and energy expenditure in rodents. However, it has become clear that this hormone has more than only a satiety-inducing function, and that there are other sources of leptin, such as the central nervous system, placenta and the gastrointestinal tract in addition to adipose tIssue. Knowing about the important role of the salivary glands in food intake and digestion, it was the objective of the present study to investigate how leptin and its receptor are expressed and distributed in the major salivary glands of humans. We found leptin distributed throughout the major salivary glands with obvious intracellular concentrations in granula. In contrast, immunostaining for the leptin receptor was found exclusively in the membranes of the glandular cells. A high density of the leptin receptor was localised in the epithelia of the duct lumen. PCR analysis proved the autonomous expression of leptin by the salivary glands independently from adipocytes. Accordingly the long receptor isoform was expressed by any examined tIssue. In the light of recent findings of leptin influencing the growth of rodent salivary glands, the presence and distribution of leptin and its receptor suggests an autocrine role of salivary leptin within the glands.

  15. Quantitative Analysis of Human Salivary Gland-Derived Intact Proteome Using Top-Down Mass Spectrometry

    SciTech Connect

    Wu, Si; Brown, Joseph N.; Tolic, Nikola; Meng, Da; Liu, Xiaowen; Zhang, Haizhen; Zhao, Rui; Moore, Ronald J.; Pevzner, Pavel A.; Smith, Richard D.; Pasa-Tolic, Ljiljana

    2014-05-31

    There are several notable challenges inherent to fully characterizing the entirety of the human saliva proteome using bottom-up approaches, including polymorphic isoforms, post-translational modifications, unique splice variants, deletions, and truncations. To address these challenges, we have developed a top-down based liquid chromatography-mass spectrometry (LC-MS) approach, which cataloged 20 major human salivary proteins with a total of 83 proteoforms, containing a broad range of post-translational modifications. Among these proteins, several previously reported disease biomarker proteins were identified at the intact protein level, such as beta-2 microglobulin (B2M). In addition, intact glycosylated proteoforms of several saliva proteins were also characterized, including intact N-glycosylated protein prolactin inducible protein (PIP) and O-glycosylated acidic protein rich protein (aPRP). These characterized proteoforms constitute an intact saliva proteoform database, which was used for quantitative comparison of intact salivary proteoforms among six healthy individuals. Human parotid (PS) and submandibular/sublingual gland (SMSL) secretion samples (2 μg of protein each) from six healthy individuals were compared using RPLC coupled with the 12T FTICR mass spectrometer. Significantly different protein and PTM patterns were resolved with high reproducibility between PS and SMSL glands. The results from this study provide further insight into the potential mechanisms of PTM pathways in oral glandular secretion, expanding our knowledge of this complex yet easily accessible fluid. Intact protein LC-MS approach presented herein can potentially be applied for rapid and accurate identification of biomarkers from only a few microliters of human glandular saliva.

  16. Association of mast cells with calcification in the human pineal gland.

    PubMed

    Maślińska, Danuta; Laure-Kamionowska, Milena; Deręgowski, Krzysztof; Maśliński, Sławomir

    2010-01-01

    Increased pineal calcifications and decreased pineal melatonin biosynthesis, both age related, support the notion of a pineal bio-organic timing mechanism. The role of calcification in the pathogenesis of pineal gland dysfunction remains unknown but the available data document that calcification is an organized, regulated process, rather than a passive aging phenomenon. The cellular biology and micro-environmental conditions required for calcification remain poorly understood but most studies have demonstrated evidence that mast cells are strongly implicated in this process. The aim of the present study was to examine the phenotype of mast cells associated with early stages and with the progressive development of calcification in the human pineal gland. The study was performed on pineal samples of 170 fetuses and children whose brains were autopsied and diagnosed during 1998-2002. The representative cerebral and pineal specimens were stained with haematoxylin and eosin or the von Kossa staining technique and for the distribution of mast cell tryptase, mast cell chymase, histamine H4 receptor and vascular network using biotinylated Ulex europaeus agglutinin. Tryptase mast cells were found in all stages of pineal gland development independently of the presence of local tissue lesions. All of them were always localized in the close vicinity of the blood vessels and expressed immunoreactivity to histamine H4 receptor antibody. Immunolocalization of mast cells by chymase antibody (and following dual immunostaining with both chymase and tryptase antibodies) demonstrated that these cells were few in number and were located in the subcapsular region of the gland. In our study, all functional mast cells that underwent activation and were co-localized with deposits of calcium did not contain chymase. All of them were stained with tryptase and represent the MC-T phenotype. Tryptase mast cells and extracellular tryptase were often associated with areas of early and more

  17. Glucagon like peptide-1 receptor expression in the human thyroid gland.

    PubMed

    Gier, Belinda; Butler, Peter C; Lai, Chi K; Kirakossian, David; DeNicola, Matthew M; Yeh, Michael W

    2012-01-01

    Glucagon like peptide-1 (GLP-1) mimetic therapy induces medullary thyroid neoplasia in rodents. We sought to establish whether C cells in human medullary thyroid carcinoma, C cell hyperplasia, and normal human thyroid express the GLP-1 receptor. Thyroid tissue samples with medullary thyroid carcinoma (n = 12), C cell hyperplasia (n = 9), papillary thyroid carcinoma (n = 17), and normal human thyroid (n = 15) were evaluated by immunofluorescence for expression of calcitonin and GLP-1 receptors. Coincident immunoreactivity for calcitonin and GLP-1 receptor was consistently observed in both medullary thyroid carcinoma and C cell hyperplasia. GLP-1 receptor immunoreactivity was also detected in 18% of papillary thyroid carcinoma (three of 17 cases). Within normal human thyroid tissue, GLP-1 receptor immunoreactivity was found in five of 15 of the examined cases in about 35% of the total C cells assessed. In humans, neoplastic and hyperplastic lesions of thyroid C cells express the GLP-1 receptor. GLP-1 receptor expression is detected in 18% papillary thyroid carcinomas and in C cells in 33% of control thyroid lobes. The consequence of long-term pharmacologically increased GLP-1 signaling on these GLP-1 receptor-expressing cells in the thyroid gland in humans remains unknown, but appropriately powered prospective studies to exclude an increase in medullary or papillary carcinomas of the thyroid are warranted.

  18. Glucagon Like Peptide-1 Receptor Expression in the Human Thyroid Gland

    PubMed Central

    Gier, Belinda; Butler, Peter C.; Lai, Chi K.; Kirakossian, David; DeNicola, Matthew M.

    2012-01-01

    Background: Glucagon like peptide-1 (GLP-1) mimetic therapy induces medullary thyroid neoplasia in rodents. We sought to establish whether C cells in human medullary thyroid carcinoma, C cell hyperplasia, and normal human thyroid express the GLP-1 receptor. Methods: Thyroid tissue samples with medullary thyroid carcinoma (n = 12), C cell hyperplasia (n = 9), papillary thyroid carcinoma (n = 17), and normal human thyroid (n = 15) were evaluated by immunofluorescence for expression of calcitonin and GLP-1 receptors. Results: Coincident immunoreactivity for calcitonin and GLP-1 receptor was consistently observed in both medullary thyroid carcinoma and C cell hyperplasia. GLP-1 receptor immunoreactivity was also detected in 18% of papillary thyroid carcinoma (three of 17 cases). Within normal human thyroid tissue, GLP-1 receptor immunoreactivity was found in five of 15 of the examined cases in about 35% of the total C cells assessed. Conclusions: In humans, neoplastic and hyperplastic lesions of thyroid C cells express the GLP-1 receptor. GLP-1 receptor expression is detected in 18% papillary thyroid carcinomas and in C cells in 33% of control thyroid lobes. The consequence of long-term pharmacologically increased GLP-1 signaling on these GLP-1 receptor-expressing cells in the thyroid gland in humans remains unknown, but appropriately powered prospective studies to exclude an increase in medullary or papillary carcinomas of the thyroid are warranted. PMID:22031513

  19. Structure of the tight junctions of the human eccrine sweat gland.

    PubMed

    Briggman, J V; Bank, H L; Bigelow, J B; Graves, J S; Spicer, S S

    1981-12-01

    The human eccrine sweat gland contains two anatomically and functionally discrete segments: the secretory coil, which produces an isotonic or slightly hypertonic precursor fluid, and the coiled duct, which reabsorbs Na+ and Cl- to yield a hypotonic sweat. We examined the freeze-fracture morphology of tight junctions from isolated secretory coil and coiled duct segments to assess indirectly the contribution of paracellular ion transport in secretion and resorption in the sweat gland. In the secretory coil, tight junctions of the intercellular canaliculus and main lumen consisted of approximately 9 and 6, closely spaced, parallel or anastomosing elements, respectively. Tight junctions of the coiled duct were similar in appearance to those at the main lumen of the secretory coil. In both the secretory coil and coiled duct, and average of 2 to 3, widely spaced junctional elements were usually observed basolateral to the closely spaced junctional elements in the region corresponding to the location of the zonula adherens in Epon sections. The complexity of the tight junctions of the secretory coil exceeded what we expected for an epithelium secreting an isosmotic fluid. The elaborate tight junctions of the coiled duct support other evidence for an intermediate to high transepithelial resistance.

  20. Influence of Meibomian Gland Expression Methods on Human Lipid Analysis Results.

    PubMed

    Kunnen, Carolina M E; Brown, Simon H J; Lazon de la Jara, Percy; Holden, Brien A; Blanksby, Stephen J; Mitchell, Todd W; Papas, Eric B

    2016-01-01

    To compare the lipid composition of human meibum across three different meibum expression techniques. Meibum was collected from five healthy non-contact lens wearers (aged 20-35 years) after cleaning the eyelid margin using three meibum expression methods: cotton buds (CB), meibomian gland evaluator (MGE) and meibomian gland forceps (MGF). Meibum was also collected using cotton buds without cleaning the eyelid margin (CBn). Lipids were analyzed by chip-based, nano-electrospray mass spectrometry (ESI-MS). Comparisons were made using linear mixed models. Tandem MS enabled identification and quantification of over 200 lipid species across ten lipid classes. There were significant differences between collection techniques in the relative quantities of polar lipids obtained (P<.05). The MGE method returned smaller polar lipid quantities than the CB approaches. No significant differences were found between techniques for nonpolar lipids. No significant differences were found between cleaned and non-cleaned eyelids for polar or nonpolar lipids. Meibum expression technique influences the relative amount of phospholipids in the resulting sample. The highest amounts of phospholipids were detected with the CB approaches and the lowest with the MGE technique. Cleaning the eyelid margin prior to expression was not found to affect the lipid composition of the sample. This may be a consequence of the more forceful expression resulting in cell membrane contamination or higher risk of tear lipid contamination as a result of reflex tearing. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Imaging of sebaceous glands of human skin by three-dimensional ultrasound microscopy and its relation to elasticity.

    PubMed

    Kumagai, Kazutoshi; Koike, Hideyuki; Kudo, Yukina; Nagaoka, Ryo; Kubo, Kiyono; Kobayashi, Kazuto; Saijo, Yoshifumi

    2011-01-01

    High frequency ultrasound imaging has realized high resolution in vivo imaging of the biological tissues at a microscopic level. Human skin structure, especially sebaceous glands at the deep part of the dermis, was observed by three-dimensional ultrasound microscopy with the central frequency of 120 MHz. The visco-elasticity and surface sebum level of the observed region were measured by established testing devices. Both sebaceous glands density and surface sebum level were higher in cheek than those in forearm. The viscosity of forearm was lower than that of cheek. These results suggest that sebaceous glands may act as cushions of the skin besides their classical role of secreting sebum and some hormones. High frequency ultrasound imaging contributes to the evaluation of human skin aging.

  2. Subunit structure of deglycosylated human and swine trachea and Cowper's gland mucin glycoproteins.

    PubMed

    Sangadala, S; Kim, D; Brewer, J M; Mendicino, J

    1991-03-27

    The oligosaccharide chains in human and swine trachea and Cowper's gland mucin glycoproteins were completely removed in order to examine the subunit structure and properties of the polypeptide chains of these glycoproteins. The carbohydrate, which constitutes more than 70% of these glycoproteins, was removed by two treatments with trifluoromethanesulfonic acid for 3 h at 3 degrees and periodate oxidation by a modified Smith degradation. All of the sialic acid, fucose, galactose, N-acetylglucosamine and N-acetylgalactosamine present in these glycoproteins was removed by these procedures. The deglycosylated polypeptide chains were purified and characterized. The size of the monomeric forms of all three polypeptide chains were very similar. Data obtained by gel filtration, release of amino acids during hydrolysis with carboxypeptidase B and gel electrophoresis in the presence of 0.1% dodecyl sulfate showed that a major fraction from each of the three mucin glycoproteins had a molecular size of about 67 kDa. All of the deglycosylated chains had a tendency to aggregate. Digestion with carboxypeptidases showed that human and swine trachea mucin glycoproteins had identical carboxyl terminal sequences, -Val-Ala-Phe-Tyr-Leu-Lys-Arg-COOH. Cowper's gland mucin glycoprotein had a similar carboxyl terminal sequence, -Val-Ala-Tyr-Leu-Phe-Arg-Arg-COOH. The yield of amino acids after long periods of hydrolysis with carboxypeptidases showed that at least 85% of the polypeptide chains in each of the deglycosylated preparations have these sequences. These results suggested that the polypeptide chains in these deglycosylated mucin glycoprotein preparations were relatively homogeneous. The deglycosylated polypeptide chains as well as the intact mucin glycoproteins had blocked amino terminii. The purified polypeptide chains were digested with trypsin-TCPK, and S. aureus V8 protease and the resulting peptides were isolated by gel electrophoresis in the presence of 0.1% dodecyl sulfate

  3. Changes in PACAP immunoreactivity in human milk and presence of PAC1 receptor in mammary gland during lactation.

    PubMed

    Csanaky, Katalin; Banki, Eszter; Szabadfi, Krisztina; Reglodi, Dora; Tarcai, Ibolya; Czegledi, Levente; Helyes, Zsuzsanna; Ertl, Tibor; Gyarmati, Judit; Szanto, Zalan; Zapf, Istvan; Sipos, Erika; Shioda, Seiji; Tamas, Andrea

    2012-11-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with widespread occurrence in the nervous system and peripheral organs, including the mammary gland. Previously, we have shown that PACAP38 is present in the human milk at higher levels than in respective blood samples. However, it is not known how PACAP levels and the expression of PAC1 receptor change during lactation. Therefore, the aim of our study was to investigate PACAP38-like immunoreactivity (PACAP38-LI) in human colostrums and transitional and mature milk during lactation and to compare the expression of PAC1 receptors in lactating and non-lactating mammary glands. We found that PACAP38-LI was significantly higher in human colostrum samples than in the transitional and mature milk. PACAP38-LI did not show any significant changes within the first 10-month period of lactation, but a significant increase was observed thereafter, up to the examined 17th month. Weak expression of PAC1 receptors was detected in non-lactating sheep and human mammary glands, but a significant increase was observed in the lactating sheep samples. In summary, the present study is the first to show changes of PACAP levels in human milk during lactation. The presence of PACAP in the milk suggests a potential role in the development of newborn, while the increased expressions of PAC1 receptors on lactating breast may indicate a PACAP38/PAC1 interaction in the mammary gland during lactation.

  4. First evidence of TRPV5 and TRPV6 channels in human parathyroid glands: possible involvement in neoplastic transformation.

    PubMed

    Giusti, Laura; Cetani, Filomena; Da Valle, Ylenia; Pardi, Elena; Ciregia, Federica; Donadio, Elena; Gargini, Claudia; Piano, Ilaria; Borsari, Simona; Jaber, Ali; Caputo, Antonella; Basolo, Fulvio; Giannaccini, Gino; Marcocci, Claudio; Lucacchini, Antonio

    2014-10-01

    The parathyroid glands play an overall regulatory role in the systemic calcium (Ca(2+)) homeostasis. The purpose of the present study was to demonstrate the presence of the Ca(2+) channels transient receptor potential vanilloid (TRPV) 5 and TRPV6 in human parathyroid glands. Semi-quantitative and quantitative PCR was carried out to evaluate the presence of TRPV5 and TRPV6 mRNAs in sporadic parathyroid adenomas and normal parathyroid glands. Western blot and immunocytochemical assays were used to assess protein expression, cellular localization and time expression in primary cultures from human parathyroid adenoma. TRPV5 and TRPV6 transcripts were then identified both in normal and pathological tissues. Predominant immunoreactive bands were detected at 75-80 kD for both vanilloid channels. These channels co-localized with the calcium-sensing receptor (CASR) on the membrane surface, but immunoreactivity was also detected in the cytosol and around the nuclei. Our data showed that western blotting recorded an increase of protein expression of both channels in adenoma samples compared with normal glands suggesting a potential relation with the cell calcium signalling pathway and the pathological processes of these glands.

  5. De novo epidermal regeneration using human eccrine sweat gland cells: higher competence of secretory over absorptive cells.

    PubMed

    Pontiggia, Luca; Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Oliveira, Carol; Braziulis, Erik; Klar, Agnieszka S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

    2014-06-01

    In our previous work, we showed that human sweat gland-derived epithelial cells represent an alternative source of keratinocytes to grow a near normal autologous epidermis. The role of subtypes of sweat gland cells in epidermal regeneration and maintenance remained unclear. In this study, we compare the regenerative potential of both secretory and absorptive sweat gland cell subpopulations. We demonstrate the superiority of secretory over absorptive cells in forming a new epidermis on two levels: first, the proliferative and colony-forming efficiencies in vitro are significantly higher for secretory cells (SCs), and second, SCs show a higher frequency of successful epidermis formation as well as an increase in the thickness of the formed epidermis in the in vitro and in vivo functional analyses using a 3D dermo-epidermal skin model. However, the ability of forming functional skin substitutes is not limited to SCs, which supports the hypothesis that multiple subtypes of sweat gland epithelial cells hold regenerative properties, while the existence and exact localization of a keratinocyte stem cell population in the human eccrine sweat gland remain elusive.

  6. Three-dimensional organotypic culture of human salivary glands: the slice culture model.

    PubMed

    Su, X; Fang, D; Liu, Y; Ramamoorthi, M; Zeitouni, A; Chen, W; Tran, S D

    2016-10-01

    A challenge in studying human salivary glands is to maintain the cells ex vivo in their three-dimensional (3D) morphology with an intact native extracellular matrix (ECM) environment. This paper established a human salivary 3D organotypic slice culture model that could maintain its physiological functions as well as allowing a direct visualization of the cells. Human salivary biopsies from six patients were embedded in agarose and submerged in cold buffer for thin (50 μm) sectioning using a vibratome. 'Salivary slices' were mechanically supported by a porous membrane insert that allowed an air-liquid interface and cultured in serum-free culture media. Cell viability, proliferation, apoptosis, physiological functions, and gene expression were assessed during 14 days of culture. Human salivary slices maintained cell survival (70-40%) and proliferation (6-17%) for 14 days ex vivo. The protein secretory (amylase) function decreased, but fluid (intracellular calcium mobilization) function was maintained. Acinar, ductal, and myoepithelial cell populations survived and maintained their 3D organization within the slice culture model. The human salivary slice culture model kept cells alive ex vivo for 14 days as well as maintaining their 3D morphology and physiological functions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Fiber optic tracheal detection device

    NASA Astrophysics Data System (ADS)

    Souhan, Brian E.; Nawn, Corinne D.; Shmel, Richard; Watts, Krista L.; Ingold, Kirk A.

    2017-02-01

    Poorly performed airway management procedures can lead to a wide variety of adverse events, such as laryngeal trauma, stenosis, cardiac arrest, hypoxemia, or death as in the case of failed airway management or intubation of the esophagus. Current methods for confirming tracheal placement, such as auscultation, direct visualization or capnography, may be subjective, compromised due to clinical presentation or require additional specialized equipment that is not always readily available during the procedure. Consequently, there exists a need for a non-visual detection mechanism for confirming successful airway placement that can give the provider rapid feedback during the procedure. Based upon our previously presented work characterizing the reflectance spectra of tracheal and esophageal tissue, we developed a fiber-optic prototype to detect the unique spectral characteristics of tracheal tissue. Device performance was tested by its ability to differentiate ex vivo samples of tracheal and esophageal tissue. Pig tissue samples were tested with the larynx, trachea and esophagus intact as well as excised and mounted on cork. The device positively detected tracheal tissue 18 out of 19 trials and 1 false positive out of 19 esophageal trials. Our proof of concept device shows great promise as a potential mechanism for rapid user feedback during airway management procedures to confirm tracheal placement. Ongoing studies will investigate device optimizations of the probe for more refined sensing and in vivo testing.

  8. Chloride transport in a human submandibular gland cell line studied by X-ray microanalysis.

    PubMed

    Roomans, G M

    1998-08-01

    Ion transport properties of the human submandibular gland cell line A253 were investigated by X-ray microanalysis. The cells were grown on ultrathin plastic films on titanium grids. After the experiment, where the cells were exposed to various agonists and inhibitors, the specimens were briefly rinsed in distilled water, frozen, and freeze-dried. The elemental composition of the cultured cells most closely resembled that of striated duct cells. Beta-adrenergic stimulation caused a small decrease in the cellular Cl- and K+ concentration, but cholinergic stimulation had no effect. Also stimulation with cAMP caused a decrease in Cl- and K+; this decrease could be inhibited by the chloride channel blocker NPPB. Loss of Cl- and K+ could also be elicited by exposure to a hypotonic solution. The results suggest that there may be several types of chloride channel present in A253 cells.

  9. Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands

    PubMed Central

    Li, Yong; Stoll, Stefan W.; Sekhon, Sahil; Talsma, Caroline; Camhi, Maya I.; Jones, Jennifer L.; Lambert, Sylviane; Marley, Hue; Rittié, Laure; Grachtchouk, Marina; Fritz, Yi; Ward, Nicole L.; Elder, James T.

    2016-01-01

    To explore the role of amphiregulin in inflammatory epidermal hyperplasia, we overexpressed human AREG (hAREG) in FVB/N mice using a bovine K5 promoter. A construct containing AREG coding sequences flanked by 5′ and 3′ untranslated region sequences (AREG-UTR) led to a >10-fold increase in hAREG expression compared to an otherwise-identical construct containing only the coding region (AREG-CDR). AREG-UTR mice developed tousled, greasy fur as well as elongated nails and thickened, erythematous tail skin. No such phenotype was evident in AREG-CDR mice. Histologically, AREG-UTR mice presented with marked epidermal hyperplasia of tail skin (2.1-fold increase in epidermal thickness with a 9.5-fold increase in Ki-67+ cells) accompanied by significantly increased CD4+ T-cell infiltration. Dorsal skin of AREG-UTR mice manifested lesser but still significant increases in epidermal thickness and keratinocyte hyperplasia. AREG-UTR mice also developed marked and significant sebaceous gland enlargement, with corresponding increases in Ki-67+ cells. To determine the response of AREG-UTR animals to a pro-inflammatory skin challenge, topical imiquimod (IMQ) or vehicle cream was applied to dorsal and tail skin. IMQ increased dorsal skin thickness similarly in both AREG-UTR and wild type mice (1.7- and 2.2-fold vs vehicle, P < 0.001 each), but had no such effect on tail skin. These results confirm that keratinocyte expression of hAREG elicits inflammatory epidermal hyperplasia, and are consistent with prior reports of tail epidermal hyperplasia and increased sebaceous gland size in mice expressing human epigen. PMID:26519132

  10. Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands.

    PubMed

    Li, Yong; Stoll, Stefan W; Sekhon, Sahil; Talsma, Caroline; Camhi, Maya I; Jones, Jennifer L; Lambert, Sylviane; Marley, Hue; Rittié, Laure; Grachtchouk, Marina; Fritz, Yi; Ward, Nicole L; Elder, James T

    2016-03-01

    To explore the role of amphiregulin in inflammatory epidermal hyperplasia, we overexpressed human AREG (hAREG) in FVB/N mice using a bovine K5 promoter. A construct containing AREG coding sequences flanked by 5' and 3' untranslated region sequences (AREG-UTR) led to a >10-fold increase in hAREG expression compared to an otherwise-identical construct containing only the coding region (AREG-CDR). AREG-UTR mice developed tousled, greasy fur as well as elongated nails and thickened, erythematous tail skin. No such phenotype was evident in AREG-CDR mice. Histologically, AREG-UTR mice presented with marked epidermal hyperplasia of tail skin (2.1-fold increase in epidermal thickness with a 9.5-fold increase in Ki-67(+) cells) accompanied by significantly increased CD4+ T-cell infiltration. Dorsal skin of AREG-UTR mice manifested lesser but still significant increases in epidermal thickness and keratinocyte hyperplasia. AREG-UTR mice also developed marked and significant sebaceous gland enlargement, with corresponding increases in Ki-67(+) cells. To determine the response of AREG-UTR animals to a pro-inflammatory skin challenge, topical imiquimod (IMQ) or vehicle cream was applied to dorsal and tail skin. IMQ increased dorsal skin thickness similarly in both AREG-UTR and wild type mice (1.7- and 2.2-fold vs vehicle, P < 0.001 each), but had no such effect on tail skin. These results confirm that keratinocyte expression of hAREG elicits inflammatory epidermal hyperplasia, and are consistent with prior reports of tail epidermal hyperplasia and increased sebaceous gland size in mice expressing human epigen.

  11. Differences in Human Meibum Lipid Composition with Meibomian Gland Dysfunction Using NMR and Principal Component Analysis

    PubMed Central

    Foulks, Gary N.; Yappert, Marta C.; Milliner, Sarah E.

    2012-01-01

    Purpose. Nuclear magnetic resonance (NMR) spectroscopy has been used to quantify lipid wax, cholesterol ester terpenoid and glyceride composition, saturation, oxidation, and CH2 and CH3 moiety distribution. This tool was used to measure changes in human meibum composition with meibomian gland dysfunction (MGD). Methods. 1H-NMR spectra of meibum from 39 donors with meibomian gland dysfunction (Md) were compared to meibum from 33 normal donors (Mn). Results. Principal component analysis (PCA) was applied to the CH2/CH3 regions of a set of training NMR spectra of human meibum. PCA discriminated between Mn and Md with an accuracy of 86%. There was a bias toward more accurately predicting normal samples (92%) compared with predicting MGD samples (78%). When the NMR spectra of Md were compared with those of Mn, three statistically significant decreases were observed in the relative amounts of CH3 moieties at 1.26 ppm, the products of lipid oxidation above 7 ppm, and the ═CH moieties at 5.2 ppm associated with terpenoids. Conclusions. Loss of the terpenoids could be deleterious to meibum since they exhibit a plethora of mostly positive biological functions and could account for the lower level of cholesterol esters observed in Md compared with Mn. All three changes could account for the higher degree of lipid order of Md compared with age-matched Mn. In addition to the power of NMR spectroscopy to detect differences in the composition of meibum, it is promising that NMR can be used as a diagnostic tool. PMID:22131391

  12. WISP-1 overexpression upregulates cell proliferation in human salivary gland carcinomas via regulating MMP-2 expression

    PubMed Central

    Li, Fu-Jun; Wang, Xin-Juan; Zhou, Xiao-Li

    2016-01-01

    Background WISP-1 is a member of the CCN family of growth factors and has been reported to play an important role in tumorigenesis by triggering downstream events via integrin signaling. However, little is known about the role of WISP-1 in proliferation of salivary gland carcinoma (SGC) cells. Methods In this study, we investigated the WISP-1 expression in SGC tissues via immunohistochemical staining, Western blotting assay, and real-time quantitative polymerase chain reaction method, and then evaluated the regulatory role of WISP-1 in the growth of SGC A-253 cells. In addition, the role of MMP-2 in the WISP-1-mediated growth regulation was also investigated. Results It was demonstrated that the WISP-1 expression was upregulated at both mRNA and protein levels in 15 of 21 SGC tumor tissues, compared to the non-tumor tissues (five of 21), associated with the lymph node dissection and bone invasion. The in vitro CCK-8 assay and colony-forming assay demonstrated that the exogenous WISP-1 treatment or the WISP-1 overexpression promoted the growth of A-253 cells. In addition, we confirmed that the WISP-1 overexpression upregulated the MMP-2 expression in A-253 cells with the gain-of-function and loss-of-function strategies, and that the MMP-2 knockdown attenuated the WISP-1-mediated growth promotion of A-253 cells. Conclusion We found that WISP-1 was overexpressed in the human SGCs, and the WISP-1 overexpression promoted the salivary gland cell proliferation via upregulating MMP-2 expression. Our study recognized the oncogenic role of WISP-1 in human SGCs, which could serve as a potential target for anticancer therapy. PMID:27799801

  13. Dynamic Observation of Sweat Glands of Human Finger Tip Using All-Optical-Fiber High-Speed Optical Coherence Tomography

    NASA Astrophysics Data System (ADS)

    Ohmi, Masato; Nohara, Kenji; Ueda, Yoshihiro; Fuji, Toshie; Haruna, Masamitsu

    2005-06-01

    High-speed optical coherence tomography (OCT) makes it possible to perform a time-sequential imaging of biological tissue and small organs. In this paper, we demonstrate in vivo observation of dynamics of sweat glands of human finger tip using high-speed OCT with push-pull driven fiber-optic PZT phase modulators. Movement of a sweat droplet through a micro spiral duct can be tracked clearly. An interesting function of sweat glands is found out in time-sequential OCT imaging.

  14. New laser tracheal tube

    NASA Astrophysics Data System (ADS)

    Ungemach, Josef; Foth, Hans-Jochen; Hoermann, Karl; Preponis, E.

    1996-09-01

    The complication of a laser induced tube fire during surgery was first published in 1979. The protection of tracheal tubes against ignition is necessary to enable a safe laser surgery of the upper airway. in an experimental study a new compound tube was tested: this tube had a higher laser resistance than a pure metal tube. The damage threshold of this tube was tested against the emission of various lasers as CO2. The metal tube was damaged within seconds at CO2 laser power densities of 103 W/cm2 whereas the damage threshold of the compound tube was 3.106 W/cm2. We compared the compound laser tube to the so far used metal tube in a prospective clinical trial in our department of ENT in patients undergoing CO2-laser surgery of the upper airway. 66 patients were included into the study: 33 received the compound tube, 33 the metal tube. During endotracheal intubation the handling of the compound tube was better. During laser surgery high airway pressures occured more often with the metal tube. Whereas kinking was the problem of the compound tubes. Destruction of cuffs occured in both groups but did not cause any complications. No tube or cuff fire was noticed.

  15. Development and structure of the glandopreputial sulcus of the human clitoris with a special reference to glandopreputial glands.

    PubMed

    van der Putte, Sebastian C J; Sie-Go, Daisy M D S

    2011-01-01

    The structure and development of the sulcus between the glans and prepuce of the human clitoris have hardly been investigated. Interest in its structure was raised when in the female, in contrast to the male, glands were found to develop from the solid lamella-like precursor of the glandopreputial sulcus. It prompted a further histological analysis of the sulcus in female fetuses and newborn and an extension of that study to clitorises of adult women. The investigation showed that in the clitoris, in contrast to the penis, the transformation of the glandopreputial lamella into the open sulcus was mostly incomplete and apparently remained so throughout life. As a most striking and probably exclusively female feature, two to eight eccrine glands developed from the base of the lamella in fetuses older than 14.5 weeks gestation. These glands formed secretory coils near and occasionally inside the adjacent distal corpora cavernosa. Some glands showed atresia, cystic dilatation, and squamous metaplasia. A remarkably similar picture was observed in the adult clitorises, in which the secretory coils were often found between the large blood vessels and nerves to the glans and were connected to the sulcus by long excretory ducts. All glands revealed unmistakably eccrine features. It is suggested that their secretion moistens the female glandopreputial sulcus, which is not lubricated by urethral secretion as in the male. The findings may explain the rare clitoral phimosis, cysts, and some pilonidal sinuses. 2010 Wiley-Liss, Inc.

  16. Expression of nuclear receptors (AhR, PXR, CAR) and transcription factor (Nrf2) in human parotid gland.

    PubMed

    Droździk, Agnieszka; Kowalczyk, Robert; Urasińska, Elzbieta; Kurzawski, Mateusz

    2013-01-01

    Nuclear receptors and transcription factors coordinate expression of many genes, and regulation of their expression determines cellular response to various endo- and exogenous factors. There is paucity of data regarding expression of nuclear receptors and factors in salivary glands. In the present study, a focus was placed on human parotid gland expression of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR, NR1I2), constitutive androstane receptor (CAR, NR1I3) and nuclear factor E2-related factor 2 (Nrf2). Parotid salivary tissue was obtained from patients undergoing the gland dissection. Quantitative real-time PCR aimmunohistochemical staining were used for expression studies. The highest mRNA expression was documented for NFE2L2 coding for Nrf2. Lower expression was seen in the case of AHR gene coding for AhR. PXR was constitutively present at very low level and CAR expression was below the limit of quantification. Immunohistochemical evaluation of the parotid gland specimens revealed cytoplasmic Nrf2 expression in striated duct cells as well as within myoepithelial cells. Acinar cells were mostly negative for Nrf2. Expression of AhR was found within the cytoplasm in striated duct cells. Acinar and myoepithelial cells were negative for AhR. Having in mind their role in regulating function of many enzymes and transmembrane transporters, expression of these factors seem play a role in salivary gland physiology, pathology as well as drug transport and metabolism.

  17. Human postmortem lacrimal and submandibular glands stored in RNAlater are suitable for molecular, biochemical, and cell biological studies

    PubMed Central

    Hawley, Dillon; Aluri, Hema; Armaos, Helene; Kim, Gina; Kublin, Claire

    2016-01-01

    Purpose Gene expression and protein analysis studies require high-quality human tissue which is a challenge and difficult to obtain through live human biopsies. Human postmortem lacrimal gland (LG) and submandibular gland (SMG) tissues have the potential to provide an invaluable source for studying the mechanisms involved in LG and SMG dysfunction. Therefore, we aimed to test the suitability of post-mortem LG and SMG for molecular, biochemical, and cell biological studies. Methods LG and SMG tissue from healthy donors was collected and immediately placed in RNAlater solution and then shipped overnight at 4 °C. After receipt, each gland was divided into three pieces for RNA, protein, and histological analysis, respectively. Total RNA isolated from each LG and SMG was analyzed for RNA integrity using an Agilent Bioanalyzer and reverse transcription–PCR (RT–PCR). For histology, tissues were embedded in paraffin and stained with hematoxylin and eosin. For protein analysis, lysates were prepared and processed for sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and western blotting. Results When the LG and SMG samples were preserved in RNAlater, the RNA integrity number (RIN) values from the LG and SMG were >7.0 from all three donors, while the RNAs from tissue not preserved in RNAlater were of poorer quality. The gene and/or protein expression of E-cadherin, aquaporin 5, alpha-smooth muscle actin (α-SMA), β-actin, and GAPDH was preserved in all samples. In addition, histological analyses showed normal tubuloacinar structures of all glands with serous and mucous producing acini within lobules interspersed with adipose fat. Conclusions In this study, we determined that RNA, protein, and histological sections obtained from postmortem human LG and SMG tissue preserved in RNAlater were of high quality. This would provide a viable source of human LG and SMG tissue suitable for studies of diseases that affect these glands, such as Sj

  18. Minor salivary glands as a major source of secretory immunoglobin A in the human oral cavity.

    PubMed

    Crawford, J M; Taubman, M A; Smith, D J

    1975-12-19

    Secretory immunoglobulin A is the predominant immunoglobulin in labial minor salivary gland secretions. Its mean concentration is four times higher in these secretions than in parotid gland secretion. The minor salivary glands can produce 30 to 35 percent of the immunoglobulin A that enters the oral cavity. This, together with the potential accessibility of these glands to antigenic stimulation, suggest that they may be an important source of the immune factors that are involved in the regulation of the microorganisms in the oral environment.

  19. Oral mucocele/ranula: Another human immunodeficiency virus-related salivary gland disease?

    PubMed

    Syebele, Kabunda; Munzhelele, Thifhelimbilu I

    2015-05-01

    To describe clinical characteristics of oral mucoceles/ranulas, with a focus on human immunodeficiency virus (HIV)-related salivary gland diseases. A descriptive and clinical study, with review of patient data. We reviewed 113 referred cases of oral mucocele. The following anatomical sites were identified: lip, tongue, and floor of the mouth (simple ranulas), as well as plunging ranulas. The age and gender data of the patients with oral mucoceles were recorded. The HIV status of the patients and other information were reviewed. There were 30 (26.5%) males and 83 (73.5%) females. Most patients were below 30 years of age, with the peak frequency in the first and second decade. Ranula (simple and plunging) represented 84.1% of the mucocele locations. Mucocele on the lips represented 10.6%. Seventy-two (63.7%) patients were HIV positive; and 97.2% of them had ranulas. Thirty-eight (33.6%) patients presented with plunging ranulas; and 92.1% of them were HIV positive, compared with two patients presenting with plunging ranulas in the HIV-negative group. These results strongly suggest that an HIV-positive patient is statistically (P < 0.001) more at risk of presenting with not only a simple, but also a plunging ranula type. This study presents a different clinical picture of oral mucoceles/ranulas, as observed in HIV-positive patients. Additionally, it suggests a possible clinical link between the two pathologies. The authors strongly support the suggestion that oral mucocele/ranula is an HIV-related salivary gland disease. 4. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  20. [Inhibition of triclosan to fatty acid synthase from goose uropygial glands and human breast cancer cells in vitro].

    PubMed

    Wang, Ying-Qiang; Lai, Bing-Sen; Anderson, Vernon E

    2003-03-01

    It has been indicated that fatty acid synthase (FAS) is abnormally overexpressed in human breast cancer compared with normal human tissue. Inhibition of FAS induces apoptosis of human breast cancer cells. The aim of this study was to observe the inhibition of triclosan on FAS from goose uropygial glands for establishing the method and to study the inhibition of triclosan on FAS from human breast cancer SKBr3 cells in vitro. The goose uropygial glands FAS was purified by ultra-centrifugation and Superdex PG 200 chromatography; the human breast cancer SKBr3 cell FAS was partially purified by ultra-centrifugation. The FAS was interacted with different concentrations of Triclosan with different times before catalyzing. Then the substrates of FAS were added to the reaction system. The inhibitory activities of triclosan against the FAS were investigated using spectrophotometric assays. In the goose uropygial gland group, FAS was purified as a single band at 250kDa with SDS-PAGE. The inhibitory activities of triclosan(12.5 micromol/L) at 0, 5, and 10 minute on FAS were 26.40%, 28.30%, and 43.93%, respectively. The inhibitory activities of triclosan (25.00 micromol/L) at 0, 5, and 10 minute on FAS were 46.22%, 50.28%, and 97.05%, respectively. The inhibitory activities of triclosan (100.00 micromol/L) at 0, 5, and 10 minute on FAS were 98.11%, 97.75%, and 97.37%, respectively. In human SKBr3 breast cancer cell group, the inhibitory activities of triclosan (25, 50, 100, and 200 micromol/L) at 5 minute on FAS were 20.00%, 26.67%, 60.00%, and 100%, respectively. Triclosan inhibits the FAS from goose uropygial glands and human breast cancer SKBr3 cells. The inhibitory activities depended on the concentrations of triclosan and the interaction times between triclosan and FAS before catalyzing.

  1. A novel TMEM16A splice variant lacking the dimerization domain contributes to calcium-activated chloride secretion in human sweat gland epithelial cells.

    PubMed

    Ertongur-Fauth, Torsten; Hochheimer, Andreas; Buescher, Joerg Martin; Rapprich, Stefan; Krohn, Michael

    2014-11-01

    Sweating is an important physiological process to regulate body temperature in humans, and various disorders are associated with dysregulated sweat formation. Primary sweat secretion in human eccrine sweat glands involves Ca(2+) -activated Cl(-) channels (CaCC). Recently, members of the TMEM16 family were identified as CaCCs in various secretory epithelia; however, their molecular identity in sweat glands remained elusive. Here, we investigated the function of TMEM16A in sweat glands. Gene expression analysis revealed that TMEM16A is expressed in human NCL-SG3 sweat gland cells as well as in isolated human eccrine sweat gland biopsy samples. Sweat gland cells express several previously described TMEM16A splice variants, as well as one novel splice variant, TMEM16A(acΔe3) lacking the TMEM16A-dimerization domain. Chloride flux assays using halide-sensitive YFP revealed that TMEM16A is functionally involved in Ca(2+) -dependent Cl(-) secretion in NCL-SG3 cells. Recombinant expression in NCL-SG3 cells showed that TMEM16A(acΔe3) is forming a functional CaCC, with basal and Ca(2+) -activated Cl(-) permeability distinct from canonical TMEM16A(ac). Our results suggest that various TMEM16A isoforms contribute to sweat gland-specific Cl(-) secretion providing opportunities to develop sweat gland-specific therapeutics for treatment of sweating disorders.

  2. [Quantitative analysis of age-related changes of human major salivary glands using magnetic resonance imaging].

    PubMed

    Xu, Liang; Zhao, Danlei; Zhang, Hongli; Tian, Ye; Fan, Guohua; Shen, Junkang; Gong, Jianping; Qian, Minghui

    2015-01-20

    To analyze the age-related characteristics of volumes, signal intensities (SIs) of T1-weighted images (T1WI), T2-weighted images (T2WI) and apparent diffusion coefficients (ADCs) of three major salivary glands. A total of 300 subjects with normal salivary glands were divided into 4 different age groups and examined with a 1.5 T magnetic resonance (MR) unit. T1WI, T2WI and diffusion-weighted MR images (DW MRI) were obtained and bilateral parotid, submandibular and sublingual glands segmented manually. The volumes, T1WI, T2WI SIs and ADCs of three major salivary glands were measured. And the relative SIs (RSIs) were assessed by comparing with cerebrospinal fluid. The volumes, T1WI and T2WI RSIs of parotid glands were significantly correlated with age (P < 0.01) and showed similar significant tendencies of growing from minority to middle age and decreasing slightly after old age. Significant differences existed between minority and middle age groups in all above-mentioned parameters (P < 0.01). The ADCs of submandibular glands also showed that there was a significant difference between the minority and middle age groups (P < 0.01). MRI may be applied for studying the morphological and functional changes of normal major salivary glands with aging. Thus clinical rationales can be provided for assessing the subjects of any age during salivary gland imaging and aging-related researches.

  3. Dynamic analysis of eccrin sweat glands on human fingertips by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Haruna, Masamitsu; Ohmi, Masato; Ueda, Yoshihiro; Yamada, Akihiro; Saigusa, Hiroyuki

    2008-02-01

    OCT is highly potential for dynamic analysis of eccrin sweat glands. It is found in our experiment that the spiral lumen of an active sweat gland expands drastically in response to mental stress. Mental-stress-induced sweating is analyzed quantitatively based on time-sequential OCT images.

  4. Ultrasonic delivery of silica-gold nanoshells for photothermolysis of sebaceous glands in humans: Nanotechnology from the bench to clinic.

    PubMed

    Paithankar, Dilip; Hwang, Byeong Hee; Munavalli, Girish; Kauvar, Arielle; Lloyd, Jenifer; Blomgren, Richard; Faupel, Linda; Meyer, Todd; Mitragotri, Samir

    2015-05-28

    Recent advances in nanotechnology have provided numerous opportunities to transform medical therapies for the treatment of diseases including cancer, atherosclerosis, and thrombosis. Here, we report, through in vitro studies and in vivo human pilot clinical studies, the use of inert, inorganic silica-gold nanoshells for the treatment of a widely prevalent and researched, yet poorly treated disease of acne. We use ~150nm silica-gold nanoshells, tuned to absorb near-IR light and near-IR laser irradiation to thermally disrupt overactive sebaceous glands in the skin which define the etiology of acne-related problems. Low-frequency ultrasound was used to facilitate deep glandular penetration of the nanoshells. Upon delivery of the nanoshells into the follicles and glands, followed by wiping of superficial nanoshells from skin surface and exposure of skin to near-infrared laser, nanoshells localized in the follicles absorb light, get heated, and induce focal thermolysis of sebaceous glands. Pilot human clinical studies confirmed the efficacy of ultrasonically-delivered silica-gold nanoshells in inducing photothermal disruption of sebaceous glands without damaging collateral skin.

  5. Endoscopic treatment of tracheal stenosis.

    PubMed

    Freitag, Lutz; Darwiche, Kaid

    2014-02-01

    For all cases of tracheal obstructions surgery should be considered first. Interventional endoscopic procedures can provide immediate relief. Intraluminally growing tumors can be resected with laser, argon-plasma coagulation, an electrosurgical knife or cryo-probe. Photodynamic therapy of smaller tracheal tumors can be curative. Narrowing from intramural tumor growth or wall destruction requires internal splinting with an airway stent. Scar strictures can be dilated with balloons but the biotrauma may stimulate new scarring. In benign strictures and malacias, tracheal stents should only be placed if all other methods are exhausted. Complications including stent migration, mucostasis, halitosis and granulation tissue development must be considered. Most important for a good outcome is a multidisciplinary approach. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Pineal gland in old age; quantitative and qualitative morphological study of 168 human autopsy cases.

    PubMed

    Hasegawa, A; Ohtsubo, K; Mori, W

    1987-04-21

    Age-related changes of human pineal gland were studied morphologically on 168 autopsy cases. Pineal weight in the formalin-fixed condition was 99 +/- 56 mg in males (n = 88, mean age 78 years) and 91 +/- 41 mg in females (n = 80, mean age 79 years), which showed no sexual difference (P = 0.290). There was no correlation between pineal weight and age of the patient (r = 0.0678, P = 0.191, n = 168). The pineal volume calculated as a spheroid was directly proportional to the weight (r = 0.904, n = 167, P = 0.000). A significant correlation existed between pineal weight and the degree of calcification (r = 0.231, P = 0.002, n = 156). The density of the pineals decreased with age (r = -0.164, P = 0.017, n = 167). The degree of calcification and cyst formation did not increase with age, but the grade of cyst formation was related to the pineal volume (P = 0.0002). Some pineals of the patients over 90 years old showed no calcification and appeared indistinguishable from the ones of the younger subjects. The weight and volume of the pineals of the patients with hypertension was appreciably greater than those of the non-hypertensive patients. These results indicate that human pineals do not necessarily degenerate progressively after involution.

  7. The Spectrophotometric Sulfo-Phospho-Vanillin Assessment of Total Lipids in Human Meibomian Gland Secretions

    PubMed Central

    McMahon, Anne; Lu, Hua

    2013-01-01

    Human meibomian gland secretions (meibum) are the major lipid component of the human preocular tear film. The predominant lipid classes found in meibum include waxes (WE), cholesteryl esters (CE), and varying amounts of cholesterol (Chl). The classical sulfo-phospho-vanillin assay (SPVA), adapted for a microplate reader, was used to quantitate lipids in meibum. To account for varying reactivities of different lipids in SPVA, a model meibomian lipid mixture (MMx) that approximated the WE/CE/Chl composition of meibum was developed and used to quantitate meibomian lipids. The overall SPV responses of MMx and meibum were found to be close, with similar intermediate and final reaction products for both. Saturated WE that had not been expected to be reactive were found to be SPV-positive. A reaction mechanism for these compounds in SPVA which involves the formation of alkenyl ethers is proposed and discussed. Tested proteins were non-reactive in SPVA. Thus, by comparing the results of gravimetric analyses of meibum samples with the results of a properly calibrated SPVA, it was estimated that the SPV-reactive lipid content of dry meibum in tested samples was about 78 % (w/w). The SPV method can also be adopted for analyzing other types of complex lipids secretions, such as sebum, as well as whole lipid extracts from other lipid-enriched organs and tissues, if proper standards are chosen. PMID:23345137

  8. The spectrophotometric sulfo-phospho-vanillin assessment of total lipids in human meibomian gland secretions.

    PubMed

    McMahon, Anne; Lu, Hua; Butovich, Igor A

    2013-05-01

    Human meibomian gland secretions (meibum) are the major lipid component of the human preocular tear film. The predominant lipid classes found in meibum include waxes (WE), cholesteryl esters (CE), and varying amounts of cholesterol (Chl). The classical sulfo-phospho-vanillin assay (SPVA), adapted for a microplate reader, was used to quantitate lipids in meibum. To account for varying reactivities of different lipids in SPVA, a model meibomian lipid mixture (MMx) that approximated the WE/CE/Chl composition of meibum was developed and used to quantitate meibomian lipids. The overall SPV responses of MMx and meibum were found to be close, with similar intermediate and final reaction products for both. Saturated WE that had not been expected to be reactive were found to be SPV-positive. A reaction mechanism for these compounds in SPVA which involves the formation of alkenyl ethers is proposed and discussed. Tested proteins were non-reactive in SPVA. Thus, by comparing the results of gravimetric analyses of meibum samples with the results of a properly calibrated SPVA, it was estimated that the SPV-reactive lipid content of dry meibum in tested samples was about 78 % (w/w). The SPV method can also be adopted for analyzing other types of complex lipids secretions, such as sebum, as well as whole lipid extracts from other lipid-enriched organs and tissues, if proper standards are chosen.

  9. Expression of PACAP and PAC1 Receptor in Normal Human Thyroid Gland and in Thyroid Papillary Carcinoma.

    PubMed

    Bardosi, Sebastian; Bardosi, Attila; Nagy, Zsuzsanna; Reglodi, Dora

    2016-10-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor. PACAP and PAC1 receptor expressions were investigated from thyroid gland samples of patients with papillary carcinomas. The staining intensity of follicular epithelial cells and thyroid colloid of tumor tissue was compared to that of tumor-free tissue in the same thyroid glands in a semi-quantitative way. Our results reveal that both PACAP(-like) and PAC1 receptor(-like) immunoreactivities are altered in papillary carcinoma. Stronger PACAP immunoreactivity was observed in active follicles. Colloidal PACAP immunostaining was either lacking or very weak, and more tumorous cells displayed strong apical immunoreactivity. Regarding PAC1 receptor, cells of the normal thyroid tissue showed strong granular expression, which was lacking in the tumor cells. The cytoplasm of tumor cells displayed weak, minimal staining, while in a few tumor cells we observed strong PAC1 receptor expression. This pattern was similar to that observed in the PACAP expression, but fewer in number. In summary, we showed alteration of PACAP and PAC1 receptor expression in human thyroid papillary carcinoma, indicating that PACAP regulation is disturbed in tumorous tissue of the thyroid gland. The exact role of PACAP in thyroid tumor growth should be further explored.

  10. Down regulation and nuclear localization of human beta-defensin-1 in pleomorphic adenomas of salivary glands.

    PubMed

    Pantelis, Annette; Wenghoefer, Matthias; Haas, Susanne; Merkelbach-Bruse, Sabine; Pantelis, Dimitrios; Jepsen, Søren; Bootz, Friedrich; Winter, Jochen

    2009-06-01

    Although antimicrobial peptides (AMPs) appear to have diverse functional activities in innate immunity, a few reports suggest a potential role of human beta-defensin (hBD)-1 in tumor suppression. The aim of the present study was to compare the expression patterns of hBD-1, -2 and -3 in various features of human salivary gland tissues, such as healthy parenchyma, chronic sialadenitis and intraglandular pleomorphic adenomas, with their adjacent normal tissues. Twenty human salivary gland specimens (five healthy, five chronic sialadenitis, five pleomorphic adenomas and five adenoma adjacent normal tissues (AANTs)) were investigated for mRNA expression levels of hBD-1, -2 and -3 by quantitative real-time RT-PCR. Additionally, immunohistochemistry for the hBD-1, -2 and -3 peptides was performed for analysis of localization. Considerably increased, 80-fold higher hBD-1 and increased hBD-3 mRNA expression levels compared to healthy salivary gland tissues were detected in chronic sialadenitis. In pleomorphic adenomas hBD-2 expression levels were lower, but hBD-1 expression levels were significant decreased (p=0.03) compared to healthy parenchyma. Interestingly, the AANTs showed a 48-fold higher expression of hBD-1 and increased hBD-3 expression compared to the healthy salivary gland. Immunohistochemistry of the tumors showed nuclear hBD-1 localization. For the first time, it was shown that hBD-1 gene expression is significantly decreased in pleomorphic adenomas, while simultaneously the protein is localized in the nucleus. Increased expression levels in glandular inflammation have been described previously albeit not in AANTs. These data support the hypothesis that hBD-1 might be a potential tumor suppressor also in benign salivary gland tumors in addition to other genetic alterations.

  11. Tracheal Sounds Acquisition Using Smartphones

    PubMed Central

    Reyes, Bersain A.; Reljin, Natasa; Chon, Ki H.

    2014-01-01

    Tracheal sounds have received a lot of attention for estimating ventilation parameters in a non-invasive way. The aim of this work was to examine the feasibility of extracting accurate airflow, and automating the detection of breath-phase onset and respiratory rates all directly from tracheal sounds acquired from an acoustic microphone connected to a smartphone. We employed the Samsung Galaxy S4 and iPhone 4s smartphones to acquire tracheal sounds from N = 9 healthy volunteers at airflows ranging from 0.5 to 2.5 L/s. We found that the amplitude of the smartphone-acquired sounds was highly correlated with the airflow from a spirometer, and similar to previously-published studies, we found that the increasing tracheal sounds' amplitude as flow increases follows a power law relationship. Acquired tracheal sounds were used for breath-phase onset detection and their onsets differed by only 52 ± 51 ms (mean ± SD) for Galaxy S4, and 51 ± 48 ms for iPhone 4s, when compared to those detected from the reference signal via the spirometer. Moreover, it was found that accurate respiratory rates (RR) can be obtained from tracheal sounds. The correlation index, bias and limits of agreement were r2 = 0.9693, 0.11 (−1.41 to 1.63) breaths-per-minute (bpm) for Galaxy S4, and r2 = 0.9672, 0.097 (–1.38 to 1.57) bpm for iPhone 4s, when compared to RR estimated from spirometry. Both smartphone devices performed similarly, as no statistically-significant differences were found. PMID:25196108

  12. Tracheal sounds acquisition using smartphones.

    PubMed

    Reyes, Bersain A; Reljin, Natasa; Chon, Ki H

    2014-07-30

    Tracheal sounds have received a lot of attention for estimating ventilation parameters in a non-invasive way. The aim of this work was to examine the feasibility of extracting accurate airflow, and automating the detection of breath-phase onset and respiratory rates all directly from tracheal sounds acquired from an acoustic microphone connected to a smartphone. We employed the Samsung Galaxy S4 and iPhone 4s smartphones to acquire tracheal sounds from N = 9 healthy volunteers at airflows ranging from 0.5 to 2.5 L/s. We found that the amplitude of the smartphone-acquired sounds was highly correlated with the airflow from a spirometer, and similar to previously-published studies, we found that the increasing tracheal sounds' amplitude as flow increases follows a power law relationship. Acquired tracheal sounds were used for breath-phase onset detection and their onsets differed by only 52 ± 51 ms (mean ± SD) for Galaxy S4, and 51 ± 48 ms for iPhone 4s, when compared to those detected from the reference signal via the spirometer. Moreover, it was found that accurate respiratory rates (RR) can be obtained from tracheal sounds. The correlation index, bias and limits of agreement were r² = 0.9693, 0.11 (-1.41 to 1.63) breaths-per-minute (bpm) for Galaxy S4, and r² = 0.9672, 0.097 (-1.38 to 1.57) bpm for iPhone 4s, when compared to RR estimated from spirometry. Both smartphone devices performed similarly, as no statistically-significant differences were found.

  13. Idiopathic tracheal stenosis: a clinicopathologic study of 63 cases and comparison of the pathology with chondromalacia.

    PubMed

    Mark, Eugene J; Meng, Fanqing; Kradin, Richard L; Mathisen, Douglas J; Matsubara, Osamu

    2008-08-01

    Tracheal stenosis in adults usually is the result of mechanical injuries either from direct trauma or intubation. Rarely do cases develop in patients without such a precedent history, and there are few reports of the pathology of idiopathic tracheal stenosis (ITS). We reviewed clinicopathologically, 63 tracheal resections for tracheal stenosis in patients who had no antecedent explanation for their stenosis. We contrasted these 63 cases with 34 cases of tracheal stenosis owing to chondromalacia (CM) after mechanical injury. All 63 cases occurred in females, with a mean age of 49 years. The most common symptom was dyspnea on exertion. The average duration of symptoms was greater than 2 years. One-third of the patients gave a history of gastroesophageal reflux. All but one of the cases occurred in the subglottic region and/or upper one-third of the trachea. Pathologically, most cases showed extensive keloidal fibrosis and dilation of mucus glands, a finding that was not obvious in most cases of CM. ITS has relatively normal cartilage with smooth inner and outer perichondrium, whereas CM has extensive degeneration of cartilage with irregular border of inner perichondrium observable at shirt sleeve magnification. Immunohistochemical staining for estrogen receptor and progesterone receptor was positive in fibroblasts cells in most cases. ITS is a rare disease and restricted to females. It may represent some form of fibromatosis. ITS can be distinguished histologically from CM in tracheal resection specimens in most cases.

  14. Radioisotope measurement of the velocity of tracheal mucus

    SciTech Connect

    Russo, K.J.; Palmer, D.W.; Beste, D.J.; Carl, G.A.; Belson, T.P.; Pelc, L.R.; Toohill, R.J.

    1985-04-01

    A radioisotope scanning technique for measuring the velocity of tracheal mucus has been developed utilizing a canine model. A solution of stannous phytate labeled with /sup 99m/Tc is introduced percutaneously into the lower trachea and the upward movement of the leading edge of the radioactivity is followed by repeat scanning at 2-minute intervals using a modified rectilinear scanner, thus allowing calculation of the velocity of the mucus. It is believed that this technique may be of value in studying the effect of experimentally induced tracheal injuries on mucus velocity. Possible applications of the technique for the study of the velocity of mucus in the human trachea are discussed.

  15. Enhanced Edar Signalling Has Pleiotropic Effects on Craniofacial and Cutaneous Glands

    PubMed Central

    Chang, Shie Hong; Jobling, Stephanie; Brennan, Keith; Headon, Denis J.

    2009-01-01

    The skin carries a number of appendages, including hair follicles and a range of glands, which develop under the influence of EDAR signalling. A gain of function allele of EDAR is found at high frequency in human populations of East Asia, with genetic evidence suggesting recent positive selection at this locus. The derived EDAR allele, estimated to have reached fixation more than 10,000 years ago, causes thickening of hair fibres, but the full spectrum of phenotypic changes induced by this allele is unknown. We have examined the changes in glandular structure caused by elevation of Edar signalling in a transgenic mouse model. We find that sebaceous and Meibomian glands are enlarged and that salivary and mammary glands are more elaborately branched with increased Edar activity, while the morphology of eccrine sweat and tracheal submucosal glands appears to be unaffected. Similar changes to gland sizes and structures may occur in human populations carrying the derived East Asian EDAR allele. As this allele attained high frequency in an environment that was notably cold and dry, increased glandular secretions could represent a trait that was positively selected to achieve increased lubrication and reduced evaporation from exposed facial structures and upper airways. PMID:19855838

  16. Enhanced Edar signalling has pleiotropic effects on craniofacial and cutaneous glands.

    PubMed

    Chang, Shie Hong; Jobling, Stephanie; Brennan, Keith; Headon, Denis J

    2009-10-26

    The skin carries a number of appendages, including hair follicles and a range of glands, which develop under the influence of EDAR signalling. A gain of function allele of EDAR is found at high frequency in human populations of East Asia, with genetic evidence suggesting recent positive selection at this locus. The derived EDAR allele, estimated to have reached fixation more than 10,000 years ago, causes thickening of hair fibres, but the full spectrum of phenotypic changes induced by this allele is unknown. We have examined the changes in glandular structure caused by elevation of Edar signalling in a transgenic mouse model. We find that sebaceous and Meibomian glands are enlarged and that salivary and mammary glands are more elaborately branched with increased Edar activity, while the morphology of eccrine sweat and tracheal submucosal glands appears to be unaffected. Similar changes to gland sizes and structures may occur in human populations carrying the derived East Asian EDAR allele. As this allele attained high frequency in an environment that was notably cold and dry, increased glandular secretions could represent a trait that was positively selected to achieve increased lubrication and reduced evaporation from exposed facial structures and upper airways.

  17. Morphology of pineal glands in human foetuses and infants with brain lesions.

    PubMed

    Laure-Kamionowska, Milena; Maślińska, Danuta; Deregowski, Krzysztof; Czichos, Elzbieta; Raczkowska, Barbara

    2003-01-01

    The pineal gland is an organ involved in regulation of homeostasis and body rhythms. It plays an important role in the growth foetuses and adaptation of newborns to new environmental conditions. The requirements of foetuses and newborns progressively change during development. The purpose of the study was to evaluate morphological changes of pineal glands in foetuses and infants with brain lesions. The results of our study showed that parenchyma of developing pineal glands was susceptible to injury in most autopsied foetal and infantile cases. Morphological changes in pineal glands were found in 90% of autopsied brains but 100% of the cases had infections. The lesions in the pineal included mainly haemorrhagic, necrotic and cystic changes. In our autopsied foetuses and children, morphological changes in pineal glands were concomitant with various lesions of brain parenchyma. All results of our study lead to the conclusion that the pineal gland during its development is very susceptible to injury. The failure of normal pineal gland development and subsequent impaired production of melatonin decrease resistance of newborns and children to various environmental harmful agents.

  18. Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland.

    PubMed

    Maronde, Erik; Saade, Anastasia; Ackermann, Katrin; Goubran-Botros, Hany; Pagan, Cecile; Bux, Roman; Bourgeron, Thomas; Dehghani, Faramarz; Stehle, Jörg H

    2011-08-01

    Time of day is communicated to the body through rhythmic cues, including pineal gland melatonin synthesis, which is restricted to nighttime. Whereas in most rodents transcriptional regulation of the arylalkylamine N-acetyltransferase (Aanat) gene is essential for rhythmic melatonin synthesis, investigations into nonrodent mammalian species have shown post-transcriptional regulation to be of central importance, with molecular mechanisms still elusive. Therefore, human pineal tissues, taken from routine autopsies were allocated to four time-of-death groups (night/dawn/day/dusk) and analyzed for daytime-dependent changes in phosphorylated AANAT (p31T-AANAT) and in acetyl-serotonin-methyltransferase (ASMT) expression and activity. Protein content, intracellular localization, and colocalization of p31T-AANAT and ASMT were assessed, using immunoblotting, immunofluorescence, and immunoprecipitation techniques. Fresh sheep pineal gland preparations were used for comparative purposes. The amount of p31T-AANAT and ASMT proteins as well as their intracellular localization showed no diurnal variation in autoptic human and fresh sheep pineal glands. Moreover, in human and sheep pineal extracts, AANAT could not be dephosphorylated, which was at variance to data derived from rat pineal extracts. P31T-AANAT and ASMT were often found to colocalize in cellular rod-like structures that were also partly immunoreactive for the pinealocyte process-specific marker S-antigen (arrestin) in both, human and sheep pinealocytes. Protein-protein interaction studies with p31T-AANAT, ASMT, and S-antigen demonstrated a direct association and formation of robust complexes, involving also 14-3-3. This work provides evidence for a regulation principle for AANAT activity in the human pineal gland, which may not be based on a p31T-AANAT phosphorylation/dephosphorylation switch, as described for other mammalian species.

  19. Step-by-step protocol to perfuse and dissect the mouse parotid gland and isolation of high-quality RNA from murine and human parotid tissue.

    PubMed

    Watermann, Christoph; Valerius, Klaus Peter; Wagner, Steffen; Wittekindt, Claus; Klussmann, Jens Peter; Baumgart-Vogt, Eveline; Karnati, Srikanth

    2016-04-01

    Macroscopic identification and surgical removal of the mouse parotid gland is demanding because of its anatomic location and size. Moreover, the mouse parotid gland contains high concentrations of RNases, making it difficult to isolate high-quality RNA. So far, appropriate methods for optimal perfusion-fixation and dissection of mouse parotid glands, as well as the isolation of high quality RNA from this tissue, are not available. Here we present a simple, optimized, step-by-step surgical method to perfuse and isolate murine parotid glands. We also compared two common RNA extraction methods (RNeasy Mini Kit versus TRIzol) for their yields of high-quality, intact RNA from human and murine parotid gland tissues that were either snap-frozen or immersed in RNAlater stabilization solution. Mouse parotid tissue that was perfused and immersed in RNAlater and human samples immersed in RNAlater exhibited the best RNA quality, independent of the isolation method.

  20. The gsalpha gene: predominant maternal origin of transcription in human thyroid gland and gonads.

    PubMed

    Mantovani, Giovanna; Ballare, Emilia; Giammona, Enza; Beck-Peccoz, Paolo; Spada, Anna

    2002-10-01

    Mutations in the guanine nucleotide binding alpha-subunit 1 gene (GNAS1) cause Albright's hereditary osteodistrophy, and the parent of transmission determines variable phenotypic expression of the disease. This has suggested that GNAS1 may be under tissue-specific imprinting control, although studies so far available have failed to clearly define the pattern of GNAS1 expression in humans. To establish if GNAS1 is imprinted in human endocrine tissues, we selected 14 thyroid, 10 granulosa cell, 13 pituitary (3 normal glands, 7 GH-secreting adenomas, and 3 nonfunctioning adenomas), 3 adrenal, and 11 lymphocyte samples shown to be heterozygous for a known polymorphism in exon 5. RNA from these tissues was analyzed by RT-PCR, and expression from both parental alleles was evaluated by enzymatic digestion and subsequent quantification of the resulting fragments. The parental origin of Gs alpha was assessed by evaluating neuroendocrine secretory protein 55 and extra large alphas-like protein transcripts, which have been shown to be monoallelically and parent-specifically expressed from the maternal and paternal allele, respectively. By this approach, the great majority of thyroid (n = 12), ovarian (n = 7), and pituitary (n = 11) samples showed an almost exclusive or significantly predominant expression of the maternal allele over the paternal one, whereas in lymphocyte and adrenal samples both alleles were equally expressed. Our results provide evidence for a predominant maternal origin of GNAS1 transcripts in different human adult endocrine tissues, particularly thyroid, ovary, and pituitary, and strongly suggest that this mechanism may play a crucial role in the determination of the phenotypic expression of Albright's hereditary osteodistrophy.

  1. Stereology of the Thyroid Gland in Indo-Pacific Bottlenose Dolphin (Tursiops aduncus) in Comparison with Human (Homo sapiens): Quantitative and Functional Implications

    PubMed Central

    Kot, Brian Chin Wing; Lau, Thomas Yue Huen; Cheng, Sammy Chi Him

    2013-01-01

    The mammalian thyroid gland maintains basal metabolism in tissues for optimal function. Determining thyroid volume is important in assessing growth and involution. Volume estimation is also important in stereological studies. Direct measurements of colloid volume and nuclear-to-cytoplasmic ratio of the follicular cells may provide important information about thyroid gland function such as hormone storage and secretion, which helps understand the changes at morphological and functional levels. The present study determined the colloid volume using simple stereological principle and the nuclear-to-cytoplasmic ratio of 4 Indo-Pacific bottlenose dolphins and 2 human thyroid glands. In both dolphin and human thyroid glands, the size of the follicles tended to be quite variable. The distribution of large and small follicles within the thyroid gland was also found to be random in both the dolphin and human thyroid gland; however, the size of follicles appeared to decrease as a function of increasing age in the dolphin thyroid gland. The mean colloid volume of the dolphin thyroid gland and human thyroid gland was 1.22×105 µm3 and 7.02×105 µm3 respectively. The dolphin and human subjects had a significant difference in the mean colloid volume. The mean N/C ratio of the dolphin thyroid follicular epithelia and human follicular epithelia was 0.50 and 0.64 respectively. The dolphin and human subjects had a significant difference in the mean N/C ratio. This information contributes to understanding dolphin thyroid physiology and its structural adaptations to meet the physical demands of the aquatic environment, and aids with ultrasonography and corrective therapy in live subjects. PMID:23690927

  2. Stereology of the thyroid gland in Indo-Pacific bottlenose dolphin (Tursiops aduncus) in comparison with human (Homo sapiens): quantitative and functional implications.

    PubMed

    Kot, Brian Chin Wing; Lau, Thomas Yue Huen; Cheng, Sammy Chi Him

    2013-01-01

    The mammalian thyroid gland maintains basal metabolism in tissues for optimal function. Determining thyroid volume is important in assessing growth and involution. Volume estimation is also important in stereological studies. Direct measurements of colloid volume and nuclear-to-cytoplasmic ratio of the follicular cells may provide important information about thyroid gland function such as hormone storage and secretion, which helps understand the changes at morphological and functional levels. The present study determined the colloid volume using simple stereological principle and the nuclear-to-cytoplasmic ratio of 4 Indo-Pacific bottlenose dolphins and 2 human thyroid glands. In both dolphin and human thyroid glands, the size of the follicles tended to be quite variable. The distribution of large and small follicles within the thyroid gland was also found to be random in both the dolphin and human thyroid gland; however, the size of follicles appeared to decrease as a function of increasing age in the dolphin thyroid gland. The mean colloid volume of the dolphin thyroid gland and human thyroid gland was 1.22×10(5) µm(3) and 7.02×10(5) µm(3) respectively. The dolphin and human subjects had a significant difference in the mean colloid volume. The mean N/C ratio of the dolphin thyroid follicular epithelia and human follicular epithelia was 0.50 and 0.64 respectively. The dolphin and human subjects had a significant difference in the mean N/C ratio. This information contributes to understanding dolphin thyroid physiology and its structural adaptations to meet the physical demands of the aquatic environment, and aids with ultrasonography and corrective therapy in live subjects.

  3. Expression of lipogenic factors galectin-12, resistin, SREBP-1, and SCD in human sebaceous glands and cultured sebocytes.

    PubMed

    Harrison, Wesley J; Bull, Jonathan J; Seltmann, Holger; Zouboulis, Christos C; Philpott, Michael P

    2007-06-01

    The transcription factors CCAAT enhancer-binding protein alpha, beta, and delta, and peroxisome proliferator-activated receptor gamma are known to be crucial to the differentiation of adipocytes and are expressed in sebaceous gland cells. As lipogenesis is key to both adipocyte and sebocyte differentiation we hypothesize that sebocytes follow a similar program of differentiation to adipocytes. We have investigated the expression of known adipogenic factors resistin, galectin-12, sterol response-element-binding protein-1 (SREBP-1) and stearoyl-CoA desaturase in the immortalized sebaceous gland cell line SZ95 and whole skin. Reverse transcriptase-PCR analysis showed the expression of galectin-12, resistin, SREBP-1, and stearoyl-CoA desaturase mRNAs in SZ95 sebocytes. Immunoreactivity was observed for galectin-12 and SREBP-1 in the nuclei and resistin in the cytoplasm of basal sebocytes, and stearoyl CoA desaturase in the cytoplasm of basal and luminal sebocytes of human scalp skin. Expression of galectin-12, resistin, and SREBP-1 in SZ95 sebocytes was confirmed by Western blot analysis. These data provide further evidence that pathways of differentiation in adipocytes and sebocytes could be similar and therefore further understanding of sebaceous gland differentiation and lipogenesis and potential therapies for sebaceous gland disorders may be obtained from our knowledge of adipocyte differentiation.

  4. Tracheal allotransplantation after withdrawal of immunosuppressive therapy.

    PubMed

    Delaere, Pierre; Vranckx, Jan; Verleden, Geert; De Leyn, Paul; Van Raemdonck, Dirk

    2010-01-14

    Reconstruction of long-segment tracheal defects requires a vascularized allograft. We report successful tracheal allotransplantation after indirect revascularization of the graft in a heterotopic position. Immunosuppressive therapy was administered before the operation, and the tracheal allograft was wrapped in the recipient's forearm fascia. Once revascularization was achieved, the mucosal lining was replaced progressively with buccal mucosa from the recipient. At 4 months, the tracheal chimera was fully lined with mucosa, which consisted of respiratory epithelium from the donor and buccal mucosa from the recipient. After withdrawal of immunosuppressive therapy, the tracheal allograft was moved to its correct anatomical position with an intact blood supply. No treatment-limiting adverse effects occurred.

  5. MRI-based three-dimensional thermal physiological characterization of thyroid gland of human body.

    PubMed

    Jin, Chao; He, Zhi Zhu; Yang, Yang; Liu, Jing

    2014-01-01

    This article is dedicated to present a MRI (magnetic resonance imaging) based three-dimensional finite element modeling on the thermal manifestations relating to the pathophysiology of thyroid gland. An efficient approach for identifying the metabolic dysfunctions of thyroid has also been demonstrated through tracking the localized non-uniform thermal distribution or enhanced dynamic imaging. The temperature features over the skin surface and thyroid domain have been characterized using the numerical simulation and experimental measurement which will help better interpret the thermal physiological mechanisms of the thyroid under steady-state or water-cooling condition. Further, parametric simulations on the hypermetabolism symptoms of hyperthyroidism and thermal effects within thyroid domain caused by varying breathing airflow in the trachea and blood-flow in artery and vein were performed. It was disclosed that among all the parameters, the airflow volume has the largest effect on the total heat flux of thyroid surface. However, thermal contributions caused by varying the breathing frequency and blood-flow velocity are negligibly small. The present study suggests a generalized way for simulating the close to reality physiological behavior or process of human thyroid, which is of significance for disease diagnosis and treatment planning. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

  6. Different bindings to lectin in human submandibular gland after enzymatic digestion.

    PubMed

    Takai, Y; Noda, Y; Sumitomo, S; Sagara, S; Mori, M

    1986-01-01

    Lectin binding affinities were described in human submandibular gland (SMG) in the paraffin sections following alpha-amylase, sialidase, and trypsin digestions. Lectins in the present study were used Con A (Glc, Man binding lectins), PNA, and SBA(Gal, GalNAc), RCA-1(Gal), DBA(GalNAc), WGA(GlcNAc), and UEA-1(Fuc). Lectin stainings in serous and mucous acinar cells and ductal epithelia were reported to compare enzyme treated and nontreated sections. Amylase treatment showed increasing Con A staining in connective tissue fibers and no marked changes in SMG to lectin bindings. Sialidase digestion was characteristically intense in PNA and SBA bindings in SMG cells, and also enhanced staining to UEA-1 in serous and duct cells and to WGA in mucous and duct cells were noted. Trypsin digestion indicated a slight increase to Con A binding, and was relatively strong to UEA-1 in serous and duct cells and a little strong to WGA. The results suggested that SMG serous cells contain higher amounts of Gal, GalNAc, and Fuc residues; and mucous cells were also abundant in Gal, GalNAc, and GlcNAc residues.

  7. A practical guide for the study of human and murine sebaceous glands in situ.

    PubMed

    Hinde, Eleanor; Haslam, Iain S; Schneider, Marlon R; Langan, Ewan A; Kloepper, Jennifer E; Schramm, Carolin; Zouboulis, Christos C; Paus, Ralf

    2013-10-01

    The skin of most mammals is characterised by the presence of sebaceous glands (SGs), whose predominant constituent cell population is sebocytes, that is, lipid-producing epithelial cells, which develop from the hair follicle. Besides holocrine sebum production (which contributes 90% of skin surface lipids), multiple additional SG functions have emerged. These range from antimicrobial peptide production and immunomodulation, via lipid and hormone synthesis/metabolism, to the provision of an epithelial progenitor cell reservoir. Therefore, in addition to its involvement in common skin diseases (e.g. acne vulgaris), the unfolding diversity of SG functions, both in skin health and disease, has raised interest in this integral component of the pilosebaceous unit. This practical guide provides an introduction to SG biology and to relevant SG histochemical and immunohistochemical techniques, with emphasis placed on in situ evaluation methods that can be easily employed. We propose a range of simple, established markers, which are particularly instructive when addressing specific SG research questions in the two most commonly investigated species in SG research, humans and mice. To facilitate the development of reproducible analysis techniques for the in situ evaluation of SGs, this methods review concludes by suggesting quantitative (immuno-)histomorphometric methods for standardised SG evaluation.

  8. In-vitro depth-dependent hyperthermia of human mammary gland adenocarcinoma.

    PubMed

    Dunn, Andrew W; Zhang, Yu; Mast, David; Pauletti, Giovanni M; Xu, Hong; Zhang, Jiaming; Ewing, Rodney C; Shi, Donglu

    2016-12-01

    Nanoparticle mediated photothermal ablation of cancerous tissue shows promising results and applicability as a highly efficacious treatment method. As a majority of the photothermal work has been conducted with minimal attenuation of the laser before reaching the nanoparticles within surface seeded tumors in-vivo or through buffered media in-vitro, it is important to understand the effects of greater laser attenuation on photothermal efficacy mediated by changes in the scattering and absorption of the laser. Photothermal efficacy using a near infrared (NIR) 785nm laser irradiating polystyrene (PS) stabilized magnetite (Fe3O4) nanoparticles (PS-Fe3O4) is examined on MDA-MB-231 human mammary gland adenocarcinoma in-vitro. Agarose gel columns of various heights were created to simulate soft tissue and subsequently used for NIR laser attenuation. Polystyrene was found to significantly improve magnetite nanoparticle stability in serum containing media and modified Hank's Balanced Salt Solution and was able to induce significant hyperthermic ablation at mass concentrations which also did not elicit significant innate toxicity. Furthermore it was found that the polystyrene coating significantly reduced innate toxicity over 48h compared to uncoated magnetite. Agar gel layers provided similar optical attenuation in the NIR region to skin and prostate. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Prevalence of human papilloma virus infection in patients with male accessory gland infection.

    PubMed

    La Vignera, S; Vicari, E; Condorelli, R A; Franchina, C; Scalia, G; Morgia, G; Perino, A; Schillaci, R; Calogero, A E

    2015-04-01

    The frequency of human papillomavirus (HPV) infection in the semen of patients with male accessory gland infection (MAGI) was evaluated. One hundred infertile patients with MAGI were classified into group A: patients with an inflammatory MAGI (n = 48) and group B: patients with a microbial form (n = 52). Healthy age-matched fertile men (34.0 ± 4.0 years) made up the control group (n = 20). Amplification of HPV DNA was carried out by HPV-HS Bio nested polymerase chain reaction for the detection of HPV DNA sequences within the L1 ORF. Ten patients in group A (20.8%) and 15 patients in group B (28.8%) had a HPV infection; two controls (10.0%) had HPV infection. Patients with MAGI had a significantly higher frequency of HPV infection compared with controls; patients with a microbial MAGI had significantly higher frequency of HPV infection compared with patients with an inflammatory form (both P < 0.05). Patients with MAGI and HPV had a slight, but significantly lower sperm progressive motility and normal morphology compared with patients with MAGI HPV-negative (P < 0.05). Elevated frequency of HPV infection occurred in patients with MAGI, suggesting that HPV should be investigated in the diagnostic work-up of these patients. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  10. Human axillary apocrine glands: proteins involved in the apocrine secretory mechanism.

    PubMed

    Stoeckelhuber, Mechthild; Schubert, Christoph; Kesting, Marco R; Loeffelbein, Denys J; Nieberler, Markus; Koehler, Claudia; Welsch, Ulrich

    2011-02-01

    The apocrine secretory mechanism is a mode of secretion by which the apical part of the cell cytoplasm is pinched off, which leads to the formation of an aposome. The distinct mechanism of formation and decapitation of the aposome is not well investigated. Only few proteins are known that are involved in this secretory mechanism. We studied the human axillary apocrine gland and looked at proteins associated with cytokinesis, a process that is comparable to the pinching-off mechanism of apocrine glandular cells. By immunohistochemistry, we detected actin, myosin II, cytokeratin 7 and 19, α- and β-tubulin, anillin, cofilin, syntaxin 2, vamp8/endobrevin and septin 2. In highly active glandular cells, these proteins are located at the base of the apical protrusion when the aposome is in the process of being released or are concentrated in the cap of the apical protrusion. These findings demonstrate new insights on apocrine secretory mechanisms and point to similarities to the terminal step of cytokinesis, which is regulated by a SNARE-mediated membrane fusion event.

  11. Morbid obesity and tracheal intubation.

    PubMed

    Brodsky, Jay B; Lemmens, Harry J M; Brock-Utne, John G; Vierra, Mark; Saidman, Lawrence J

    2002-03-01

    The tracheas of obese patients may be more difficult to intubate than those of normal-weight patients. We studied 100 morbidly obese patients (body mass index >40 kg/m(2)) to identify which factors complicate direct laryngoscopy and tracheal intubation. Preoperative measurements (height, weight, neck circumference, width of mouth opening, sternomental distance, and thyromental distance) and Mallampati score were recorded. The view during direct laryngoscopy was graded, and the number of attempts at tracheal intubation was recorded. Neither absolute obesity nor body mass index was associated with intubation difficulties. Large neck circumference and high Mallampati score were the only predictors of potential intubation problems. Because in all but one patient the trachea was intubated successfully by direct laryngoscopy, the neck circumference that requires an intervention such as fiberoptic bronchoscopy to establish an airway remains unknown. We conclude that obesity alone is not predictive of tracheal intubation difficulties. In 100 morbidly obese patients, neither obesity nor body mass index predicted problems with tracheal intubation. However, a high Mallampati score (greater-than-or-equal to 3) and large neck circumference may increase the potential for difficult laryngoscopy and intubation.

  12. Estimation of parenchymal cell content of human parathyroid glands using the image analyzing computer technique.

    PubMed Central

    Grimelius, L.; Akerström, G.; Johansson, H.; Lundqvist, H.

    1978-01-01

    By means of the image analyzing computer technique, a complete determination of the parenchymal tissue distribution in serially sectioned parathyroid glands were accomplished. The technique had good reproducibility. Taking into account the shrinkage of the different tissue components during histotechnical procedures and the tissue densities, it was possible to calculate the parenchymal cell mass of unfixed glands. The cell distribution varied considerably, and in most glands as many as 10 sections at different levels had to be examined to get a reliable ratio between the parenchymal and fat cell tissue. The results seriously question the validity of histopathologic examination of one or a few sections of parathyroid glands in evaluation of the parenchymal cell mass, as well as diagnoses based on examination of partial glandular biopsy specimens. PMID:717545

  13. [Research progress of tracheal prosthesis in reconstructing trachea].

    PubMed

    Xu, Hong; Shi, Hongcan; Chen, Huimin

    2007-05-01

    To review the recent research progress of base and clinical application of tracheal replacement. Literature concerning tracheal prosthesis and the current achievements were extensively and comprehensively reviewed. Most tracheal lesions can be resected and achieve primary reconstruction, but the resectable length was limited. Tracheal replacement was an efficient and feasible way to substitute the defects resulting from extended resection. New techniques such as tissue engineering, tracheal transplantation, new tracheal prosthesis of biomaterials break fresh ground for the more rapid development of tracheal surgery.

  14. Production of functional human nerve growth factor from the saliva of transgenic mice by using salivary glands as bioreactors.

    PubMed

    Zeng, Fang; Li, Zicong; Zhu, Qingchun; Dong, Rui; Zhao, Chengcheng; Li, Guoling; Li, Guo; Gao, Wenchao; Jiang, Gelong; Zheng, Enqin; Cai, Gengyuan; Moisyadi, Stefan; Urschitz, Johann; Yang, Huaqiang; Liu, Dewu; Wu, Zhenfang

    2017-01-24

    The salivary glands of animals have great potential to act as powerful bioreactors to produce human therapeutic proteins. Human nerve growth factor (hNGF) is an important pharmaceutical protein that is clinically effective in the treatment of many human neuronal and non-neuronal diseases. In this study, we generated 18 transgenic (TG) founder mice each carrying a salivary gland specific promoter-driven hNGF transgene. A TG mouse line secreting high levels of hNGF protein in its saliva (1.36 μg/mL) was selected. hNGF protein was successfully purified from the saliva of these TG mice and its identity was verified. The purified hNGF was highly functional as it displayed the ability to induce neuronal differentiation of PC12 cells. Furthermore, it strongly promoted proliferation of TF1 cells, above the levels observed with mouse NGF. Additionally, saliva collected from TG mice and containing unpurified hNGF was able to significantly enhance the growth of TF1 cells. This study not only provides a new and efficient approach for the synthesis of therapeutic hNGF but also supports the concept that salivary gland from TG animals is an efficient system for production of valuable foreign proteins.

  15. Production of functional human nerve growth factor from the saliva of transgenic mice by using salivary glands as bioreactors

    PubMed Central

    Zeng, Fang; Li, Zicong; Zhu, Qingchun; Dong, Rui; Zhao, Chengcheng; Li, Guoling; Li, Guo; Gao, Wenchao; Jiang, Gelong; Zheng, Enqin; Cai, Gengyuan; Moisyadi, Stefan; Urschitz, Johann; Yang, Huaqiang; Liu, Dewu; Wu, Zhenfang

    2017-01-01

    The salivary glands of animals have great potential to act as powerful bioreactors to produce human therapeutic proteins. Human nerve growth factor (hNGF) is an important pharmaceutical protein that is clinically effective in the treatment of many human neuronal and non-neuronal diseases. In this study, we generated 18 transgenic (TG) founder mice each carrying a salivary gland specific promoter-driven hNGF transgene. A TG mouse line secreting high levels of hNGF protein in its saliva (1.36 μg/mL) was selected. hNGF protein was successfully purified from the saliva of these TG mice and its identity was verified. The purified hNGF was highly functional as it displayed the ability to induce neuronal differentiation of PC12 cells. Furthermore, it strongly promoted proliferation of TF1 cells, above the levels observed with mouse NGF. Additionally, saliva collected from TG mice and containing unpurified hNGF was able to significantly enhance the growth of TF1 cells. This study not only provides a new and efficient approach for the synthesis of therapeutic hNGF but also supports the concept that salivary gland from TG animals is an efficient system for production of valuable foreign proteins. PMID:28117418

  16. The evolution of sweat glands

    NASA Astrophysics Data System (ADS)

    Folk, G. Edgar; Semken, A.

    1991-09-01

    Mammals have two kinds of sweat glands, apocrine and eccrine, which provide for thermal cooling. In this paper we describe the distribution and characteristics of these glands in selected mammals, especially primates, and reject the suggested development of the eccrine gland from the apocrine gland during the Tertiary geological period. The evidence strongly suggests that the two glands, depending on the presence or absence of fur, have equal and similar functions among mammals; apocrine glands are not primitive. However, there is a unique and remarkable thermal eccrine system in humans; we suggest that this system evolved in concert with bipedalism and a smooth hairless skin.

  17. Endothelin in human brain and pituitary gland: Presence of immunoreactive endothelin, endothelin messenger ribonucleic acid, and endothelin receptors

    SciTech Connect

    Takahashi, K.; Ghatei, M.A.; Jones, P.M.; Murphy, J.K.; Lam, H.C.; O'Halloran, D.J.; Bloom, S.R. )

    1991-03-01

    The presence of immunoreactive (IR) endothelin, endothelin mRNA, and endothelin receptors in human brain and pituitary gland has been studied by RIA, Northern blot hybridization, and receptor assay. IR endothelin was detected in all five brain regions examined (cerebral cortex, cerebellum, brain stem, basal ganglia, and hypothalamus) (6-10 fmol/g wet wt) and spinal cord (22 +/- 6 fmol/g wet wt, n = 7, mean +/- SEM). Higher concentrations of IR endothelin were found in the pituitary gland (147 +/- 30 fmol/g wet wt). Fast protein liquid chromatographic analysis of the IR endothelin in pituitary gland showed a large IR peak in the position of endothelin-3 and a smaller peak in the position of endothelin-1, whereas IR endothelin in the hypothalamus and brain stem was mainly endothelin-1. Endothelin messenger RNA was detected by Northern blot hybridization in the pituitary but not in hypothalamus. The receptor assay showed that 125I-endothelin-1 binding sites were present in large numbers in all five brain regions but were much less abundant in the pituitary gland. Binding capacity and dissociation constant were 5052 +/- 740 fmol/mg protein and 0.045 +/- 0.007 nM in brain stem and 963 +/- 181 fmol/mg protein and 0.034 +/- 0.009 nM in hypothalamus. In the pituitary gland, there were two classes of binding sites for endothelin with dissociation constants of 0.059 +/- 0.002 nM (binding capacity = 418 +/- 63 fmol/mg protein) and 0.652 +/- 0.103 nM (binding capacity = 1717 +/- 200 fmol/mg protein). Endothelin-1, -2 and -3 were almost equipotent in displacing the binding (IC50 approximately 0.04 nM). These findings are in accord with the possibility that endothelin acts as a neurotransmitter, neuromodulator or neurohormone in man.

  18. Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas.

    PubMed

    Van de Laar, Emily; Clifford, Monica; Hasenoeder, Stefan; Kim, Bo Ram; Wang, Dennis; Lee, Sharon; Paterson, Josh; Vu, Nancy M; Waddell, Thomas K; Keshavjee, Shaf; Tsao, Ming-Sound; Ailles, Laurie; Moghal, Nadeem

    2014-12-31

    The large airways of the lungs (trachea and bronchi) are lined with a pseudostratified mucociliary epithelium, which is maintained by stem cells/progenitors within the basal cell compartment. Alterations in basal cell behavior can contribute to large airway diseases including squamous cell carcinomas (SQCCs). Basal cells have traditionally been thought of as a uniform population defined by basolateral position, cuboidal cell shape, and expression of pan-basal cell lineage markers like KRT5 and TP63. While some evidence suggests that basal cells are not all functionally equivalent, few heterogeneously expressed markers have been identified to purify and study subpopulations. In addition, few signaling pathways have been identified that regulate their cell behavior. The goals of this work were to investigate tracheal basal cell diversity and to identify new signaling pathways that regulate basal cell behavior. We used flow cytometry (FACS) to profile cell surface marker expression at a single cell level in primary human tracheal basal cell cultures that maintain stem cell/progenitor activity. FACS results were validated with tissue staining, in silico comparisons with normal basal cell and lung cancer datasets, and an in vitro proliferation assay. We identified 105 surface markers, with 47 markers identifying potential subpopulations. These subpopulations generally fell into more (~ > 13%) or less abundant (~ < 6%) groups. Microarray gene expression profiling supported the heterogeneous expression of these markers in the total population, and immunostaining of large airway tissue suggested that some of these markers are relevant in vivo. 24 markers were enriched in lung SQCCs relative to adenocarcinomas, with four markers having prognostic significance in SQCCs. We also identified 33 signaling receptors, including the MST1R/RON growth factor receptor, whose ligand MST1/MSP was mitogenic for basal cells. This work provides the largest description to date of

  19. Human Meibum Lipid Conformation and Thermodynamic Changes with Meibomian-Gland Dysfunction

    PubMed Central

    Borchman, Douglas; Yappert, Marta C.; Bell, James; Wells, Emily; Neravetla, Shantanu; Greenstone, Victoria

    2011-01-01

    Purpose. Instability of the tear film with rapid tear break-up time is a common feature of aqueous-deficient and evaporative dry eye diseases, suggesting that there may be a shared structural abnormality of the tear film that is responsible for the instability. It may be that a change in the normal meibum lipid composition and conformation causes this abnormality. Principle component analyses of infrared spectra of human meibum indicate that human meibum collected from normal donors (Mn) is less ordered than meibum from donors with meibomian gland dysfunction (Md). In this study the conformation of Md was quantified to test this finding. Methods. Changes in lipid conformation with temperature were measured by infrared spectroscopy. There were two phases to our study. In phase 1, the phase transitions of human samples, Mn and Md, were measured. In phase 2, the phase transitions of model lipid standards composed of different waxes and cholesterol esters were measured. Results. The phase-transition temperature was significantly higher (4°C) for the Md compared with the Mn of age-matched donors with no history of dry-eye symptoms. Most (82%) of the phase-transition temperatures measured for Md were above the values for Mn. The small change in the transition temperature was amplified in the average lipid order (stiffness) at 33.4°C. The average lipid order at 33.4°C for Md was significantly higher (30%, P = 0.004) than for Mn. The strength of lipid–lipid interactions was 72% higher for Md than for Mn. The ability of one lipid to influence the melting of adjacent lipids is termed cooperativity. There were no significant differences between Mn and Md in phase-transition cooperativity, nor was there a difference between Mn and Md in the minimum order or maximum order that Mn and Md achieved at very low and very high temperatures, respectively. The model wax studies showed that the phase transition of complex mixtures of natural lipids was set by the level of

  20. Size and location of thyroid gland in the fetal period.

    PubMed

    Ozguner, Gülnur; Sulak, Osman

    2014-05-01

    The present study's purpose was to examine the size and location of the thyroid gland using anatomic dissection methods on fetal cadavers. This study was performed on 200 spontaneously aborted human fetuses (100 males and 100 females) aged between 9 and 40 weeks of gestation. Fetuses without any external and internal pathology or anomaly were included in this study. Fetuses were divided into four groups based on gestational ages as follows: first group 9-12 weeks (first trimester), second group 13-25 weeks (second trimester), third group 26-37 weeks (third trimester) and fourth group 38-40 weeks (full term). The fetuses were also grouped into monthly cohorts as follows: 9-12 weeks, 3rd month; 13-16 weeks, 4th month; 17-20 weeks, 5th month; 21-24 weeks, 6th month; 25-28 weeks, 7th month; 29-32 weeks, 8th month; 33-36 weeks, 9th month; and 37-40 weeks, 10th month. The anterior necks of fetuses were dissected and the thyroid glands exposed. Vertebral and laryngeal levels and the dimensions (width, length, thickness and weight) of the fetal thyroid glands were determined by anatomical dissection methods. The dimensions and ratios of the fetal thyroid gland (weight/fetal body weight) were evaluated. The mean values and standard deviations of all parameters by gestational weeks, months, and trimesters were calculated. It was found that all parameters increased with gestational age. No significant differences were observed between genders in all parameters (P > 0.05). There were no significant differences between the right and the left sides for parameters of the thyroid glands. The levels of the superior poles of the thyroid lobes were located at the cervical (C) C1-C3 vertebral bodies. The levels of the inferior poles of the thyroid lobes were located at C4-C5 vertebral bodies. The levels of the superior poles of thyroid lobes were located between the upper ½ and lower ½ of the thyroid cartilage or cricoid cartilage. The levels of the inferior poles of the thyroid

  1. DISSECTING LIPID METABOLISM IN MEIBOMIAN GLANDS OF HUMANS AND MICE: AN INTEGRATIVE STUDY REVEALS A NETWORK OF METABOLIC REACTIONS NOT DUPLICATED IN OTHER TISSUES

    PubMed Central

    Butovich, Igor A.; McMahon, Anne; Wojtowicz, Jadwiga C.; Lin, Feng; Mancini, Ronald; Itani, Kamel

    2016-01-01

    Lipids comprise the bulk of the Meibomian gland secretion (meibum) which is produced by meibocytes. Complex arrays of lipogenic reactions in Meibomian glands, which we collectively call meibogenesis, have not been explored on molecular level yet. Our goals were to elucidate the possible biosynthetic pathways that underlie generation of meibum, reveal similarities in, and differences between, lipid metabolism in Meibomian glands and other organs and tissues, and integrate Meibomian gland studies into the field of general metabolomics. Specifically, we have conducted detailed analyses of human and mouse specimens using genomic, immunohistochemical, and lipidomic approaches. Among equally highly expressed genes found in Meibomian glands of both species were those related to fatty acid elongation, branching, desaturation, esterification, reduction of fatty acids to alcohols, and cholesterol biosynthesis. Importantly, corresponding lipid products were detected in meibum of both species using lipidomic approaches. For the first time, a cohesive, unifying biosynthetic scheme that connects genomic, lipidomic, and immunohistochemical observations is outlined and discussed. PMID:27032494

  2. Tracheal epithelial-myoepithelial carcinoma associated with sarcoid-like reaction: A case report

    PubMed Central

    Dong, Huawei; Tatsuno, Brent K.; Betancourt, Jaime; Oh, Scott S.

    2014-01-01

    Epithelial-myoepithelial carcinomas are rare tumors that primarily originate in the salivary glands but have also been found in the tracheobronchial tree. We report the first case of epithelial-myoepithelial carcinoma associated with sarcoidosis. A 61 year old Hispanic man presented with altered mental status and hypercalcemia. Imaging revealed diffuse intra-thoracic and intra-abdominal lymphadenopathy. A diagnostic bronchoscopy was performed where an incidental tracheal nodule was discovered and biopsied. Pathology was consistent with epithelial-myoepithelial carcinoma. Lymph node biopsy demonstrated non-caseating granulomas consistent with sarcoidosis. Patient underwent tracheal resection of the primary tumor with primary tracheal reconstruction. Hypercalcemia subsequently normalized with clinical improvement. Repeat CT imaging demonstrated complete resolution of lymphadenopathy. Our findings are suggestive of a possible paraneoplastic sarcoid-like reaction to the epithelial-myoepithelial carcinoma with associated lymphadenopathy and symptomatic hypercalcemia. PMID:26029574

  3. AAV5-mediated gene transfer to the parotid glands of non-human primates

    PubMed Central

    Voutetakis, A; Zheng, C; Cotrim, AP; Mineshiba, F; Afione, S; Roescher, N; Swaim, WD; Metzger, M; Eckhaus, MA; Donahue, RE; Dunbar, CE; Chiorini, JA; Baum, BJ

    2010-01-01

    Salivary glands are potentially useful target sites for multiple clinical applications of gene transfer. Previously, we have shown that serotype 2 adeno-associated viral (AAV2) vectors lead to stable gene transfer in the parotid glands of rhesus macaques. As AAV5 vectors result in considerably greater transgene expression in murine salivary glands than do AAV2 vectors, herein we have examined the use of AAV5 vectors in macaques at two different doses (n = 3 per group; 1010 or 3 × 1011 particles per gland). AAV5 vector delivery, as with AAV2 vectors, led to no untoward clinical, hematological or serum chemistry responses in macaques. The extent of AAV5-mediated expression of rhesus erythropoietin (RhEpo) was dose-dependent and similar to that seen with an AAV2 vector. However, unlike results with the AAV2 vector, AAV5 vector-mediated RhEpo expression was transient. Maximal expression peaked at day 56, was reduced by ~80% on day 84 and thereafter remained near background levels until day 182 (end of experiment). Quantitative PCR studies of high-dose vector biodistribution at this last time point showed much lower AAV5 copy numbers in the targeted parotid gland (~1.7%) than found with the same AAV2 vector dose. Molecular analysis of the conformation of vector DNA indicated a markedly lower level of concatamerization for the AAV5 vector compared with that of a similar AAV2 vector. In addition, cellular immunological studies suggest that host response differences may occur with AAV2 and AAV5 vector delivery at this mucosal site. The aggregate data indicate that results with AAV5 vectors in murine salivary glands apparently do not extend to macaque glands. PMID:19759566

  4. Direct reprogramming of human fibroblasts into sweat gland-like cells.

    PubMed

    Zhao, Zhiliang; Xu, Mengyao; Wu, Meng; Ma, Kui; Sun, Mengli; Tian, Xiaocheng; Zhang, Cuiping; Fu, Xiaobing

    2015-01-01

    The skin of patients with an extensive deep burn injury is repaired by a process that leaves a hypertrophic scar without sweat glands and therefore loses the function of perspiration. The aim of this study was to identify whether the key factors related to sweat gland development could directly reprogram fibroblasts into sweat gland-like cells. After introducing the NF-κB and Lef-1 genes into fibroblasts, we found that stably transfected fibroblasts expressed specific markers of sweat glands, including CEA, CK7, CK14 and CK19, both at the protein and mRNA levels. The immunofluorescence staining also showed positive expression of CEA, CK7, CK14 and CK19 in induced fibroblasts, but there were no positive cells in the control groups. The expression of Shh and Cyclin D1, downstream genes of NF-κB and Lef-1, were also significantly increased during regeneration. The induced fibroblasts were implanted into an animal model. Twenty days later, iodine-starch perspiration tests showed that 7 out of the 10 cell-treated paws were positive for perspiration, with a distinctive black point-like area appearing in the center of the paw. Contralateral paws tested negative. Histological examination of skin biopsies from experimental and control paws revealed that sweat glands were fully reconstructed in the test paws, with integral, secretory and ductal portions, but were not present in the control paws. This is the first report of successful reprogramming of fibroblasts into sweat gland-like cells, which will provide a new cell source for sweat gland regeneration in patients with extensive deep burns.

  5. Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer.

    PubMed

    Cerliani, Juan P; Vanzulli, Silvia I; Piñero, Cecilia Pérez; Bottino, María C; Sahores, Ana; Nuñez, Myriam; Varchetta, Romina; Martins, Rubén; Zeitlin, Eduardo; Hewitt, Stephen M; Molinolo, Alfredo A; Lanari, Claudia; Lamb, Caroline A

    2012-06-01

    Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-β-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P < 0.01; Spearman correlation) between FGFR-2 and -3 expressions and a weaker correlation of each receptor with estrogen receptor expression. FGFR-4 correlated with c-erbB2 over expression. We conclude that FGFR-2 and -3 may be mechanistically linked and can be potential targets for treatment of estrogen receptor-positive breast cancer patients.

  6. Tracheal microaspiration in adult cystic fibrosis.

    PubMed

    Ledson, M J; Wilson, G E; Tran, J; Walshaw, M J

    1998-01-01

    Gastro-oesophageal reflux (GOR) has been implicated in the aetiology of lung disease. Cystic fibrosis (CF) patients have a high incidence of GOR symptoms with demonstrable episodes of oesophageal acidification. We studied 24-hour ambulatory tracheal and oesophageal pH in 11 CF patients with GOR symptoms to identify any episodes of tracheal acidification and define their temporal relation to oesophageal reflux and respiratory symptoms. 8 patients had evidence of significant GOR (DeMeester score mean 58; range 17-107) and in 6 it was gross (DeMeester score > 30). 4 patients had tracheal acidification (defined as tracheal pH < 5.5): all had greatly raised DeMeester scores. Two patterns of lowered tracheal pH were seen: a gradual drift downwards of tracheal pH to < 5.5 which recovered slowly, and an acute fall in tracheal pH to < 5.5 with rapid recovery. Only one patient had a fall in peak expiratory flow in conjunction with a decline in tracheal pH, and no association was found between the presence of tracheal microaspiration and pulmonary function. We conclude that tracheal acidification occurs in adult CF patients with GOR.

  7. A preliminary study of human pineal gland concretions: structural and chemical analysis.

    PubMed

    Galliani, I; Falcieri, E; Giangaspero, F; Valdrè, G; Mongiorgi, R

    1990-07-01

    Acervuli and fragments of pineal gland obtained from 33 subjects of both sexes and age ranging from 1 to 87 years, (30 autopsy and 3 biopsy specimens) were analyzed by light microscopy, transmission and scanning electron microscopy, X-ray diffraction and X-ray energy dispersive microanalysis. It was found that primary mineralization occurs in an organic matrix formed by pinealocytes and that hydroxyapatite also takes place in mineral deposition. From our analysis, the formation of acervuli appears to be age and sex independent and can be possibly related to the secretory activity of the gland.

  8. [Modern diagnostics of tracheal stenosis].

    PubMed

    Müller, A

    2004-06-01

    Numerous new modalities in computertomography (CT), in particular Multislice-Spiral-CT and Virtual Endoscopy, and novel developments in endoscopy and spirometry gave us reason to review the current state of the art in diagnostics of tracheal stenosis (TS). This review evaluates the literature of the last decade regarding new trends and methods in diagnostics of tracheal stenosis. Pros and cons are discussed, and the future trends are highlighted. Spiral-CT scans at collimated slices of < or = 3 mm, PITCH < or = 1.5 and a segmentation level of - 350 HE permit a valid measurement of tracheal lumina. The flow-volume-plot is still the most important investigation to evaluate respiratory function in TS. Peak-Flow-Meters are suitable for patient self monitoring. The selective estimation of the TS related airway resistance using in situ measurements and numerical flow simulation studies are likely to reach importance in future. The ability to obtain exact measures from endoscopic recordings using EndoScan serves quality control in endoscopy. An objective comparison of different treatments becomes possible. Endosonography and methods for in-vitro tissue analysis (Optical Coherence Tomography) are more focused on the early diagnosis of malignant lesions. The Synopsis of endoscopy, CT-scan and spirometry provides the highest diagnostic accuracy today.

  9. Confocal microscopy with double immunofluorescence staining reveals the functional transient receptor potential vanilloid subtype 1 expressed in myoepithelial cells of human submandibular glands.

    PubMed

    Ding, Qianwen; Zhang, Yan; Cong, Xin; Cai, Zhigang; Han, Jingyan; Su, Yunchao; Wu, Li-Ling; Yu, Guan-Gyan

    2012-05-01

    Myoepithelial cells (MECs) mainly surround acini and intercalated ducts in the human salivary glands. The contraction of MECs provides the expulsive force to promote salivation. We previously found functional transient receptor potential vanilloid subtype 1 (TRPV1) was expressed in rabbit and human submandibular glands and increased saliva secretion. However, it was unknown whether TRPV1 was expressed in MECs of submandibular glands. In this study, we observed the immunoflourescence of TRPV1 was not only located in serous acini and ducts but also surround the basal layer of the acinus and intercalated ducts of human submandibular glands. Double immunofluorescence staining revealed colocalization of TRPV1 with calponin, vimentin, and α-smooth muscle actin, which indicated the myoepithelial expression of TRPV1. Treating submandibular gland tissues with capsaicin, an agonist of TRPV1, substantially increased the phosphorylation of the 20-kDa regulatory light-chain subunit of myosin (MLC(20) ), a crucial molecule for contraction of smooth muscle cells, in MECs. Pretreatment with capsazepine, a specific TRPV1 inhibitor, blocked capsaicin-induced MLC(20) phosphorylation. These results suggest that TRPV1 is expressed in MECs of the human submandibular gland and mediates myoepithelial contraction via a mechanism involving MLC(20) phosphorylation.

  10. Prostaglandin protection of human isolated gastric glands against indomethacin and ethanol injury. Evidence for direct cellular action of prostaglandin.

    PubMed Central

    Tarnawski, A; Brzozowski, T; Sarfeh, I J; Krause, W J; Ulich, T R; Gergely, H; Hollander, D

    1988-01-01

    Isolated human gastric glands from surgical specimens were preincubated in an oxygenated medium with placebo or 16,16 dimethyl prostaglandin E2 (dmPGE2) and incubated at 37 degrees C in either medium alone, medium containing 4.43 mM indomethacin or medium containing 8% ethanol. We assessed the viability of gland cells with fast green exclusion, release of lactate dehydrogenase (LDH) into the medium, and ultrastructural damage by scanning and transmission electron microscopy. Both indomethacin and ethanol significantly reduced the viability of placebo-pretreated glands, increased LDH release into the medium, and produced prominent ultrastructural damage. DmPGE2 significantly reduced both indomethacin and ethanol-induced injury, increased the number of viable cells, reduced LDH release, and diminished the extent of ultrastructural damage. These studies indicate that PG protection of gastric mucosal cells has a direct cellular action that is not limited to replacement of depleted endogenous PGs. PG protection in our experiments did not depend on PG's previously described systemic actions, such as protection of the microvessels, preservation of the mucosal blood flow, or stimulation of bicarbonate and mucus secretion. Images PMID:3350966

  11. Gas Exchange Models for a Flexible Insect Tracheal System.

    PubMed

    Simelane, S M; Abelman, S; Duncan, F D

    2016-06-01

    In this paper two models for movement of respiratory gases in the insect trachea are presented. One model considers the tracheal system as a single flexible compartment while the other model considers the trachea as a single flexible compartment with gas exchange. This work represents an extension of Ben-Tal's work on compartmental gas exchange in human lungs and is applied to the insect tracheal system. The purpose of the work is to study nonlinear phenomena seen in the insect respiratory system. It is assumed that the flow inside the trachea is laminar, and that the air inside the chamber behaves as an ideal gas. Further, with the isothermal assumption, the expressions for the tracheal partial pressures of oxygen and carbon dioxide, rate of volume change, and the rates of change of oxygen concentration and carbon dioxide concentration are derived. The effects of some flow parameters such as diffusion capacities, reaction rates and air concentrations on net flow are studied. Numerical simulations of the tracheal flow characteristics are performed. The models developed provide a mathematical framework to further investigate gas exchange in insects.

  12. Split gland

    DOEpatents

    Petranto, Joseph J.

    1989-01-01

    A split gland having only three parts is described. The gland has substantially the same stability to the relative motion of the constituent half-gland members during the attachment process to a female fitting as have more complicated designs. Ease of manufacture and use result from the reduction in complexity of the present invention.

  13. Split gland

    DOEpatents

    Petranto, J.J.

    1989-09-05

    A split gland having only three parts is described. The gland has substantially the same stability to the relative motion of the constituent half-gland members during the attachment process to a female fitting as have more complicated designs. Ease of manufacture and use result from the reduction in complexity of the present invention. 15 figs.

  14. Multipotent nestin-positive stem cells reside in the stroma of human eccrine and apocrine sweat glands and can be propagated robustly in vitro.

    PubMed

    Nagel, Sabine; Rohr, Franziska; Weber, Caroline; Kier, Janina; Siemers, Frank; Kruse, Charli; Danner, Sandra; Brandenburger, Matthias; Matthiessen, Anna Emilia

    2013-01-01

    Human skin harbours multiple different stem cell populations. In contrast to the relatively well-characterized niches of epidermal and hair follicle stem cells, the localization and niches of stem cells in other human skin compartments are as yet insufficiently investigated. Previously, we had shown in a pilot study that human sweat gland stroma contains Nestin-positive stem cells. Isolated sweat gland stroma-derived stem cells (SGSCs) proliferated in vitro and expressed Nestin in 80% of the cells. In this study, we were able to determine the precise localization of Nestin-positive cells in both eccrine and apocrine sweat glands of human axillary skin. We established a reproducible isolation procedure and characterized the spontaneous, long-lasting multipotent differentiation capacity of SGSCs. Thereby, a pronounced ectodermal differentiation was observed. Moreover, the secretion of prominent cytokines demonstrated the immunological potential of SGSCs. The comparison to human adult epidermal stem cells (EpiSCs) and bone marrow stem cells (BMSCs) revealed differences in protein expression and differentiation capacity. Furthermore, we found a coexpression of the stem cell markers Nestin and Iα6 within SGSCs and human sweat gland stroma. In conclusion the initial results of the pilot study were confirmed, indicating that human sweat glands are a new source of unique stem cells with multilineage differentiation potential, high proliferation capacity and remarkable self renewal. With regard to the easy accessibility of skin tissue biopsies, an autologous application of SGSCs in clinical therapies appears promising.

  15. Human eccrine sweat gland cells reconstitute polarized spheroids when subcutaneously implanted with Matrigel in nude mice.

    PubMed

    Li, Haihong; Zhang, Mingjun; Chen, Liyun; Li, Xuexue; Zhang, Bingna

    2016-10-01

    Increasing evidence indicates that maintenance of cell polarity plays a pivotal role in the regulation of glandular homeostasis and function. We examine the markers for polarity at different time points to investigate the formation of cell polarity during 3D reconstitution of eccrine sweat glands. Mixtures of eccrine sweat gland cells and Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 2, 3, 4, 5 and 6 weeks post-implantation, Matrigel plugs were removed and immunostained for basal collagen IV, lateral β-catenin, lateroapical ZO-1 and apical F-actin. The results showed that the cell polarity of the spheroids appeared in sequence. Formation of basal polarity was prior to lateral, apical and lateroapical polarity. Collagen IV was detected basally at 2 weeks, β-catenin laterally and ZO-1 lateroapically at 3 weeks, and F-actin apically at 4 weeks post-implantation. At week 5 and week 6, the localization and the positive percentage of collagen IV, β-catenin, ZO-1 or F-actin in spheroids was similar to that in native eccrine sweat glands. We conclude that the reconstituted 3D eccrine sweat glands are functional or potentially functional.

  16. High-resolution MRI of the human parotid gland and duct at 7 Tesla.

    PubMed

    Kraff, Oliver; Theysohn, Jens M; Maderwald, Stefan; Kokulinsky, Patrick C; Dogan, Zeynel; Kerem, Alexander; Kruszona, Stefan; Ladd, Mark E; Gizewski, Elke R; Ladd, Susanne C

    2009-09-01

    MR techniques have been reported as an alternative to conventional sialography. High-field systems (7 T) provide new contrasts coupled with increased signal-to-noise ratio, and hence higher spatial resolution. To our knowledge, no measurements of the parotid gland at 7 T have been reported. Therefore, our study aimed to optimize sequences for high-field MR imaging of the parotid gland and duct, as well as the facial nerve at 7 T and show the potential of high field imaging. A 7 T whole-body scanner was used together with a 10-cm-diameter loop coil. Various GRE (MEDIC, DESS) and TSE (PD/T2, STIR) sequences were optimized and subsequently tested on 4 healthy volunteers and 4 patients. High-resolution images were compared with 1.5 T images both quantitatively (signal-to-noise ratio, contrast-to-noise) and qualitatively (visual rating of 2 independent readers). The high 0.6 mm isotropic resolution of the 3D DESS sequence was very useful for defining an oblique orientation with most of the duct being in-plane for subsequent imaging. With the MEDIC sequence, very fine branches of the duct were visible; furthermore, MEDIC yielded a very good depiction of lymph nodes. Severe specific absorption rate problems were observed with the STIR sequence at 7 T. Gland tissue in tumor patients can be well characterized with the PD/T2 TSE. Highest contrast-to-noise between duct and gland was achieved with the 7 T DESS. At 1.5 T, only the STIR sequence showed comparable quality to the overall superiority of the 7 T sequences. The facial nerve could only be depicted close to the skull base. MR imaging at 7 T provides excellent image contrast and resolution of the parotid gland and duct. The proposed protocol offers a noninvasive examination within about 30 minutes.

  17. Calcium-sensing receptor expression and parathyroid hormone secretion in hyperplastic parathyroid glands from humans.

    PubMed

    Cañadillas, Sagrario; Canalejo, Antonio; Santamaría, Rafael; Rodríguez, Maria E; Estepa, Jose C; Martín-Malo, Alejandro; Bravo, Juan; Ramos, Blanca; Aguilera-Tejero, Escolastico; Rodríguez, Mariano; Almadén, Yolanda

    2005-07-01

    In uremic patients, severe parathyroid hyperplasia is associated with reduced parathyroid calcium-sensing receptor (CaR) expression. Thus, in these patients, a high serum Ca concentration may be required to inhibit parathyroid hormone (PTH) secretion. This study compares the magnitude of reduction in CaR expression and the degree of the abnormality in Ca-regulated PTH release in vitro. A total of 50 glands from 23 hemodialysis patients with refractory hyperparathyroidism were studied. Tissue slices were incubated in vitro to evaluate (1) the PTH secretory output in a normal Ca concentration (1.25 mM) and (2) the PTH secretory response to high (1.5 mM) and low (0.6 mM) Ca concentration. Tissue aliquots were processed for determination of CaRmRNA expression. The results showed that, corrected for DNA, parathyroid tissue with lowest CaR expression secreted more PTH than that with relatively high CaR expression (146 +/- 23 versus 60 +/- 2 pg/microg DNA; P < 0.01). Furthermore, glands with low CaR expression demonstrated a blunted PTH secretory response to both the inhibitory effect of high Ca and the stimulatory effect of low Ca. The study also showed that the larger the gland, the lower the CaRmRNA expression. Thus, large parathyroid glands produce a large amount of PTH not only as a result of the increased gland size but also because the parathyroid tissue secretory output is increased. These abnormalities in PTH regulation are related to low CaR expression.

  18. Constitution and behavior of follicular structures in the human anterior pituitary gland.

    PubMed Central

    Ciocca, D. R.; Puy, L. A.; Stati, A. O.

    1984-01-01

    The follicular structures present in the human pituitary gland were studied, at the light-microscopic level, using histochemical and immunocytochemical techniques. The antisera applied in the peroxidase-antiperoxidase procedure were anti-hFSH beta, anti-hLH beta, anti-hPRL, anti-hGH, anti-hTSH beta, anti-hLPH beta, anti-pACTH, and anti-hACTH. In the 10 normal pituitaries examined, follicles were always found in the three areas of the adenohypophysis. The wall of the pars distalis follicles showed the seven immunoreactive cell types studied, while follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells were the only ones present in the wall of the pars tuberalis follicles. Most of the cell types studied were also present in the wall of the intermediate area follicles, but these follicles had characteristics not found in the other two areas. They were very large, with frequent interconnections forming a three-dimensional network of anastomotic cavities, and the colloid had different histochemical affinity. None of the hormones studied could be detected by immunocytochemistry within the follicular colloid. Three of the ten pituitary adenomas examined showed numerous follicular structures. Some of the follicles in the adenomatous pituitaries were similar to those found in the normal adenohypophysis, but there were also follicles filled with only traces of colloid and numerous blood cells in the cavity, and follicles filled with neoformed connective tissue. In one of these cases, FSH/LH immunoreactive adenoma cells were seen in the wall of the follicles. The results obtained suggest that the finding of pituitary adenomas with follicular structures is not uncommon and that the follicles originate from the tumor cells. In addition, the follicles seem to have several functional stages, explaining the finding of different types of follicular formation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11

  19. TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.

    PubMed

    Yamamura, Yoshiko; Motegi, Katsumi; Kani, Kouichi; Takano, Hideyuki; Momota, Yukihiro; Aota, Keiko; Yamanoi, Tomoko; Azuma, Masayuki

    2012-08-01

    Sjögren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-α plays an important role in the destruction of acinar structures. Here we examined TNF-α's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF-α, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-α treatment were investigated. TNF-α-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-α. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-κB activity in the TNF-α-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-α suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IκBα cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-α in NS-SV-AC cells. Therefore, our results may indicate that TNF-α inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4.

  20. Distribution and regulation of the 25-hydroxyvitamin D3 1α-hydroxylase in human parathyroid glands.

    PubMed

    Ritter, Cynthia S; Haughey, Bruce H; Armbrecht, Harvey J; Brown, Alex J

    2012-05-01

    Parathyroid glands express the 25-hydroxyvitamin D(3) 1α-hydroxylase (1αOHase). 1,25-dihydroxyvitamin D(3) (calcitriol) synthesized by extrarenal tissues generally does not enter the circulation, but plays an autocrine/paracrine role specific to the cell type, and is regulated by the needs of that particular cell. While the role of calcitriol produced in the parathyroid glands presumably is to suppress PTH and cell growth, its regulation in this cell type has not been defined. In the present study, we found that regulation of the human parathyroid 1αOHase differs from the renal enzyme in that it is induced by FGF-23 and extracellular calcium. Hyperplastic parathyroid glands from patients with chronic kidney failure normally display a heterogeneous cellularity. We found that the 1αOHase is expressed at much higher levels in oxyphil cells than in chief cells in these patients. Recent findings indicate that oxyphil cell content is increased by treatment with calcium receptor activators (calcimimetics). Here, we demonstrate that the calcimimetic cinacalcet increases the expression of 1αOHase in human parathyroid cultures. Additionally, we found that the 1αOHase in human parathyroid cultures is functionally active, as evidenced by the ability of the enzyme to 1-hydroxylate 25(OH)D(3) in parathyroid monolayers. Calcium, as well as cinacalcet, also induced expression of the degradation enzyme 24-hydroxylase, indicating the presence of a negative feedback system in the parathyroid cells. Therefore, local production of 1αOHase suggests an autocrine/paracrine role in regulating parathyroid function and may mediate, in part, the suppression of PTH by calcium and FGF-23.

  1. Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland

    PubMed Central

    Lee, Hyun Jae; Yang, Yu-Mi; Kim, Kyubo; Shin, Dong Min; Yoon, Joo-Heon; Cho, Hyung-Ju; Choi, Jae Young

    2012-01-01

    Protease-activated receptor 2 (PAR2), a G protein-coupled receptor expressed in airway epithelia and smooth muscle, plays an important role in airway inflammation. In this study, we demonstrated that activation of PAR2 induces mucus secretion from the human airway gland and examined the underlying mechanism using the porcine and murine airway glands. The mucosa with underlying submucosal glands were dissected from the cartilage of tissues, pinned with the mucosal side up at the gas/bath solution interface of a physiological chamber, and covered with oil so that secretions from individual glands could be visualized as spherical bubbles in the oil. Secretion rates were determined by optical monitoring of the bubble diameter. The Ca2+-sensitive dye Fura2-AM was used to determine intracellular Ca2+ concentration ([Ca2+]i) by means of spectrofluorometry. Stimulation of human tracheal mucosa with PAR2-activating peptide (PAR2-AP) elevated intracellular Ca2+ and induced glandular secretion equal to approximately 30% of the carbachol response in the human airway. Porcine gland tissue was more sensitive to PAR2-AP, and this response was dependent on Ca2+ and anion secretion. When the mouse trachea were exposed to PAR2-AP, large amounts of secretion were observed in both wild type and ΔF508 cystic fibrosis transmembrane conductance regulator mutant mice but there is no secretion from PAR-2 knock out mice. In conclusion, PAR2-AP is an agonist for mucus secretion from the airway gland that is Ca2+-dependent and cystic fibrosis transmembrane conductance regulator-independent. PMID:22916223

  2. The Drosophila SRF homolog is expressed in a subset of tracheal cells and maps within a genomic region required for tracheal development.

    PubMed

    Affolter, M; Montagne, J; Walldorf, U; Groppe, J; Kloter, U; LaRosa, M; Gehring, W J

    1994-04-01

    The Drosophila homolog of the vertebrate serum response factor (SRF) was isolated by low stringency hybridization. Nucleotide sequence analysis revealed that the Drosophila SRF homolog (DSRF) codes for a protein that displays 93% sequence identity with human SRF in the MADS domain, the region required for DNA binding, dimerization and interaction with accessory factors. The DSRF gene is expressed during several phases of embryonic development. In the egg, both the RNA and the protein are maternal in origin and slowly decrease in amount during gastrulation. After germ band retraction, high levels of zygotic expression are observed in a distinct subset of peripheral tracheal cells distributed throughout the embryo. Many of these cells are at the tip of tracheal branches and are in direct contact with the target tissues. The DSRF gene was mapped to position 60C on the second chromosome, and overlapping deficiencies which remove the gene were identified. Analysis of tracheal development in embryos carrying these deletions revealed a degeneration of most of the major branches of the tracheal system. Although the initial migration of tracheal cells was not affected in those deficient embryos, many tracheal cells appeared not to maintain their correct position and continued to migrate. Thus, the DSRF gene might play a role in the proper formation and maintenance of the trachea.

  3. Correlation Between Endotracheal Tube Cuff Pressure and Tracheal Wall Pressure Using Air and Saline Filled Cuffs

    DTIC Science & Technology

    2017-01-31

    AFRL-SA-WP-SR-2017-0004 Correlation Between Endotracheal Tube Cuff Pressure and Tracheal Wall Pressure Using Air - and Saline-Filled... Air Force Research Laboratory 711th Human Performance Wing U.S. Air Force School of Aerospace Medicine Aeromedical Research Department 2510 Fifth...Correlation Between Endotracheal Tube Cuff Pressure and Tracheal Wall Pressure Using Air - and Saline-Filled Cuffs 5a. CONTRACT NUMBER FA8650-14

  4. [Protein composition of human saliva under rest and stimulation and its changes in salivary gland diseases].

    PubMed

    Eichner, H

    1977-06-16

    In 153 probands the following parameters of normal parotid gland secretion were examined: flow-rate, total protein excretion, lysozyme, amylase, phosphatase, BAEE-esterase, immunglobulin A and trypsin-inhibitor. The results were compared with secretions of parotid glands with tumors (51 patients), sialadenitis (22 patients) and sialadenosis (12 patients). Thereby differential diagnosis in sialotumors was found possible. The mose important parameters are flow-rate, protein and immunglobulin A-concentrations, Moreover it is possible to differentiate in sialadenitis and sialadenosis: lysocym secretion gives besides flow--rate protein and immunglobulin A-concentration a good parameter in differentiating both pathological findings. Discelectrophoretic and immunoelectrophoretic separations supplement the differential diagnosis in sialotumors, sialadenitis and sialadenosis. The results are discussed.

  5. Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands.

    PubMed

    Grönberg, Malin; Tsolakis, Apostolos V; Magnusson, Linda; Janson, Eva T; Saras, Jan

    2008-09-01

    Obestatin and ghrelin are two peptides derived from the same prohormone. It is well established that ghrelin is produced by endocrine cells in the gastric mucosa. However, the distribution of human obestatin immunoreactive cells is not thoroughly characterized. A polyclonal antibody that specifically recognizes human obestatin was produced. Using this antibody and a commercial antibody vs ghrelin, the distribution of obestatin and ghrelin immunoreactive cells was determined in a panel of human tissues using immunohistochemistry. The two peptides were detected in the mucosa of the gastrointestinal tract, from cardia to ileum, and in the pancreatic islets. Interestingly, epithelial cells in the ducts of mammary glands showed distinct immunoreactivity for both ghrelin and obestatin. By double immunofluorescence microscopy, it was shown that all detected cells were immunoreactive for both peptides. Furthermore, the subcellular localization of obestatin and ghrelin was essentially identical, indicating that obestatin and ghrelin are stored in the same secretory vesicles.

  6. BK virus has tropism for human salivary gland cells in vitro: Implications for transmission

    SciTech Connect

    Jeffers, Liesl K.; Madden, Vicki; Webster-Cyriaque, Jennifer

    2009-11-25

    Background: In this study, it was determined that BKV is shed in saliva and an in vitro model system was developed whereby BKV can productively infect both submandibular (HSG) and parotid (HSY) salivary gland cell lines. Results: BKV was detected in oral fluids using quantitative real-time PCR (QRTPCR). BKV infection was determined using quantitative RT-PCR, immunofluorescence and immunoblotting assays. The infectivity of BKV was inhibited by pre-incubation of the virus with gangliosides that saturated the major capsid protein, VP1, halting receptor mediated BKV entry into salivary gland cells. Examination of infected cultures by transmission electron microscopy revealed 45-50 nm BK virions clearly visible within the cells. Subsequent to infection, encapsidated BK virus was detected in the supernatant. Conclusion: We thus demonstrated that BKV was detected in oral fluids and that BK infection and replication occur in vitro in salivary gland cells. These data collectively suggest the potential for BKV oral route of transmission and oral pathogenesis.

  7. Tracheal remodelling in response to hypoxia

    PubMed Central

    Centanin, Lazaro; Gorr, Thomas A.; Wappner, Pablo

    2010-01-01

    The insect tracheal system is a continuous tubular network that ramifies into progressively thinner branches to provide air directly to every organ and tissue throughout the body. During embryogenesis the basic architecture of the tracheal system develops in a stereotypical and genetically controlled manner. Later, in larval stages, the tracheal system becomes plastic, and adapts to particular oxygen needs of the different tissues of the body. Oxygen sensing is mediated by specific prolyl-4-hydroxylases that regulate protein stability of the alpha subunit of oxygen-responsive transcription factors from the HIF family. Tracheal cells are exquisitely sensitive to oxygen levels, modulating the expression of hypoxia-inducible proteins that mediate sprouting of tracheal branches in direction to oxygen-deprived tissues. PMID:19482033

  8. Optical metabolic imaging for monitoring tracheal health

    NASA Astrophysics Data System (ADS)

    Sharick, Joe T.; Gil, Daniel A.; Choma, Michael A.; Skala, Melissa C.

    2016-04-01

    The health of the tracheal mucosa and submucosa is a vital yet poorly understood component of critical care medicine, and a minimally-invasive method is needed to monitor tracheal health in patients. Of particular interest are the ciliated cells of the tracheal epithelium that move mucus away from the lungs and prevent respiratory infection. Optical metabolic imaging (OMI) allows cellular-level measurement of metabolism, and is a compelling method for assessing tracheal health because ciliary motor proteins require ATP to function. In this pilot study, we apply multiphoton imaging of the fluorescence intensities and lifetimes of metabolic co-enzymes NAD(P)H and FAD to the mucosa and submucosa of ex vivo mouse trachea. We demonstrate the feasibility and potential diagnostic utility of these measurements for assessing tracheal health and pathophysiology at the single-cell level.

  9. [Case of perioperative tracheal laceration by electrocautery].

    PubMed

    Ariyama, Jun; Nakamura, China; Nakagawa, Hideyuki; Imanishi, Hirokazu; Mieda, Tsutomu; Terao, Kazuhisa; Kitamura, Akira

    2013-12-01

    Although tracheal laceration during surgical procedure is a rare complication, it can be life-threating. Its immediate recognition and treatment are important. A 72-year-old man with aortic valve regurgitation was scheduled for aortic valve replacement. At anesthetic induction an endotracheal tube was smoothly inserted and the tidal volume was set at 500 ml with ventilator rate of 12 min-1. After electrocautery maneuver of the upper sterna region, end-tidal carbon-oxide curve suddenly became flat. Immediately after the completion of median sternotomy air bubble was seen in the surgical field. An 8-mm longitudinal tracheal laceration at the fourth tracheal cartilage was identified. The tracheal laceration was repaired with interrupted suture and the mediastinal tissue was used to cover the suture line. Air leaks were no longer present. After surgical repair, the aortic valve replacement was performed. The postoperative courses of both tracheal laceration repair and aortic valve replacement were uneventful.

  10. Differential scanning calorimetric evaluation of human meibomian gland secretions and model lipid mixtures: transition temperatures and cooperativity of melting

    PubMed Central

    Lu, Hua; Wojtowicz, Jadwiga C.; Butovich, Igor A.

    2013-01-01

    Meibomian gland secretions (or meibum) are produced by holocrine meibomian glands and are secreted in melted form onto the ocular surface of humans and animals to form a protective tear film lipid layer (TFLL). Its protective effect strongly depends on the composition and, hence, thermotropic behavior of meibum. The goal of our study was to quantitatively evaluate the melting characteristics of human meibum and model lipid mixtures using differential scanning microcalorimetry. Standard calorimetric parameters, e.g. changes in calorimetric enthalpy, transition temperatures T(m), cooperativity of melting etc. were assessed. We found that thermotropic behavior of meibum resembled that of relatively simple mixtures of unsaturated wax esters, but showed a lower change in calorimetric enthalpy, which can be indicative of a looser packing of lipids in meibum compared with pure standards and their simple mixtures. The cooperativity of melting of meibomian lipids was comparable to that of an equimolar mixture of four oleic-acid based wax esters. We demonstrated that the phase transitions in meibum start at about 10 to 15 °C and end at 35-36 °C, with T(m) being about 30 °C. The highly asymmetrical shape of the thermotropic peak of meibum is important for the physiology and biophysics of TFLL. PMID:23578711

  11. A Case of Tracheal Adenoid Cystic Carcinoma in a Worker Exposed to Rubber Fumes

    PubMed Central

    2013-01-01

    Background Primary tracheal tumors occur infrequently, accounting for less than 0.1% of all tumors. Adenoid cystic carcinoma (ACC) is the second most common type of malignancy of the trachea after squamous cell carcinoma (SCC). Little has been reported on the risk factors for tracheal ACC. The purpose of this study is to describe a case of tracheal ACC in a patient who had been exposed to rubber fumes, and to review the relationship between tracheal ACC and rubber fumes. Case report A 48-year-old man who had been experiencing aggravation of dyspnea for several months was diagnosed as having ACC of the trachea on the basis of a pathologic examination of a biopsy specimen obtained via laser microscopy-guided resection. The patient had been exposed to rubber fumes for 10 years at a tire manufacturing factory where he worked until ACC was diagnosed. His job involved preheating and changing rubber molds during the curing process. Conclusion ACC of both the trachea and the salivary glands show very similar patterns with regard to histopathology and epidemiology and are therefore assumed to have a common etiology. Rubber manufacturing is an occupational risk factor for the development of salivary gland tumors. Further, rubber fumes have been reported to be mutagenic. The exposure level to rubber fumes during the curing process at the patient’s workplace was estimated to be close to or higher than British Occupational Exposure Limits. Therefore, tracheal ACC in this case might have been influenced by occupational exposure to rubber fumes. PMID:24472110

  12. Endocrine glands

    MedlinePlus

    ... Diabetes Gigantism Diabetes insipidus Cushing Disease Watch this video about: Pituitary gland Testes and ovaries: Lack of sex development (unclear genitalia) Thyroid: Congenital hypothyroidism Myxedema Goiter ...

  13. MO-F-CAMPUS-I-01: EIT Imaging to Monitor Human Salivary Gland Functionality: A Feasibility Study

    SciTech Connect

    Kohli, K; Karvat, A; Liu, J; Krishnan, K

    2015-06-15

    Purpose: Clinically, there exists a need to develop a non-invasive technique for monitoring salivary activity. In this study, we investigate the feasibility of a using the electrical conductivity information from Electrical Impedance Tomography (EIT) to monitor salivary flow activity. Methods: To acquire EIT data, eight Ag/AgCl ECG electrodes were placed around the mandible of the subject. An EIT scan was obtained by injecting current at 50 KHz, 0.4 mA through each pair of electrodes and recording voltage across other electrode pairs. The functional conductivity image was obtained through reconstruction of the voltage data, using Electrical Impedance Tomography and Diffuse Optical Tomography Reconstruction Software (EIDORS) in Matlab. In using EIDORS, forward solution was obtained using a user-defined finite element model shape and inverse solution was obtained using one-step Gaussian solver. EIT scans of volunteer research team members were acquired for three different physiological states: pre-stimulation, stimulation and post-stimulation. For pre-stimulation phase, data were collected in intervals of 5 minutes for 15 minutes. The salivary glands were then stimulated in the subject using lemon and the data were collected immediately. Post-stimulation data were collected at 4 different timings after stimulation. Results: Variations were observed in the electrical conductivity patterns near parotid regions between the pre- and post-stimulation stages. The three images acquired during the 15 minute pre-stimulation phase showed no major changes in the conductivity. Immediately after stimulation, electrical conductivity increased near parotid regions and 15 minutes later slowly returned to pre-stimulation level. Conclusion: In the present study involving human subjects, the change in electrical conductivity pattern shown in the EIT images, acquired at different times with and without stimulation of salivary glands, appeared to be consistent with the change in salivary

  14. Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo.

    PubMed

    Bussard, Karen M; Smith, Gilbert H

    2012-01-01

    Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo.

  15. Human Breast Cancer Cells Are Redirected to Mammary Epithelial Cells upon Interaction with the Regenerating Mammary Gland Microenvironment In-Vivo

    PubMed Central

    Bussard, Karen M.; Smith, Gilbert H.

    2012-01-01

    Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display ‘normal’ behavior when placed into ‘normal’ ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for ‘normal’ gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo. PMID:23155468

  16. In vivo single human sweat gland activity monitoring using coherent anti-Stokes Raman scattering and two-photon excited autofluorescence microscopy.

    PubMed

    Chen, X; Gasecka, P; Formanek, F; Galey, J-B; Rigneault, H

    2016-04-01

    Eccrine sweat secretion is of central importance for control of body temperature. Although the incidence of sweat gland dysfunction might appear of minor importance, it can be a real concern for people with either hypohidrosis or hyperhidrosis. However, sweat gland function remains relatively poorly explored. To investigate the function of single human sweat glands. We describe a new approach for noninvasive imaging of single sweat gland activity in human palms in vivo up to a depth of 100 μm, based on nonlinear two-photon excited autofluorescence (TPEF) and coherent anti-Stokes Raman scattering (CARS). These techniques appear to be useful compared with approaches already described for imaging single sweat gland activity, as they allow better three-dimensional spatial resolution of sweat pore inner morphology and real-time monitoring of individual sweat events. By filling the sweat pore with oil and tuning the CARS contrast at 2845 cm(-1) , we imaged the ejection of sweat droplets from a single sweat gland when oil is pushed out by sweat flow. On average, sweat events lasted for about 30 s every 3 min under the conditions studied. On the other hand, about 20% of sweat glands were found inactive. TPEF and CARS were also used to study, at the single pore level, the antiperspirant action of aluminium chlorohydrate (ACH) and to reveal, for the first time in vivo, the formation of a plug at the pore entrance, in agreement with reported ACH antiperspirant mechanisms. Although data were acquired on human palms, these techniques show great promise for a better understanding of sweat secretion physiology and should be helpful to improve the efficacy of antiperspirant formulations. © 2015 British Association of Dermatologists.

  17. First-line tracheal resection and primary anastomosis for postintubation tracheal stenosis

    PubMed Central

    Mostafa, AM; Soliman, S; Shoukry, T; El-Nori, AA; El-Bawab, HY

    2016-01-01

    Introduction Tracheal stenosis following intubation is the most common indication for tracheal resection and reconstruction. Endoscopic dilation is almost always associated with recurrence. This study investigated first-line surgical resection and anastomosis performed in fit patients presenting with postintubation tracheal stenosis. Methods Between February 2011 and November 2014, a prospective study was performed involving patients who underwent first-line tracheal resection and primary anastomosis after presenting with postintubation tracheal stenosis. Results A total of 30 patients (20 male) were operated on. The median age was 23.5 years (range: 13–77 years). Seventeen patients (56.7%) had had previous endoscopic tracheal dilation, four (13.3%) had had tracheal stents inserted prior to surgery and one (3.3%) had undergone previous tracheal resection. Nineteen patients (63.3%) had had a tracheostomy. Eight patients (26.7%) had had no previous tracheal interventions. The median time of intubation in those developing tracheal stenosis was 20.5 days (range: 0–45 days). The median length of hospital stay was 10.5 days (range: 7–21 days). The success rate for anastomoses was 96.7% (29/30). One patient needed a permanent tracheostomy. The in-hospital mortality rate was 3.3%: 1 patient died from a chest infection 21 days after surgery. There was no mortality or morbidity in the group undergoing first-line surgery for de novo tracheal lesions. Conclusions First-line tracheal resection with primary anastomosis is a safe option for the treatment of tracheal stenosis following intubation and obviates the need for repeated dilations. Endoscopic dilation should be reserved for those patients with significant co-morbidities or as a temporary measure in non-equipped centres. PMID:27138847

  18. Reconstruction of tracheal wall defect with a mesh patch of nickel-titanium shape-memory alloy.

    PubMed

    Luo, Jia-Sheng; Cui, Peng-Cheng; Gao, Peng-Fei; Nan, Hou; Liu, Zhi; Sun, Yong-Zhu

    2011-03-01

    We explored the feasibility of reconstructing tracheal wall defects with a mesh patch fashioned from a nickel-titanium shape-memory alloy. A tracheal wall defect was first constructed surgically by resecting the anterior half of the tracheal wall between the second and sixth tracheal rings. The defect was reconstructed in 8 experimental animals by replacing the resected tracheal mucosa and tracheal cartilage with a pedicle skin flap, which was then enclosed in the mesh patch. In 4 control animals, only a pedicle skin flap with strap muscles was used in the reconstruction procedure. The performance of the animals was observed after surgery. At the end of the experiments, the reconstructed segment was harvested for anatomic evaluation. In the experimental group, 1 animal died 5 days after the operation. Endoscopic and anatomic examination of the 7 animals that survived the observation period showed that the reconstructed trachea was stable, with sufficient airway space for breathing. All 4 control animals died after the operation. After observing successful completion of this operation in animals, we successfully used this method to repair a tracheal wall defect in a human victim of a traffic accident. Tracheal defects can be successfully reconstructed by use of a mesh patch of nickel-titanium shape-memory alloy as an extraluminal stent--a method that avoids complications associated with intraluminal stents.

  19. 21 CFR 868.5790 - Tracheal tube stylet.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tracheal tube stylet. 868.5790 Section 868.5790...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5790 Tracheal tube stylet. (a) Identification. A tracheal tube stylet is a device used temporarily to make rigid a flexible tracheal tube to...

  20. 21 CFR 868.5770 - Tracheal tube fixation device.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tracheal tube fixation device. 868.5770 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5770 Tracheal tube fixation device. (a) Identification. A tracheal tube fixation device is a device used to hold a tracheal tube...

  1. 21 CFR 868.5790 - Tracheal tube stylet.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tracheal tube stylet. 868.5790 Section 868.5790...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5790 Tracheal tube stylet. (a) Identification. A tracheal tube stylet is a device used temporarily to make rigid a flexible tracheal tube to...

  2. 21 CFR 868.5790 - Tracheal tube stylet.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tracheal tube stylet. 868.5790 Section 868.5790...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5790 Tracheal tube stylet. (a) Identification. A tracheal tube stylet is a device used temporarily to make rigid a flexible tracheal tube to...

  3. 21 CFR 868.5770 - Tracheal tube fixation device.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tracheal tube fixation device. 868.5770 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5770 Tracheal tube fixation device. (a) Identification. A tracheal tube fixation device is a device used to hold a tracheal tube...

  4. 21 CFR 868.5770 - Tracheal tube fixation device.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tracheal tube fixation device. 868.5770 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5770 Tracheal tube fixation device. (a) Identification. A tracheal tube fixation device is a device used to hold a tracheal tube...

  5. 21 CFR 868.5790 - Tracheal tube stylet.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tracheal tube stylet. 868.5790 Section 868.5790...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5790 Tracheal tube stylet. (a) Identification. A tracheal tube stylet is a device used temporarily to make rigid a flexible tracheal tube to...

  6. 21 CFR 868.5790 - Tracheal tube stylet.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tracheal tube stylet. 868.5790 Section 868.5790...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5790 Tracheal tube stylet. (a) Identification. A tracheal tube stylet is a device used temporarily to make rigid a flexible tracheal tube to...

  7. 21 CFR 868.5770 - Tracheal tube fixation device.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tracheal tube fixation device. 868.5770 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5770 Tracheal tube fixation device. (a) Identification. A tracheal tube fixation device is a device used to hold a tracheal tube...

  8. 21 CFR 868.5770 - Tracheal tube fixation device.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tracheal tube fixation device. 868.5770 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5770 Tracheal tube fixation device. (a) Identification. A tracheal tube fixation device is a device used to hold a tracheal tube...

  9. [A 2-month-old child with complex tracheal hypoplasia].

    PubMed

    De Cloedt, L; Papadopoulos, J; Corouge, P; Khalil, T; Van Laer, P

    2013-12-01

    We describe the case of a 2-month-old child with complex tracheal hypoplasia with bilateral bronchial hypoplasia and left pulmonary hypoplasia. Tracheal hypoplasia is complex when it is associated with critical stenosis, cricoid stenosis, bronchial hypoplasia, tracheal bronchus, or esophageal atresia with severe tracheomalacia. Slide tracheoplasty is the gold standard treatment for the complex tracheal hypoplasia.

  10. Expression of Human NSAID Activated Gene 1 in Mice Leads to Altered Mammary Gland Differentiation and Impaired Lactation

    PubMed Central

    Binder, April K.; Kosak, Justin P.; Janhardhan, Kyathanahalli S.; Moser, Glenda; Eling, Thomas E.; Korach, Kenneth S.

    2016-01-01

    Transgenic mice expressing human non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) have less adipose tissue, improved insulin sensitivity, lower insulin levels and are resistant to dietary induced obesity. The hNAG-1 expressing mice are more metabolically active with a higher energy expenditure. This study investigates female reproduction in the hNAG-1 transgenic mice and finds the female mice are fertile but have reduced pup survival after birth. Examination of the mammary glands in these mice suggests that hNAG-1 expressing mice have altered mammary epithelial development during pregnancy, including reduced occupancy of the fat pad and increased apoptosis via TUNEL positive cells on lactation day 2. Pups nursing from hNAG-1 expressing dams have reduced milk spots compared to pups nursing from WT dams. When CD-1 pups were cross-fostered with hNAG-1 or WT dams; reduced milk volume was observed in pups nursing from hNAG-1 dams compared to pups nursing from WT dams in a lactation challenge study. Milk was isolated from WT and hNAG-1 dams, and the milk was found to have secreted NAG-1 protein (approximately 25 ng/mL) from hNAG-1 dams. The WT dams had no detectable hNAG-1 in the milk. A decrease in non-esterified free fatty acids in the milk of hNAG-1 dams was observed. Altered milk composition suggests that the pups were receiving inadequate nutrients during perinatal development. To examine this hypothesis serum was isolated from pups and clinical chemistry points were measured. Male and female pups nursing from hNAG-1 dams had reduced serum triglyceride concentrations. Microarray analysis revealed that genes involved in lipid metabolism are differentially expressed in hNAG-1 mammary glands. Furthermore, the expression of Cidea/CIDEA that has been shown to regulate milk lipid secretion in the mammary gland was reduced in hNAG-1 mammary glands. This study suggests that expression of hNAG-1 in mice leads to impaired lactation and reduces pup survival due to

  11. Ultrasound-guided fetal tracheal occlusion.

    PubMed

    Fauza, Dario O; Barnewolt, Carol; Brown, Stephen D; Jennings, Russell W

    2002-03-01

    This study was aimed at examining the feasibility of fetal tracheal occlusion guided exclusively by ultrasonography and at establishing the technical principles of this procedure based on current instrumentation and ultrasound technology. Time-dated pregnant ewes underwent a small laparotomy and partial uterine exposure. Under real-time ultrasound guidance, a steerable guide wire was fed into the fetal tracheal lumen. An 8F catheter then was fed around the guide wire into the trachea. This was followed by intratracheal placement of a 2F coaxial angiographic catheter, connected to a detachable silicone balloon at its extremity, which then was inflated with saline and delivered locally. Euthanasia was performed at term. Complete tracheal occlusion was achieved in all fetuses (n = 7) intraoperatively. Operating time needed for tracheal occlusion, once access to the amniotic cavity was established, varied widely, but could be as short 1 minute. Tracheal lumen dimensions outgrew balloon diameter in 57.1% of fetuses (4 of 7), resulting in balloon dislodgment in those animals. No balloon rupture was observed. (1) Accurate access to the fetal trachea and local delivery of an occlusive detachable silicone balloon are consistently feasible exclusively under real-time ultrasound guidance with commercially available instrumentation. (2) Balloon dimensions are determining factors of displacement risk and must be selected carefully before tracheal delivery. Ultrasound-guided fetal tracheal occlusion may be a preferable alternative to surgical intervention for treatment of fetal pulmonary hypoplasia. Copyright 2002 by W.B. Saunders Company.

  12. Sonographic detection of tracheal or esophageal intubation: A cadaver study

    PubMed Central

    Tejesh, CA; Manjunath, AC; Shivakumar, S; Vinayak, PS; Yatish, B; Geetha, CR

    2016-01-01

    Background: The correct position of the endotracheal tube is confirmed by various modalities, most of which are not entirely reliable. Ultrasound is now increasingly available to anesthesiologists in the operating theater and is an attractive alternative. To investigate the usefulness of sonography in identifying the correct tracheal tube position in human cadavers. Materials and Methods: Endotracheal tubes placed randomly into trachea or esophagus was identified with a linear ultrasound probe placed transversely just above the suprasternal notch by a single anesthesiologist. Results: Of the 100 intubations performed at random, 99 were correctly identified to give a sensitivity of 100% and a specificity of 97.9%. Conclusion: Sonography is a useful technique to identify correct position of the tracheal tube. PMID:27375387

  13. Interaction of human trophoblast cells with gland-like endometrial spheroids: a model system for trophoblast invasion.

    PubMed

    Buck, V U; Gellersen, B; Leube, R E; Classen-Linke, I

    2015-04-01

    Do maternal endometrial epithelial cell (EEC) differentiation and polarity impact the invasive capacity of extravillous trophoblast (EVT) cells during early human implantation? In a three dimensional (3D) confrontation co-culture the invasiveness of the human trophoblast cell line AC-1M88 was inversely correlated with the degree of differentiation and polarization of human endometrial adenocarcinoma cell spheroids. In a previous study desmosomal and adherens junction proteins were shown to spread from a subapically restricted lateral position to the entire lateral membrane in human glandular EECs during the implantation window of the menstrual cycle. Whether this change in EEC junction localization has an impact on the interaction of EVT cells with glandular EECs during early human implantation is not known. A new 3D cell culture system was developed in order to mimic early implantation events in humans. As a model for the invasion of endometrial glands by EVT cells, spheroids of three differently differentiated and polarized endometrial adenocarcinoma cell lines were confronted with an EVT cell line in co-culture experiments. Three human adenocarcinoma EEC lines were chosen for this study because of their differences in differentiation and polarization: HEC-1-A, which is well differentiated and highly polarized, Ishikawa, which is well differentiated and moderately polarized, and RL95-2, which is moderately differentiated and poorly polarized. When the cell lines were grown in reconstituted basement membrane, they formed gland-like, multicellular spheroids. The degree of polarization within the different EEC spheroids was assessed by 3D confocal immunofluorescence microscopy detecting the basal membrane protein integrin α6, the apical tight junction-associated protein ZO-1 and the desmosomal plaque protein desmoplakin 1/2 (Dsp). Cells of the human EVT cell line AC-1M88, which is a fusion cell line of primary EVT cells and choriocarcinoma-derived JEG-3 cells, were

  14. Characterization of a novel human type II epithelial keratin K1b, specifically expressed in eccrine sweat glands.

    PubMed

    Langbein, Lutz; Rogers, Michael A; Praetzel, Silke; Cribier, Bernard; Peltre, Bernard; Gassler, Nikolaus; Schweizer, Jürgen

    2005-09-01

    In this study, we show that a novel human type II epithelial keratin, K1b, is exclusively expressed in luminal duct cells of eccrine sweat glands. Taking this luminal K1b expression as a reference, we have used antibodies against a plethora of epithelial keratins to systematically investigate their expression in the secretory globule and the two-layered sweat duct, which was divided into the intraglandular, intradermal, and intraepidermal (acrosyringium) segments, the latter being further subdivided into the sweat duct ridge and upper intraepidermal duct. We show that (i) each of the eccrine sweat gland tissue compartments expresses their own keratin patterns, (ii) the peripheral and luminal duct layers exhibit a sequential keratin expression, with both representing self-renewing cell layers, (iii) the intradermal duct and the sweat duct ridge display hitherto unknown length variations, and (iv) out of all cell layers, the luminal cell layer is the most robust layer and expresses the highest number of keratins, these being concentrated at the apical side of the cells to form the cuticle. We provide evidence that the cellular and intercellular properties of the peripheral and the luminal layers reflect adaptations to different functions.

  15. Bufadienolides from parotoid gland secretions of Cuban toad Peltophryne fustiger (Bufonidae): Inhibition of human kidney Na(+)/K(+)-ATPase activity.

    PubMed

    Perera Córdova, Wilmer H; Leitão, Suzana Guimarães; Cunha-Filho, Geraldino; Bosch, Roberto Alonso; Alonso, Isel Pascual; Pereda-Miranda, Rogelio; Gervou, Rodrigo; Touza, Natália Araújo; Quintas, Luis Eduardo M; Noël, François

    2016-02-01

    Parotoid gland secretions of toad species are a vast reservoir of bioactive molecules with a wide range of biological properties. Herein, for the first time, it is described the isolation by preparative reversed-phase HPLC and the structure elucidation by NMR spectroscopy and/or mass spectrometry of nine major bufadienolides from parotoid gland secretions of the Cuban endemic toad Peltophryne fustiger: ψ-bufarenogin, gamabufotalin, bufarenogin, arenobufagin, 3-(N-suberoylargininyl) marinobufagin, bufotalinin, telocinobufagin, marinobufagin and bufalin. In addition, the secretion was analyzed by UPLC-MS/MS which also allowed the identification of azelayl arginine. The effect of arenobufagin, bufalin and ψ-bufarenogin on Na(+)/K(+)-ATPase activity in a human kidney preparation was evaluated. These bufadienolides fully inhibited the Na(+)/K(+)-ATPase in a concentration-dependent manner, although arenobufagin (IC50 = 28.3 nM) and bufalin (IC50 = 28.7 nM) were 100 times more potent than ψ-bufarenogin (IC50 = 3020 nM). These results provided evidence about the importance of the hydroxylation at position C-14 in the bufadienolide skeleton for the inhibitory activity on the Na(+)/K(+)-ATPase. Published by Elsevier Ltd.

  16. Function of human eccrine sweat glands during dynamic exercise and passive heat stress

    NASA Technical Reports Server (NTRS)

    Kondo, N.; Shibasaki, M.; Aoki, K.; Koga, S.; Inoue, Y.; Crandall, C. G.

    2001-01-01

    The purpose of this study was to identify the pattern of change in the density of activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic constant-workload exercise and passive heat stress. Eight male subjects (22.8 +/- 0.9 yr) exercised at a constant workload (117.5 +/- 4.8 W) and were also passively heated by lower-leg immersion into hot water of 42 degrees C under an ambient temperature of 25 degrees C and relative humidity of 50%. Esophageal temperature, mean skin temperature, sweating rate (SR), and heart rate were measured continuously during both trials. The number of ASG was determined every 4 min after the onset of sweating, whereas SGO was calculated by dividing SR by ASG. During both exercise and passive heating, SR increased abruptly during the first 8 min after onset of sweating, followed by a slower increase. Similarly for both protocols, the number of ASG increased rapidly during the first 8 min after the onset of sweating and then ceased to increase further (P > 0.05). Conversely, SGO increased linearly throughout both perturbations. Our results suggest that changes in forearm sweating rate rely on both ASG and SGO during the initial period of exercise and passive heating, whereas further increases in SR are dependent on increases in SGO.

  17. Function of human eccrine sweat glands during dynamic exercise and passive heat stress

    NASA Technical Reports Server (NTRS)

    Kondo, N.; Shibasaki, M.; Aoki, K.; Koga, S.; Inoue, Y.; Crandall, C. G.

    2001-01-01

    The purpose of this study was to identify the pattern of change in the density of activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic constant-workload exercise and passive heat stress. Eight male subjects (22.8 +/- 0.9 yr) exercised at a constant workload (117.5 +/- 4.8 W) and were also passively heated by lower-leg immersion into hot water of 42 degrees C under an ambient temperature of 25 degrees C and relative humidity of 50%. Esophageal temperature, mean skin temperature, sweating rate (SR), and heart rate were measured continuously during both trials. The number of ASG was determined every 4 min after the onset of sweating, whereas SGO was calculated by dividing SR by ASG. During both exercise and passive heating, SR increased abruptly during the first 8 min after onset of sweating, followed by a slower increase. Similarly for both protocols, the number of ASG increased rapidly during the first 8 min after the onset of sweating and then ceased to increase further (P > 0.05). Conversely, SGO increased linearly throughout both perturbations. Our results suggest that changes in forearm sweating rate rely on both ASG and SGO during the initial period of exercise and passive heating, whereas further increases in SR are dependent on increases in SGO.

  18. A study of intermediate lobe differentiation in the human pituitary gland.

    PubMed

    McNicol, A M

    1986-11-01

    The immunohistochemical demonstration of neurofilament (NF) polypeptide was used to identify nerves in a series of 17 pituitary adenomas. NF-positive fibres were present in two out of five corticotroph adenomas sited deep in the anterior lobe, in one out of five sited in the intermediate zone and in two out of seven non-corticotroph adenomas. Such nerve fibres were often seen in relation to blood vessels. The distribution of alpha-MSH immunoreactive cells was examined in 25 normal pituitaries and in 23 cases of Cushing's disease. Such cells were scattered throughout the normal gland and there was no increase in numbers in pregnancy. alpha-MSH was demonstrated in 18 corticotroph adenomas in Cushing's disease. There was no correlation with the site of the tumour or the presence of nerve fibres. alpha-MSH cells were distributed normally in the para-adenomatous gland. Crooke's hyaline change and alpha-MSH coexisted in some corticotrophs. These findings support the concept that 'intermediate lobe' function, as found in animals, has no discrete anatomical location in man.

  19. Anaesthetic management in thoracoscopic distal tracheal resection.

    PubMed

    Acosta Martínez, J; Beato López, J; Domínguez Blanco, A; López Romero, J L; López Villalobos, J L

    2017-03-01

    Surgical resection of tracheal tumours, especially distal tracheal tumours, is a challenge for the anaesthesiologists involved, mainly due to difficulties in ensuring adequate control of the airway and ventilation. We report the case of a patient undergoing tracheal resection and anastomosis by VATS, emphasizing the anaesthetic management. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Cholera toxin B subunit-binding and ganglioside GM1 immuno-expression are not necessarily correlated in human salivary glands.

    PubMed

    Kirkeby, Svend

    2014-11-01

    To determine and compare the presence and in situ localization of the glycosphingolipid ganglioside GM1 in human salivary glands using the biomarkers for GM1: cholera toxin and antibodies against GM1. Immunohistochemical analyses were performed on sections of adult human submandibular, parotid and palatinal glands using cholera toxin sub-unit B and two polyclonal antibodies against ganglioside GM1 as biomarkers. Immunofluorescence microscopy showed that the toxin and antibodies were co-localized in some acini but not in others. The cholera toxin mainly reacted with the cell membranes of the mucous acini in the submandibular gland, while incubation with the antibody against GM1 gave rise to a staining of the cytoplasm. The cytoplasm in some secretory acinar cells in the parotid gland was stained by the cholera toxin, whereas only small spots on the plasma membranes reacted with anti-GM1. The plasma membranes in the parotid excretory ducts appeared to react to anti-GM1, but not to cholera toxin. Cholera toxin induces the expression of ion channels and carriers in the small intestine and increases the production of secretory mucins. Although their mutual immunohistochemical localization may differ, both cholera toxin and ganglioside GM1 are present in the mucin-producing acini from salivary glands. This could point to a relationship between ganglioside expression and production of salivary mucins.

  1. Effect of age on immunoglobulin content and volume of human labial gland saliva.

    PubMed

    Smith, D J; Joshipura, K; Kent, R; Taubman, M A

    1992-12-01

    Stimulated lower labial (LLGF) and parotid salivary volumes and IgG, IgA, and IgM concentrations were measured in 264 subjects whose ages ranged from 17 to 76 years. A significant (p < 0.001) age-related decline in LLGF output was observed for subjects over this age range. Sixty-three percent of the subjects in the 18-20-year-old group (n = 46) secreted at least 10 microL of labial saliva in a 7-10-minute period, while approximately 70% of the subjects in the two oldest groups (61-70 and 71-76 years old) secreted less than 1 microL of LLGF during this time period (n = 64). No significant gender-based differences occurred in the volumes of labial saliva secreted. Stimulated parotid salivary flow showed no age-related trend in these subjects. Lower labial gland salivary IgA concentrations in an older population (mean age +/- SD = 55.6 yr +/- 1.3) were significantly lower (p < 0.025) than IgA concentrations in a younger population (20.7 yr +/- 0.8), when IgA was expressed as microgram/mL LLGF collected. Immunoglobulin A concentrations in parotid saliva and IgG and IgM concentrations in labial and parotid saliva were not significantly different when the two age populations were compared. These data suggest that the physiological and immunological potential of labial gland saliva may decrease with age.

  2. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    SciTech Connect

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  3. Histochemical profiles of mucins in the tracheal epithelium during the posthatching period of Japanese quail.

    PubMed

    Alan, Emel; Liman, Narin

    2010-01-01

    Mucus normally protects the airway epithelium from dehydration and inhaled infectious agents and possibly toxic substances. Two components of mucus, mucin and water play major roles in the elimination of inhaled foreign material. Mucins are large carbohydrates rich glycoprotein. The objective of the present study was to determine the histochemical changes in mucin pattern of the goblet cells and intraepithelial glands of the trachea in quails during the post-hatching period using specific various staining procedures for complex carbohydrates (Periodic acid Schiff, Alcian blue-Periodic acid Schiff (pH 2.5), Aldehyde fuchsin-Alcian blue (pH 2.5), High-iron diamine-Alcian blue (pH 2.5), Periodic acid-Phenylhydrazine-Schiff). The intraepithelial alveolar glands were present at hatching and their numbers increased with the advance of age. In quail of all ages, the histochemical reactions revealed that the goblet cells and mucous cells of intraepithelial glands contained the mucins with vicinal diol groups, neutral mucin, sialomucin and sulphomucin. In all ages studied, the tracheal epithelium contained three distinct types of goblet or mucous cells producing neutral-, acid- and mixture of neutral- and acid mucins. In 1 day old, the majority of the goblet cells and gland cells contained neutral mucin or a mixture of neutral- and acid mucins, while the proportion of only acid mucin-producing cells was few. The majority of acidic mucins consisted of sulphomucin. The sialomucin-containing cells were only a few. After day 14, it was seen that the content of sialomucin in the epithelium became more diffuse toward adulthood. In conclusion, the content of mucin of tracheal epithelium was variable depending on the ages during the post-hatching period. These changes in mucin dynamics could affect the protective functions against pathogens and toxins of the tracheal epithelium.

  4. Immunocytochemical study of the GH cells in the anterior pituitary gland of human fetus II. Anencephalic fetus.

    PubMed

    Tachibana, Toshiaki; Ito, Takayasu

    2003-12-01

    In order to elucidate the effects of hypothalamic regulation on the morphology of GH cells, light and electron microscopic immunocytochemical examinations were carried out comparing GH cells in the anterior pituitary gland of anencephalic fetus with those of normal fetuses. Three types of GH cells were identified in the anterior pituitary gland of anencephalic fetus as well as in the normal fetus. Type-I is a small, round cell containing a few small secretory granules. Type-III is a large, polygonal cell with numerous large secretory granules. Type-II is a polygonal cell with medium-sized secretory granules. The Type-II GH cell was predominant in both anencephalic and normal fetuses. The most striking difference between anencephalic and normal fetuses was the presence of atypical forms of the Type II cell. These were polygonal cells containing secretory granules, which were either immunopositive or immunonegative to anti-human GH (anti-hGH) serum. Furthermore, two other types of GH cells were identified. The somatomammotroph (SM cell) contained GH and PRL in different granules within the same cell. Also, a different type of the GH cell was noted containing two varieties of secretory granules; one was immunolabeled only with anti-hGH and the other was not immunolabeled to either anti-hGH or anti-human PRL (anti-hPRL). From these results, we suggest that an absence of hypothalamic regulation in the anencehpalic does not seriously modify GH cell morphology but induces an altered GH storage pattern in some of the cells.

  5. Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland.

    PubMed

    Slominski, Andrzej T; Kim, Tae-Kang; Li, Wei; Postlethwaite, Arnold; Tieu, Elaine W; Tang, Edith K Y; Tuckey, Robert C

    2015-10-08

    To investigate whether novel pathways of vitamin D3 (D3) and 7-dehydrocholesterol (7DHC) metabolism initiated by CYP11A1 and previously characterized in vitro, occur in vivo, we analyzed samples of human serum and epidermis, and pig adrenals for the presence of intermediates and products of these pathways. We extracted human epidermis from 13 individuals and sera from 13 individuals and analyzed them by LC/qTOF-MS alongside the corresponding standards. Pig adrenal glands were also analyzed for these steroids and secosteroids. Epidermal, serum and adrenal samples showed the presence of D3 hydroxy-derivatives corresponding to 20(OH)D3, 22(OH)D3, 25(OH)D3, 1,25(OH)2D3, 20,22(OH)2D3, 20,23(OH)2D3, 20,24(OH)2D3, 20,25(OH)2D3, 20,26(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3, plus 1,20(OH)2D3 which was detectable only in the epidermis. Serum concentrations of 20(OH)D3 and 22(OH)D3 were only 30- and 15-fold lower than 25(OH)D3, respectively, and at levels above those required for biological activity as measured in vitro. We also detected 1,20,24(OH)3D3, 1,20,25(OH)3D3 and 1,20,26(OH)3D3 in the adrenals. Products of CYP11A1 action on 7DHC, namely 22(OH)7DHC, 20,22(OH)27DHC and 7-dehydropregnenolone were also detected in serum, epidermis and the adrenal. Thus, we have detected novel CYP11A1-derived secosteroids in the skin, serum and adrenal gland and based on their concentrations and biological activity suggest that they act as hormones in vivo.

  6. Tracheal mucormycosis pneumonia: a rare clinical presentation.

    PubMed

    Mohindra, Satyawati; Gupta, Bhumika; Gupta, Karan; Bal, Amanjit

    2014-11-01

    This article reports an unusual case of tracheal mucormycosis following H1N1 pneumonia and reviews previously reported cases. A 40-y-old female with a 5-y history of diabetes mellitus, adequately controlled by oral hypoglycemic agents, developed tracheal mucormycosis after successful treatment for H1N1 pneumonia. The condition was diagnosed during workup for decannulation due to subglottic and upper tracheal obstruction by necrotic chewing gum-like tissue and cartilage. The patient was managed successfully by treatment with amphotericin B and surgical intervention in the form of laryngofissure and Montgomery tube placement. A review of the literature revealed only 5 previously reported cases of tracheal mucormycosis. A high degree of suspicion, early endoscopy and biopsy, histopathological evidence of the infection, and early institution of therapy are the keys to successful outcome.

  7. Nicotine derived genotoxic effects in human primary parotid gland cells as assessed in vitro by comet assay, cytokinesis-block micronucleus test and chromosome aberrations test.

    PubMed

    Ginzkey, Christian; Steussloff, Gudrun; Koehler, Christian; Burghartz, Marc; Scherzed, Agmal; Hackenberg, Stephan; Hagen, Rudolf; Kleinsasser, Norbert H

    2014-08-01

    Genotoxic effects of nicotine were described in different human cells including salivary gland cells. Based on the high nicotine concentration in saliva of smokers or patients using therapeutic nicotine patches, the current study was performed to evaluate the genotoxic potential of nicotine in human salivary gland cells. Therefore, primary salivary gland cells from 10 patients undergoing parotid gland surgery were exposed to nicotine concentrations between 1 μM and 1000 μM for 1 h in the absence of exogenous metabolic activation. The acinar phenotype was proven by immunofluorescent staining of alpha-amylase. Genotoxic effects were evaluated using the Comet assay, the micronucleus test and the chromosome aberration test. Cytotoxicity and apoptosis were determined by trypan blue exclusion test and Caspase-3 assay. Nicotine was able to induce genotoxic effects in all three assays. The chromosome aberration test was the most sensitive and increases in numerical and structural (chromatid-type and chromosome-type) aberrations were seen at ≥1 μM, whereas increases in micronuclei frequency were detected at 10 μM and DNA damage as measured in the Comet assay was noted at >100 μM. No cytotoxic damage or influence of apoptosis could be demonstrated. Nicotine as a possible risk factor for tumor initiation in salivary glands is still discussed controversially. Our results demonstrated the potential of nicotine to induce genotoxic effects in salivary gland cells. These results were observed at saliva nicotine levels similar to those found after oral or transdermal exposure to nicotine and suggest the necessity of careful monitoring of the use of nicotine in humans.

  8. NORMAL MAMMARY GLAND MORPHOLOGY IN PUBERTAL FEMALE MICE FOLLOWING IN UTERO AND LACTATIONAL EXPOSURE TO GENISTEIN AT LEVELS COMPARABLE TO HUMAN DIETARY EXPOSURE. (R827402)

    EPA Science Inventory

    The objective of the study was to determine the effect of in utero and lactational exposure to genistein (0, 0.1, 0.5, 2.5 and 10 mg/kg/day) on mammary gland morphology in female B6D2F1 mice at levels comparable to or greater than human exposures. The effect of diethylstilbest...

  9. Three-dimensional cell shapes and arrangements in human sweat glands as revealed by whole-mount immunostaining

    PubMed Central

    Kurata, Ryuichiro; Futaki, Sugiko; Nakano, Itsuko; Fujita, Fumitaka; Tanemura, Atsushi; Murota, Hiroyuki; Katayama, Ichiro; Okada, Fumihiro

    2017-01-01

    Because sweat secretion is facilitated by mechanical contraction of sweat gland structures, understanding their structure-function relationship could lead to more effective treatments for patients with sweat gland disorders such as heat stroke. Conventional histological studies have shown that sweat glands are three-dimensionally coiled tubular structures consisting of ducts and secretory portions, although their detailed structural anatomy remains unclear. To better understand the details of the three-dimensional (3D) coiled structures of sweat glands, a whole-mount staining method was employed to visualize 3D coiled gland structures with sweat gland markers for ductal luminal, ductal basal, secretory luminal, and myoepithelial cells. Imaging the 3D coiled gland structures demonstrated that the ducts and secretory portions were comprised of distinct tubular structures. Ductal tubules were occasionally bent, while secretory tubules were frequently bent and formed a self-entangled coiled structure. Whole-mount staining of complex coiled gland structures also revealed the detailed 3D cellular arrangements in the individual sweat gland compartments. Ducts were composed of regularly arranged cuboidal shaped cells, while secretory portions were surrounded by myoepithelial cells longitudinally elongated along entangled secretory tubules. Whole-mount staining was also used to visualize the spatial arrangement of blood vessels and nerve fibers, both of which facilitate sweat secretion. The blood vessels ran longitudinally parallel to the sweat gland tubules, while nerve fibers wrapped around secretory tubules, but not ductal tubules. Taken together, whole-mount staining of sweat glands revealed the 3D cell shapes and arrangements of complex coiled gland structures and provides insights into the mechanical contraction of coiled gland structures during sweat secretion. PMID:28636607

  10. Mucus glycoprotein secretion by tracheal explants: effects of pollutants

    SciTech Connect

    Last, J.A.; Kaizu, T.

    1980-04-01

    Tracheal slices incubated with radioactive precursors in tissue culture medium secrete labeled mucus glycoproteins into the culture medium. We have used an in vivtro approach, a combined method utilizing exposure to pneumotoxins in vivo coupled with quantitation of mucus secretion rates in vitro, to study the effects of inhaled pollutants on mucus biosynthesis by rat airways. In addition, we have purified the mucus glycoproteins secreted by rat tracheal explants in order to determine putative structural changes that might by the basis for the observed augmented secretion rates after exposure of rats to H2SO4 aerosols in combination with high ambient levels of ozone. After digestion with papain, mucus glycoproteins secreted by tracheal explants may be separated into five fractions by ion-exchange chromatography, with recovery in high yield, on columns of DEAE-cellulose. Each of these five fractions, one neutral and four acidic, migrates as a single unique spot upon cellulose acetate electrophoresis at pH values of 8.6 and 1.2. The neutral fraction, which is labeled with (3H) glucosamine, does not contain radioactivity when Na2 35SO4 is used as the precursor. Acidic fractions I to IV are all labeled with either 3H-glucosamine or Na2 35SO4 as precursor. Acidic fraction II contains sialic acid as the terminal sugar on its oligosaccharide side chains, based upon its chromatographic behavior on columns of wheat-germ agglutinin-Agarose. Treatment of this fraction with neuraminidase shifts its elution position in the gradient to a lower salt concentration, coincident with acidic fraction I. After removal of terminal sialic acid residues with either neuraminidase or low pH treatment, the resultant terminal sugar on the oligosaccharide side chains is fucose. These results are identical with those observed with mucus glycoproteins secreted by cultured human tracheal explants and purified by these same techniques.

  11. Chondrodysplasia punctata presenting with tracheal obstruction.

    PubMed

    Schweiger, Claudia; Nassar, Michel N; Goebel, Debora; Rutter, Michael J

    2017-02-01

    Chondrodysplasia punctata is a group of congenital bone and cartilage disorders characterized by erratic calcification during development. Laryngeal and tracheal calcification and subsequent stenosis, while being reported in several cases of chondrodysplasia punctata, are not frequent findings and there are no proposed management techniques. We describe here a case of an infant with chondrodysplasia punctata associated to tracheal stenosis that was successfully treated with balloon dilation, and with long term follow-up. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Endocrine glands

    MedlinePlus Videos and Cool Tools

    ... and nervous systems work very closely together. The brain continuously sends instructions to the endocrine system, and ... master switchboard because it's the part of the brain that controls the endocrine system. The pituitary gland, ...

  13. Impact of duration of critical illness on the adrenal glands of human intensive care patients.

    PubMed

    Boonen, Eva; Langouche, Lies; Janssens, Thomas; Meersseman, Philippe; Vervenne, Hilke; De Samblanx, Emilie; Pironet, Zoë; Van Dijck, Lisa; Vander Perre, Sarah; Derese, Inge; Van den Berghe, Greet

    2014-11-01

    Adrenal insufficiency is considered to be prevalent during critical illness, although the pathophysiology, diagnostic criteria, and optimal therapeutic strategy remain controversial. During critical illness, reduced cortisol breakdown contributes substantially to elevated plasma cortisol and low plasma ACTH concentrations. Because ACTH has a trophic impact on the adrenal cortex, we hypothesized that with a longer duration of critical illness, subnormal ACTH adrenocortical stimulation predisposes to adrenal insufficiency. Adrenal glands were harvested 24 hours or sooner after death from 13 long intensive care unit (ICU)-stay patients, 27 short ICU-stay patients, and 13 controls. Prior glucocorticoid treatment was excluded. MAIN OUTCOME AND MEASURE(S): Microscopic adrenocortical zonational structure was evaluated by hematoxylin and eosin staining. The amount of adrenal cholesterol esters was determined by Oil-Red-O staining, and mRNA expression of ACTH-regulated steroidogenic enzymes was quantified. The adrenocortical zonational structure was disturbed in patients as compared with controls (P < .0001), with indistinguishable adrenocortical zones present only in long ICU-stay patients (P = .003 vs. controls). Adrenal glands from long ICU-stay patients, but not those of short ICU-stay patients, contained 21% less protein (P = .03) and 9% more fluid (P = .01) than those from controls, whereas they tended to weigh less for comparable adrenal surface area. There was 78% less Oil-Red-O staining in long ICU-stay patients than in controls and in short-stay patients (P = .03), the latter similar to controls (P = .31). The mRNA expression of melanocortin 2 receptor, scavenger-receptor class B, member 1, 3-hydroxy-3-methylglutaryl-CoA reductase, steroidogenic acute regulatory protein, and cytochrome P450 cholesterol side-chain cleavage enzyme was at least 58% lower in long ICU-stay patients than in controls (all P ≤ .03) and of melanocortin 2 receptor, scavenger

  14. Activation of ROS/NF-{kappa}B and Ca{sup 2+}/CaM kinase II are necessary for VCAM-1 induction in IL-1{beta}-treated human tracheal smooth muscle cells

    SciTech Connect

    Luo, S.-F.; Chang, C.-C.; Lee, I-T.; Lee, C.-W.; Lin, W.-N.; Lin, C.-C.; Yang, C.-M.

    2009-05-15

    Histone acetylation regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) plays a critical role in the expression of inflammatory genes, such as vascular cell adhesion molecule-1 (VCAM-1). Oxidative processes have been shown to induce VCAM-1 expression. Here, we investigated the mechanisms underlying IL-1{beta}-induced VCAM-1 expression in human tracheal smooth muscle cells (HTSMCs). Our results showed that IL-1{beta} enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKC{alpha} (Goe6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-{kappa}B (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection with siRNAs of MyD88, PKC{alpha}, Src, p47{sup phox}, p300, and HDAC4. Moreover, IL-1{beta} stimulated NF-{kappa}B and CaMKII phosphorylation through MyD88-dependent PI-PLC/PKC{alpha}/c-Src/ROS and PI-PLC/Ca{sup 2+}/CaM pathways, respectively. Activation of NF-{kappa}B and CaMKII may eventually lead to the acetylation of histone residues and phosphorylation of histone deacetylases. These findings suggested that IL-1{beta} induced VCAM-1 expression via these multiple signaling pathways in HTSMCs. Blockade of these pathways may reduce monocyte adhesion via VCAM-1 suppression and attenuation of the inflammatory responses in airway diseases.

  15. Activation of ROS/NF-kappaB and Ca2+/CaM kinase II are necessary for VCAM-1 induction in IL-1beta-treated human tracheal smooth muscle cells.

    PubMed

    Luo, Shue-Fen; Chang, Chia-Chi; Lee, I-Ta; Lee, Chiang-Wen; Lin, Wei-Ning; Lin, Chih-Chung; Yang, Chuen-Mao

    2009-05-15

    Histone acetylation regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) plays a critical role in the expression of inflammatory genes, such as vascular cell adhesion molecule-1 (VCAM-1). Oxidative processes have been shown to induce VCAM-1 expression. Here, we investigated the mechanisms underlying IL-1beta-induced VCAM-1 expression in human tracheal smooth muscle cells (HTSMCs). Our results showed that IL-1beta enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCalpha (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-kappaB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection with siRNAs of MyD88, PKCalpha, Src, p47(phox), p300, and HDAC4. Moreover, IL-1beta stimulated NF-kappaB and CaMKII phosphorylation through MyD88-dependent PI-PLC/PKCalpha/c-Src/ROS and PI-PLC/Ca2+/CaM pathways, respectively. Activation of NF-kappaB and CaMKII may eventually lead to the acetylation of histone residues and phosphorylation of histone deacetylases. These findings suggested that IL-1beta induced VCAM-1 expression via these multiple signaling pathways in HTSMCs. Blockade of these pathways may reduce monocyte adhesion via VCAM-1 suppression and attenuation of the inflammatory responses in airway diseases.

  16. (Meth)acrylate monomer-induced cytotoxicity and intracellular Ca(2+) mobilization in human salivary gland carcinoma cells and human gingival fibroblast cells related to monomer hydrophobicity.

    PubMed

    Atsumi, Toshiko; Fujisawa, S; Tonosaki, K

    2006-12-01

    To elucidate a possible link between the cytotoxicity and Ca(2+) mobilization by (meth)acrylates, we investigated the cell survival of and change in [Ca(2+)](i) in human salivary gland (HSG) cells (salivary gland carcinoma cell line) and human gingival fibroblasts (HGF) cells treated separately with 9 (meth)acrylate monomers used in dentistry. The cell survival was determined by the MTT method, and the [Ca(2+)](i) changes after the stimulation with the (meth)acrylate monomers were measured in floating indo-1/AM-loaded cells in Ca(2+)-free medium. For both HSG and HGF cells, the cytotoxicity of the monomers was approximately proportional to their hydrophobicity (logP). No increase in [Ca(2+)](i) was found with hydrophilic monomers, even with 10mm stimulation. [Ca(2+)](i) elevation by hydrophobic monomers occurred in a dose- and hydrophobic-dependent manner. The [Ca(2+)](i) change in HSG cells appeared as twin peaks, i.e., an initial sharp peak followed by a delayed broad one; whereas with the HGF cells only a single broad peak was seen, possibly dependent on their membrane quality. Pretreatment with n-butanol or methylmethacrylate enhanced the butylmethacrylate-induced [Ca(2+)](i) elevation, suggesting the [Ca(2+)](i) elevation by (meth)acrylate may be related to monomer hydrophobicity and cell type. The causal link between the cytotoxicity and [Ca(2+)](i) mobilization of monomers is discussed.

  17. Molecular cloning and transmembrane structure of hCLCA2 from human lung, trachea, and mammary gland.

    PubMed

    Gruber, A D; Schreur, K D; Ji, H L; Fuller, C M; Pauli, B U

    1999-06-01

    The CLCA family of Ca2+-activated Cl- channels has recently been discovered, with an increasing number of closely related members isolated from different species. Here we report the cloning of the second human homolog, hCLCA2, from a human lung cDNA library. Northern blot and RT-PCR analyses revealed additional expression in trachea and mammary gland. A primary translation product of 120 kDa was cleaved into two cell surface-associated glycoproteins of 86 and 34 kDa in transfected HEK-293 cells. hCLCA2 is the first CLCA homolog for which the transmembrane structure has been systematically studied. Glycosylation site scanning and protease protection assays revealed five transmembrane domains with a large, cysteine-rich, amino-terminal extracellular domain. Whole cell patch-clamp recordings of hCLCA2-transfected HEK-293 cells detected a slightly outwardly rectifying anion conductance that was increased in the presence of the Ca2+ ionophore ionomycin and inhibited by DIDS, dithiothreitol, niflumic acid, and tamoxifen. Expression in human trachea and lung suggests that hCLCA2 may play a role in the complex pathogenesis of cystic fibrosis.

  18. Role of Sodium Bicarbonate Cotransporters in Intracellular pH Regulation and Their Regulatory Mechanisms in Human Submandibular Glands.

    PubMed

    Namkoong, Eun; Shin, Yong-Hwan; Bae, Jun-Seok; Choi, Seulki; Kim, Minkyoung; Kim, Nahyun; Hwang, Sung-Min; Park, Kyungpyo

    2015-01-01

    Sodium bicarbonate cotransporters (NBCs) are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1) and electrogenic NBC (NBCe1), with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs) and HSG cells. Intracellular pH (pHi) was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 μM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1.

  19. Epigallocatechin-3-gallate modulates antioxidant defense enzyme expression in murine submandibular and pancreatic exocrine gland cells and human HSG cells

    PubMed Central

    Dickinson, Douglas; DeRossi, Scott; Yu, Hongfang; Thomas, Cristina; Kragor, Chris; Paquin, Becky; Hahn, Emily; Ohno, Seiji; Yamamoto, Tetsuya; Hsu, Stephen

    2015-01-01

    Sjogren’s syndrome (SS) and type 1 diabetes are prevalent autoimmune diseases in the United States. We reported previously that Epigallocatechin-3-gallate (EGCG) prevented and delayed the onset of autoimmune disease in NOD mice, a model for both Sjogren’s syndrome (SS) and type 1 diabetes. EGCG also normalized the levels of proteins related to DNA repair and antioxidant activity in NOD.B10.Sn-H2 mice, a model for primary SS, prior to disease onset. The current study examined the effect of EGCG on the expression of antioxidant enzymes in the submandibular salivary gland and the pancreas of NOD mice and cultured human salivary gland acinar cells. NOD mice consuming 0.2% EGCG daily dissolved in water showed higher protein levels of peroxiredoxin 6 (PRDX6), a major antioxidant defense protein, and catalase, while the untreated NOD mice exhibited significantly lowered levels of PRDX6. Similarly, pancreas samples from water-fed NOD mice were depleted in PRDX6 and superoxide dismutase, while EGCG-fed mice showed high levels of these antioxidant enzymes. In cultured HSG cells EGCG increased PRDX6 levels significantly, and this was inhibited by p38 and JNK inhibitors, suggesting the EGCG-mediated increase in protective antioxidant capacity is regulated in part through MAPK pathway signaling. This mechanism may explain the higher levels of PRDX6 found in EGCG-fed NOD mice. These preclinical observations warrant future preclinical and clinical studies to determine whether EGCG or green tea polyphenols could be used in novel preventive and therapeutic approaches against autoimmune diseases and salivary dysfunction involving oxidative stress. PMID:24444391

  20. Comparison of human coagulation factor VIII expression directed by cytomegalovirus and mammary gland-specific promoters in HC11 cells and transgenic mice

    PubMed Central

    Wang, Qing; Hao, Siguo; Ma, Liyuan; Zhang, Wenhao; Wan, Jiangbo; Deng, Xiaohui

    2015-01-01

    Hemophilia A is an inherited X-linked recessive bleeding disorder caused by coagulant factor VIII (FVIII) deficiency. The conventional treatment involves the administration of recombinant human FVIII (rhFVIII) preparations. In this study, the mammary gland ‘bioreactor’ is designed to specifically and efficiently express a foreign protein hFVIII in the mammary glands of transgenic mice. We constructed a P1A3-hFVIIIBD vector directed by the mammary gland-specific P1A3 promoter, and transiently transfected HC11 cells and mouse mammary glands with P1A3-hFVIIIBD or CMV-hFVIIIBD vectors directed by a ubiquitous cytomegalovirus (CMV) promoter, respectively. We also generated P1A3-hFVIIIBD and CMV-hFVIIIBD transgenic mice by microinjection, respectively. Our data indicated that both vectors effectively expressed hFVIIIBD in HC11 cells at the transcription level, and hFVIIIBD protein was efficiently expressed in mouse milk after the injection of the hFVIIIBD vectors into mouse mammary glands during lactation. In both CMV-hFVIIIBD and P1A3-hFVIIIBD transgenic mice, hFVIIIBD proteins were efficiently expressed in the mammary glands at the mRNA and protein levels. No significant difference was observed in hFVIIIBD levels between the CMV-hFVIIIBD and P1A3-hFVIIIBD transgenic mice (P > 0.05). However, the activity of hFVIII in CMV-directed transgenic mice was slightly higher than that in P1A3-directed transgenic mice (P < 0.05). While hFVIIIBD was present in multiple organs in CMV-hFVIIIBD mice, P1A3-hFVIIIBD mice showed negligible hFVIIIBD expression in organs other than the mammary glands. This study demonstrated that the mammary gland-specific P1A3-hFVIIIBD vector was more suitable for the generation of hFVIIIBD mammary gland bioreactor. PMID:26192111

  1. Comparison of human coagulation factor VIII expression directed by cytomegalovirus and mammary gland-specific promoters in HC11 cells and transgenic mice.

    PubMed

    Wang, Qing; Hao, Siguo; Ma, Liyuan; Zhang, Wenhao; Wan, Jiangbo; Deng, Xiaohui

    2015-10-01

    Hemophilia A is an inherited X-linked recessive bleeding disorder caused by coagulant factor VIII (FVIII) deficiency. The conventional treatment involves the administration of recombinant human FVIII (rhFVIII) preparations. In this study, the mammary gland 'bioreactor' is designed to specifically and efficiently express a foreign protein hFVIII in the mammary glands of transgenic mice. We constructed a P1A3-hFVIIIBD vector directed by the mammary gland-specific P1A3 promoter, and transiently transfected HC11 cells and mouse mammary glands with P1A3-hFVIIIBD or CMV-hFVIIIBD vectors directed by a ubiquitous cytomegalovirus (CMV) promoter, respectively. We also generated P1A3-hFVIIIBD and CMV-hFVIIIBD transgenic mice by microinjection, respectively. Our data indicated that both vectors effectively expressed hFVIIIBD in HC11 cells at the transcription level, and hFVIIIBD protein was efficiently expressed in mouse milk after the injection of the hFVIIIBD vectors into mouse mammary glands during lactation. In both CMV-hFVIIIBD and P1A3-hFVIIIBD transgenic mice, hFVIIIBD proteins were efficiently expressed in the mammary glands at the mRNA and protein levels. No significant difference was observed in hFVIIIBD levels between the CMV-hFVIIIBD and P1A3-hFVIIIBD transgenic mice (P > 0.05). However, the activity of hFVIII in CMV-directed transgenic mice was slightly higher than that in P1A3-directed transgenic mice (P < 0.05). While hFVIIIBD was present in multiple organs in CMV-hFVIIIBD mice, P1A3-hFVIIIBD mice showed negligible hFVIIIBD expression in organs other than the mammary glands. This study demonstrated that the mammary gland-specific P1A3-hFVIIIBD vector was more suitable for the generation of hFVIIIBD mammary gland bioreactor.

  2. Photothermolysis of sebaceous glands in human skin ex vivo with a 1,708 nm Raman fiber laser and contact cooling.

    PubMed

    Alexander, Vinay V; Ke, Kevin; Xu, Zhao; Islam, Mohammed N; Freeman, Michael J; Pitt, Bertram; Welsh, Michael J; Orringer, Jeffrey S

    2011-08-01

    Wavelengths near ∼1,720 nm are of interest for targeting fat/lipid-rich tissues due to the high absorption coefficient of human fat and low water scattering and absorption. In this study, a 1,708 nm laser was built and shown to selectively target fat/lipid adjacent to porcine heart and dermis and then used to damage dermal sebaceous glands in human skin. STUDY DESIGN AND MATERIALS: An all-fiber 1,708 nm laser with ∼4 W maximum power was designed and built. Selectivity for targeting fat/lipid was studied by exposing porcine heart and skin tissue cross-sections to the 1,708 nm laser. Human skin treatments to damage sebaceous glands were performed both with and without cold window cooling. Histochemical evaluation on the frozen sections was performed using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Histochemical analysis of porcine tissue cross-sections showed that 1,708 nm laser can selectively damage pericardial fat(heart) and subcutaneous fat(skin) with little to no damage to the myocardium and the dermis, respectively. In human skin, histochemical evaluation without contact cooling showed damage to both epidermis and dermis. With cooling, epidermis was spared and damage was observed in dermis extending ∼0.4-1.65 mm from the skin surface at an average laser fluence of ∼80 J/cm(2). Selective damage of sebaceous glands was suggested but not definitively demonstrated. We have developed an all-fiber 1,708 nm laser capable of damaging majority of the sebaceous glands in the dermis and thus may have potential applications in the treatment of conditions such as acne vulgaris whose pathophysiology involves disorders of sebaceous glands. Copyright © 2011 Wiley-Liss, Inc.

  3. Indications and interventional options for non-resectable tracheal stenosis

    PubMed Central

    Bacon, Jenny Louise; Patterson, Caroline Marie

    2014-01-01

    Non-specific presentation and normal examination findings in early disease often result in tracheal obstruction being overlooked as a diagnosis until patients present acutely. Once diagnosed, surgical options should be considered, but often patient co-morbidity necessitates other interventional options. Non-resectable tracheal stenosis can be successfully managed by interventional bronchoscopy, with therapeutic options including airway dilatation, local tissue destruction and airway stenting. There are common aspects to the management of tracheal obstruction, tracheomalacia and tracheal fistulae. This paper reviews the pathogenesis, presentation, investigation and management of tracheal disease, with a focus on tracheal obstruction and the role of endotracheal intervention in management. PMID:24624290

  4. Tracheal and bronchial stenoses and other obstructive conditions

    PubMed Central

    Schweiger, Claudia; Cohen, Aliza P.

    2016-01-01

    Although tracheal stenosis and bronchial stenosis are relatively rare in the pediatric population, they are both associated with significant morbidity and mortality. While most cases of congenital tracheal stenosis in children present as complete tracheal rings (CTRs), other congenital tracheal obstructions are also encountered in clinical practice. In addition, acquired obstructive tracheal conditions stemming from endotracheal trauma or previous surgical interventions may occur. Many affected children also have associated cardiovascular malformations, further complicating their management. Optimal management of children with tracheal or bronchial stenoses requires comprehensive diagnostic evaluation and optimization prior to surgery. Slide tracheoplasty has been the operative intervention of choice in the treatment of the majority of these children. PMID:28066618

  5. Recurred Post-intubation Tracheal Stenosis Treated with Bronchoscopic Cryotherapy.

    PubMed

    Jung, Ye-Ryung; Taek Jeong, Joon; Kyu Lee, Myoung; Kim, Sang-Ha; Joong Yong, Suk; Jeong Lee, Seok; Lee, Won-Yeon

    Post-intubation tracheal stenosis accounts for the greatest proportion of whole-cause tracheal stenosis. Treatment of post-intubation tracheal stenosis requires a multidisciplinary approach. Surgery or an endoscopic procedure can be used, depending on the type of stenosis. However, the efficacy of cryotherapy in post-intubation tracheal stenosis has not been validated. Here, we report a case of recurring post-intubation tracheal stenosis successfully treated with bronchoscopic cryotherapy that had previously been treated with surgery. In this case, cryotherapy was effective in treating web-like fibrous stenosis, without requiring more surgery. Cryotherapy can be considered as an alternative or primary treatment for post-intubation tracheal stenosis.

  6. The normal trachea is cleaned by MUC5B mucin bundles from the submucosal glands coated with the MUC5AC mucin.

    PubMed

    Ermund, Anna; Meiss, Lauren N; Rodriguez-Pineiro, Ana M; Bähr, Andrea; Nilsson, Harriet E; Trillo-Muyo, Sergio; Ridley, Caroline; Thornton, David J; Wine, Jeffrey J; Hebert, Hans; Klymiuk, Nikolai; Hansson, Gunnar C

    2017-10-21

    To understand the mucociliary clearance system, mucins were visualized by light, confocal and electron microscopy, and mucus was stained by Alcian blue and tracked by video microscopy on tracheal explants of newborn piglets. We observed long linear mucus bundles that appeared at the submucosal gland openings and were transported cephalically. The mucus bundles were shown by mass spectrometry and immunostaining to have a core made of MUC5B mucin and were coated with MUC5AC mucin produced by surface goblet cells. The transport speed of the bundles was slower than the airway surface liquid flow. We suggest that the goblet cell MUC5AC mucin anchors the mucus bundles and thus controls their transport. Normal clearance of the respiratory tree of pigs and humans, both rich in submucosal glands, is performed by thick and long mucus bundles. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. A milk protein gene promoter directs the expression of human tissue plasminogen activator cDNA to the mammary gland in transgenic mice

    SciTech Connect

    Pittius, C.W.; Hennighausen, L.; Lee, E.; Westphal, H.; Nicols, E.; Vitale, J.; Gordon, K. )

    1988-08-01

    Whey acidic protein (WAP) is a major whey protein in mouse milk. Its gene is expressed in the lactating mammary gland and is inducible by steroid and peptide hormones. A series of transgenic mice containing a hybrid gene in which human tissue plasminogen activator (tPA) cDNA is under the control of the murine WAP gene promoter had previously been generated. In this study, 21 tissues from lactating and virgin transgenic female mice containing the WAP-tPA hybrid gene were screened for the distribution of murine WAP and human tPA transcripts. Like the endogenous WAP RNA, WAP-tPA RNA was expressed predominantly in mammary gland tissue and appeared to be inducible by lactation. Whereas WAP transcripts were not detected in 22 tissues of virgin mice, low levels of WAP-tPA RNA, which were not modulated during lactation, were found in tongue, kidney, and sublingual gland. These studies demonstrate that the WAP gene promoter can target the expression of a transgene to the mammary gland and that this expression is inducible during lactation.

  8. The presence of monoiodinated derivates of daidzein and genistein in human urine and its effect on thyroid gland function.

    PubMed

    Sosvorová, Lucie; Mikšátková, Petra; Bičíková, Marie; Kaňová, Nataša; Lapčík, Oldřich

    2012-08-01

    Dietary supplements used by women during menopause are usually based on plant extracts containing isoflavonoids, daidzein and genistein. Genistein is a known inhibitor of many enzymes, including thyroid peroxidase (TPO). In the thyroid follicle, genistein acts as its alternate substrate for the formation of genistein iodinated derivatives. The aim of this study was to search for daidzein- and genistein-iodinated derivatives in urine of isoflavonoid-supplemented women. Additionally, selected phytoestrogens, steroid and thyroid hormones before and after three months of phytoestrogen supplementation were estimated. Urinary levels of free phytoestrogen increased significantly after therapy. They ranged between 0.3-1600, 0.6-670 and 0-206 nmol/L for daidzein, genistein and S-equol, respectively. Monoiodinated derivatives of genistein were observed (0-504 pmol/L) in 60% of the investigated samples. Steroid and thyroid hormone levels were within the normal range and were not significantly altered. The presence of monoiodinated derivates in human urine confirmed that genistein and daidzein may enter human thyroid follicles and influence TPO. Since the levels of the free thyroid hormones were not affected, we propose that the use of phytoestrogen dietary supplements is not associated with the development of thyroid-gland disorders in subjects with adequate iodine intake. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Unsolved Mysteries of the Human Mammary Gland: Defining and Redefining the Critical Questions from the Lactation Consultant's Perspective.

    PubMed

    Marasco, Lisa Ann

    2014-12-01

    Despite advances in knowledge about human lactation, clinicians face many problems when advising mothers who are experiencing breastfeeding difficulties that do not respond to normal management strategies. Primary insufficient milk production is now being acknowledged, but incidence rates have not been well studied. Many women have known histories of infertility, polycystic ovary syndrome, obesity, hypertension, insulin resistance, thyroid dysfunction, hyperandrogenism or other hormonal imbalances, while others have no obvious risk factors. Some present with obviously abnormal breasts that are pubescent, tuberous/tubular or asymmetric in shape, raising the question of insufficient mammary gland tissue. Other women have breasts that appear within normal limits yet do not lactate normally. Endocrine disruptors may underlie some of these cases but their impact on human milk production has not been well explored. Similarly, any problem with prolactin such as a deficiency in serum prolactin or receptor number, receptor resistance, or poor bioavailability or bioactivity could underlie some cases of insufficient lactation, yet these possibilities are rarely investigated. A weak or suppressed milk ejection reflex, often assumed to be psychosomatic, could be related to thyroid dysfunction or caused by downstream post-receptor pathway problems. In the absence of sufficient data regarding these situations, desperate mothers may turn to non-evidence-based remedies, sometimes at considerable cost and unknown risk. Research targeted to these clinical dilemmas is critical in order to develop evidence-based strategies and increase breastfeeding duration and success rates.

  10. Morphological, diagnostic and surgical features of ectopic thyroid gland: a review of literature.

    PubMed

    Guerra, Germano; Cinelli, Mariapia; Mesolella, Massimo; Tafuri, Domenico; Rocca, Aldo; Amato, Bruno; Rengo, Sandro; Testa, Domenico

    2014-01-01

    Ectopic thyroid tissue remains a rare developmental abnormality involving defective or aberrant embryogenesis of the thyroid gland during its passage from the floor of the primitive foregut to its usual final position in pre-tracheal region of the neck. Its specific prevalence accounts about 1 case per 100.000-300.000 persons and one in 4.000-8.000 patients with thyroid disease show this condition. The cause of this defect is not fully known. Despite genetic factors have been associated with thyroid gland morphogenesis and differentiation, just recently some mutation has been associated with human thyroid ectopy. Lingual region in the most common site of thyroid ectopy but ectopic thyroid tissue were found in other head and neck locations. Nevertheless, aberrant ectopic thyroid tissue has been found in other places distant from the neck region. Ectopic tissue is affected by different pathological changes that occur in the normal eutopic thyroid. Patients may present insidiously or as an emergency. Diagnostic management of thyroid ectopy is performed by radionuclide thyroid imaging, ultrasonography, CT scan, MRI, biopsy and thyroid function tests. Asymptomatic euthyroid patients with ectopic thyroid do not usually require therapy but are kept under observation. For those with symptoms, treatment depends on size of the gland, nature of symptoms, thyroid function status and histological findings. Surgical excision is often required as treatment for this condition.

  11. P2Y2 Nucleotide Receptor Activation Up-regulates Vascular Cell Adhesion Molecular-1 Expression and Enhances Lymphocyte Adherence to a Human Submandibular Gland Cell Line

    PubMed Central

    Baker, Olga J.; Camden, Jean M.; Rome, Danny E.; Seye, Cheikh I.; Weisman, Gary A.

    2007-01-01

    Sjögren’s syndrome (SS) is a chronic inflammatory autoimmune disease that causes salivary and lacrimal gland tissue destruction resulting in impaired secretory function. Although lymphocytic infiltration of salivary epithelium is associated with SS, the mechanisms involved have not been adequately elucidated. Our previous studies have shown that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is up-regulated in response to damage or stress of salivary gland epithelium, and in salivary glands of the NOD.B10 mouse model of SS-like autoimmune exocrinopathy. Additionally, we have shown that P2Y2R activation up-regulates vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells leading to the binding of monocytes. The present study demonstrates that activation of the P2Y2R in dispersed cell aggregates from rat submandibular gland (SMG) and in human submandibular gland ductal cells (HSG) up-regulates the expression of VCAM-1. Furthermore, P2Y2R activation mediated the up-regulation of VCAM-1 expression in HSG cells leading to increased adherence of lymphocytic cells. Inhibitors of EGFR phosphorylation and metalloprotease activity abolished P2Y2R-mediated VCAM-1 expression and decreased lymphocyte binding to HSG cells. Moreover, silencing of EGFR expression abolished UTP-induced VCAM-1 up-regulation in HSG cells. These results suggest that P2Y2R activation in salivary gland cells increases the EGFR-dependent expression of VCAM-1 and the binding of lymphocytes, a pathway relevant to inflammation associated with SS. PMID:17599409

  12. P2Y2 nucleotide receptor activation up-regulates vascular cell adhesion molecule-1 [corrected] expression and enhances lymphocyte adherence to a human submandibular gland cell line.

    PubMed

    Baker, Olga J; Camden, Jean M; Rome, Danny E; Seye, Cheikh I; Weisman, Gary A

    2008-01-01

    Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that causes salivary and lacrimal gland tissue destruction resulting in impaired secretory function. Although lymphocytic infiltration of salivary epithelium is associated with SS, the mechanisms involved have not been adequately elucidated. Our previous studies have shown that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is up-regulated in response to damage or stress of salivary gland epithelium, and in salivary glands of the NOD.B10 mouse model of SS-like autoimmune exocrinopathy. Additionally, we have shown that P2Y2R activation up-regulates vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells leading to the binding of monocytes. The present study demonstrates that activation of the P2Y2R in dispersed cell aggregates from rat submandibular gland (SMG) and in human submandibular gland ductal cells (HSG) up-regulates the expression of VCAM-1. Furthermore, P2Y2R activation mediated the up-regulation of VCAM-1 expression in HSG cells leading to increased adherence of lymphocytic cells. Inhibitors of EGFR phosphorylation and metalloprotease activity abolished P2Y2R-mediated VCAM-1 expression and decreased lymphocyte binding to HSG cells. Moreover, silencing of EGFR expression abolished UTP-induced VCAM-1 up-regulation in HSG cells. These results suggest that P2Y2R activation in salivary gland cells increases the EGFR-dependent expression of VCAM-1 and the binding of lymphocytes, a pathway relevant to inflammation associated with SS.

  13. Activation of Alternative Wnt Signaling Pathways in Human Mammary Gland and Breast Cancer Cells

    DTIC Science & Technology

    2006-06-01

    signalling, the antagonistic role of Wnt5a on canonical Wnt signalling, and the fact that the genes regulated by either of these pathways differ in...differentiation, apoptosis, and migration. Wnt/Frizzled signaling is now linked to human hereditary disorders with retinal vascular defects, implicating...www.physiologyonline.org fact that the role of FrzA in vascular biology is not well understood. Wnt Signaling Comes into Play in Human Vascular

  14. Management of Post-Intubation Tracheal Membrane Ruptures.

    PubMed

    Eliçora, Aykut; Akgül, Aslı G; Topçu, Salih; Özbay, Serkan; Hoşten, Tülay; Sezer, Hüseyin F; Eliçora, Sultan Şevik

    2016-07-01

    Iatrogenic tracheal rupture is a rare complication after intubation. Overinflation of the tracheal cuff was speculated to be a frequent cause of tracheal rupture. The surgical approach is a widespread treatment for tracheal ruptures. The aim of this study is to evaluate the results of conservative and surgical therapy approaches in tracheal rupture cases inflicted by tracheal intubation. Data on 12 patients who experienced tracheal ruptures secondary to intubation were reviewed. The average age of the patients was 58 years (range of 38 to 81 years). Six patients were men and 6 patients were women. Four of the patients were performed thoracotomy for primary surgery and underwent surgical therapy. 8 patients were treated conservatively. The results of both approaches were evaluated. Patients, who underwent both conservative and surgical therapy, were completely recovered. There was no rupture originated complication or death. Both conservative and surgical therapies are appropriate for treatment of membranous tracheal rupture.

  15. Engineering of human tracheal tissue with collagen-enforced poly-lactic-glycolic acid non-woven mesh: a preliminary study in nude mice.

    PubMed

    Wu, Wei; Feng, Xue; Mao, Tianqiu; Feng, Xinghua; Ouyang, Hong-Wei; Zhao, Guifang; Chen, Fulin

    2007-06-01

    The purpose of the current study is to fabricate tissue engineered trachea with poly-lactic-glycolic acid (PLGA) non-woven mesh enforced by collagen type I. PLGA fibres coated with collagen solution were put together and fabricated into the shape of a human trachea, after drying and cross-linking treatment, a non-woven mesh with "C" shape formed. Chondrocytes from sheep nasal septum cartilage were expanded in vitro and seeded into PLGA/collagen non-woven mesh in the density of 5.0 x 10(7)mL(-1). After 5 days of in vitro incubation, six Cell-PLGA/collagen composites were implanted subcutaneously into the back of 6 nude mice to prefabricate a tissue engineering trachea. Eight weeks later, the cartilage formation was observed by gross inspection and histological examination. Cartilage-like tissue in the shape of the initial PLGA/collagen scaffold had been regenerated successfully without obvious inflammatory response. The tissue engineered trachea cartilage consisted of evenly spaced lacunae embedded in matrix stained red with safranin-O staining. The amount of GAGs in tissue engineered trachea cartilage reached 71.42% of normal value in native cartilage. This study demonstrated that collagen-enforced PLGA non-woven mesh facilitated the adhesion and proliferation of chondrocytes, it also owned adequate mechanical strength to serve as an ideal scaffold for trachea tissue engineering without internal support.

  16. Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells.

    PubMed

    Seagrave, Jeanclare; Albrecht, Helmut H; Hill, David B; Rogers, Duncan F; Solomon, Gail

    2012-10-31

    Therapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Several types of drugs are available with different possible modes of action. We examined the effects of guaifenesin (GGE), N-acetylcysteine (NAC) and ambroxol (Amb) on differentiated human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC. After IL-13 pre-treatment (3 days), the cultures were treated with GGE, NAC or Amb (10-300 μM) in the continued presence of IL-13. Cellular and secreted MUC5AC, mucociliary transport rates (MTR), mucus rheology at several time points, and the antioxidant capacity of the drugs were assessed. IL-13 increased MUC5AC content (~25%) and secretion (~2-fold) and decreased MTR, but only slightly affected the G' (elastic) or G" (viscous) moduli of the secretions. GGE significantly inhibited MUC5AC secretion and content in the IL-13-treated cells in a concentration-dependent manner (IC50s at 24 hr ~100 and 150 μM, respectively). NAC or Amb were less effective. All drugs increased MTR and decreased G' and G" relative to IL-13 alone. Cell viability was not affected and only NAC exhibited antioxidant capacity. Thus, GGE effectively reduces cellular content and secretion of MUC5AC, increases MTR, and alters mucus rheology, and may therefore be useful in treating airway mucus hypersecretion and mucostasis in airway diseases.

  17. Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells

    PubMed Central

    2012-01-01

    Background Therapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Several types of drugs are available with different possible modes of action. We examined the effects of guaifenesin (GGE), N-acetylcysteine (NAC) and ambroxol (Amb) on differentiated human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC. Methods After IL-13 pre-treatment (3 days), the cultures were treated with GGE, NAC or Amb (10–300 μM) in the continued presence of IL-13. Cellular and secreted MUC5AC, mucociliary transport rates (MTR), mucus rheology at several time points, and the antioxidant capacity of the drugs were assessed. Results IL-13 increased MUC5AC content (~25%) and secretion (~2-fold) and decreased MTR, but only slightly affected the G’ (elastic) or G” (viscous) moduli of the secretions. GGE significantly inhibited MUC5AC secretion and content in the IL-13-treated cells in a concentration-dependent manner (IC50s at 24 hr ~100 and 150 μM, respectively). NAC or Amb were less effective. All drugs increased MTR and decreased G’ and G” relative to IL-13 alone. Cell viability was not affected and only NAC exhibited antioxidant capacity. Conclusions Thus, GGE effectively reduces cellular content and secretion of MUC5AC, increases MTR, and alters mucus rheology, and may therefore be useful in treating airway mucus hypersecretion and mucostasis in airway diseases. PMID:23113953

  18. BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands.

    PubMed

    Alves, Daniel Berretta Moreira; Bingle, Lynne; Bingle, Colin David; Lourenço, Silvia Vanessa; Silva, Andréia Aparecida; Pereira, Débora Lima; Vargas, Pablo Agustin

    2017-01-16

    The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

  19. Mechanisms of pneumothorax following tracheal intubation.

    PubMed

    Berg, L F; Mafee, M F; Campos, M; Applebaum, E L

    1988-01-01

    To investigate the mechanism by which pneumothorax may occur as a complication of tracheal intubation, we submitted four cats to tracheotomy and three to tracheal intubation. To simulate the dissection of air along fascial planes following tracheotomy, we placed catheters in either the pretracheal or subcutaneous plane and applied positive pressure to the catheters. The cats undergoing tracheal intubation were ventilated with excessive positive pressure. Computed tomography was used to document the progression of pneumothorax. High positive pressures during mechanical ventilation led to pneumothorax and pneumomediastinum, and the mechanism was primarily the dissection of air along the perivascular sheaths of the pulmonary arteries, presumably due to rupture of perivascular alveoli. Dissection of air along the pretracheal fascia following tracheotomy produced pneumomediastinum but not pneumothorax. This suggests that pneumothorax occurring clinically is more likely a complication of assisted ventilation than a complication of tracheotomy surgery.

  20. Characterization of bipotential epidermal progenitors derived from human sebaceous gland: contrasting roles of c-Myc and beta-catenin.

    PubMed

    Lo Celso, Cristina; Berta, Melanie A; Braun, Kristin M; Frye, Michaela; Lyle, Stephen; Zouboulis, Christos C; Watt, Fiona M

    2008-05-01

    The current belief is that the epidermal sebaceous gland (SG) is maintained by unipotent stem cells that are replenished by multipotent stem cells in the hair follicle (HF) bulge. However, sebocytes can be induced by c-Myc (Myc) activation in interfollicular epidermis (IFE), suggesting the existence of bipotential stem cells. We found that every SZ95 immortalized human sebocyte that underwent clonal growth in culture generated progeny that differentiated into both sebocytes and cells expressing involucrin and cornifin, markers of IFE and HF inner root sheath differentiation. The ability to generate involucrin positive cells was also observed in a new human sebocyte line, Seb-E6E7. SZ95 xenografts differentiated into SG and IFE but not HF. SZ95 cells that expressed involucrin had reduced Myc levels; however, this did not correlate with increased expression of the Myc repressor Blimp1, and Blimp1 expression did not distinguish cells undergoing SG, IFE, or HF differentiation in vivo. Overexpression of Myc stimulated sebocyte differentiation, whereas overexpression of beta-catenin stimulated involucrin and cornifin expression. In transgenic mice simultaneous activation of Myc and beta-catenin revealed mutual antagonism: Myc blocked ectopic HF formation and beta-catenin reduced SG differentiation. Overexpression of the Myc target gene Indian hedgehog did not promote sebocyte differentiation in culture and cyclopamine treatment, while reducing proliferation, did not block Myc induced sebocyte differentiation in vivo. Our studies provide evidence for a bipotential epidermal stem cell population in an in vitro model of human epidermal lineage selection and highlight the importance of Myc as a regulator of sebocyte differentiation.

  1. TGF-β antagonist attenuates fibrosis but not luminal narrowing in experimental tracheal stenosis.

    PubMed

    Antón-Pacheco, Juan L; Usategui, Alicia; Martínez, Iván; García-Herrero, Carmen M; Gamez, Antonio P; Grau, Montserrat; Martínez, Ana M; Rodríguez-Peralto, José L; Pablos, José L

    2017-03-01

    Acquired tracheal stenosis (ATS) is an unusual disease often secondary to prolonged mechanical trauma. Acquired tracheal stenosis pathogenesis involves inflammation and subsequent fibrosis with narrowing of the tracheal lumen. Transforming growth factor-β1 (TGF-β) represents a pivotal factor in most fibrotic processes, and therefore a potential target in this context. The aim of this study is to analyze the role of TGF-β as a target for anti-fibrotic interventions in tracheal stenosis. Human stenotic tracheobronchial tissues from patients with benign airway stenosis and normal controls from pneumonectomy specimens were analyzed. Tracheal stenosis was induced in adult NZ rabbits by a circumferential thermal injury to the mucosa during open surgery and re-anastomosis. Rabbits were treated postoperatively with a peritracheal collagen sponge containing a TGF-β peptide antagonist (p17) or vehicle. Fibrosis was determined by Masson's trichrome staining, and smooth muscle cell α-actin(+) (α-SMA(+) Confirm accuracy.) myofibroblasts, connective tissue growth factor (CTGF), and p-Smad2/3 expression by immunohistochemistry. Human and rabbit stenotic tissues showed extensive submucosal fibrosis, characterized by significantly increased α-SMA(+) myofibroblasts and CTGF expression. In human stenotic lesions, increased p-Smad2/3(+) nuclei were also observed. p17 treatment significantly reduced the fibrotic thickness, as well as the density of α-SMA(+) myofibroblasts and CTGF(+) cells in rabbit stenotic lesions, but failed to improve the luminal area. ATS is characterized by a TGF-β dependent fibrotic process, but reduction of the fibrotic component by TGF-β1 antagonist therapy was not sufficient to improve tracheal narrowing, suggesting that fibrosis may not be the main contributor to luminal stenosis. NA. Laryngoscope, 127:561-567, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Gonadotrope and thyrotrope development in the human and mouse anterior pituitary gland.

    PubMed

    Pope, Caroline; McNeilly, Judy R; Coutts, Shiona; Millar, Mike; Anderson, Richard A; McNeilly, Alan S

    2006-09-01

    Genes and orthologous intrinsic and extrinsic factors critical for embryonic pituitary gonadotrope and thyrotrope cell differentiation have been identified mainly in rodents, but data on the human are very limited. In human fetal pituitaries examined between 14 and 19 weeks of gestation using immunofluorescent confocal microscopy, we found that most fetal gonadotropes expressed alpha-GSU, LHbeta, and FSHbeta gonadotropin subunits while almost no cells expressed alpha-GSU and LHbeta alone. Gonadotropes expressing alpha-GSU and FSHbeta only were detected in both male and female pituitaries, increasing in proportion to total gonadotropes in both males and females from 14 (approximately 4.5%) to 19 weeks (approximately 16.5%) with a peak in males of 45.5% compared with females of 16.5% at 17 weeks of gestation. When FSHbeta or LHbeta genes were expressed, gonadotropes were non-dividing. This profile of human fetal gonadotrope development differs from the current mouse model. Furthermore, while expression of alpha-GSU appears to be the lead protein in gonadotropes, in thyrotropes which ultimately express alpha-GSU with TSHbeta, we observed that most if not all thyrotropes were TSHbeta-positive but alpha-GSU-negative until around 19 weeks in human, and e15 in mouse, fetal pituitaries. Furthermore, the TSHbeta-only thyrotropes were dividing, and TSHbeta rather than alpha-GSU was the lead protein in thyrotrope development. Thus, while biologically active dimeric FSH and LH can be produced by the human fetal pituitary by 14 weeks, dimeric biologically active TSH will only be produced from around 17 weeks of gestation. The mechanism(s) responsible for the different molecular regulation of alpha-GSU gene expression in gonadotropes and thyrotropes in the developing human fetal pituitary now requires investigation.

  3. Localization of Na(+)-K(+)-ATPase α/β, Na(+)-K(+)-2Cl-cotransporter 1 and aquaporin-5 in human eccrine sweat glands.

    PubMed

    Zhang, Mingjun; Zeng, Shaopeng; Zhang, Lei; Li, Haihong; Chen, Lu; Zhang, Xiang; Li, Xuexue; Lin, Changmin; Shu, Shenyou; Xie, Sitian; He, Yunpu; Mao, Xiaoyan; Peng, Lihong; Shi, Lungang; Yang, Lvjun; Tang, Shijie; Fu, Xiaobing

    2014-10-01

    In order to evaluate the function of the repaired or regenerated eccrine sweat glands, we must first localize the proteins involved in sweat secretion and absorption in normal human eccrine sweat glands. In our studies, the cellular localization of Na(+)-K(+)-ATPase α/β, Na(+)-K(+)-2Cl-cotransporter 1 (NKCC1) and aquaporin-5 (AQP5) in eccrine sweat glands were detected by immunoperoxidase labeling. The results showed that Na(+)-K(+)-ATPase α was immunolocalized in the cell membrane of the basal layer and suprabasal layer cells of the epidermis, the basolateral membrane of the secretory coils, and the cell membrane of the outer cells and the basolateral membrane of the luminal cells of the ducts. The localization of Na(+)-K(+)-ATPase β in the secretory coils was the same as Na(+)-K(+)-ATPase α, but Na(+)-K(+)-ATPase β labeling was absent in the straight ducts and epidermis. NKCC1 labeling was seen only in the basolateral membrane of the secretory coils. AQP5 was strongly localized in the apical membrane and weakly localized in the cytoplasm of secretory epithelial cells. The different distribution of these proteins in eccrine sweat glands was related to their functions in sweat secretion and absorption.

  4. 21 CFR 868.5750 - Inflatable tracheal tube cuff.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Inflatable tracheal tube cuff. 868.5750 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5750 Inflatable tracheal tube cuff. (a) Identification. An inflatable tracheal tube cuff is a device used to provide an airtight...

  5. 21 CFR 868.5750 - Inflatable tracheal tube cuff.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Inflatable tracheal tube cuff. 868.5750 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5750 Inflatable tracheal tube cuff. (a) Identification. An inflatable tracheal tube cuff is a device used to provide an airtight...

  6. 21 CFR 868.5795 - Tracheal tube cleaning brush.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tracheal tube cleaning brush. 868.5795 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5795 Tracheal tube cleaning brush. (a) Identification. A tracheal tube cleaning brush is a device consisting of a brush with plastic bristles...

  7. 21 CFR 868.5795 - Tracheal tube cleaning brush.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tracheal tube cleaning brush. 868.5795 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5795 Tracheal tube cleaning brush. (a) Identification. A tracheal tube cleaning brush is a device consisting of a brush with plastic bristles...

  8. 21 CFR 868.5750 - Inflatable tracheal tube cuff.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Inflatable tracheal tube cuff. 868.5750 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5750 Inflatable tracheal tube cuff. (a) Identification. An inflatable tracheal tube cuff is a device used to provide an airtight...

  9. 21 CFR 868.5795 - Tracheal tube cleaning brush.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tracheal tube cleaning brush. 868.5795 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5795 Tracheal tube cleaning brush. (a) Identification. A tracheal tube cleaning brush is a device consisting of a brush with plastic bristles...

  10. 21 CFR 868.5750 - Inflatable tracheal tube cuff.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inflatable tracheal tube cuff. 868.5750 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5750 Inflatable tracheal tube cuff. (a) Identification. An inflatable tracheal tube cuff is a device used to provide an airtight...

  11. 21 CFR 868.5795 - Tracheal tube cleaning brush.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tracheal tube cleaning brush. 868.5795 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5795 Tracheal tube cleaning brush. (a) Identification. A tracheal tube cleaning brush is a device consisting of a brush with plastic bristles...

  12. 21 CFR 868.5750 - Inflatable tracheal tube cuff.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Inflatable tracheal tube cuff. 868.5750 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5750 Inflatable tracheal tube cuff. (a) Identification. An inflatable tracheal tube cuff is a device used to provide an airtight...

  13. 21 CFR 868.5795 - Tracheal tube cleaning brush.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tracheal tube cleaning brush. 868.5795 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5795 Tracheal tube cleaning brush. (a) Identification. A tracheal tube cleaning brush is a device consisting of a brush with plastic bristles...

  14. Ixeris dentata-induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells.

    PubMed

    Lee, Hwa-Young; Lee, Geum-Hwa; Kim, Hye-Kyung; Kim, Seung Hyun; Park, Kyung pyo; Chae, Han-Jung; Kim, Hyung-Ryong

    2013-12-01

    The endoplasmic reticulum (ER) is an organelle which controls synthesis of secretory and membrane proteins. Alterations in protein folding capacity, leading to ER stress, can be observed in patients with diabetes and related diseases such as xerostomia. The objectives of this study were to investigate the effects of Ixeris dentata (IXD) extract, which has been used for diabetes treatment, and compounds purified from IXD, 8-epidesacylcynaropicrin-3-O-beta-glucopyranoside (ID-57D), on amylase synthesis and secretion in human salivary gland (HSG) cells exposed to a high concentration of glucose. A high concentration of glucose in the experimental medium of cultured cells can model diabetes in vitro. IXD extracts and ID-57D increased oxidative folding-associated protein expression, including p-IRE-1α, PDI and ERO-1α, with the enhanced oxidative folding pattern seen in HSG cells transiently exposed to a high concentration of glucose. Moreover, the treatments reduced the ER stress response, such as the expression of GRP78, maintaining amylase synthesis and secretion in chronically glucose-exposed HSG cells. This study suggests the potential therapeutic value of IXD extract for the treatment of diabetes or its complications such as xerostomia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Presence of immunoreactive glucagon in healthy and diseased human thyroid. Evidence of glucagon synthesis by this gland.

    PubMed

    Menéndez-Patterson, A; Blázquez, E

    1984-06-01

    Significant amounts of immunoreactive glucagon (IRG) were determined in acid-ethanol and acid-saline extracts of human thyroid. Glucagon content of healthy thyroid, expressed as ng/g wet tissue or pg/mg protein, was significantly greater after an acid-alcohol extraction than after an acid-saline one. Furthermore IRG in acid-alcohol extracts of healthy tissue was greater than in acid alcohol extracts of diseased thyroid, while with an acid-saline procedure glucagon content was greater in the extracts of pathological tissues. No significant differences in the IRG content between calcified or follicular thyroid nodules and nodular goiter were found. Aliquots of the tissue extracts, fractionated on Bio-Gel P-30 or Sephadex G-100 columns, gave a 3,500 mol wt immunoreactive peak suggesting the existence of a polypeptide with the same size and immunological properties as pancreatic glucagon. Also, active glucagon synthesis by pieces of thyroid was established by the incorporation of L3-H-tryptophan into a 3,500 mol wt polypeptide with specific immune reaction to 30K antiserum. These results suggest that thyroid gland could represent a source of extrapancreatic glucagon in men, and therefore contribute to the circulating levels of this hormone.

  16. In vivo enhancement of chemosensitivity of human salivary gland cancer cells by overexpression of TGF-beta stimulated clone-22.

    PubMed

    Omotehara, F; Uchida, D; Hino, S; Begum, N M; Yoshida, H; Sato, M; Kawamata, H

    2000-01-01

    We have isolated transforming growth factor-beta-stimulated clone-22 (TSC-22) cDNA as an anti-cancer drug-inducible gene in a human salivary gland cancer cell line, TYS. We have previously reported that TSC-22 negatively regulates the growth of TYS cells, and that overexpression of TSC-22 protein in TYS cells enhanced the in vitro chemosensitivity of the cells. In this study, we examined the in vivo chemosensitivity of TSC-22-expressing TYS cells. TSC-22-expressing TYS cells formed tumors in nude mice, but tumors formed by TSC-22-expressing TYS cells were significantly smaller than tumors formed by control cells (p<0.001, one way ANOVA). Furthermore, intraperitoneal injection of 5-fluorouracil (5-FU) markedly inhibited the growth of the TSC-22-expressing TYS tumors, but did not affect the growth of control tumors. It was found by TUNEL assay that TSC-22-expressing TYS tumors were induced to undergo apoptosis by 5-FU treatment. These findings suggest that overexpression of TSC-22 protein in TYS cells enhances the in vivo chemosensitivity of the cells to 5-FU via induction of apoptosis.

  17. Involvement of PPARgamma in oxidative stress-mediated prostaglandin E(2) production in SZ95 human sebaceous gland cells.

    PubMed

    Zhang, Qiwei; Seltmann, Holger; Zouboulis, Christos C; Konger, Raymond L

    2006-01-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is thought to play a role in sebaceous gland cell function. We previously demonstrated in human epidermoid carcinoma KB cells that UVB irradiation activates PPARgamma via the generation of multiple oxidized glycerophosphocholine species with PPARgamma ligand activity. UVB-induced cyclooxygenase 2 (COX-2) expression was also shown to be PPARgamma-dependent. We therefore reasoned that PPARgamma activation and PPARgamma-dependent COX-2 expression may occur as a general consequence of oxidative stress. The present studies were designed to examine the effects of the oxidant tert-butylhydroperoxide (TBH) on PPARgamma activation and COX-2 expression in SZ95 sebocytes. We first verified that functional PPARgamma is expressed and activated by UVB irradiation in these cells. We next demonstrated that TBH increased PPARgamma reporter activity in SZ95 sebocytes. Increased COX-2 protein, mRNA expression, and prostaglandin E(2) (PGE(2)) production was observed after TBH or PPARgamma agonist treatment. The ability of PPARgamma agonists and TBH to induce COX-2 expression and PGE(2) production was blocked by pretreatment with the specific PPARgamma antagonist GW9662. Finally, TBH and PPARgamma agonists failed to elicit a PGE(2) response in SZ95 sebocytes stably expressing a dominant-negative PPARgamma. This study illustrates the importance of the PPARgamma system in regulating cellular responses to oxidative stress.

  18. Generation of TALE nickase-mediated gene-targeted cows expressing human serum albumin in mammary glands.

    PubMed

    Luo, Yan; Wang, Yongsheng; Liu, Jun; Cui, Chenchen; Wu, Yongyan; Lan, Hui; Chen, Qi; Liu, Xu; Quan, Fusheng; Guo, Zekun; Zhang, Yong

    2016-02-08

    Targeting exogenous genes at milk protein loci via gene-targeting technology is an ideal strategy for producing large quantities of pharmaceutical proteins. Transcription-activator-like effector (TALE) nucleases (TALENs) are an efficient genome-editing tool. However, the off-target effects may lead to unintended gene mutations. In this study, we constructed TALENs and TALE nickases directed against exon 2 of the bovine β-lactoglobulin (BLG) locus. The nickases can induce a site-specific DNA single-strand break, without inducing double-strand break and nonhomologous end joining mediated gene mutation, and lower cell apoptosis rate than TALENs. After co-transfecting the bovine fetal fibroblasts with human serum albumin (HSA) gene-targeting vector and TALE nickase expression vectors, approximately 4.8% (40/835) of the cell clones contained HSA at BLG locus. Unexpectedly, one homozygous gene-targeted cell clone (1/835, 0.1%) was obtained by targeting both alleles of BLG in a single round of transfection. The recombinant protein mimicking the endogenous BLG was highly expressed and correctly folded in the mammary glands of the targeted cows, and the expression level of HSA was significantly increased in the homozygous targeted cows. Results suggested that the combination of TALE nickase-mediated gene targeting and somatic cell nuclear transfer is a feasible and safe approach in producing gene-targeted livestock.

  19. Generation of TALE nickase-mediated gene-targeted cows expressing human serum albumin in mammary glands

    PubMed Central

    Luo, Yan; Wang, Yongsheng; Liu, Jun; Cui, Chenchen; Wu, Yongyan; Lan, Hui; Chen, Qi; Liu, Xu; Quan, Fusheng; Guo, Zekun; Zhang, Yong

    2016-01-01

    Targeting exogenous genes at milk protein loci via gene-targeting technology is an ideal strategy for producing large quantities of pharmaceutical proteins. Transcription- activator-like effector (TALE) nucleases (TALENs) are an efficient genome-editing tool. However, the off-target effects may lead to unintended gene mutations. In this study, we constructed TALENs and TALE nickases directed against exon 2 of the bovine β-lactoglobulin (BLG) locus. The nickases can induce a site-specific DNA single-strand break, without inducing double-strand break and nonhomologous end joining mediated gene mutation, and lower cell apoptosis rate than TALENs. After co-transfecting the bovine fetal fibroblasts with human serum albumin (HSA) gene-targeting vector and TALE nickase expression vectors, approximately 4.8% (40/835) of the cell clones contained HSA at BLG locus. Unexpectedly, one homozygous gene-targeted cell clone (1/835, 0.1%) was obtained by targeting both alleles of BLG in a single round of transfection. The recombinant protein mimicking the endogenous BLG was highly expressed and correctly folded in the mammary glands of the targeted cows, and the expression level of HSA was significantly increased in the homozygous targeted cows. Results suggested that the combination of TALE nickase-mediated gene targeting and somatic cell nuclear transfer is a feasible and safe approach in producing gene-targeted livestock. PMID:26853907

  20. Tracheal lipoma mimicking obstructive lung disease.

    PubMed

    Mota, Vinícius Turano; Maia, José Geraldo Soares; Barbosa, Ana Teresa Fernandes; Fernandes, Diego Franco Silveira; Rocha, Emanuelly Botelho

    2010-01-01

    Tracheal tumors are rare and can be difficult to diagnose due to their capacity to mimic other obstructive lung diseases, such as asthma and COPD. We report the case of a female patient with a tracheal tumor. She had previously been treated for asthma and COPD, with little response to the treatment. The onset of infectious complications prompted further investigation. Chest CT images suggested the presence of a tumor, which was confirmed by fiberoptic bronchoscopy. The tumor was endoscopically resected. However, the patient evolved to death due to pneumonia and septic shock.

  1. CFTR and calcium-activated chloride channels in primary cultures of human airway gland cells of serous or mucous phenotype.

    PubMed

    Fischer, Horst; Illek, Beate; Sachs, Lorne; Finkbeiner, Walter E; Widdicombe, Jonathan H

    2010-10-01

    Using cell culture models, we have investigated the relative importance of cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCC) in Cl secretion by mucous and serous cells of human airway glands. In transepithelial recordings in Ussing chambers, the CFTR inhibitor CFTR(inh)-172 abolished 60% of baseline Cl secretion in serous cells and 70% in mucous. Flufenamic acid (FFA), an inhibitor of CaCC, reduced baseline Cl secretion by ∼20% in both cell types. Methacholine and ATP stimulated Cl secretion in both cell types, which was largely blocked by treatment with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and partially by mucosal FFA or CFTR(inh)-172 with the exception of methacholine responses in mucous cells, which were not blocked by FFA and partially (∼60%) by CFTR(inh)-172. The effects of ionomycin on short-circuit current (I(sc)) were less than those of ATP or methacholine. Forskolin stimulated Cl secretion only if Cl in the mucosal medium was replaced by gluconate. In whole cell patch-clamp studies of single isolated cells, cAMP-induced Cl currents were ∼3-fold greater in serous than mucous cells. Ionomycin-induced Cl currents were 13 times (serous) or 26 times (mucous) greater than those generated by cAMP and were blocked by FFA. In serous cells, mRNA for transmembrane protein 16A (TMEM16A) was ∼10 times more abundant than mRNA for CFTR. In mucous cells it was ∼100 times more abundant. We conclude: 1) serous and mucous cells both make significant contributions to gland fluid secretion; 2) baseline Cl secretion in both cell types is mediated predominantly by CFTR, but CaCC becomes increasingly important after mediator-induced elevations of intracellular Ca; and 3) the high CaCC currents seen in patch-clamp studies and the high TMEM16A expression in intact polarized cells sheets are not reflected in transepithelial current recordings.

  2. Tamoxifen-induced adduct formation and cell stress in human endometrial glands.

    PubMed

    Andersson, Helén; Helmestam, Malin; Zebrowska, Anna; Olovsson, Matts; Brittebo, Eva

    2010-01-01

    The beneficial effects of tamoxifen in the prevention and treatment of breast cancer are compromised by an increased risk of endometrial polyps, hyperplasia, and cancer. Tamoxifen is metabolized to an array of metabolites with estrogenic effects but also to reactive intermediates that may form protein and DNA adducts. The aim of this study was to investigate cellular [(3)H]tamoxifen adduct formation by light microscopic autoradiography and cell stress by immunohistochemical analysis of glucose-regulating protein 78 (GRP78), nuclear factor kappaB (NF-kappaB), and caspase 3 in human endometrial explants after short-term incubation with tamoxifen. The cellular expression of tamoxifen-metabolizing enzymes in human endometrial biopsy samples was also determined by immunohistochemistry. The results showed selective [(3)H]tamoxifen adduct formation in glandular and surface epithelia after incubation with a nontoxic concentration of [(3)H]tamoxifen (6 nM). There was also a selective expression of the endoplasmic reticulum stress chaperone GRP78 and activated caspase 3 at these sites after incubation with cytotoxic concentrations of tamoxifen (10-100 microM). The cell stress was preferentially observed in samples from women in the proliferative menstrual phase. No treatment-related expression of NF-kappaB was observed. Constitutive expression of the tamoxifen-metabolizing enzymes CYP1B1, CYP2A6, CYP2B6, CYP2C8/9/19, CYP2D6, and SULT2A1 in glandular and surface epithelia was shown, but there was a large interindividual variation. The colocalization of [(3)H]tamoxifen adducts, expression of GRP78, caspase 3, and tamoxifen-metabolizing enzymes in human glandular and surface epithelia suggest a local bioactivation of tamoxifen at these sites and that epithelial cells are early target sites for tamoxifen-induced cell stress.

  3. Calcium-binding protein, spermatid-specific 1 is expressed in human salivary glands and contains an anti-inflammatory motif.

    PubMed

    St Laurent, Chris D; St Laurent, Katherine E; Mathison, Ron D; Befus, A Dean

    2015-04-01

    Salivary glands are involved in the production and exocrine and endocrine secretion of biologically active proteins, polypeptides, and hormones involved in growth and differentiation, homeostasis, and digestion. We have previously studied the prohormone submandibular rat 1 (SMR1), product of the Vcsa1 gene, which is highly expressed in the testes and salivary glands of rats, and can be cleaved to produce polypeptides with analgesic, erectile function, and anti-inflammatory activities. Humans lack the Vcsa1 gene, but homologous sequences and functions for analgesia and erectile function exist in the human genes Prol1, SMR3a, and SMR3b located on the human chromosomal region close to where Vcsa1 lies in the rat. Here we show the human protein calcium-binding protein spermatid-specific 1 (CABS1) contains a similar sequence to the anti-inflammatory sequence in rat SMR1, thus CABS1 may be another human gene with homologous function to Vcsa1. Using Western blot and PCR, we discovered that the human protein CABS1, previously thought to only be expressed in the testes, is also expressed in the salivary glands and lung, in a tissue-specific manner. Peptides derived from CABS1 were tested in an in vivo mouse model of lipopolysaccharide (LPS)-induced neutrophilia and an ex vivo rat model of antigen-induced intestinal anaphylaxis and significantly reduced both neutrophil accumulation in bronchoalveolar lavage fluid and antigen-induced ileal contractions, respectively. Thus human CABS1 has a peptide motif homologous to the anti-inflammatory peptide sequence of rat SMR1. Whether this similarity of CABS1 extends to the neuroendocrine regulation of the anti-inflammatory activity seen for SMR1 remains to be determined.

  4. Calcium-binding protein, spermatid-specific 1 is expressed in human salivary glands and contains an anti-inflammatory motif

    PubMed Central

    St. Laurent, Chris D.; St. Laurent, Katherine E.; Mathison, Ron D.

    2015-01-01

    Salivary glands are involved in the production and exocrine and endocrine secretion of biologically active proteins, polypeptides, and hormones involved in growth and differentiation, homeostasis, and digestion. We have previously studied the prohormone submandibular rat 1 (SMR1), product of the Vcsa1 gene, which is highly expressed in the testes and salivary glands of rats, and can be cleaved to produce polypeptides with analgesic, erectile function, and anti-inflammatory activities. Humans lack the Vcsa1 gene, but homologous sequences and functions for analgesia and erectile function exist in the human genes Prol1, SMR3a, and SMR3b located on the human chromosomal region close to where Vcsa1 lies in the rat. Here we show the human protein calcium-binding protein spermatid-specific 1 (CABS1) contains a similar sequence to the anti-inflammatory sequence in rat SMR1, thus CABS1 may be another human gene with homologous function to Vcsa1. Using Western blot and PCR, we discovered that the human protein CABS1, previously thought to only be expressed in the testes, is also expressed in the salivary glands and lung, in a tissue-specific manner. Peptides derived from CABS1 were tested in an in vivo mouse model of lipopolysaccharide (LPS)-induced neutrophilia and an ex vivo rat model of antigen-induced intestinal anaphylaxis and significantly reduced both neutrophil accumulation in bronchoalveolar lavage fluid and antigen-induced ileal contractions, respectively. Thus human CABS1 has a peptide motif homologous to the anti-inflammatory peptide sequence of rat SMR1. Whether this similarity of CABS1 extends to the neuroendocrine regulation of the anti-inflammatory activity seen for SMR1 remains to be determined. PMID:25632019

  5. Standard methods for tracheal mite research

    USDA-ARS?s Scientific Manuscript database

    This chapter, for the COLOSS Beebook from the Bee Research Center in Switzerland, summarizes all the current information about the tracheal mite (Acarapis woodi) infesting honey bees (Apis mellifera). The chapter covers the effects on bees, its life history, and its range, as well as the identifica...

  6. Optical Coherence Tomography Evaluation of Tracheal Inflammation

    DTIC Science & Technology

    2004-09-01

    0.50). A dose - response curve shows a weak correlation between the increase in mucosal thickness with dosage of S Pneumoniae inoculated (Figure 5...10000 100000 1000000 Figure 5: Dose response curve for septic tracheal mucosal thickness. DISCUSSION These studies confirm the feasibility of high

  7. Strategies for diagnosis and treatment of iatrogenic tracheal ruptures.

    PubMed

    Deja, M; Menk, M; Heidenhain, C; Spies, C D; Heymann, A; Weidemann, H; Branscheid, D; Weber-Carstens, S

    2011-12-01

    Management of tracheal ruptures in critically ill patients is challenging. Conservative treatment has been described, but in mechanically ventilated patients with distal tracheal ruptures surgical repair might be inevitable. Strategies for diagnosis and treatment of tracheal ruptures and handling of mechanical ventilation remain to be clarified. Our aim was to comprise a structured diagnostic and treatment protocol for patients suspicious of tracheal injury, including detailed principles of mechanical ventilation and specific indications for conservative or surgical treatment. Patients with tracheal ruptures were compared in accordance to the need of mechanical ventilation and to indication for surgical repair. In patients suffering from tracheal ruptures affecting the whole tracheal wall and with protrusion of mediastinal structures into the lumen surgery was indicated. We compared ventilatory, hemodynamic and clinical parameters between the different patient groups. We report our structured approach in diagnostics and treatment of tracheal ruptures and place special emphasis on respiratory management. Seventeen patients with tracheal rupture were identified. In 8 patients surgical repair was performed 1.8±1.5 days after diagnosis. Previous to surgery, ventilation parameters improved significantly: plateau pressure decreased, percentage of assisted spontaneous breathing increased and compliance improved. Conservative treatment was successful in long-term ventilated patients (13.7±8 days) even when suffering from distal lesions. Invasiveness of mechanical ventilation and obstruction of tracheal lumen might indicate conservative or surgical treatment strategies in long-term ventilated patients suffering from iatrogenic tracheal rupture. Indications for surgical repair remain to be further clarified.

  8. Role of Keratinocyte Growth Factor in the Differentiation of Sweat Gland-Like Cells From Human Umbilical Cord-Derived Mesenchymal Stem Cells

    PubMed Central

    Xu, Yongan; Hong, Yucai; Xu, Mengyan; Ma, Kui; Fu, Xiaobing

    2016-01-01

    Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have higher proliferation potency and lower immune resistance than human bone marrow MSCs and can differentiate into various functional cells. Many regulatory factors, including keratinocyte growth factor (KGF), are involved in the development of skin and cutaneous appendages. Although KGF is important in wound healing, the role of KGF in hUC-MSC differentiation remains unknown. In our previous work, we found the mixing medium (nine parts of basic sweat-gland [SG] medium plus one part of conditioned heat-shock SG medium) could induce hUC-MSC differentiation to sweat gland-like cells (SGCs). In this study, we further improved the inducing medium and determined the effects of KGF in hUC-MSC differentiation. We found KGF expression in the SGCs and that recombinant human KGF could induce hUC-MSC differentiation into SGCs, suggesting KGF plays a pivotal role in promoting hUC-MSC differentiation to SGCs. Furthermore, the SGCs differentiated from hUC-MSCs were applied to severely burned skin of the paw of an in vivo severe combined immunodeficiency mouse burn model. Burned paws treated with SGCs could regenerate functional sparse SGs 21 days after treatment; the untreated control paws could not. Collectively, these results demonstrated that KGF is a critical growth factor for SGC differentiation from hUC-MSCs and the differentiated SGCs from hUC-MSCs may have a potential therapeutic application for regeneration of destroyed SGs and injured skin. Significance There is growing evidence demonstrating a potential therapeutic application of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in injured skin. In the current study, conditioned media and chemically defined media with recombinant human keratinocyte growth factor (KGF) could induce hUC-MSC differentiation into sweat gland-like cells (SGCs). Moreover, the differentiated SGCs from hUC-MSCs could regenerate functional sparse sweat glands in a

  9. Functional effects of proinflammatory factors present in Sjögren's syndrome salivary microenvironment in an in vitro model of human salivary gland.

    PubMed

    Arce-Franco, Mayte; Dominguez-Luis, María; Pec, Martina K; Martínez-Gimeno, Carlos; Miranda, Pablo; Alvarez de la Rosa, Diego; Giraldez, Teresa; García-Verdugo, José María; Machado, José David; Díaz-González, Federico

    2017-09-19

    Primary Sjögren's syndrome (pSS) is an autoimmune exocrinopathy in which the role that the immune response plays in reducing exocrine gland function, including the glandular microenvironment of cytokines, has not been fully understood. Epithelial cells from biopsies of human parotid gland (HPG) were used to establish a model of human salivary gland in vitro. In this model, the functional consequences of several proinflammatory soluble factors present in the pSS glandular microenvironment were assessed. Stimulation with isoproterenol and calcium produced a significant increase in the basal activity of amylase in the HPG cell supernatants. Under these conditions, the presence of TNF-α and CXCL12 increased amylase mRNA cellular abundance, but reduced the amylase activity in the cell-free supernatant in a dose-dependent manner. IL-1β and IFN-γ, but not TGF-β, also diminished amylase secretion by HPG cells. These results suggest that the glandular microenvironment of cytokine, by acting post-transcriptionally, may be responsible, at least in part, for the reduced exocrine function observed in pSS patients. These data may help to a better understanding of the pathogenesis of SS, which in turn would facilitate the identification of new therapeutic targets for this disorder.

  10. Air-Q laryngeal airway for rescue and tracheal intubation.

    PubMed

    Ads, Ayman; Auerbach, Frederic; Ryan, Kelly; El-Ganzouri, Abdel R

    2016-08-01

    We report the successful use of the Air-Q laryngeal airway (Air-Q LA) as a ventilatory device and a conduit for tracheal intubation to rescue the airway in a patient with difficult airway and tracheal stenosis. This is the first case report of the device to secure the airway after two episodes of hypoxemia in the operating room and intensive care unit. Consent for submission of this case report was obtained from our institution's human studies institutional review board given that the patient died a few months after his discharge from the hospital before his personal consent could be obtained and before preparation of this report. All personal identifiers that could lead to his identification have been removed from this report. A 59-year-old man was scheduled for a flexible and rigid bronchoscopy with possible laser excision of tracheal stenosis. He had a history of hypertension, atrial fibrillation, and diabetes. Assessment of airway revealed a thyromental distance of 6.5 cm, Mallampati class II, and body weight of 110 kg. He had hoarseness and audible inspiratory/expiratory stridor with Spo2 90% breathing room air. After induction and muscle relaxation, tracheal intubation and flexible bronchoscopy were achieved without incident. The patient was then extubated and a rigid bronchoscopy was attempted but failed with Spo2 dropping to 92%; rocuronium 60 mg was given, and reintubation was accomplished with a 7.5-mm endotracheal tube. A second rigid bronchoscopy attempt failed, with Spo2 dropping to 63%. Subsequent direct laryngoscopy revealed a bloody hypopharynx. A size 4.5 Air-Q LA was placed successfully and confirmed with capnography, and Spo2 returned to 100%. The airway was suctioned through the Air-Q LA device, and the airway was secured using a fiberoptic bronchoscope to place an endotracheal tube of 7.5-mm internal diameter. The case was canceled because of edema of the upper airway from multiple attempts with rigid bronchoscopy. The patient was transported

  11. The Proteomes of Human Parotid and Submandibular/Sublingual Gland Salivas Collected as the Ductal Secretions

    PubMed Central

    Denny, Paul; Hagen, Fred K.; Hardt, Markus; Liao, Lujian; Yan, Weihong; Arellanno, Martha; Bassilian, Sara; Bedi, Gurrinder S.; Boontheung, Pinmannee; Cociorva, Daniel; Delahunty, Claire M.; Denny, Trish; Dunsmore, Jason; Faull, Kym F.; Gilligan, Joyce; Gonzalez-Begne, Mireya; Halgand, Frédéric; Hall, Steven C.; Han, Xuemei; Henson, Bradley; Hewel, Johannes; Hu, Shen; Jeffrey, Sherry; Jiang, Jiang; Loo, Joseph A.; Ogorzalek Loo, Rachel R.; Malamud, Daniel; Melvin, James E.; Miroshnychenko, Olga; Navazesh, Mahvash; Niles, Richard; Park, Sung Kyu; Prakobphol, Akraporn; Ramachandran, Prasanna; Richert, Megan; Robinson, Sarah; Sondej, Melissa; Souda, Puneet; Sullivan, Mark A.; Takashima, Jona; Than, Shawn; Wang, Jianghua; Whitelegge, Julian P.; Witkowska, H. Ewa; Wolinsky, Lawrence; Xie, Yongming; Xu, Tao; Yu, Weixia; Ytterberg, Jimmy; Wong, David T.; Yates, John R.; Fisher, Susan J.

    2009-01-01

    Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications—914 in parotid and 917 in submandibular/sublingual saliva—were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes ranging from structural functions to enzymatic/catalytic activities. As expected, the majority mapped to the extracellular and secretory compartments. An immunoblot approach was used to validate the presence in saliva of a subset of the proteins identified by mass spectrometric approaches. These experiments focused on novel constituents and proteins for which the peptide evidence was relatively weak. Ultimately, information derived from the work reported here and related published studies can be used to translate blood-based clinical laboratory tests into a format that utilizes saliva. Additionally, a catalogue of the salivary proteome of healthy individuals allows future analyses of salivary samples from individuals with oral and systemic diseases, with the goal of identifying biomarkers with diagnostic and/or prognostic value for these conditions; another possibility is the discovery of therapeutic targets. PMID:18361515

  12. Canine mammary gland tumors.

    PubMed

    Sorenmo, Karin

    2003-05-01

    The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.

  13. Association between tracheal pepsin, a reliable marker of gastric aspiration, and head of bed elevation among ventilated neonates.

    PubMed

    Garland, J S; Alex, C P; Johnston, N; Yan, J C; Werlin, S L

    2014-01-01

    To determine the frequency of tracheal pepsin in ventilated neonates and whether the angle of head elevation was associated with tracheal pepsin. Serial trachael samples (at 3, 7, 14, 21 and 28 days of ventilation) were obtained from intubated, ventilated very low birth weight infants. Presence of tracheal pepsin was determined by Western blot analysis using a specific anti-human pepsin antibody. Tracheal pepsin was detected in 35/66 (53%) of the ventilated neonates (birthweight: 798 ± 268 grams [mean ± standard deviation]). Neonates whose head elevation was in the upper quartile (≥14 degrees) during the first sampling time (day 3) were less likely (4/16 vs 9/10, P = 0.0013) to have tracheal pepsin when compared to neonates whose head elevation was in the lowest quartile (≤8 degrees). Pepsin, a marker for gastric secretion aspiration, was detected in 53% of ventilated low birth weight neonates; early elevation of the head of the bed was associated with a lower rate of tracheal pepsin.

  14. Surgical intervention strategies for congenital tracheal stenosis associated with a tracheal bronchus based on the location of stenosis.

    PubMed

    Morita, Keiichi; Yokoi, Akiko; Fukuzawa, Hiroaki; Hisamatsu, Chieko; Endo, Kosuke; Okata, Yuichi; Tamaki, Akihiko; Mishima, Yasuhiko; Oshima, Yoshihiro; Maeda, Kosaku

    2016-09-01

    The aim of this study was to determine the appropriate surgical intervention strategies for congenital tracheal stenosis (CTS) associated with a tracheal bronchus based on the location of stenosis. The medical records of 13 pediatric patients with CTS associated with a tracheal bronchus at a single institution between January 2006 and December 2015 were retrospectively reviewed. Type 1: tracheal stenosis above the right upper lobe bronchus (RULB) (n = 1). One patient underwent slide tracheoplasty and was successfully extubated. Type 2: tracheal stenosis below the RULB (n = 7). Tracheal end-to-end anastomosis was performed before 2014, and one patient failed to extubate. Posterior-anterior slide tracheoplasty was performed since 2014, and all three patients were successfully extubated. Type 3: tracheal stenosis above the RULB to the carina (n = 5). One patient underwent posterior-anterior slide tracheoplasty and was successfully extubated. Two patients with left-right slide tracheoplasty and another two patients with tracheal end-to-end anastomosis for the stenosis below the RULB could not be extubated. Tracheal end-to-end anastomosis or slide tracheoplasty can be selected for tracheal stenosis above the RULB according to the length of stenosis. Posterior-anterior slide tracheoplasty appears feasible for tracheal stenosis below the RULB or above the RULB to the carina.

  15. Anatomy, biogenesis, and regeneration of salivary glands

    PubMed Central

    Holmberg, Kyle V.; Hoffman, Matthew P.

    2014-01-01

    An overview of the anatomy and biogenesis of salivary glands is important in order to understand the physiology, functions and disorders associated with saliva. A major disorder of salivary glands is salivary hypofunction and resulting xerostomia, or dry mouth, which affects hundreds of thousands of patients per year who suffer from salivary gland diseases or undergo head and neck cancer treatment. There is currently no curative therapy for these patients. To improve these patients’ quality of life, new therapies are being developed based on findings in salivary gland cell and developmental biology. Here we discuss the anatomy and biogenesis of the major human salivary glands and the rodent submandibular gland (SMG), which has been used extensively as a research model. We also include a review of recent research on the identification and function of stem cells in salivary glands, and the emerging field of research suggesting nerves play an instructive role during development and may be essential for adult gland repair and regeneration. Understanding the molecular mechanisms involved in gland biogenesis provides a template for regenerating, repairing or reengineering diseased or damaged adult human salivary glands. We provide an overview of three general approaches currently being developed to regenerate damaged salivary tissue, including gene therapy, stem cell-based therapy, and tissue engineering. In the future, it may be that a combination of all three will be used to repair, regenerate and reengineer functional salivary glands in patients to increase the secretion of their saliva, the focus of this monograph. PMID:24862590

  16. Anatomy, biogenesis and regeneration of salivary glands.

    PubMed

    Holmberg, Kyle V; Hoffman, Matthew P

    2014-01-01

    An overview of the anatomy and biogenesis of salivary glands is important in order to understand the physiology, functions and disorders associated with saliva. A major disorder of salivary glands is salivary hypofunction and resulting xerostomia, or dry mouth, which affects hundreds of thousands of patients each year who suffer from salivary gland diseases or undergo head and neck cancer treatment. There is currently no curative therapy for these patients. To improve these patients' quality of life, new therapies are being developed based on findings in salivary gland cell and developmental biology. Here we discuss the anatomy and biogenesis of the major human salivary glands and the rodent submandibular gland, which has been used extensively as a research model. We also include a review of recent research on the identification and function of stem cells in salivary glands, and the emerging field of research suggesting that nerves play an instructive role during development and may be essential for adult gland repair and regeneration. Understanding the molecular mechanisms involved in gland biogenesis provides a template for regenerating, repairing or reengineering diseased or damaged adult human salivary glands. We provide an overview of 3 general approaches currently being developed to regenerate damaged salivary tissue, including gene therapy, stem cell-based therapy and tissue engineering. In the future, it may be that a combination of all three will be used to repair, regenerate and reengineer functional salivary glands in patients to increase the secretion of their saliva, the focus of this monograph.

  17. Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model

    PubMed Central

    2012-01-01

    Introduction Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology approach to identify disease-related gene modules and signaling pathways that overlap between humans and mice. Methods Parotid gland tissues were harvested from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies, salivary glands were harvested from C57BL/6.NOD-Aec1Aec2 mice at various times during development of pSS-like disease. RNA was analyzed with Affymetrix HG U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples. The images were processed with Affymetrix software. Weighted-gene co-expression network analysis was used to identify disease-related and functional pathways. Results Nineteen co-expression modules were identified in human parotid tissue, of which four were significantly upregulated and three were downregulated in pSS patients compared with non-pSS sicca patients and controls. Notably, one of the human disease-related modules was highly preserved in the mouse model, and was enriched with genes involved in immune and inflammatory responses. Further comparison between these two species led to the identification of genes associated with leukocyte recruitment and germinal center formation. Conclusion Our systems biology analysis of genome-wide expression data from salivary gland tissue of pSS patients and from a pSS mouse model identified common dysregulated biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis. PMID:23116360

  18. Massive aspiration past the tracheal tube cuff caused by closed tracheal suction system.

    PubMed

    Dave, Mital H; Frotzler, Angela; Madjdpour, Caveh; Koepfer, Nelly; Weiss, Markus

    2011-01-01

    Aspiration past the tracheal tube cuff has been recognized to be a risk factor for the development of ventilator-associated pneumonia (VAP). This study investigated the effect of closed tracheal suctioning on aspiration of fluid past the tracheal tube cuff in an in vitro benchtop model. High-volume low pressure tube cuffs of 7.5 mm internal diameter (ID) were placed in a 22 mm ID artificial trachea connected to a test lung. Positive pressure ventilation (PPV) with 15 cm H₂O peak inspiratory pressure and 5 cm H₂O positive end-expiratory pressure (PEEP) was used. A closed tracheal suction system (CTSS) catheter (size 14Fr) was attached to the tracheal tube and suction was performed for 5, 10, 15, or 20 seconds under 200 or 300 cm H₂O suction pressures. Amount of fluid (mL) aspirated along the tube cuff and the airway pressure changes were recorded for each suction procedure. Fluid aspiration during different suction conditions was compared using Kruskal-Wallis and Mann-Whitney test (Bonferroni correction [α = .01]). During 10, 15, and 20 seconds suction, airway pressure consistently dropped down to -8 to -13 cm H₂O (P < .001) from the preset level. Fluid aspiration was never observed under PPV + PEEP but occurred always during suctioning. Aspiration along the tube cuff was higher with -300 cm H₂O than with -200 cm H₂O suction pressure (P < .001) and was much more during 15 and 20 seconds suction time as compared to 5 seconds (P < .001). Massive aspiration of fluid occurs along the tracheal tube cuff during suction with the closed tracheal suction system. © SAGE Publications 2011.

  19. Tumor necrosis factor-alpha enhances neutrophil adhesiveness: induction of vascular cell adhesion molecule-1 via activation of Akt and CaM kinase II and modifications of histone acetyltransferase and histone deacetylase 4 in human tracheal smooth muscle cells.

    PubMed

    Lee, Chiang-Wen; Lin, Chih-Chung; Luo, Shue-Fen; Lee, Hui-Chun; Lee, I-Ta; Aird, William C; Hwang, Tsong-Long; Yang, Chuen-Mao

    2008-05-01

    Up-regulation of vascular cell adhesion molecule-1 (VCAM-1) involves adhesions between both circulating and resident leukocytes and the human tracheal smooth muscle cells (HTSMCs) during airway inflammatory reaction. We have demonstrated previously that tumor necrosis factor (TNF)-alpha-induced VCAM-1 expression is regulated by mitogen-activated protein kinases, nuclear factor-kappaB, and p300 activation in HTSMCs. In addition to this pathway, phosphorylation of Akt and CaM kinase II has been implicated in histone acetyltransferase and histone deacetylase 4 (HDAC4) activation. Here, we investigated whether these different mechanisms participated in TNF-alpha-induced VCAM-1 expression and enhanced neutrophil adhesion. TNF-alpha significantly increased HTSMC-neutrophil adhesions, and this effect was associated with increased expression of VCAM-1 on the HTSMCs and was blocked by the selective inhibitors of Src [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1)], epidermal growth factor receptor [EGFR; 4-(3'-chloroanilino)-6,7-dimethoxy-quinazoline, (AG1478)], phosphatidylinositol 3-kinase (PI3K) [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride(LY294002) and wortmannin],calcium[1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester; BAPTA-AM], phosphatidylinositol-phospholipase C (PLC) [1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122)], protein kinase C (PKC) [12-(2-cyanoethyl)-6,7,12, 13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (Gö6976), rottlerin, and 3-1-[3-(amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl) maleimide (bisindolylmaleimide IX) (Ro 31-8220)], CaM (calmidazolium chloride), CaM kinase II [(8R(*),9S(*),11S(*))-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3,9, 10-tetrahydro-8,11-epoxy, 1H,8H, 11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one (KT5926) and 1-[N,O-bis(5-isoquinolinesulfonyl

  20. Identification of cholinergic chemosensory cells in mouse tracheal and laryngeal glandular ducts.

    PubMed

    Krasteva-Christ, G; Soultanova, A; Schütz, B; Papadakis, T; Weiss, C; Deckmann, K; Chubanov, V; Gudermann, T; Voigt, A; Meyerhof, W; Boehm, U; Weihe, E; Kummer, W

    2015-11-01

    Specialized epithelial cells in the respiratory tract such as solitary chemosensory cells and brush cells sense the luminal content and initiate protective reflexes in response to the detection of potentially harmful substances. The majority of these cells are cholinergic and utilize the canonical taste signal transduction cascade to detect "bitter" substances such as bacterial quorum sensing molecules. Utilizing two different mouse strains reporting expression of choline acetyltransferase (ChAT), the synthesizing enzyme of acetylcholine (ACh), we detected cholinergic cells in the submucosal glands of the murine larynx and trachea. These cells were localized in the ciliated glandular ducts and were neither found in the collecting ducts nor in alveolar or tubular segments of the glands. ChAT expression in tracheal gland ducts was confirmed by in situ hybridization. The cholinergic duct cells expressed the brush cell marker proteins, villin and cytokeratin-18, and were immunoreactive for components of the taste signal transduction cascade (Gα-gustducin, transient receptor potential melastatin-like subtype 5 channel = TRPM5, phospholipase C(β2)), but not for carbonic anhydrase IV. Furthermore, these cells expressed the bitter taste receptor Tas2r131, as demonstrated utilizing an appropriate reporter mouse strain. Our study identified a previously unrecognized presumptive chemosensory cell type in the duct of the airway submucosal glands that likely utilizes ACh for paracrine signaling. We propose that these cells participate in infection-sensing mechanisms and initiate responses assisting bacterial clearance from the lower airways.

  1. Expression and secretion of human proinsulin-B10 from mouse salivary glands: implications for the treatment of type I diabetes mellitus.

    PubMed

    Rowzee, Anne M; Perez-Riveros, Paola J; Zheng, Changyu; Krygowski, Sarah; Baum, Bruce J; Cawley, Niamh X

    2013-01-01

    Adenovirus (Ad) mediated expression of therapeutic proteins from salivary glands can result in the delivery of biologically active proteins into the circulation where they impart their physiological function. In recent years, Ad vector delivery to salivary glands (SGs) has emerged as a viable option for gene therapy. Here, we engineered a variant of human proinsulin (hProinsulin-B10) into an Ad vector and demonstrated its ability to transduce cell lines, and express a bioactive protein that induces the phosphorylation of AKT, a key insulin signaling molecule. We also examined its expression in mice following delivery of the vector to the parotid gland (PTG), the submandibular gland (SMG) or to the liver via the tail vein and assessed transgenic protein expression and vector containment for each delivery method. In all cases, hProinsulin-B10 was expressed and secreted into the circulation. Lower levels of circulating hProinsulin-B10 were obtained from the PTG while higher levels were obtained from the tail vein and the SMG; however, vector particle containment was best when delivered to the SMG. Expression of hProinsulin-B10 in the SMG of chemically induced diabetic mice prevented excessive hyperglycemia observed in untreated mice. These results demonstrate that hProinsulin-B10 can be expressed and secreted into the circulation from SGs and can function physiologically in vivo. The ability to remediate a diabetic phenotype in a model of type 1 diabetes mellitus is the first step in an effort that may lead to a possible therapy for diabetes.

  2. Salivary gland biopsy

    MedlinePlus

    Biopsy - salivary gland ... You have several pairs of salivary glands that drain into your mouth: A major pair in front of the ears (parotid glands) Another major pair beneath your jaw (submandibular ...

  3. Thymus Gland Anatomy

    MedlinePlus

    ... historical Searches are case-insensitive Thymus Gland, Adult, Anatomy Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Thymus Gland, Adult, Anatomy Description: Anatomy of the thymus gland; drawing shows ...

  4. Adrenal Gland Disorders

    MedlinePlus

    ... adrenal gland disorders include Genetic mutations Tumors including pheochromocytomas Infections A problem in another gland, such as the pituitary, which helps to regulate the adrenal gland Certain medicines Treatment depends on which problem you have. Surgery or ...

  5. Adrenal Gland Tumors: Statistics

    MedlinePlus

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  6. Relationship Between Adverse Tracheal Intubation Associated Events and PICU Outcomes.

    PubMed

    Parker, Margaret M; Nuthall, Gabrielle; Brown, Calvin; Biagas, Katherine; Napolitano, Natalie; Polikoff, Lee A; Simon, Dennis; Miksa, Michael; Gradidge, Eleanor; Lee, Jan Hau; Krishna, Ashwin S; Tellez, David; Bird, Geoffrey L; Rehder, Kyle J; Turner, David A; Adu-Darko, Michelle; Nett, Sholeen T; Derbyshire, Ashley T; Meyer, Keith; Giuliano, John; Owen, Erin B; Sullivan, Janice E; Tarquinio, Keiko; Kamat, Pradip; Sanders, Ronald C; Pinto, Matthew; Bysani, G Kris; Emeriaud, Guillaume; Nagai, Yuki; McCarthy, Melissa A; Walson, Karen H; Vanderford, Paula; Lee, Anthony; Bain, Jesse; Skippen, Peter; Breuer, Ryan; Tallent, Sarah; Nadkarni, Vinay; Nishisaki, Akira

    2017-04-01

    Tracheal intubation in PICUs is a common procedure often associated with adverse events. The aim of this study is to evaluate the association between immediate events such as tracheal intubation associated events or desaturation and ICU outcomes: length of stay, duration of mechanical ventilation, and mortality. Prospective cohort study with 35 PICUs using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children: NEAR4KIDS) from January 2013 to June 2015. Desaturation defined as Spo2 less than 80%. PICUs participating in NEAR4KIDS. All patients less than18 years of age undergoing primary tracheal intubations with ICU outcome data were analyzed. Five thousand five hundred four tracheal intubation encounters with median 108 (interquartile range, 58-229) tracheal intubations per site. At least one tracheal intubation associated event was reported in 892 (16%), with 364 (6.6%) severe tracheal intubation associated events. Infants had a higher frequency of tracheal intubation associated event or desaturation than older patients (48% infants vs 34% for 1-7 yr and 18% for 8-17 yr). In univariate analysis, the occurrence of tracheal intubation associated event or desaturation was associated with a longer mechanical ventilation (5 vs 3 d; p < 0.001) and longer PICU stay (14 vs 11 d; p < 0.001) but not with PICU mortality. The occurrence of severe tracheal intubation associated events was associated with longer mechanical ventilation (5 vs 4 d; p < 0.003), longer PICU stay (15 vs 12 d; p < 0.035), and PICU mortality (19.9% vs 9.6%; p < 0.0001). In multivariable analyses, the occurrence of tracheal intubation associated event or desaturation was significantly associated with longer mechanical ventilation (+12%; 95% CI, 4-21%; p = 0.004), and severe tracheal intubation associated events were independently associated with increased PICU mortality (OR = 1.80; 95% CI, 1.24-2.60; p = 0.002), after adjusted for patient

  7. [Video laryngoscopic tracheal intubation under sedation].

    PubMed

    Masquère, P; Lonjaret, L; Fourcade, O; Minville, V

    2013-05-01

    We report a video laryngoscopic tracheal intubation under sedation in a patient with a hip fracture. Preoperative assessment revealed signs of difficult airway management linked to a cervical spine immobilization. Here we describe an alternative method to awake fiber optic flexible intubation. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  8. [Surgery of traumatic tracheal and tracheobronchial injuries].

    PubMed

    Palade, E; Passlick, B

    2011-02-01

    Tracheal injuries are altogether rare events and can be divided into three broad categories: tracheobronchial injuries caused by external violence, iatrogenic ruptures of the trachea and inhalation trauma. Successful management of tracheobronchial injuries requires a fast and straightforward diagnostic evaluation. In all severely injured patients with cervicothoracic involvement an injury of the tracheobronchial system should be actively excluded. Although it is commonly agreed that posttraumatic injuries require surgical intervention the management of iatrogenic injuries is presently shifting towards a more conservative treatment.

  9. Tolerance Following Organophosphate Poisoning of Tracheal Muscle

    DTIC Science & Technology

    1984-12-13

    tracheal function. Bronchoconstriction can be elicited in dogs by stimulation of the cervical branch vagus nerve (1,2,3), This effect appears to be...Widdicombe. The effect of vagotomy» vagal cooling and efferent vagal stimulation on breathing and lung mechanics of rabbits. J. Physiol. London...respect to [?H]QNB and tissue concentrations and was time- and pH-dependent. The association of [pH]QNE (180 pM) with the muscarinic receptors

  10. A rare complication of tracheal intubation

    PubMed Central

    Shukeri, Wan Fadzlina Wan Muhd; Hassan, Wan Mohd Nazaruddin Wan; Nadarajan, Chandran

    2016-01-01

    Accidental endobronchial intubation is a frequent complication in critically ill patients requiring tracheal intubation (TI). If such complication occurs, it is more often the right main bronchus that is intubated due to anatomical reasons. Left main bronchus (LMB) intubation is rare. Here, we report a case with auscultatory, bronchoscopic, and radiographic evidence of accidental LMB intubation in a pregnant woman with dengue shock syndrome. We highlight this case to increase awareness about this possible-but-rare complication of TI. PMID:27275080

  11. Recurred Post-intubation Tracheal Stenosis Treated with Bronchoscopic Cryotherapy

    PubMed Central

    Jung, Ye-Ryung; Taek Jeong, Joon; Kyu Lee, Myoung; Kim, Sang-Ha; Joong Yong, Suk; Jeong Lee, Seok; Lee, Won-Yeon

    2016-01-01

    Post-intubation tracheal stenosis accounts for the greatest proportion of whole-cause tracheal stenosis. Treatment of post-intubation tracheal stenosis requires a multidisciplinary approach. Surgery or an endoscopic procedure can be used, depending on the type of stenosis. However, the efficacy of cryotherapy in post-intubation tracheal stenosis has not been validated. Here, we report a case of recurring post-intubation tracheal stenosis successfully treated with bronchoscopic cryotherapy that had previously been treated with surgery. In this case, cryotherapy was effective in treating web-like fibrous stenosis, without requiring more surgery. Cryotherapy can be considered as an alternative or primary treatment for post-intubation tracheal stenosis. PMID:27853078

  12. Tracheal stenosis in a blue-billed currasow (Crax alberti).

    PubMed

    Evans, Alina; Atkins, Adrienne; Citino, Scott B

    2009-06-01

    A blue-billed curassow (Crax alberti) was anesthetized for a preshipment physical exam. Sixteen days later, the curassow presented with acute onset of dyspnea and respiratory stridor. The bird was stabilized by placement of an air sac canula. Tracheal stenosis was diagnosed with radiographs. It was suspected that the tracheal stenosis was due to trauma from a previous endotracheal tube placement. A tracheal resection and anastomosis was performed. Three days postoperatively the air sac canula was removed. Although there were increased respiratory sounds, the trachea had not completely restrictured. Ten months later, the currasow presented for dyspnea and died shortly thereafter. There was mycotic airsacculitis with Aspergillus organisms present. Tracheal stenosis in birds after tracheal intubation is a frequently discussed condition with very little published material available. This report describes a case of tracheal stenosis postintubation and the surgical treatment and subsequent complications that followed.

  13. Surgical Reconstruction for Severe Tracheal Obstruction in Morquio A Syndrome.

    PubMed

    Pizarro, Christian; Davies, Ryan R; Theroux, Mary; Spurrier, Ellen A; Averill, Lauren W; Tomatsu, Shunji

    2016-10-01

    Progressive tracheal obstruction is commonly seen in Morquio A syndrome and can lead to life-threatening complications. Although tracheostomy can address severe upper airway obstruction, lower airway obstruction, commonly associated with a narrow thoracic inlet and vascular compression, requires an alternative approach. We describe the case of a 16-year-old patient with Morquio A syndrome whose near-fatal tracheal obstruction was relieved by timely surgical tracheal vascular reconstruction with dramatic resolution of his respiratory symptoms.

  14. Heat Tolerance and the Peripheral Effects of Anticholinergics. 1. A Non-Invasive Method for Estimating the Cholinergic Sensitivity of the Eccrine Glands in Humans.

    DTIC Science & Technology

    1985-01-30

    used as sensitive index of anticholiinergic drug potency. Independently, we developed 1 human sweat gland assayd d+ fftf -ng from theirs in several...derived from an assembly of 4 evaporative capsules with .pecially designed electronics, is our primary measurement [3]. Sweat counts are determined on...can be defined. Apparatus. The anode assembly consists of a machined 11.5 cm x 3.7 cm PlexigTas block containing four 0.9 cm D Ag/AgCl buttons removed

  15. Tracheal intubation with a camera embedded in the tube tip (Vivasight(™) ).

    PubMed

    Huitink, J M; Koopman, E M; Bouwman, R A; Craenen, A; Verwoert, M; Krage, R; Visser, I E; Erwteman, M; van Groeningen, D; Tijink, R; Schauer, A

    2013-01-01

    We studied tracheal intubation in manikins and patients with a camera embedded in the tip of the tracheal tube (Vivasight(™) ). Four people in two teams and two individuals attempted intubation of a manikin through an i-gel(™) 10 times each. The tracheas of 12 patients with a Mallampati grade of 1 were intubated with a Vivasight tracheal tube through a Berman airway, passed over a Frova(™) introducer. All 60 manikin intubations were successful, taking a mean (SD) time of 1.4 (0.5) s. The fastest intubation was performed in 0.5 s. All 12 participants' tracheas were successfully intubated in a median (IQR [range]) time of 90 (70-120 [50-210]) s. Seven participants complained of a sore throat, comparable with earlier findings for standard laryngoscopy and intubation: five mild; one moderate; and one severe. Tracheal intubation with the Vivasight through the i-gel or Berman airway is an alternative to existing techniques, against which it should be compared in randomised controlled trials in human participants. It has potential as a fast airway rescue technique.

  16. Complete tracheal rupture after a failed suicide attempt.

    PubMed

    Costache, Victor S; Renaud, Claire; Brouchet, Laurent; Toma, Tudor; Le Balle, François; Berjaud, Jean; Dahan, Marcel

    2004-04-01

    Tracheal rupture is life-threatening and its management poses a considerable challenge to both anesthesiologists and surgeons. We report the case of a 44-year-old patient with a complete tracheal rupture after a failed suicide attempt by hanging. A rare bilateral injury of the laryngeal nerves was associated. An original tracheal intubation was performed using the video unit for thoracoscopy. The severity of the lesions required the placement of a tracheostomy cannula after the tracheal repair. The postoperative course was uneventful. The patient was discharged on the 12th day, with a remaining moderate dysphonia.

  17. Endodermal Wnt signaling is required for tracheal cartilage formation.

    PubMed

    Snowball, John; Ambalavanan, Manoj; Whitsett, Jeffrey; Sinner, Debora

    2015-09-01

    Tracheobronchomalacia is a common congenital defect in which the walls of the trachea and bronchi lack of adequate cartilage required for support of the airways. Deletion of Wls, a cargo receptor mediating Wnt ligand secretion, in the embryonic endoderm using ShhCre mice inhibited formation of tracheal-bronchial cartilaginous rings. The normal dorsal-ventral patterning of tracheal mesenchyme was lost. Smooth muscle cells, identified by Acta2 staining, were aberrantly located in ventral mesenchyme of the trachea, normally the region of Sox9 expression in cartilage progenitors. Wnt/β-catenin activity, indicated by Axin2 LacZ reporter, was decreased in tracheal mesenchyme of Wls(f/f);Shh(Cre/+) embryos. Proliferation of chondroblasts was decreased and reciprocally, proliferation of smooth muscle cells was increased in Wls(f/f);Shh(Cre/+) tracheal tissue. Expression of Tbx4, Tbx5, Msx1 and Msx2, known to mediate cartilage and muscle patterning, were decreased in tracheal mesenchyme of Wls(f/f);Shh(Cre/+) embryos. Ex vivo studies demonstrated that Wnt7b and Wnt5a, expressed by the epithelium of developing trachea, and active Wnt/β-catenin signaling are required for tracheal chondrogenesis before formation of mesenchymal condensations. In conclusion, Wnt ligands produced by the tracheal epithelium pattern the tracheal mesenchyme via modulation of gene expression and cell proliferation required for proper tracheal cartilage and smooth muscle differentiation.

  18. Endodermal Wnt signaling is required for tracheal cartilage formation

    PubMed Central

    Snowball, John; Ambalavanan, Manoj; Whitsett, Jeffrey; Sinner, Debora

    2015-01-01

    Tracheobronchomalacia is a common congenital defect in which the walls of the trachea and bronchi lack of adequate cartilage required for support of the airways. Deletion of Wls, a cargo receptor mediating Wnt ligand secretion, in the embryonic endoderm using ShhCre mice inhibited formation of tracheal-bronchial cartilaginous rings. The normal dorsal-ventral patterning of tracheal mesenchyme was lost. Smooth muscle cells, identified by Acta2 staining, were aberrantly located in ventral mesenchyme of the trachea, normally the region of Sox9 expression in cartilage progenitors. Wnt/β-catenin activity, indicated by Axin2 LacZ reporter, was decreased in tracheal mesenchyme of Wlsf/f;ShhCre/+ embryos. Proliferation of chondroblasts was decreased and reciprocally, proliferation of smooth muscle cells was increased in Wlsf/f;ShhCre/+ tracheal tissue. Expression of Tbx4, Tbx5, Msx1 and Msx2, known to mediate cartilage and muscle patterning, were decreased in tracheal mesenchyme of Wlsf/f;ShhCre/+ embryos. Ex vivo studies demonstrated that Wnt7b and Wnt5a, expressed by the epithelium of developing trachea, and active Wnt/β-catenin signaling are required for tracheal chondrogenesis before formation of mesenchymal condensations. In conclusion, Wnt ligands produced by the tracheal epithelium pattern the tracheal mesenchyme via modulation of gene expression and cell proliferation required for proper tracheal cartilage and smooth muscle differentiation. PMID:26093309

  19. Tracheal bronchus: a cause of prolonged atelectasis in intubated children.

    PubMed

    O'Sullivan, B P; Frassica, J J; Rayder, S M

    1998-02-01

    Tracheal bronchus is a common anomaly that occurs in approximately 2% of people. Two children with multiple medical problems which led to endotracheal intubation are described. The hospital course for each child was complicated by persistent right upper lobe atelectasis. The presence of a tracheal bronchus was not recognized in either case initially; identification of this anatomic variant allowed appropriate changes in airway management. The potential for tracheal bronchus to cause, or be associated with, localized pulmonary problems is reviewed. The diagnosis of tracheal bronchus should be considered early in the course of intubated patients with right upper lobe complications.

  20. The effect of decellularization of tracheal allografts on leukocyte infiltration and of recellularization on regulatory T cell recruitment.

    PubMed

    Haykal, Siba; Zhou, Yingzhe; Marcus, Paula; Salna, Michael; Machuca, Tiago; Hofer, Stefan O P; Waddell, Thomas K

    2013-07-01

    Tracheal transplantation without immunosuppressive therapy has been accomplished with a tissue-engineering approach using decellularized biological scaffolds in combination with recipient progenitor cells. The mechanisms of immune response directed towards these tracheal allografts have not been fully determined. In this study, we evaluated the immunogenicity of these grafts at the protein level, and functionally, in vitro and in vivo in a large animal model. Long-segment circumferential tracheal allografts were decellularized using two different protocols and recellularized using recipient mesenchymal stromal cells (MSC) and tracheal epithelial progenitor cells (TEC). Residual MHCI and MHCII immunostaining was found surrounding the submucosal glands despite cyclical decellularization. In an in vitro lymphocyte proliferation assay, CD4+ T cells continued to proliferate on decellularized pieces and this proliferation was inhibited by co-culture with autologous MSC. Allografts were heterotopically transplanted under a muscle flap in the neck of the recipients and decellularization was found to delay leukocyte infiltration but resulted in eventual cartilage degradation. Recellularization prevented this infiltration up to 3 weeks post-transplantation and allowed for preservation of the cartilage. The immune cells found within these grafts included a significant number of CD4+CD25+Foxp3+ regulatory T cells. Furthermore, gene expression of anti-inflammatory cytokines, such as IL-10 and TGF-β1, involved in proliferation, differentiation and function of regulatory T cells was found in these grafts. These results indicate that the immunological modification induced by recellularized tracheal scaffolds is an active process involving the recruitment of immunosuppressive cells, rather than simply the removal of donor-derived antigenic components.

  1. Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods.

    PubMed

    Nagahashi, Masayuki; Yamada, Akimitsu; Miyazaki, Hiroshi; Allegood, Jeremy C; Tsuchida, Junko; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P; Adams, Barbara J; Rashid, Omar M; Milstien, Sheldon; Wakai, Toshifumi; Spiegel, Sarah; Takabe, Kazuaki

    2016-06-01

    The tumor microenvironment is a determining factor for cancer biology and progression. Sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphKs), is a bioactive lipid mediator that regulates processes important for cancer progression. Despite its critical roles, the levels of S1P in interstitial fluid (IF), an important component of the tumor microenvironment, have never previously been measured due to a lack of efficient methods for collecting and quantifying IF. The purpose of this study is to clarify the levels of S1P in the IF from murine mammary glands and its tumors utilizing our novel methods. We developed an improved centrifugation method to collect IF. Sphingolipids in IF, blood, and tissue samples were measured by mass spectrometry. In mice with a deletion of SphK1, but not SphK2, levels of S1P in IF from the mammary glands were greatly attenuated. Levels of S1P in IF from mammary tumors were reduced when tumor growth was suppressed by oral administration of FTY720/fingolimod. Importantly, sphingosine, dihydro-sphingosine, and S1P levels, but not dihydro-S1P, were significantly higher in human breast tumor tissue IF than in the normal breast tissue IF. To our knowledge, this is the first reported S1P IF measurement in murine normal mammary glands and mammary tumors, as well as in human patients with breast cancer. S1P tumor IF measurement illuminates new aspects of the role of S1P in the tumor microenvironment.

  2. Pit-1/growth hormone factor 1 splice variant expression in the rhesus monkey pituitary gland and the rhesus and human placenta.

    PubMed

    Schanke, J T; Conwell, C M; Durning, M; Fisher, J M; Golos, T G

    1997-03-01

    We have examined the expression of Pit-1 messenger RNA (mRNA) splice variants in the nonhuman primate pituitary and in rhesus and human placenta. Full-length complementary DNAs (cDNAs) representing Pit-1 and the Pit-1 beta splice variants were cloned from a rhesus monkey pituitary cDNA library and were readily detectable by RT-PCR with rhesus pituitary gland RNA. The Pit-1T variant previously reported in mouse pituitary tumor cell lines was not detectable in normal rhesus pituitary tissue, although two novel splice variants were detected. A cDNA approximating the rat Pit-1 delta 4 variant was cloned but coded for a truncated and presumably nonfunctional protein. Only by using a nested RT-PCR approach were Pit-1 and Pit-1 beta variants consistently detectable in both human and rhesus placental tissue. The Pit-1 beta variant mRNA was not detectable in JEG-3 choriocarcinoma cells unless the cells were stimulated with 8-Br-cAMP. Immunoblot studies with nuclear extracts from primary rhesus syncytiotrophoblast cultures or JEG-3 choriocarcinoma cells indicated that although mRNA levels were very low, Pit-1 protein was detectable in differentiated cytotrophoblasts, and levels increased after treatment with 8-Br-cAMP. Two major species of Pit-1 protein were detected that corresponded to the two major bands in rat pituitary GH3 cell nuclear extracts. Low levels of slightly larger bands also were seen, which may represent Pit-1 beta protein or phosphorylated species. We conclude that Pit-1 splice variants expressed in the primate pituitary gland differ from those in the rodent gland and that the Pit-1 and Pit-1 beta mRNAs expressed in the placenta give rise to a pattern of protein expression similar to that seen in pituitary cells, which is inducible by treatment with 8-Br-cAMP.

  3. In vivo readout of CFTR function: ratiometric measurement of CFTR-dependent secretion by individual, identifiable human sweat glands.

    PubMed

    Wine, Jeffrey J; Char, Jessica E; Chen, Jonathan; Cho, Hyung-Ju; Dunn, Colleen; Frisbee, Eric; Joo, Nam Soo; Milla, Carlos; Modlin, Sara E; Park, Il-Ho; Thomas, Ewart A C; Tran, Kim V; Verma, Rohan; Wolfe, Marlene H

    2013-01-01

    To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (~50) individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer that contained dispersed, water soluble dye particles that partitioned into the sweat bubbles, making them highly visible. CFTR-independent secretion (M-sweat) was stimulated with methacholine, which binds to muscarinic receptors and elevates cytosolic calcium. CFTR-dependent secretion (C-sweat) was stimulated with a β-adrenergic cocktail that elevates cytosolic cAMP while blocking muscarinic receptors. A C-sweat/M-sweat ratio was determined on a gland-by-gland basis to compensate for differences unrelated to CFTR function, such as gland size. The average ratio provides an approximately linear readout of CFTR function: the heterozygote ratio is ~0.5 the control ratio and for CF subjects the ratio is zero. During assay development, we measured C/M ratios in 6 healthy controls, 4 CF heterozygotes, 18 CF subjects and 4 subjects with 'CFTR-related' conditions. The assay discriminated all groups clearly. It also revealed consistent differences in the C/M ratio among subjects within groups. We hypothesize that these differences reflect, at least in part, levels of CFTR expression, which are known to vary widely. When C-sweat rates become very low the C/M ratio also tended to decrease; we hypothesize that this nonlinearity reflects ductal fluid absorption. We also discovered that M-sweating potentiates the subsequent C-sweat response. We then used potentiation as a surrogate for drugs that can increase CFTR-dependent secretion. This bioassay provides an additional method for assessing CFTR function in vivo, and is well suited for within-subject tests of systemic, CFTR-directed therapeutics.

  4. Peroxisome proliferator-activated receptor gamma in the human pituitary gland: expression and splicing pattern in adenomas versus normal pituitary.

    PubMed

    Occhi, G; Albiger, N; Berlucchi, S; Gardiman, M; Scanarini, M; Scienza, R; Fassina, A; Mantero, F; Scaroni, C

    2007-07-01

    Pituitary adenomas are slow-growing tumours arising within the pituitary gland. If secreting, they give rise to well-known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARgamma in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real-time polymerase chain reaction, PPARgamma was expressed as much in adrenocorticotrophic hormone (ACTH)-secreting and ACTH-silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARgamma detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARgamma expression in approximately one-half of analysed samples. The intra- and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARgamma-ligand treatment. Moreover, the higher level of PPARgamma expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients.

  5. Isolation of differentially expressed cDNAs during ferret tracheal development: application of differential display PCR.

    PubMed

    Sehgal, A; Presente, A; Dudus, L; Engelhardt, J F

    1996-01-01

    The technique of differential display polymerase chain reaction (DD-PCR) was used to identify cDNA sequences, which are temporally expressed during ferret tracheal airway development. Such differentially expressed cDNAs may ultimately prove to be useful markers in elucidating mechanisms of epithelial differentiation and submucosal gland development in the airway. Using two sets of oligonucleotide primers 15 differentially amplified cDNAs were isolated by comparative reverse transcriptase (RT) PCR of 6-h and 3-day postnatal tracheal poly-A mRNA. In situ hybridization was used to assess the reliability of this method and confirm the differential mRNA expression patterns of cloned cDNAs. Results of in situ hybridization analysis demonstrated that 10 of the 15 cDNA sequences gave a temporally regulated pattern of expression, which was concordant with that of the differential display. Furthermore, sequence analysis of the 15 isolated cDNAs revealed that the majority of clones were amplified from two inverted decamer primers. These findings demonstrate the lack of poly-T priming in the differential display reaction, which suggests that this method may yield substantially more information regarding the coding sequence of cloned genes. In support of this observation, 6 of the 15 cDNA sequences contained one complete open reading frame. Although the majority of cDNAs demonstrated no homology to sequence data bases at the DNA or amino acid level, clone FT-4, which demonstrated a differential expression pattern limited to 3-day tracheal time points, was composed of a 10-amino acid repeat domain that was structurally similar to neuropeptide anthoRFamide and barley D hordein seed protein. A second interesting clone, FT-3, demonstrated an infrequent pattern of expression within a subset of epithelial cells limited to early developmental time points (6 h) and was dramatically reduced by 3 days postnatally. Several additional clones with no homologies to previously cloned genes

  6. Pepsin, a marker of gastric contents, is increased in tracheal aspirates from preterm infants who develop bronchopulmonary dysplasia.

    PubMed

    Farhath, Sabeena; He, Zhaoping; Nakhla, Tarek; Saslow, Judy; Soundar, Sam; Camacho, Jeanette; Stahl, Gary; Shaffer, Stephen; Mehta, Devendra I; Aghai, Zubair H

    2008-02-01

    The objective of this study was to study the association between pepsin in tracheal aspirate samples and the development of bronchopulmonary dysplasia in preterm infants. Serial tracheal aspirate samples were collected during the first 28 days from mechanically ventilated preterm neonates. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen at 36 weeks' postmenstrual age. An enzymatic assay with a fluorescent substrate was used to detect pepsin. Total protein was measured by the Bradford assay to correct for the dilution during lavage. Immunohistochemistry using antibody against human pepsinogen was performed in 10 lung tissue samples from preterm infants. A total of 256 tracheal aspirate samples were collected from 59 preterm neonates. Pepsin was detected in 234 (91.4%) of 256 of the tracheal aspirate samples. Twelve infants had no bronchopulmonary dysplasia, 31 infants developed bronchopulmonary dysplasia, and 16 infants died before 36 weeks' postmenstrual age. The mean pepsin concentration was significantly lower in infants with no bronchopulmonary dysplasia compared with those who developed bronchopulmonary dysplasia or developed bronchopulmonary dysplasia/died before 36 weeks' postmenstrual age. Moreover, the mean pepsin level was significantly higher in infants with severe bronchopulmonary dysplasia compared with moderate bronchopulmonary dysplasia. The mean pepsin level in tracheal aspirate samples from the first 7 days was also lower in infants with no bronchopulmonary dysplasia compared with those who developed bronchopulmonary dysplasia or developed bronchopulmonary dysplasia/died before 36 weeks' postmenstrual age. Pepsinogen was not localized in the lung tissues by immunohistochemistry. The concentration of pepsin was increased in the tracheal aspirate of preterm infants who developed bronchopulmonary dysplasia or died before 36 weeks' postmenstrual age. Recovery of pepsin in tracheal aspirate samples is secondary to gastric

  7. [Carbon-carbon materials and composites for experimental tracheal reconstruction].

    PubMed

    Liu, Xin; Jiang, Zhao-yang; Qin, Yong

    2010-08-01

    The Carbon fiber reinforced carbon matrix composites were employed for reconstruction of large circumferential defect of the cervical trachea. The biocompatibility and biofunctionality of the new type carbonaceous tracheal prosthesis were evaluated, and the feasibility for cervical tracheal reconstruction discussed. Two types of carbonaceous tracheal prosthesis with different weaving methods of carbon fiber were used on eight healthy canines. Three to six tracheal cartilage rings were resected circumferentially. The 2 cm long tracheal prosthesis was transplanted into canines and the anastomosis was completed by end-to-end, tracheal-into-prosthesis and prosthesis-into-tracheal method. The function of breathing, eating and infection was observed after surgery. Four months later, the five survival canines were sacrificed and the prosthesis with surrounding tissues was removed for observation by optical microscopy and scanning electron microscopy. All dogs had cough symptom in different degree lasted 1 - 4 weeks after surgery. Two dogs with tracheal-into-prosthesis anastomosis showed eating disorders in different degree. One canine died due to airway obstruction caused by dislocation of prosthesis within three weeks after operation. Another two deaths in 11th week and 12th week were attributed to suffocation because of hypergranulation and scar formation. Prosthesis was surrounded by connective tissues and anchored firmly to the neighboring tissues. Most part of the luminal surface of tracheal prosthesis was not covered by respiratory mucosa. However, the inner layer showed scant re-epithelialization beyond the anastomosis. The implantation of the carbonaceous tracheal prosthesis can maintain the normal respiratory function of the experimental canines, but hypergranulation and scar formation around the end of the tracheal prosthesis and epithelium on the luminal surface of the prosthesis are questions still remained to be solved.

  8. Salivary Gland Disorders

    MedlinePlus

    Your salivary glands are in your mouth. You have three pairs of major salivary glands and hundreds of small (minor) glands. They make ... contains antibodies that can kill germs. Problems with salivary glands can cause them to become irritated and swollen. ...

  9. Hepatocyte growth factor promoting the proliferation of human eccrine sweat gland epithelial cells is relative to AKT signal channel and β-catenin.

    PubMed

    Lei, Xia; Wu, Jinjin; Liu, Bo; Lu, Yuangang

    2012-01-01

    Hepatocyte growth factor (HGF) is a multi-effective molecule, playing important roles in organ growth, tumorigenesis and trauma healing. This experiment aims at studying the promoting function of HGF on the proliferation of human eccrine sweat gland epithelial cells (hESGc) and its relative signal channels. After HGF at different concentrations were added into cells, MTT was adopted to detect the cell proliferations, Annexin-V/PI the cell apoptosis, and Westernblot the expressions of p-AKT, AKT, p-ERK, p-GSK3β, p-IKBα, and β-catenin in hESGc. After adding siRNA c-Met to block HGF or LY294002 to inhibit p-AKT, we used MTT to detect the proliferation of hESGc and Westernblot to detect the expression of β-catenin. As a result, 20-40 ng/mL HGF could promote the proliferation of hESGc and inhibit its apoptosis. HGF could promote the expressions of p-AKT1/2/3, p-ERK, p-GSK3β, p-IKBα, and β-catenin. The additions of siRNA c-Met to block HGF or LY294002 to inhibit p-AKT could downregulate β-catenin and inhibit the proliferation promotion caused by HGF. Consequently, we concluded HGF can promote the proliferation of human eccrine sweat gland epithelial cells, which is relative to AKT signal channel and β-catenin.

  10. Intrauterine tracheal obstruction, a new treatment for congenital diaphragmatic hernia, decreases amniotic fluid sodium and chloride concentrations in the fetal lamb.

    PubMed Central

    Evrard, V A; Flageole, H; Deprest, J A; Vandenberghe, K; Verhaeghe, J; Lerut, T E

    1997-01-01

    OBJECTIVE: To evaluate the effect of fetal tracheal occlusion on sodium and chloride concentrations in amniotic and tracheal fluid. SUMMARY BACKGROUND DATA: Intrauterine tracheal occlusion has been proposed to reverse pulmonary hypoplasia, an important prognostic factor in congenital diaphragmatic hernia. In early human trials, technical failure of the obstructive device has been reported. METHODS: Eight fetal lambs (gestational age = 95 days) were subjected to fetal tracheoscopy, and amniotic and tracheal fluid samples were taken. In multiple pregnancies (n = 6), amniotic fluid was also sampled from the contralateral amniotic sac and used as a control. Subsequently, endotracheal obstruction, using a detachable balloon, was performed. After 14 days, all fetuses were delivered, and sodium and chloride concentrations in amniotic and tracheal fluid were measured again. Statistical analysis was done using a two-tailed Student's t test, paired or unpaired as appropriate. RESULTS: In controls, between 95 and 109 days gestational age, no significant changes occurred in sodium or chloride concentrations in amniotic or tracheal fluid. After 2 weeks of tracheal obstruction, however, chloride and sodium concentrations in amniotic fluid decreased (chloride = 76.7 mEq/L vs. 107.6 mEq/L, p = 0.0003; sodium = 109.6 mEq/L vs. 125.9 +/- 5.2 mEq/L, p = 0.019). A concomitant increase in chloride and sodium concentration was observed in tracheal fluid (chloride = 145.4 mEq/L vs. 130.0 mEq/L, p = 0.047; sodium = 153.1 mEq/L vs. 142.9 mEq/L, p = 0.051). When comparing groups at 109 days, chloride and sodium concentrations in amniotic fluid were markedly lower in the treated group versus controls (p = 0.0004 and p = 0.05 for chloride and sodium, respectively). CONCLUSION: Complete tracheal occlusion in ovine fetuses results in a significant decrease of amniotic fluid sodium and chloride concentrations. PMID:9409574

  11. Tissue-engineered tracheal reconstruction using three-dimensionally printed artificial tracheal graft: preliminary report.

    PubMed

    Chang, Jae Won; Park, Su A; Park, Ju-Kyeong; Choi, Jae Won; Kim, Yoo-Suk; Shin, Yoo Seob; Kim, Chul-Ho

    2014-06-01

    Three-dimensional printing has come into the spotlight in the realm of tissue engineering. We intended to evaluate the plausibility of 3D-printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial tracheal defects. MSCs from rabbit bone marrow were expanded and cultured. A half-pipe-shaped 3DP polycaprolactone scaffold was coated with the MSCs seeded in fibrin. The half-pipe tracheal graft was implanted on a 10 × 10-mm artificial tracheal defect in four rabbits. Four and eight weeks after the operation, the reconstructed sites were evaluated bronchoscopically, radiologically, histologically, and functionally. None of the four rabbits showed any sign of respiratory distress. Endoscopic examination and computed tomography showed successful reconstruction of trachea without any collapse or blockage. The replaced tracheas were completely covered with regenerated respiratory mucosa. Histologic analysis showed that the implanted 3DP tracheal grafts were successfully integrated with the adjacent trachea without disruption or granulation tissue formation. Neo-cartilage formation inside the implanted graft was sufficient to maintain the patency of the reconstructed trachea. Scanning electron microscope examination confirmed the regeneration of the cilia, and beating frequency of regenerated cilia was not different from those of the normal adjacent mucosa. The shape and function of reconstructed trachea using 3DP scaffold coated with MSCs seeded in fibrin were restored successfully without any graft rejection. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  12. Detection of Pepsin in Tracheal Secretions After Forced Small-Volume Aspirations of Gastric Juice

    PubMed Central

    Metheny, Norma A.; Dahms, Thomas E.; Chang, Yie-Hwa; Stewart, Barbara J.; Frank, Patricia A.; Clouse, Ray E.

    2009-01-01

    Background Detecting small-volume aspirations of gastric contents is an important but difficult task. A potentially useful method for this purpose is assaying tracheal secretions for pepsin, an expected constituent of gastric juice. Methods A 2-group experimental design was used. The primary subjects were 161 experimental and 21 control New Zealand white rabbits; 161 acutely ill humans provided the gastric juice used in the project. The animals were anesthetized before being intubated and mechanically ventilated. Three separate boluses of human gastric juice mixed with dye-stained enteral formula were instilled into the experimental animals’ tracheas; the 21 control animals received only 0.9% sodium chloride solution. At the beginning of each experiment, 0.4 mL/kg of the substance was infused over a 30-minute period; the infusion was then stopped and 90 minutes were allowed to elapse before endotracheal suctioning was performed. This procedure was repeated at hour 2 and hour 4. After completion of the multiple aspiration portion of the study, 23 additional animals were subjected to a single aspiration of 0.4 mL/kg of a mixture of human gastric juice and dye-stained enteral formula; secretions were obtained at 2 hours, 4 hours, and 6 hours. An immunoassay was used to test for pepsin in all of the tracheal secretions. Results In the 3-aspiration group, pepsin was found in all of the secretions from 92.5% (149/161) of the experimental animals; in contrast, no pepsin was found in any of the secretions from the 20 control animals. In the single-aspiration group, pepsin was found in all of the tracheal secretions from the 23 animals at 2 hours and 4 hours and 21 of the 23 animals at 6 hours. Conclusions The immunoassay used in this animal model study was able to detect pepsin in >90% of the experimental animals’ tracheal secretions after multiple or single forced aspirations of gastric juice. The extent to which pepsin can be detected in the tracheal secretions of

  13. [Clinic, diagnosis and treatment of tracheal stenosis].

    PubMed

    Delgado Pecellín, I; González Valencia, J P; Machuca Contreras, M; Pineda Mantecón, M

    2009-05-01

    New surgical techniques have been developed for treatment of tracheal stenosis (TS) over the last few years. The aim of the present study is to examine the clinical, therapeutic characteristics and progress of the cases of TS diagnosed in our hospital from January 2004 to August 2007. We have reviewed the clinical history, focusing on age at diagnosis, clinical signs and symptoms, baseline pathology, previous history of mechanical ventilation, degree of stenosis, diagnostic technique, treatment and progress. A total of 16 cases were found, (2 congenital and 14 acquired). Mean age at diagnosis was 8.8 months (23 days-2.5 years). Of these, 14 patients had been intubated (3-44 days). Clinical suspicion was prompted by inspiratory stridor (44%), difficulty to be extubated or intubated (28%) and recurrent laryngotracheitis (39%). Three patients received CO(2) laser therapy and suffered a high number of restenosis and required re-interventions. Three patients underwent costal cartilage tracheoplasty and tracheal-cricoid split, showing a good prognosis and one patient underwent a slide tracheoplasty. Five patients with only a few clinical signs and mild stenosis, were managed on a wait and see basis. One patient with tracheal membrane underwent resection of the stenosed portion and end-to-end anastomosis with favourable progress. Another patient had a partial cricotracheal resection but suffered three restenoses. Two patients underwent surgical correction of the vascular ring. Asymptomatic patients may receive conservative therapy. In the case of short-segment stenosis, resection and end-to-end anastomosis is the therapy of choice and the long-segment stenosis has obtained good results by means of slide tracheoplasty, which involved no deaths and a very low morbidity.

  14. Pathology of the parathyroid glands in hyperparathyroidism.

    PubMed

    Baloch, Zubair W; LiVolsi, Virginia A

    2013-08-01

    This paper reviews the embryology, histology and pathology of the human parathyroid glands. It emphasizes those pathologic lesions which are found in the setting of clinical hyperparathyroidism. Also discussed are certain molecular features of hyperfunctioning parathyroid glands. The difficulties encountered in parathyroid FNA are reviewed and illustrated.

  15. Adrenal gland disorders.

    PubMed

    Berry, Matthew E

    2009-01-01

    Medical imaging of the adrenal glands is an important aspect of the diagnosis of any adrenal gland disorder. This article discusses the normal anatomy and functions of the adrenal glands, as well as specific adrenal gland disorders and how they are diagnosed and treated. Radiologic technologists need to understand the causes, signs, symptoms, diagnosis and management of disorders that prevent the adrenal glands from functioning properly.

  16. A novel translational model of percutaneous fetoscopic endoluminal tracheal occlusion - baboons (Papio spp.).

    PubMed

    Mari, Giancarlo; Deprest, Jan; Schenone, Mauro; Jackson, Scott; Samson, Jacques; Brocato, Brian; Tate, Danielle; Sullivan, Ryan; White, Garry; Dhanireddy, Reddy; Mandrell, Timothy; Gupta, Sonali; Skobowjat, Cezary; Slominski, Andrzej; Cohen, Harris L; Schlabritz-Loutsevitch, Natalia

    2014-01-01

    Percutaneous fetoscopic endoluminal reversible tracheal occlusion (FETO) was developed to prevent the pulmonary complications of fetal congenital diaphragmatic herniation. There is an urgent need to establish the closest to human translational model of FETO in order to improve fetal outcomes and to determine new clinical approaches and applications. Seven non-human primates underwent two subsequent surgeries: the first, the FETO in the experimental group (n = 3) or sham operation in the control animals (S-FETO, n = 4) at 132-142 days of gestation (dGA); the second, the reversal of occlusion or sham operation at 162 ± 5 dGA. Maternal stress axis, complete blood count, and biochemical parameters were evaluated and newborn tracheal radiography was performed. The average pregnancy duration and neonatal weights in the FETO group did not differ from the animals in the S-FETO group. There was no bleeding or premature fetal membrane rupture during the procedures in any of the baboons. The maximal tracheal width was 7.02 ± 0.6 mm in the FETO versus 5.46 ± 0.6 mm in S-FETO group. This is the very first report of a successful FETO model in non-human primates. Similarities to human tracheomegaly were for the first time documented in any model studied. © 2014 S. Karger AG, Basel.

  17. Tracheal agenesis: A report of two cases

    PubMed Central

    Desai, AV; Rao, Sudha; Shanbhag, PR; Rupani, M

    2016-01-01

    Tracheal agenesis is an extremely rare congenital anomaly involving the respiratory system. It is generally associated with anomalies of other systems. Antenatal diagnosis of this condition is difficult; therefore, it presents as a medical emergency in the labor room. Intubation in these babies is difficult. As many of these babies are born prematurely, respiratory distress syndrome (RDS) adds to the management difficulties. Here, we describe two babies with this lethal anomaly and RDS where esophageal intubation and surfactant therapy proved beneficial. Furthermore, described are other associated anomalies. PMID:27424553

  18. Bilobar atelectasis after difficult tracheal intubation.

    PubMed

    Sprung, J; Lozada, L J; Zanettin, G; Banoub, M

    1997-12-01

    Acute intra-operative collapse of a lobe without apparent cause is rare. We report a case of transient bilobar atelectasis that developed without any apparent cause after a difficult tracheal intubation in a healthy young patient. Intrabronchial obstruction was ruled out by bronchoscopy. The bilobar atelectasis developed acutely and resolved quickly with mechanical ventilation. The characteristics of the lung collapse were atypical, suggesting either its reflex nature or acute reduction of lung volume owing to intubation-induced coughing. We present a review of the mechanisms of atelectasis.

  19. Synchrotron imaging of the grasshopper tracheal system: morphological and physiological components of tracheal hypermetry

    PubMed Central

    Henry, Joanna R.; Kirkton, Scott D.; Westneat, Mark W.; Fezzaa, Kamel; Lee, Wah-Keat; Harrison, Jon F.

    2009-01-01

    As grasshoppers increase in size during ontogeny, they have mass specifically greater whole body tracheal and tidal volumes and ventilation than predicted by an isometric relationship with body mass and body volume. However, the morphological and physiological bases to this respiratory hypermetry are unknown. In this study, we use synchrotron imaging to demonstrate that tracheal hypermetry in developing grasshoppers (Schistocerca americana) is due to increases in air sacs and tracheae and occurs in all three body segments, providing evidence against the hypothesis that hypermetry is due to gaining flight ability. We also assessed the scaling of air sac structure and function by assessing volume changes of focal abdominal air sacs. Ventilatory frequencies increased in larger animals during hypoxia (5% O2) but did not scale in normoxia. For grasshoppers in normoxia, inflated and deflated air sac volumes and ventilation scaled hypermetrically. During hypoxia (5% O2), many grasshoppers compressed air sacs nearly completely regardless of body size, and air sac volumes scaled isometrically. Together, these results demonstrate that whole body tracheal hypermetry and enhanced ventilation in larger/older grasshoppers are primarily due to proportionally larger air sacs and higher ventilation frequencies in larger animals during hypoxia. Prior studies showed reduced whole body tracheal volumes and tidal volume in late-stage grasshoppers, suggesting that tissue growth compresses air sacs. In contrast, we found that inflated volumes, percent volume changes, and ventilation were identical in abdominal air sacs of late-stage fifth instar and early-stage animals, suggesting that decreasing volume of the tracheal system later in the instar occurs in other body regions that have harder exoskeleton. PMID:19710392

  20. Synchrotron imaging of the grasshopper tracheal system : morphological and physiological components of tracheal hypermetry.

    SciTech Connect

    Greenlee, K. J.; Henry, J. R.; Kirkton, S. D.; Westneat, M. W.; Fezzaa, K.; Lee, W.; Harrison, J. F.; North Dakota State Univ.; Arizona State Univ.; Union Coll.; Field Museum of Natural History

    2009-11-01

    As grasshoppers increase in size during ontogeny, they have mass specifically greater whole body tracheal and tidal volumes and ventilation than predicted by an isometric relationship with body mass and body volume. However, the morphological and physiological bases to this respiratory hypermetry are unknown. In this study, we use synchrotron imaging to demonstrate that tracheal hypermetry in developing grasshoppers (Schistocerca americana) is due to increases in air sacs and tracheae and occurs in all three body segments, providing evidence against the hypothesis that hypermetry is due to gaining flight ability. We also assessed the scaling of air sac structure and function by assessing volume changes of focal abdominal air sacs. Ventilatory frequencies increased in larger animals during hypoxia (5% O{sub 2}) but did not scale in normoxia. For grasshoppers in normoxia, inflated and deflated air sac volumes and ventilation scaled hypermetrically. During hypoxia (5% O{sub 2}), many grasshoppers compressed air sacs nearly completely regardless of body size, and air sac volumes scaled isometrically. Together, these results demonstrate that whole body tracheal hypermetry and enhanced ventilation in larger/older grasshoppers are primarily due to proportionally larger air sacs and higher ventilation frequencies in larger animals during hypoxia. Prior studies showed reduced whole body tracheal volumes and tidal volume in late-stage grasshoppers, suggesting that tissue growth compresses air sacs. In contrast, we found that inflated volumes, percent volume changes, and ventilation were identical in abdominal air sacs of late-stage fifth instar and early-stage animals, suggesting that decreasing volume of the tracheal system later in the instar occurs in other body regions that have harder exoskeleton.

  1. A pilot study of pepsin in tracheal and oral secretions.

    PubMed

    Schallom, Marilyn; Tricomi, Sally M; Chang, Yie-Hwa; Metheny, Norma A

    2013-09-01

    Because reflux of gastric juice into the oropharynx must precede its aspiration into the lungs, it is reasonable to hypothesize that the detection of pepsin (the major gastric enzyme in gastric juice) in oral secretions may provide a relatively noninvasive method of predicting risk for aspiration. To describe the incidence of pepsin in oral and tracheal secretions collected concurrently from a sample of 50 gastric-fed patients undergoing mechanical ventilation. An exploratory descriptive design with a convenience sample from 4 medical and surgical intensive care units. An oral secretion and a tracheal secretion were collected concurrently from each patient (yielding a sample of 50 oral and 50 tracheal secretions). The tracheal secretions were obtained via the inline suction system with an attached sputum trap; oral secretions were obtained via a Yankauer suction tip with an attached sputum trap. All specimens were assayed for pepsin by the Western blot method. Oral secretions from 10 patients (20%) and tracheal secretions from 2 patients (4%) were pepsin-positive. Both patients with pepsin-positive tracheal secretions also had pepsin-positive oral secretions. Pepsin was not found in the tracheal secretions from the remaining 8 patients with pepsin-positive oral secretions. Although reflux of gastric juice into the oropharynx must precede its aspiration into the lungs, individual reflux events do not necessarily lead to aspiration. Thus, it is reasonable that we found pepsin 5 times more often in oral secretions than in tracheal secretions.

  2. Tracheal rupture in a cat: diagnosis by computed tomography.

    PubMed

    Bhandal, Jitender; Kuzma, Alan

    2008-06-01

    A cat was presented with a history of worsening generalized subcutaneous emphysema following dental prophylaxis. Tentative diagnosis of tracheal rupture was made. The location and extent of the tear was confirmed with the help of computed tomography. This is the 1st computed tomographic description of tracheal rupture in the veterinary literature.

  3. Complete tracheal duplication with unilateral atelectasis in an adult.

    PubMed

    Chihaya, Keisuke; Yamashiro, Tsuneo; Matsuoka, Shin; Nobuyama, Seiichi; Handa, Hiroshi; Inoue, Takeo; Kida, Hirotaka; Kurimoto, Noriaki; Matsushita, Shoichiro; Fujikawa, Atsuko; Kurihara, Yasuyuki; Mineshita, Masamichi; Miyazawa, Teruomi; Nakajima, Yasuo

    2014-01-01

    Duplication of the trachea is an extremely rare condition that has been infrequently reported in the medical literature. We report an adult case with complete tracheal duplication associated with unilateral atelectasis, which was incidentally detected by computed tomography. Tracheal duplication should be considered as a possible cause of severe atelectasis in adults.

  4. Pyramidal lobe of the thyroid gland and the thyroglossal duct remnant: a study using human fetal sections.

    PubMed

    Takanashi, Yoshitaka; Honkura, Yohei; Rodriguez-Vazquez, Jose Francisco; Murakami, Gen; Kawase, Tetsuaki; Katori, Yukio

    2015-01-01

    To investigate developmental changes in the thyroglossal duct, we observed serial sagittal sections of eight embryos (crown-rump length (CRL) 6-12 mm; approximately 5-6 weeks of gestation) as well as serial horizontal or cross-sections of 70 embryos and fetuses (CRL 15-110 mm; 6-15 weeks). In the sagittal sections, the thyroglossal duct was identified as a small sheet or mass of relatively large cells with vacuolization anterior, superior or inferior to the fourth pharyngeal arch artery. However, we found no continuous duct-like structure that reached the thyroid gland. Thus, previous classical schemes might have overestimated the continuity of the duct. Among cross-sections of 70 specimens, we found the thyroglossal duct remnant in only two specimens (CRL 15 mm and 100 mm), in contrast to the pyramidal lobe, which was seen in one-third of the specimens. The duct remnant ran downward along the lateral edge of the hyoid body to reach the anterior aspect of the thyroid cartilage. However, the connection between the pyramidal lobe and the duct remnant was interrupted by the anterior cervical muscles. Therefore, it was unlikely that the thyroglossal duct remnant would more frequently be evident in fetuses than in adults. The highly tortuous course of the duct along the lingual aspect of the hyoid body, which has been reported previously, appeared to become established near term. Descent of the thyroid gland was not evident after the CRL 20 mm stage (6 weeks): the gland appeared to retain its position at the level of the third-sixth cervical vertebrae. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. On the use of unsealed polypropylene mesh as tracheal replacement.

    PubMed

    Behrend, Matthias; Kluge, Eva; Schüttler, Wolfgang

    2006-01-01

    The necessity of a cervical tracheal replacement arises with thyroid carcinoma, which occasionally infiltrates the trachea extensively, the rare primary tracheal tumors and, sporadically, benign stenoses. In the present study, we used an uncoated porous polypropylene prosthesis as cervical tracheal replacement in sheep. Specifically, we implanted a tracheal prosthesis of polypropylene mesh as a cervical tracheal replacement in five sheep, protecting the airways with self-expanding stents. Healing-in of the prostheses was checked bronchoscopically. The animals were killed after increasing survival times (7, 28, 64, 68, and >90 days), and incorporation of the prosthesis was examined macroscopically, microangiographically and histologically. Although medium-term survival was possible with a sufficiently wide airway, all animals were ultimately euthanized because of complications (airway stenosis, prolapse of prosthesis). Nevertheless, the results show that replacement of the cervical trachea with a polypropylene mesh can be successful under different experimental conditions.

  6. Fibrosarcoma of the trachea with severe tracheal obstruction

    PubMed Central

    Roncoroni, A. J.; Puy, R. J. M.; Goldman, E.; Fonseca, R.; Olmedo, Gloria

    1973-01-01

    Roncoroni, A. J., Puy, R. J. M., Goldman, E., Fonseca, R., and Olmedo, G. (1973).Thorax,28, 777-781. Fibrosarcoma of the trachea with severe tracheal obstruction. A patient with a tracheal fibrosarcoma is reported. The tumour was located just above the thoracic inlet and produced severe obstruction predominantly during expiration. An abnormal effort independent flow pattern was seen during inspiration in isovolume pressure-flow studies. Endoscopic resection induced temporary symptomatic remission, and airway resistance and expiratory flows became normal. Subsequently he required resection of eight tracheal rings with end-to-end tracheal anastomosis. Obstructive granulomata then developed at the suture sites, necessitating endoscopic removal. Later tracheal stenosis responded to periodic dilatation. Images PMID:4787990

  7. The management of congenital tracheal stenosis.

    PubMed

    Elliott, Martin; Roebuck, Derek; Noctor, Clair; McLaren, Clare; Hartley, Ben; Mok, Quen; Dunne, Catherine; Pigott, Nick; Patel, Chirag; Patel, Alpesh; Wallis, Colin

    2003-12-01

    This paper reviews current concepts and results in the management of congenital tracheal stenosis (CTS). Diagnostic options are considered and the requirements for successful management defined. Chief amongst these is a multi-disciplinary approach with individualised patient management. Severe long-segment CTS represents the biggest challenge to clinicians and the worst problems for affected families. Near-death episodes are frequent in affected infants and some cannot be ventilated and require ECMO. Associated cardiovascular anomalies are frequent. Patients require immediate resuscitation and transfer to a specialist unit. After careful assessment, accurate diagnosis and discussion, primary resection and end-to-end repair with a slide technique should always be the first option, with concomitant repair of associated cardiac anomalies. If this is impossible because of the severity of the lesion, some form of patch tracheoplasty will be indicated. Cardiopulmonary bypass is often required. Patches include pericardium, autograft trachea, carotid artery, cartilage, and allograft trachea. Mortality ranges from 0 to 30% in the literature, which largely comprises single-centre long-term experience. Recurrence is common and can be managed by stenting and tracheal homograft implantation. Long-term quality of life of survivors is little reported but seems good. Physiological data are lacking. To improve results, we suggest a treatment algorithm to rationalise care.

  8. Over-expression of TSC-22 (TGF-beta stimulated clone-22) markedly enhances 5-fluorouracil-induced apoptosis in a human salivary gland cancer cell line.

    PubMed

    Uchida, D; Kawamata, H; Omotehara, F; Miwa, Y; Hino, S; Begum, N M; Yoshida, H; Sato, M

    2000-06-01

    We have recently isolated TSC-22 (transforming growth factor-beta-stimulated clone-22) cDNA as an anticancer, drug-inducible (with vesnarinone) gene in a human salivary gland cancer cell line, TYS. We have also reported that TSC-22 negatively regulates the growth of TYS cells and that down-regulation of TSC-22 in TYS cells plays a major role in salivary gland tumorigenesis (Nakashiro et al, 1998). In this study, we transfected TYS cells with an expression vector encoding the TSC-22-GFP (green fluorescent protein) fusion protein, and we established TSC-22-GFP-expressing TYS cell clones. Next, we examined (a) the subcellular localization of the fusion protein, (b) the sensitivity of the transfectants to several anticancer drugs (5-fluorouracil, cis-diaminedichloroplatinum, peplomycin), and (c) induction of apoptotic cell death in the transfectants by 5-fluorouracil treatment. The TSC-22-GFP fusion protein was clearly localized to the cytoplasm, but not to the nucleus. Over-expression of the TSC-22-GFP fusion protein did not affect cell growth, but significantly increased the sensitivity of the cells to the anticancer drugs (p < 0.01; one-way ANOVA). Furthermore, over-expression of the TSC-22-GFP fusion protein markedly enhanced 5-fluorouracil-induced apoptosis. These findings suggest that over-expression of TSC-22-GFP protein in TYS cells enhances the chemosensitivity of the cells via induction of apoptosis.

  9. The rat gene homologous to the human gene 9–27 is involved in the development of the mammary gland

    PubMed Central

    Zucchi, I.; Montagna, C.; Susani, L.; Vezzoni, P.; Dulbecco, R.

    1998-01-01

    We have developed a model system for studying differentiation in the mammary gland, by using two clonal cultures deriving from a rat breast adenocarcinoma. They differ in the ability to form domes, structures the significance of which is unknown. By using the subtractive cDNA library approach, we isolated a cDNA that is highly expressed in the dome-forming cells, and identical to the rat8 gene and highly homologous to the human 9–27 gene. Antisense treatment of the dome-forming cells specifically and reproducibly abolishes dome formation, while forced expression of the gene in non-dome-forming cells causes morphological changes suggestive of “flat” domes. In situ hybridization on rat tissues shows that the gene is expressed in epithelia, especially in those forming tubular structures, suggesting a relatedness between these structures and domes. Cytokeratin 8 and E cadherin are strongly expressed in the domes but not outside them, suggesting that the rat8 gene triggers the cells to express molecules that tighten the lateral connections between the cells; the process is likely to parallel that occurring during the differentiation of the mammary gland. PMID:9448288

  10. Comparative aspects of mammary gland development and homeostasis

    USDA-ARS?s Scientific Manuscript database

    Mammary glands are crucial to the reproductive strategy of mammals and the milk of domesticated ruminants serves as an important source of nutrients for the human population. The majority of mammary gland development occurs postnatally and the mammary gland undergoes cyclical periods of growth, dif...

  11. Effects of premedication with oral gabapentin on intraocular pressure changes following tracheal intubation in clinically normal dogs.

    PubMed

    Trbolova, Alexandra; Ghaffari, Masoud Selk; Capik, Igor

    2017-09-19

    Gabapentin is an antiepileptic drug widely approved as an add-on therapy for epilepsy treatment in human and dogs. There is a clinical impression that gabapentin is a suitable drug which attenuates the IOP elevation associated with tracheal intubation in humans. The present study performed to determine the effects of oral gabapentin on intraocular pressure (IOP) changes following tracheal intubation in dogs. Twenty adult healthy dogs were randomly assigned to treatment (n = 10) and control (n = 10) groups. Dogs in the treatment group received oral gabapentin (50 mg/kg) 2 h before induction of anesthesia and dogs in the control group received oral gelatin capsule placebo at the same time. The dogs were anesthetized with propofol 6 mg/kg, and anesthesia was maintained with a constant infusion of 0.2 mg/kg/min of propofol for 20 min. IOP were measured immediately before induction and then repeated immediately after induction, as well as 5 min, 10 min and 15 min following tracheal intubation in both groups. IOP was significantly higher immediately after induction, and 5 min after tracheal intubation when compared with IOP reading before induction in the control group. There was no statistically significant change in IOPs immediately after induction, and 5 min after tracheal intubation in comparison to the values before induction in the treatment group. Based on the findings of this study, preanesthetic oral administration of gabapentin significantly prevents an increase in the IOP associated with tracheal intubation in dogs anesthetized with propofol.

  12. Inhibitory effects of silibinin on proliferation and lung metastasis of human high metastasis cell line of salivary gland adenoid cystic carcinoma via autophagy induction

    PubMed Central

    Jiang, Canhua; Jin, Shufang; Jiang, Zhisheng; Wang, Jie

    2016-01-01

    Objective To investigate the possible mechanisms and effects of silibinin (SIL) on the proliferation and lung metastasis of human lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC-M). Methods A methyl thiazolyl tetrazolium assay was performed to detect the inhibitory effects of SIL on the proliferation of ACC-M cells in vitro. Fluorescence microscopy and transmission electron microscopy were used to observe the autophagic process. Western blot was performed to detect the expression of microtube-related protein 1 light-chain 3 (LC3). An experimental adenoid cystic carcinoma (ACC) lung metastasis model was established in nude mice to detect the impacts of SIL on lung weight and lung cancer nodules. Immunohistochemistry was used to detect the expressions of LC3 in human ACC samples and normal salivary gland tissue samples. Results SIL inhibited the proliferation of ACC-M cells in a dose- and time-dependent manner, and inductively increased the autophagic bodies in ACC-M cells. Furthermore, SIL could increase the expression of LC3 in ACC-M cells and promote the conversion of LC3-I into LC3-II in a dose- and time-dependent manner. In the ACC lung metastasis model, the lung weight and left and right lung nodules in the SIL-treated group were significantly less than those in the control group (P<0.05). The expressions of LC3-I and LC3-II as well as the positive expression rate of LC3 (80%) significantly increased, but the positive expression of LC3 in human ACC (42.22%) reduced significantly. Conclusion SIL could inhibit the proliferation and lung metastasis of ACC-M cells by possibly inducing tumor cells autophagy. PMID:27822066

  13. TU-C-12A-05: Repeatability Study of Reduced Field-Of-View Diffusion-Weighted MRI On Human Thyroid Gland

    SciTech Connect

    Shukla-Dave, A; Lu, Y; Hatzoglou, V; Stambuk, H; Mazaheri, Y; Banerjee, S; Shankaranarayanan, A; Deasy, J

    2014-06-15

    Purpose: To investigate the repeatability of reduced field-of-view diffusion-weighted imaging (rFOV DWI) in quantifying apparent diffusion coefficients (ADCs) for human thyroid glands in a clinical setting. Methods: Nine healthy human volunteers were enrolled and underwent 3T MRI exams. For each volunteer, 3 longitudinal exams (2 weeks apart) with 2 repetitive sessions within each exam, including rFOV and conventional full field-of-view (fFOV) DWI scans, were performed. In the acquired DWI images, a fixed-size region of interest (ROI; diameter=8mm) was placed on thyroid glands to calculate ADC. ADC was calculated using a monoexponential function with a noise correction scheme. The repeatability of ADC was assessed by using coefficient variation (CV) across sessions or exams, which was defined to be: r = 1-CV, 0 < r < 1, where CV=STD/m, STD is the standard deviation of ADC, and m is the average of ADC across sessions or exams. An experienced radiologist assessed and scored rFOV and fFOV DW images based on image characteristics (1, nondiagnostic; 2, poor; 3, satisfactory; 4, good; and 5, excellent).Analysis of variance (ANOVA) was performed to compare ADC values, CV of ADC, repeatability of ADC across sessions and exams, and radiologic scores between rFOV and fFOV DWI techniques. Results: There was no significant difference in ADC values across sessions and exams either in rFOV or fFOV DWI. The average CVs of both rFOV and fFOV DWI were less than 13%. The repeatability of ADC measurement between rFOV and fFOV DWI was not significantly different. The overall image quality was significantly higher with rFOV DWI than with fFOV DWI. Conclusion: This study suggested that ADCs from both rFOV and fFOV DWI were repeatable, but rFOV DWI had superior imaging quality for human thyroid glands in a clinical setting.

  14. Salivary glands - "an unisex organ'?

    PubMed

    Konttinen, Y T; Stegaev, V; Mackiewicz, Z; Porola, P; Hänninen, A; Szodoray, P

    2010-10-01

    Usually no distinction is made between female and male salivary glands although cyclic changes of and ⁄ or differences in serum and salivary sex steroid concentrations characterize women and men. Moreover, sexual dimorphism is well recognized in salivary glands of rodents.Salivary glands contain estrogen and androgen receptors and are, according to modern high throughput technologies,subjected to gender differences not explainable by gene dose effects by the X chromosome alone. Because sex steroids are lipophilic, it is often thought that approximately 10% of them passively diffuse from plasma to saliva. Indeed, saliva can find use as sample material in sports medicine, pediatrics, veterinary medicine and behavioral sciences. Last but not least, humans and other primates are unique in that they have a reticular zone in their adrenal cortex, which produces dehydroepiandrosterone and androstendione pro-hormones. These are processed in peripheral tissues, not only in female breast and uterus and male prostate, but also in salivary glands by an intracrine enzymatic machinery to active 17b-estradiol,dihydrotestosterone and others, to satisfy and buffer against a constantly changing needs caused by circadian,menstrual, pregnancy and chronobiological hormonal changes in the systemic circulation. Female dominance of Sjögren's syndrome and certain forms of salivary gland cancer probably reflect these gender-based differences.

  15. Tracheal decannulation protocol in patients affected by traumatic brain injury.

    PubMed

    Zanata, Isabel de Lima; Santos, Rosane Sampaio; Hirata, Gisela Carmona

    2014-04-01

    Introduction The frequency of tracheostomy in patients with traumatic brain injury (TBI) contrasts with the lack of objective criteria for its management. The study arose from the need for a protocol in the decision to remove the tracheal tube. Objective To evaluate the applicability of a protocol for tracheal decannulation. Methods A prospective study with 20 patients, ranging between 21 and 85 years of age (average 33.55), 4 of whom were women (20%) and 16 were men (80%). All patients had been diagnosed by a neurologist as having TBI, and the anatomical region of the lesion was known. Patients were evaluated following criteria for tracheal decannulation through a clinical evaluation protocol developed by the authors. Results Decannulation was performed in 12 (60%) patients. Fourteen (70%) had a score greater than 8 on the Glasgow Coma Scale and only 2 (14%) of these were not able to undergo decannulation. Twelve (60%) patients maintained the breathing pattern with occlusion of the tube and were successfully decannulated. Of the 20 patients evaluated, 11 (55%) showed no signs suggestive of tracheal aspiration, and of these, 9 (82%) began training on occlusion of the cannula. The protocol was relevant to establish the beginning of the decannulation process. The clinical assessment should focus on the patient's condition to achieve early tracheal decannulation. Conclusion This study allowed, with the protocol, to establish six criteria for tracheal decannulation: level of consciousness, respiration, tracheal secretion, phonation, swallowing, and coughing.

  16. Tracheal Decannulation Protocol in Patients Affected by Traumatic Brain Injury

    PubMed Central

    Zanata, Isabel de Lima; Santos, Rosane Sampaio; Hirata, Gisela Carmona

    2014-01-01

    Introduction The frequency of tracheostomy in patients with traumatic brain injury (TBI) contrasts with the lack of objective criteria for its management. The study arose from the need for a protocol in the decision to remove the tracheal tube. Objective To evaluate the applicability of a protocol for tracheal decannulation. Methods A prospective study with 20 patients, ranging between 21 and 85 years of age (average 33.55), 4 of whom were women (20%) and 16 were men (80%). All patients had been diagnosed by a neurologist as having TBI, and the anatomical region of the lesion was known. Patients were evaluated following criteria for tracheal decannulation through a clinical evaluation protocol developed by the authors. Results Decannulation was performed in 12 (60%) patients. Fourteen (70%) had a score greater than 8 on the Glasgow Coma Scale and only 2 (14%) of these were not able to undergo decannulation. Twelve (60%) patients maintained the breathing pattern with occlusion of the tube and were successfully decannulated. Of the 20 patients evaluated, 11 (55%) showed no signs suggestive of tracheal aspiration, and of these, 9 (82%) began training on occlusion of the cannula. The protocol was relevant to establish the beginning of the decannulation process. The clinical assessment should focus on the patient's condition to achieve early tracheal decannulation. Conclusion This study allowed, with the protocol, to establish six criteria for tracheal decannulation: level of consciousness, respiration, tracheal secretion, phonation, swallowing, and coughing. PMID:25992074

  17. Iontophoretic beta-adrenergic stimulation of human sweat glands: possible assay for cystic fibrosis transmembrane conductance regulator activity in vivo.

    PubMed

    Shamsuddin, A K M; Reddy, M M; Quinton, P M

    2008-08-01

    With the advent of numerous candidate drugs for therapy in cystic fibrosis (CF), there is an urgent need for easily interpretable assays for testing their therapeutic value. Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) abolished beta-adrenergic but not cholinergic sweating in CF. Therefore, the beta-adrenergic response of the sweat gland may serve both as an in vivo diagnostic tool for CF and as a quantitative assay for testing the efficacy of new drugs designed to restore CFTR function in CF. Hence, with the objective of defining optimal conditions for stimulating beta-adrenergic sweating, we have investigated the components and pharmacology of sweat secretion using cell cultures and intact sweat glands. We studied the electrical responses and ionic mechanisms involved in beta-adrenergic and cholinergic sweating. We also tested the efficacy of different beta-adrenergic agonists. Our results indicated that in normal subjects the cholinergic secretory response is mediated by activation of Ca(2+)-dependent Cl(-) conductance as well as K(+) conductances. In contrast, the beta-adrenergic secretory response is mediated exclusively by activation of a cAMP-dependent CFTR Cl(-) conductance without a concurrent activation of a K(+) conductance. Thus, the electrochemical driving forces generated by beta-adrenergic agonists are significantly smaller compared with those generated by cholinergic agonists, which in turn reflects in smaller beta-adrenergic secretory responses compared with cholinergic secretory responses. Furthermore, the beta-adrenergic agonists, isoproprenaline and salbutamol, induced sweat secretion only when applied in combination with an adenylyl cyclase activator (forskolin) or a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, aminophylline or theophylline). We surmise that to obtain consistent beta-adrenergic sweat responses, levels of intracellular cAMP above that achievable with a beta-adrenergic agonist alone are

  18. Exposure to polychlorinated biphenyls and the thyroid gland - examining and discussing possible longitudinal health effects in humans.

    PubMed

    Gaum, Petra M; Lang, Jessica; Esser, André; Schettgen, Thomas; Neulen, Joseph; Kraus, Thomas; Gube, Monika

    2016-07-01

    Many previous studies have dealt with the effect of polychlorinated biphenyls (PCBs) on the thyroid gland, but their findings are inconsistent. One problem of these studies has been their use of cross-sectional designs. The aim of the current study is to investigate longitudinal effects of PCBs on the thyroid gland, focusing on: morphological changes in thyroid tissue (i.e. thyroid volume), changes in thyroid hormones and in thyroid antibodies. A total of 122 individuals (Mage=44.7) were examined over a period of four years (t(1) until t(4)). Medical history was collected via interviews, an ultrasound examination was performed and blood samples were taken to determine plasma PCB levels, thyroid stimulating hormone (TSH), free triiodthyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOab), thyreoglobulin antibodies (TGab) and thyroid-stimulating hormone receptor antibodies (TSHRab). Rank correlation coefficients and mixed effect models were performed controlling for age and total lipids. There were negative correlations between higher chlorinated biphenyls and fT3, cross-sectionally as well as longitudinally. We also found an interaction effect of higher-chlorinated PCBs over time for fT4 as well as TSHRab. In case of high exposure, a decrease in fT4 and an increase in TSHRab level were found over time. In regards to the other variables, our findings yielded no clear results in the examined time period. This is the first study to shows a PCB-related effect on fT3, fT4 and TSHRab over a four year period. The data also suggest that morphological and antibody findings remain inconsistent and do not allow for unambiguous interpretation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Human IgG1 and IgG4: the main antibodies against Triatoma infestans (Hemiptera: Reduviidae) salivary gland proteins.

    PubMed

    Nascimento, R J; Santana, J M; Lozzi, S P; Araújo, C N; Teixeira, A R

    2001-09-01

    The Triatoma infestans salivary gland proteins (TSGP) can induce local and systemic hypersensitivity reactions in humans. IgG antibodies against TSGP were present in higher levels in sera of Chagas disease patients, and in individuals living in triatomine-infested areas than in controls living in triatomine-free areas. TSGP-specific IgG1 was found in sera of Chagas patients, and of individuals living in triatomine-infested rural areas, and uniquely specific IgG4 was present in sera of Chagas patients living in triatomine-infested areas, reactive against TSGP. Unique specificities were not detected in sera of individuals reacting against the ubiquitous mosquito Culex quinquifasciatus saliva proteins (CSGP). In conclusion, IgG1 reactive against TSGP is the main antibody present in individuals living in the triatomine-infested study areas. Also, IgG4 is found in the sera of insect-transmitted Chagas disease patients living in study areas.

  20. Salivary Gland Cancer: Risk Factors

    MedlinePlus

    ... Cancer > Salivary Gland Cancer: Risk Factors Request Permissions Salivary Gland Cancer: Risk Factors Approved by the Cancer.Net ... f t k e P Types of Cancer Salivary Gland Cancer Guide Cancer.Net Guide Salivary Gland Cancer ...

  1. Do Cyclosporine A, an IL-1 Receptor Antagonist, Uridine Triphosphate, Rebamipide, and/or Bimatoprost Regulate Human Meibomian Gland Epithelial Cells?

    PubMed Central

    Kam, Wendy R.; Liu, Yang; Ding, Juan; Sullivan, David A.

    2016-01-01

    Purpose Researchers have hypothesized that treatment with cyclosporine A (CyA), interleukin-1 receptor antagonists (IL-1RA; e.g., anakinra), P2Y2 receptor agonists (e.g., uridine triphosphate; UTP), and rebamipide may alleviate human meibomian gland dysfunction (MGD) and/or dry eye disease. Investigators have also proposed that prostaglandin analogues (e.g., bimatoprost) may induce MGD. Our goal was to determine whether these compounds directly influence human meibomian gland epithelial cell (HMGEC) function. Methods Multiple concentrations of each compound were tested for effects on immortalized (I) HMGEC morphology and survival. Nontoxic dosages were used for our studies. Immortalized HMGEC were cultured in the presence of vehicle, CyA, IL-1RA, UTP, rebamipide, or bimatoprost for up to 6 days in various media. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract), differentiation (azithromycin), and signaling pathway activation (insulin-like growth factor 1). Cells were analyzed for neutral lipid staining, lysosome accumulation, lipid composition, and phosphatidylinositol-3-kinase/Akt (AKT), phosphorylation. Results Our findings demonstrate that CyA, IL-1RA, UTP, rebamipide, and bimatoprost had no effect on the proliferation; neutral lipid content; lysosome number; or levels of free cholesterol, triglycerides, or phospholipids in IHMGECs. Cylosporine A, IL-1RA, rebamipide, and bimatoprost significantly reduced the phosphorylation of AKT, as compared to control. Of interest, tested doses of CyA above 8 nM killed the IHMGECs. Conclusions Our results show that CyA, IL-1RA, UTP, rebamipide, and bimatoprost do not influence the proliferation or differentiation of IHMGEC. However, with the exception of UTP, these compounds do decrease the activity of the AKT signaling pathway, which is known to promote cell survival. PMID:27552406

  2. Do Cyclosporine A, an IL-1 Receptor Antagonist, Uridine Triphosphate, Rebamipide, and/or Bimatoprost Regulate Human Meibomian Gland Epithelial Cells?

    PubMed

    Kam, Wendy R; Liu, Yang; Ding, Juan; Sullivan, David A

    2016-08-01

    Researchers have hypothesized that treatment with cyclosporine A (CyA), interleukin-1 receptor antagonists (IL-1RA; e.g., anakinra), P2Y2 receptor agonists (e.g., uridine triphosphate; UTP), and rebamipide may alleviate human meibomian gland dysfunction (MGD) and/or dry eye disease. Investigators have also proposed that prostaglandin analogues (e.g., bimatoprost) may induce MGD. Our goal was to determine whether these compounds directly influence human meibomian gland epithelial cell (HMGEC) function. Multiple concentrations of each compound were tested for effects on immortalized (I) HMGEC morphology and survival. Nontoxic dosages were used for our studies. Immortalized HMGEC were cultured in the presence of vehicle, CyA, IL-1RA, UTP, rebamipide, or bimatoprost for up to 6 days in various media. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract), differentiation (azithromycin), and signaling pathway activation (insulin-like growth factor 1). Cells were analyzed for neutral lipid staining, lysosome accumulation, lipid composition, and phosphatidylinositol-3-kinase/Akt (AKT), phosphorylation. Our findings demonstrate that CyA, IL-1RA, UTP, rebamipide, and bimatoprost had no effect on the proliferation; neutral lipid content; lysosome number; or levels of free cholesterol, triglycerides, or phospholipids in IHMGECs. Cylosporine A, IL-1RA, rebamipide, and bimatoprost significantly reduced the phosphorylation of AKT, as compared to control. Of interest, tested doses of CyA above 8 nM killed the IHMGECs. Our results show that CyA, IL-1RA, UTP, rebamipide, and bimatoprost do not influence the proliferation or differentiation of IHMGEC. However, with the exception of UTP, these compounds do decrease the activity of the AKT signaling pathway, which is known to promote cell survival.

  3. Analysis of the Composition of Lipid in Human Meibum from Normal Infants, Children, Adolescents, Adults, and Adults with Meibomian Gland Dysfunction Using 1H-NMR Spectroscopy

    PubMed Central

    Shrestha, Rashmi K.; Foulks, Gary N.; Yappert, Marta C.; Milliner, Sarah E.

    2011-01-01

    Purpose. This study represents a first step toward the evaluation of possible compositional differences in meibum from normal donors (Mn) and donors with meibomian gland dysfunction (Md) by 1H-NMR spectroscopy. The results highlight the applicability of 1H-NMR spectroscopy for the quantitative analysis of waxes, cholesteryl esters, and glycerides in meibum lipid (ML). Methods. Meibum was obtained from 41 normal donors and 51 donors with meibomian gland dysfunction (MGD). 1H-NMR spectroscopy was used to quantify the amount of waxes, glycerides, and cholesteryl esters in human meibum. Results. The relative amount of cholesteryl esters in Mn increased with age and was 40% (P < 0.05) lower in Md. Interestingly, the relative levels of cholesteryl esters in infant meibum were comparable to those in Md. The relative amounts of glycerides were not affected significantly by age or MGD. Conclusions. The changes in cholesteryl ester could be used as a molecular marker for MGD and could potentially be applied to follow the efficacy of drug therapy in the treatment of MGD. The similarity of the levels of cholesteryl esters in infant meibum and Md suggests that the relative amounts of these meibum components alone are unlikely to be responsible for the increased stability of the infant tear film and decreased stability of the tear film with MGD. This study reveals the complexity of human MLs and the changes that occur with age and disease. Understanding the factors that lead to such variations is of utmost relevance in the design of effective therapies. PMID:21849420

  4. Pituitary Gland Disorders Overview

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Clinical Trials Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  5. Parathyroid glands (image)

    MedlinePlus

    The 4 parathyroid glands are located near or attached to the back side of the thyroid gland and produce pararthyroid hormone (PTH). Parathyroid hormone regulates calcium, phosphorus, and magnesium balance within ...

  6. Salivary gland tumors

    MedlinePlus

    ... cancers Salivary duct stones Salivary gland infections Dehydration Sarcoidosis Sjögren syndrome The most common type of salivary ... Cancer Cirrhosis Salivary duct stones Salivary gland infections Sarcoidosis Tumor Review Date 10/30/2015 Updated by: ...

  7. Adrenal Gland Cancer

    MedlinePlus

    ... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

  8. Introduction of the human growth hormone gene into the guinea pig mammary gland by in vivo transfection promotes sustained expression of human growth hormone in the milk throughout lactation.

    PubMed

    Hens, J R; Amstutz, M D; Schanbacher, F L; Mather, I H

    2000-10-18

    We tested the feasibility of transfecting mammary tissue in vivo with an expression plasmid encoding the human growth hormone (hGH) gene, under the control of the cytomegalovirus promoter. Guinea pig mammary glands were transfected with plasmid DNA infused through the nipple canal and expression was monitored in control and transfected glands by radioimmunoassay of milk samples for hGH. Sustained expression of hGH throughout lactation was attained with a polyion transfection complex shown to be optimal for the transfection of bovine mammary cells, in vitro. However, contrary to expectations, hGH expression was consistently 5- to 10-fold higher when DEAE-dextran was used alone for transfection. Thus polyion complexes which are optimal for the transfection of cells in vitro may not be optimal in vivo. The highest concentrations of hGH in milk were obtained when glands were transfected within 3 days before parturition. This method may have application for studying the biological role or physical properties of recombinant proteins expressed in low quantities, or for investigating the regulation of gene promoters without the need to construct viral vectors or produce transgenic animals.

  9. Preferential expression of OVOL1 in inner root sheath of hair, sebaceous gland, eccrine duct and their neoplasms in human skin.

    PubMed

    Mitoma, Chikage; Nakahara, Takeshi; Uchi, Hiroshi; Ito, Takamichi; Inatomi, Yusuke; Ide, Takatoshi; Jinnai, Shunichi; Jinnai, Naomi; Iwasaki, Nahoko; Sakamoto, Keiko; Kimura, Nanae; Maeda, Ayami; Kuma, Yuki; Maehara, Eriko; Tsutsumi, Midori; Kido-Nakahara, Makiko; Hirota, Tomomitsu; Tamari, Mayumi; Furue, Masutaka

    2014-08-01

    OVOL1 is an important transcription factor for epidermal keratinization, which suppresses proliferation and switches on the differentiation of keratinocytes. A recent genome-wide association study has revealed that OVOL1 is one of the genes associated with susceptibility to atopic dermatitis. Although it is known to be expressed in murine skin and hair follicles, no investigations have focused on its localization in human skin. In the present study, we thus immunolocalized the expression of OVOL1 in normal and diseased human skin. In normal human skin, OVOL1 was preferentially expressed in the suprabasal layer of the epidermis, inner root sheath of hair, mature sebocytes and the ductal portion of the eccrine glands. Compared to this, no remarkable change in the expression of OVOL1 was observed among inflammatory skin diseases. The expression of OVOL1 was evident in eccrine poroma and hidradenoma. Moreover, it was overexpressed in Bowen's disease and sebaceous adenoma, in sharp contrast to its downregulation in their more malignant counterparts, squamous cell carcinoma and sebaceous carcinoma. OVOL1 may play an important role in human skin morphogenesis and tumorigenesis.

  10. Anisotropic properties of tracheal smooth muscle tissue.

    PubMed

    Sarma, P A; Pidaparti, R M; Meiss, R A

    2003-04-01

    The anisotropic (directional-dependent) properties of contracting tracheal smooth muscle tissue are estimated from a computational model based on the experimental data of length-dependent stiffness. The area changes are obtained at different muscle lengths from experiments in which stimulated muscle undergoes unrestricted shortening. Then, through an interative process, the anisotropic properties are estimated by matching the area changes obtained from the finite element analysis to those derived from the experiments. The results obtained indicate that the anisotropy ratio (longitudinal stiffness to transverse stiffness) is about 4 when the smooth muscle undergoes 70% strain shortening, indicating that the transverse stiffness reduces as the longitudinal stiffness increases. It was found through a sensitivity analysis from the simulation model that the longitudinal stiffness and the in-plane shear modulus are not very sensitive as compared to major Poisson's ratio to the area changes of the muscle tissue. Copyright 2003 Wiley Periodicals, Inc.

  11. Snake Envenomation Causing Distant Tracheal Myonecrosis

    PubMed Central

    Khimani, Amina; Mcnierney, Afton; Surani, Sara; Surani, Salim

    2013-01-01

    Snakebites are often believed to be poisonous. However, this is not always the case. In fact, each bite differs from snake to snake, depending on if the snake is poisonous and if there is envenomation. Venom in pit viper snakebites is often associated with local necrosis. The abundant literature selections and research articles justify local myonecrosis due to envenomation, but there is not much in the literature regarding myonecrosis at a site distant from the snakebite. We hereby present a case of a 42-year-old man who was transferred to our emergency department after a rattlesnake bit him twice. The patient, besides developing local myonecrosis at the site of the snakebite, developed necrosis of the scrotum as well as tracheal pressure myonecrosis at the site of the endotracheal tube balloon. In this review, we will attempt to discuss the myonecrosis pathophysiology and management related to the rattle snakebite. PMID:24083047

  12. Effect of tracheal suctioning on aspiration past the tracheal tube cuff in mechanically ventilated patients

    PubMed Central

    2012-01-01

    Background This clinical study evaluated the effect of a suctioning maneuver on aspiration past the cuff during mechanical ventilation. Methods Patients intubated for less than 48 hours with a PVC-cuffed tracheal tube, under mechanical ventilation with a PEEP ≥5 cm H2O and under continuous sedation, were included in the study. At baseline the cuff pressure was set at 30 cm H2O. Then 0.5ml of blue dye diluted with 3 ml of saline was instilled into the subglottic space just above the cuff. Tracheal suctioning was performed using a 16-French suction catheter with a suction pressure of – 400 mbar. A fiberoptic bronchoscopy was performed before and after the suctioning maneuver, looking for the presence of blue dye in the folds within the cuff wall or in the trachea under the cuff. The sealing of the cuff was defined by the absence of leakage of blue dye either in the cuff wall or in the trachea under the cuff. Results Twenty-five patients were included. The size of the tracheal tube was 7-mm ID for 5 patients, 7.5-mm ID for 16 patients, and 8-mm ID for four patients. Blue dye was never seen in the trachea under the cuff before suctioning and only in one patient (4%) after the suctioning maneuver. Blue dye was observed in the folds within the cuff wall in 6 of 25 patients before suctioning and 11 of 25 after (p = 0.063). Overall, the incidence of sealing of the cuff was 76% before suctioning and 56% after (p = 0.073). Conclusions In patients intubated with a PVC-cuffed tracheal tube and under mechanical ventilation with PEEP ≥5 cm H2O and a cuff pressure set at 30 cm H2O, a single tracheal suctioning maneuver did not increase the risk of aspiration in the trachea under the cuff. Trial registration ClinicalTrials.gov, number NCT01170156 PMID:23134813

  13. Salivary gland progenitor cell biology provides a rationale for therapeutic salivary gland regeneration.

    PubMed

    Lombaert, I M A; Knox, S M; Hoffman, M P

    2011-07-01

    An irreversible loss of salivary gland function often occurs in humans after removal of salivary tumors, after therapeutic radiation of head and neck tumors, as a result of Sjögren's syndrome and in genetic syndromes affecting gland development. The permanent loss of gland function impairs the oral health of these patients and broadly affects their quality of life. The regeneration of functional salivary gland tissue is thus an important therapeutic goal for the field of regenerative medicine and will likely involve stem/progenitor cell biology and/or tissue engineering approaches. Recent reports demonstrate how both innervation of the salivary gland epithelium and certain growth factors influence progenitor cell growth during mouse salivary gland development. These advances in our understanding suggest that developmental mechanisms of mouse salivary gland development may provide a paradigm for postnatal regeneration of both mice and human salivary glands. Herein, we will discuss the developmental mechanisms that influence progenitor cell biology and the implications for salivary gland regeneration.

  14. Wnt Signaling Regulates Airway Epithelial Stem Cells in Adult Murine Submucosal Glands.

    PubMed

    Lynch, Thomas J; Anderson, Preston J; Xie, Weiliang; Crooke, Adrianne K; Liu, Xiaoming; Tyler, Scott R; Luo, Meihui; Kusner, David M; Zhang, Yulong; Neff, Traci; Burnette, Daniel C; Walters, Katherine S; Goodheart, Michael J; Parekh, Kalpaj R; Engelhardt, John F

    2016-06-24

    Wnt signaling is required for lineage commitment of glandular stem cells (SCs) during tracheal submucosal gland (SMG) morphogenesis from the surface airway epithelium (SAE). Whether similar Wnt-dependent processes coordinate SC expansion in adult SMGs following airway injury remains unknown. We found that two Wnt-reporters in mice (BAT-gal and TCF/Lef:H2B-GFP) are coexpressed in actively cycling SCs of primordial glandular placodes and in a small subset of adult SMG progenitor cells that enter the cell cycle 24 hours following airway injury. At homeostasis, these Wnt reporters showed nonoverlapping cellular patterns of expression in the SAE and SMGs. Following tracheal injury, proliferation was accompanied by dynamic changes in Wnt-reporter activity and the analysis of 56 Wnt-related signaling genes revealed unique temporal changes in expression within proximal (gland-containing) and distal (gland-free) portions of the trachea. Wnt stimulation in vivo and in vitro promoted epithelial proliferation in both SMGs and the SAE. Interestingly, slowly cycling nucleotide label-retaining cells (LRCs) of SMGs were spatially positioned near clusters of BAT-gal positive serous tubules. Isolation and culture of tet-inducible H2B-GFP LRCs demonstrated that SMG LRCs were more proliferative than SAE LRCs and culture expanded SMG-derived progenitor cells outcompeted SAE-derived progenitors in regeneration of tracheal xenograft epithelium using a clonal analysis competition assay. SMG-derived progenitors were also multipotent for cell types in the SAE and formed gland-like structures in xenografts. These studies demonstrate the importance of Wnt signals in modulating SC phenotypes within tracheal niches and provide new insight into phenotypic differences of SMG and SAE SCs. Stem Cells 2016.

  15. Expression of S100A2 and S100P in human eccrine sweat glands and their application in differentiating secretory coil-like from duct-like structures in the 3D reconstituted eccrine sweat spheroids.

    PubMed

    Li, Haihong; Zhang, Mingjun; Chen, Liyun; Zhang, Bingna; Zhang, Cuiping

    2017-03-28

    Secretory coils and ducts are two components of eccrine sweat glands with different structures and functions. In our previous study, we combined keratins and α-SMA to distinguish between secretory coils and ducts. However, the key deficiency of the method was that none of the antibodies used was specific for ducts. In this study, we first examined the co-localization of K5/K7, α-SMA/K14, K7/S100P and α-SMA/S100A2 by double-immunofluorescence staining to confirm the localization of S100P and S100A2 in native human eccrine sweat glands, and second we identified secretory coil-like and duct-like structures in the 3D reconstituted eccrine sweat gland spheroids by double-immunofluorescence staining for K7/S100P and α-SMA/S100A2. In native human eccrine sweat glands, S100A2 immunoreactivity was confined to the outer layer and S100P to the inner layer of the duct. In 12-week Matrigel plugs containing eccrine sweat gland cells, double-immunofluorescence staining for K7/S100P and α-SMA/S100A2 could easily distinguish duct-like structures from secretory coil-like structures. We conclude that S100A2 and S100P can be used as specific duct markers in eccrine sweat glands, and combined use of S100P or S100A2 with keratins enables easy to distinction between secretory coils and ducts.

  16. Tracheal intubation and sore throat: a mechanical explanation.

    PubMed

    Chandler, M

    2002-02-01

    Although tracheal intubation remains a valuable tool, it may result in pressure trauma and sore throat. The evidence for an association between these sequelae is not conclusive and sore throat may be caused at the time of intubation. This hypothesis was tested in a mechanical model and the results from tracheal intubation compared with those from insertion of a laryngeal mask airway, which is associated with a lower incidence of sore throat. Use of the model suggests that the tracheal tube and laryngeal mask airway impinge on the pharyngeal wall in different manners and involve different mechanisms for their conformation to the upper airway, but that in a static situation, the forces exerted on the pharyngeal wall are low with both devices. It also suggests that the incidence of sore throat should be lower for softer and smaller tracheal tubes and that the standard 'Magill' curve (radius of curvature 140 +/- 20 mm) is about optimum for the average airway.

  17. Tracheal Stenosis Because of Wegener Granulomatosis Misdiagnosed as Asthma.

    PubMed

    O'Hear, Kelley E; Ingrande, Jerry; Brodsky, Jay B; Morton, John M; Sung, Chih-Kwang

    2016-05-15

    We describe a patient with Wegener granulomatosis whose complaint of wheezing was incorrectly attributed to asthma. Anesthesiologists must recognize that tracheal stenosis is extremely common in Wegener granulomatosis and can mimic other causes of wheezing.

  18. Reresection for recurrent stenosis after primary tracheal repair

    PubMed Central

    Madariaga, Maria Lucia

    2016-01-01

    Failure of the anastomosis after primary tracheal reconstruction for benign disease is uncommon. Here we review the available evidence on tracheal restenosis and the results of second reconstructions. Factors associated with failed primary anastomosis are examined. Temporizing immediate and alternative long-term management with T-tube or tracheostomy is described, emphasizing the role of tracheal stenting in abating the urgency for reoperation. From available evidence, elective reoperative treatment of failed tracheal reconstruction should be considered in selected patients after careful review and reversal of patient- and operation-specific factors that initiated failure. Referral to a high-volume center with a deep bench of nursing, anesthesiologic and surgical expertise is recommended for reoperation. PMID:26981266

  19. Re-epithelialization: a key element in tracheal tissue engineering.

    PubMed

    Zhang, Hengyi; Fu, Wei; Xu, Zhiwei

    2015-11-01

    Trachea-tissue engineering is a thriving new field in regenerative medicine that is reaching maturity and yielding numerous promising results. In view of the crucial role that the epithelium plays in the trachea, re-epithelialization of tracheal substitutes has gradually emerged as the focus of studies in tissue-engineered trachea. Recent progress in our understanding of stem cell biology, growth factor interactions and transplantation immunobiology offer the prospect of optimization of a tissue-engineered tracheal epithelium. In addition, advances in cell culture technology and successful applications of clinical transplantation are opening up new avenues for the construction of a tissue-engineered tracheal epithelium. Therefore, this review summarizes current advances, unresolved obstacles and future directions in the reconstruction of a tissue-engineered tracheal epithelium.

  20. Immunohistochemical detection of angiotensin receptors AT1 and AT2 in normal rat pituitary gland, estrogen-induced rat pituitary tumor and human pituitary adenomas.

    PubMed

    Pawlikowski, Marek

    2006-01-01

    Male rat pituitary glands, diethylstilbestrol (DES)-induced rat pituitary tumors and 12 human pituitary adenomas were immunostained with antibodies raised against AT1 and AT2 angiotensin receptor proteins. Positive immunostaining of AT1 was observed in a subpopulation of anterior and intermediate pituitary lobe cells as well as in some nerve endings of the neurohypophysis. In the DES-induced rat pituiary tumors, the subpopulation of AT1-immunnopositive cells was smaller than in the non-tumoral anterior pituitary. In human pituitary adenomas, weak AT1 immunostaining was found in 5 tumors. In the remaining adenomas, the AT1 immunostaining was trace (doubtful) or absent. The AT1 immunostaining in the peritumoral non-neoplastic pituitary tissue was stronger than that observed in the tumors. The normal rat pituitaries and rat tumors did not show immunostaining with anti-AT2 antibody. In human pituitary adenomas, the tumoral cells were AT2- negative but moderate to strong AT2 immunostaining was observed in intratumoral blood vessel walls. The data suggest that the experimental (in rat) and spontaneous (in man) pituitary tumorigenesis is associated with the down-regulation of AT1 receptors. The expression of AT2 receptors, in turn, may be connected with the process of tumoral neo-angiogenesis.

  1. Mice expressing myrAKT1 in the mammary gland develop carcinogen-induced ER-positive mammary tumors that mimic human breast cancer.

    PubMed

    Blanco-Aparicio, Carmen; Pérez-Gallego, Lucía; Pequeño, Belén; Leal, Juan F M; Renner, Oliver; Carnero, Amancio

    2007-03-01

    AKT1/PKB is a serine/threonine protein kinase that regulates biological processes such as proliferation, apoptosis and growth in a variety of cell types. To assess the oncogenic capability of an activated form of AKT in vivo we have generated several transgenic mouse lines that overexpress in the mammary epithelium the murine Akt1 gene modified with a myristoylation signal, which renders active this protein by localizing it to the plasma membrane. We demonstrate that expression of myristoylated AKT in the mammary glands increases the susceptibility of these mice to the induction of mammary tumors of epithelial origin by the carcinogen 9,10-dimethyl-1,2 benzanthracene (DMBA). We have found that while carcinogen-treated wild-type mice show mostly mammary tumors of sarcomatous origin, AKT transgenic mice treated with DMBA developed mainly adenocarcinoma or adenosquamous tumors, all of them displaying activated AKT. We analyzed other possible molecular alterations cooperating with AKT and found that neither Ras nor beta-catenin/Wnt pathways seemed altered nor p53 mutated. We have found that 100% of mammary DMBA-induced tumors and benign lesions in myrAKT mice are estrogen receptor (ERalpha)-positive and are more frequent than in wild-type littermates. These data show that AKT activation cooperates with deregulation of the estrogen receptor in the DMBA-induced mammary tumorigenesis model and recapitulate two characteristics of some human breast tumors. Thus, our model might provide a preclinical relevant model system to study the role of AKT and ERalpha in breast tumorigenesis and the response of mammary gland tumors to chemotherapeutics.

  2. Protein kinase Cδ is required for ErbB2-driven mammary gland tumorigenesis and negatively correlates with prognosis in human breast cancer.

    PubMed

    Allen-Petersen, B L; Carter, C J; Ohm, A M; Reyland, M E

    2014-03-06

    Protein kinase C δ (PKCδ) regulates apoptosis in the mammary gland, however, the functional contribution of PKCδ to the development or progression of breast cancer has yet to be determined. Meta-analysis of ErbB2-positive breast cancers shows increased PKCδ expression, and a negative correlation between PKCδ expression and prognosis. Here, we present in-vivo evidence that PKCδ is essential for the development of mammary gland tumors in a ErbB2-overexpressing transgenic mouse model, and in-vitro evidence that PKCδ is required for proliferative signaling downstream of the ErbB2 receptor. Mouse mammary tumor virus (MMTV)-ErbB2 mice lacking PKCδ (δKO) have increased tumor latency compared with MMTV-ErbB2 wild-type (δWT) mice, and the tumors show a dramatic decrease in Ki-67 staining. To explore the relationship between PKCδ and ErbB2-driven proliferation more directly, we used MCF-10A cells engineered to express a synthetic ligand-inducible form of the ErbB2 receptor. Depletion of PKCδ with short hairpin RNA inhibited ligand-induced growth in both two-dimensional (2D) (plastic) and three-dimensional (3D) (Matrigel) culture, and correlated with decreased phosphorylation of the ErbB2 receptor and reduced activation of Src and MAPK/ERK pathways. Similarly, in human breast cancer cell lines in which ErbB2 is overexpressed, depletion of PKCδ suppresses proliferation, Src and ERK activation. PKCδ appears to drive proliferation through the formation of an active ErbB2/PKCδ/Src signaling complex, as depletion of PKCδ disrupts association of Src with the ErbB2 receptor. Taken together, our studies present the first evidence that PKCδ is a critical regulator of ErbB2-mediated tumorigenesis, and suggest further investigation of PKCδ as a target in ErbB2-positive breast cancer.

  3. AAV2-mediated transfer of the human aquaporin-1 cDNA restores fluid secretion from irradiated miniature pig parotid glands

    PubMed Central

    Gao, Runtao; Yan, Xing; Zheng, Changyu; Goldsmith, Corinne M.; Afione, Sandra; Hai, Bo; Xu, Junji; Zhou, Jian; Zhang, Chunmei; Chiorini, John A.; Baum, Bruce J.; Wang, Songlin

    2010-01-01

    Previously (Shan et al, 2005), we reported that adenoviral vector-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to minipig parotid glands following irradiation (IRti) transiently restored salivary flow to near normal levels. This study evaluated a serotype 2, adeno-associated viral (AAV2) vector for extended correction of IR (single dose; 20 Gy)-induced, parotid salivary hypofunction in minipigs. Sixteen weeks following IR, parotid salivary flow decreased by 85-90%. AAV2hAQP1 administration at week 17 transduced only duct cells and resulted in a dose-dependent increase in salivary flow to ∼35% of pre-IR levels (to ∼1ml/10min) after 8 weeks (peak response). Administration of a control AAV2 vector or saline, was without effect. Little change was observed in clinical chemistry and hematology values after AAV2hAQP1 delivery. Vector treated animals generated high anti-AAV2 neutralizing antibody titers by week 4 (∼1:1600) and significant elevations in salivary (∼15%), but not serum, GM-CSF levels. Following vector administration, salivary [Na+] was dramatically increased, from ∼10mM to ∼55 (at 4 weeks) and 39 mM (8 weeks). The findings demonstrate that localized delivery of AAV2hAQP1 to IR-damaged parotid glands leads to increased fluid secretion from surviving duct cells, and may be useful in providing extended relief of salivary hypofunction in previously irradiated patients. PMID:20882054

  4. The appearance, density, and distribution of Merkel cells in human embryonic and fetal skin: their relation to sweat gland and hair follicle development.

    PubMed

    Kim, D K; Holbrook, K A

    1995-03-01

    The density and distribution of Merkel cells in human embryonic and fetal skin were studied using an immunolabeling technique on epidermal and dermal sheets obtained by ethylenediamine tetraacetic acid separation. Merkel cells were identified by the known cytokeratin markers CK20 and CK18. Merkel cells showed CK20 immunoreactivity as early as 56 d estimated gestational age (EGA) in the palmar epidermis (133.11 +/- 44.27 cells/mm2). The density increased rapidly, reaching a maximum of more than 1400 cells/mm2 at 80-90 d EGA. At this stage, the cells became distributed along the primary epidermal ridges. In the palmar epidermis of fetuses older than 100 d EGA, the distribution of Merkel cells showed the same pattern, but the density then decreased gradually. Merkel cells were not observed in ductal and glandular portions of eccrine sweat glands. In the epidermal sheets of hairy skin, a few cells were first seen in the fetus at 75 d EGA. At 100 d EGA, only a few Merkel cells were observed, mostly in the hair pegs and bulbous hair pegs. In the older fetus, ring-like arrangements and aggregates of Merkel cells were prominent in the infundibulum and bulge of hair follicles, respectively. Merkel cells were both globular and dendritic in shape. The ratio of dendritic to globular cells increased gradually until the period of highest Merkel cell density in both the glabrous and hairy skin. All Merkel cells located in the dermis were globular in shape. In accord with the results obtained, we postulate that Merkel cells may have some functional role in the formation and proliferation of eccrine sweat glands and hair follicle anlagen in developing skin.

  5. Characterization of Stem-Like Cells in Mucoepidermoid Tracheal Paediatric Tumor

    PubMed Central

    Lim, Mei Ling; Ooi, Brandon Nick Sern; Jungebluth, Philipp; Sjöqvist, Sebastian; Hultman, Isabell; Lemon, Greg; Gustafsson, Ylva; Asmundsson, Jurate; Baiguera, Silvia; Douagi, Iyadh; Gilevich, Irina; Popova, Alina; Haag, Johannes Cornelius; Rodríguez, Antonio Beltrán; Lim, Jianri; Liedén, Agne; Nordenskjöld, Magnus; Alici, Evren; Baker, Duncan; Unger, Christian; Luedde, Tom; Vassiliev, Ivan; Inzunza, Jose; Ährlund-Richter, Lars; Macchiarini, Paolo

    2014-01-01

    Stem cells contribute to regeneration of tissues and organs. Cells with stem cell-like properties have been identified in tumors from a variety of origins, but to our knowledge there are yet no reports on tumor-related stem cells in the human upper respiratory tract. In the present study, we show that a tracheal mucoepidermoid tumor biopsy obtained from a 6 year-old patient contained a subpopulation of cells with morphology, clonogenicity and surface markers that overlapped with bone marrow mesenchymal stromal cells (BM-MSCs). These cells, designated as MEi (mesenchymal stem cell-like mucoepidermoid tumor) cells, could be differentiated towards mesenchymal lineages both with and without induction, and formed spheroids in vitro. The MEi cells shared several multipotent characteristics with BM-MSCs. However, they displayed differences to BM-MSCs in growth kinectics and gene expression profiles relating to cancer pathways and tube development. Despite this, the MEi cells did not possess in vivo tumor-initiating capacity, as proven by the absence of growth in situ after localized injection in immunocompromised mice. Our results provide an initial characterization of benign tracheal cancer-derived niche cells. We believe that this report could be of importance to further understand tracheal cancer initiation and progression as well as therapeutic development. PMID:25229469

  6. Characterization of stem-like cells in mucoepidermoid tracheal paediatric tumor.

    PubMed

    Lim, Mei Ling; Ooi, Brandon Nick Sern; Jungebluth, Philipp; Sjöqvist, Sebastian; Hultman, Isabell; Lemon, Greg; Gustafsson, Ylva; Asmundsson, Jurate; Baiguera, Silvia; Douagi, Iyadh; Gilevich, Irina; Popova, Alina; Haag, Johannes Cornelius; Rodríguez, Antonio Beltrán; Lim, Jianri; Liedén, Agne; Nordenskjöld, Magnus; Alici, Evren; Baker, Duncan; Unger, Christian; Luedde, Tom; Vassiliev, Ivan; Inzunza, Jose; Ahrlund-Richter, Lars; Macchiarini, Paolo

    2014-01-01

    Stem cells contribute to regeneration of tissues and organs. Cells with stem cell-like properties have been identified in tumors from a variety of origins, but to our knowledge there are yet no reports on tumor-related stem cells in the human upper respiratory tract. In the present study, we show that a tracheal mucoepidermoid tumor biopsy obtained from a 6 year-old patient contained a subpopulation of cells with morphology, clonogenicity and surface markers that overlapped with bone marrow mesenchymal stromal cells (BM-MSCs). These cells, designated as MEi (mesenchymal stem cell-like mucoepidermoid tumor) cells, could be differentiated towards mesenchymal lineages both with and without induction, and formed spheroids in vitro. The MEi cells shared several multipotent characteristics with BM-MSCs. However, they displayed differences to BM-MSCs in growth kinectics and gene expression profiles relating to cancer pathways and tube development. Despite this, the MEi cells did not possess in vivo tumor-initiating capacity, as proven by the absence of growth in situ after localized injection in immunocompromised mice. Our results provide an initial characterization of benign tracheal cancer-derived niche cells. We believe that this report could be of importance to further understand tracheal cancer initiation and progression as well as therapeutic development.

  7. Development of surgical protocol for implantation of tracheal prostheses in sheep.

    PubMed

    Dupret-Bories, Agnès; Schultz, Philippe; Vrana, Nihal Engin; Lavalle, Philippe; Vautier, Dominique; Debry, Christian

    2011-01-01

    This article documents experiments performed in ewes to design an artificial larynx. The artificial larynx is composed of a hollow, porous tube that elongates the trachea and is capped with a valve that acts as a laryngeal sphincter. Through an industrial collaboration, our team developed a porous biomaterial that can be colonized by cervical tissues. This biomaterial has been used in animals to replace part of the trachea, but it is meant to eventually substitute for laryngeal cartilage. The tracheal prosthesis is a hollow cylindrical tube composed of titanium microbeads. We performed a study in large animals to establish an optimal surgical protocol for tracheal replacement in humans. The study included 11 sheep (n = 11) and compared 5 methods of implantation. We successfully established an optimal three-step surgical protocol to make the porous-titanium tracheal prosthesis functional: (1) large lumen endoprosthetics, (2) colonization by the peripheral tissues, and (3) endoprosthetic epithelialization. This study is the first step in developing an artificial larynx because it successfully identifies a biomaterial capable of extending the trachea to allow it to open at the junction of the upper aerodigestive tracts.

  8. Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model

    PubMed Central

    Wang, Ting; Zhang, Jie; Wang, Juan; Pei, Ying-Hua; Qiu, Xiao-Jian; Wang, Yu-Ling

    2016-01-01

    Background: Currently available silicone and metallic stents for tracheal stenosis are associated with many problems. Granulation proliferation is one of the main complications. The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model, as well as the pharmacokinetic features and safety profiles of the coated drug. Methods: Eight beagles were randomly divided into a control group (bare-metal stent group, n = 4) and an experimental group (paclitaxel-eluting stent group, n = 4). The observation period was 5 months. One beagle in both groups was sacrificed at the end of the 1st and 3rd months, respectively. The last two beagles in both groups were sacrificed at the end of 5th month. The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups. Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent. The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent. Results: Compared with the control group, the proliferation of granulation tissue in the experimental group was significantly reduced. The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation (up to 70.9%). Then, the release slowed down gradually. By the 5th month, the release reached up to 98.5%. During the observation period, a high concentration of the drug in the trachea (in the stented and adjacent unstented areas) and lung tissue was not noted, and the blood test showed no side effect. Conclusions: The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo, suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future. PMID:27824004

  9. Measurement of tracheal mucous transport rate in the horse

    SciTech Connect

    Nelson, R.; Hampe, D.W.

    1983-06-01

    Tracheal mucous transport rates were measured in 12 nonanesthetized horses after an intratracheal injection of 99mtechnetium-sulfur colloid. The transport rate of the subsequent bolus of radioactivity was determined, using a portable scaler rate meter fitted with a high-energy gamma-scintillation probe. A gamma-scintillation camera was used to verify bolus form and movement in 1 horse. The mean tracheal mucous transport rate was 1.66 +/- 0.24 cm/min.

  10. Tracheal cartilaginous sleeve with cricoid cartilage involvement in Pfeiffer syndrome.

    PubMed

    Elloy, Marianne Dawn; Cochrane, Lesley Ann; Wyatt, Michelle

    2006-03-01

    Pfeiffer syndrome is one of a group of craniosynostosis syndromes in which rare tracheal anomalies have been described. This group of patients have a poor prognosis, and mortality can be related to airway complications and respiratory distress. We report a case of type II Pfeiffer syndrome with tracheal cartilaginous sleeve and cricoid cartilage involvement. We discuss our strategy for the management of the airway of this patient.

  11. Conservative management of intraoperative tracheal injury during cardiac operations.

    PubMed

    Kayatta, Michael O; Vasquez, Julio C; DeLaRosa, Jacob

    2014-04-01

    Iatrogenic intraoperative tracheal injuries are rare in cardiac operations. Management of this complication is not well described because of the low incidence and lack of reported cases. We present an 82-year-old woman who sustained a tracheal injury during aortic valve replacement. Soft tissue coverage of the trachea was obtained, the original cardiac operation was completed, and she was otherwise managed conservatively. She recovered without further complication and was discharged home 1 week after the surgical procedure.

  12. A Pilot Study of Pepsin in Tracheal and Oral Secretions

    PubMed Central

    Schallom, Marilyn; Tricomi, Sally M.; Chang, Yie-Hwa; Metheny, Norma A.

    2013-01-01

    Background Because reflux of gastric juice into the oropharynx must precede its aspiration into the lungs, it is reasonable to hypothesize that the detection of pepsin (the major gastric enzyme in gastric juice) in oral secretions may provide a relatively non-invasive method to predict risk for aspiration. Objective The purpose of this pilot study was to describe the incidence of pepsin in oral and tracheal secretions collected concurrently from a sample of 50 mechanically ventilated, gastric-fed patients. Methods The study used an exploratory descriptive design with a convenience sample from four medical and surgical intensive care units. A single oral and tracheal secretion was collected concurrently from each patient (yielding a sample of 50 oral and 50 tracheal secretions). The tracheal secretions were obtained via the inline suction system with an attached sputum trap; oral secretions were obtained via a yankauer suction tip with an attached sputum trap. All specimens were assayed for pepsin by the Western Blot method. Results Oral secretions from ten patients (20%) were pepsin-positive while tracheal secretions from two patients (4%) were pepsin-positive. Both patients with pepsin-positive tracheal secretions also had pepsin-positive oral secretions. Pepsin was not found in the tracheal secretions from the remaining eight patients with pepsin-positive oral secretions. Conclusions Although reflux of gastric juice into the oropharynx must precede its aspiration into the lungs, individual reflux events do not necessarily lead to aspiration. Thus, it is reasonable that we found pepsin 5-times more often in oral secretions than in tracheal secretions. PMID:23996420

  13. Tracheal papillomatosis treated with Nd-Yag laser resection.

    PubMed

    Hunt, J M; Pierce, R J

    1988-10-01

    We report a case of tracheal papillomatosis in a 69-year-old woman who presented with stridor and functional evidence of large airway obstruction. She was successfully treated by endobronchial resection using a Neodymium Yag laser. This provided lasting symptomatic relief of dyspnea. Respiratory papillomatosis is a disease predominantly of the childhood larynx and its presentation with predominant tracheal involvement late in life is extremely uncommon. Laser therapy provides an extremely effective treatment modality for this condition.

  14. [Comparative ultrastructural study of parotid gland, lacrimal gland and pituitary gland between miniature pig and mouse].

    PubMed

    Yan, Xing; Hai, Bo; Sun, Yi-lin; Zhang, Chun-mei; Wang, Song-ling

    2009-02-01

    To study the ultrastructure of parotid glands, lacrimal glands and pituitary glands between miniature pig and mouse. Five adult miniature pigs and 5 mice were studied. Ultrastructure of their parotid glands, lacrimal glands, and pituitary glands was observed. The secretary granules in acinar cell of miniature pig parotid glands showed higher density and more aequalis than those of mice. The cell apparatus in acinar cell of mouse parotid glands were more plentiful than those of miniature pigs. The secretary granules on blood vessel wall were richer in parotid gland of miniature pigs compared with mouse parotid gland. Lacrimal gland had the similar ultrastructure to parotid gland in these two animals. Many blood vessel antrum were found in pituitary glands of these two animals. Compared with mouse parotid glands, there are more secretary granules in acinar cells and vascular endothelial cells in miniature pig parotid glands, which might enter blood stream and have function of endocrine secretion.

  15. Tracheal extubation in children: halothane versus isoflurane, anesthetized versus awake.

    PubMed

    Pounder, D R; Blackstock, D; Steward, D J

    1991-04-01

    The authors compared the incidence of respiratory complications and arterial hemoglobin desaturation during emergence from anesthesia in children whose tracheas were extubated while they were anesthetized or after they were awake and to whom halothane or isoflurane had been administered. One hundred children 1-4 yr of age undergoing minor urologic surg