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Sample records for interstitial cell function

  1. Experimental depletion of different renal interstitial cell populations

    International Nuclear Information System (INIS)

    Bohman, S.O.; Sundelin, B.; Forsum, U.; Tribukait, B.

    1988-01-01

    To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

  2. Advanced sickle cell associated interstitial lung disease presenting ...

    African Journals Online (AJOL)

    Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by ...

  3. Functional innervation of Guinea-pig bladder interstitial cells of cajal subtypes: neurogenic stimulation evokes in situ calcium transients.

    Directory of Open Access Journals (Sweden)

    Susannah M Gray

    Full Text Available Several populations of interstitial cells of Cajal (ICC exist in the bladder, associated with intramural nerves. Although ICC respond to exogenous agonists, there is currently no evidence of their functional innervation. The objective was to determine whether bladder ICC are functionally innervated. Guinea-pig bladder tissues, loaded with fluo-4AM were imaged with fluorescent microscopy and challenged with neurogenic electrical field stimulation (EFS. All subtypes of ICC and smooth muscle cells (SMC displayed spontaneous Ca(2+-oscillations. EFS (0.5 Hz, 2 Hz, 10 Hz evoked tetrodotoxin (1 µM-sensitive Ca(2+-transients in lamina propria ICC (ICC-LP, detrusor ICC and perivascular ICC (PICC associated with mucosal microvessels. EFS responses in ICC-LP were significantly reduced by atropine or suramin. SMC and vascular SMC (VSM also responded to EFS. Spontaneous Ca(2+-oscillations in individual ICC-LP within networks occurred asynchronously whereas EFS evoked coordinated Ca(2+-transients in all ICC-LP within a field of view. Non-correlated Ca(2+-oscillations in detrusor ICC and adjacent SMC pre-EFS, contrasted with simultaneous neurogenic Ca(2+ transients evoked by EFS. Spontaneous Ca(2+-oscillations in PICC were little affected by EFS, whereas large Ca(2+-transients were evoked in pre-EFS quiescent PICC. EFS also increased the frequency of VSM Ca(2+-oscillations. In conclusion, ICC-LP, detrusor ICC and PICC are functionally innervated. Interestingly, Ca(2+-activity within ICC-LP networks and between detrusor ICC and their adjacent SMC were synchronous under neural control. VSM and PICC Ca(2+-activity was regulated by bladder nerves. These novel findings demonstrate functional neural control of bladder ICC. Similar studies should now be carried out on neurogenic bladder to elucidate the contribution of impaired nerve-ICC communication to bladder pathophysiology.

  4. On the in vivo function of the mitral heart valve leaflet: insights into tissue-interstitial cell biomechanical coupling.

    Science.gov (United States)

    Lee, Chung-Hao; Zhang, Will; Feaver, Kristen; Gorman, Robert C; Gorman, Joseph H; Sacks, Michael S

    2017-10-01

    There continues to be a critical need for developing data-informed computational modeling techniques that enable systematic evaluations of mitral valve (MV) function. This is important for a better understanding of MV organ-level biomechanical performance, in vivo functional tissue stresses, and the biosynthetic responses of MV interstitial cells (MVICs) in the normal, pathophysiological, and surgically repaired states. In the present study, we utilized extant ovine MV population-averaged 3D fiducial marker data to quantify the MV anterior leaflet (MVAL) deformations in various kinematic states. This approach allowed us to make the critical connection between the in vivo functional and the in vitro experimental configurations. Moreover, we incorporated the in vivo MVAL deformations and pre-strains into an enhanced inverse finite element modeling framework (Path 1) to estimate the resulting in vivo tissue prestresses [Formula: see text] and the in vivo peak functional tissue stresses [Formula: see text]. These in vivo stress estimates were then cross-verified with the results obtained from an alternative forward modeling method (Path 2), by taking account of the changes in the in vitro and in vivo reference configurations. Moreover, by integrating the tissue-level kinematic results into a downscale MVIC microenvironment FE model, we were able to estimate, for the first time, the in vivo layer-specific MVIC deformations and deformation rates of the normal and surgically repaired MVALs. From these simulations, we determined that the placement of annuloplasty ring greatly reduces the peak MVIC deformation levels in a layer-specific manner. This suggests that the associated reductions in MVIC deformation may down-regulate MV extracellular matrix maintenance, ultimately leading to reduction in tissue mechanical integrity. These simulations provide valuable insight into MV cellular mechanobiology in response to organ- and tissue-level alternations induced by MV disease or

  5. Respiratory muscle function in interstitial lung disease.

    Science.gov (United States)

    Walterspacher, Stephan; Schlager, Daniel; Walker, David J; Müller-Quernheim, Joachim; Windisch, Wolfram; Kabitz, Hans-Joachim

    2013-07-01

    Interstitial lung diseases limit daily activities, impair quality of life and result in (exertional) dyspnoea. This has mainly been attributed to a decline in lung function and impaired gas exchange. However, the contribution of respiratory muscle dysfunction to these limitations remains to be conclusively investigated. Interstitial lung disease patients and matched controls performed body plethysmography, a standardised 6-min walk test, volitional tests (respiratory drive (P0.1), global maximal inspiratory mouth occlusion pressure (PImax), sniff nasal pressure (SnPna) and inspiratory muscle load) and nonvolitional tests on respiratory muscle function and strength (twitch mouth and transdiaphragmatic pressure during bilateral magnetic phrenic nerve stimulation (TwPmo and TwPdi)). 25 patients and 24 controls were included in the study. PImax and SnPna remained unaltered (both p>0.05), whereas P0.1 and the load on the inspiratory muscles were higher (both prespiratory muscle strength remains preserved. Central respiratory drive and the load imposed on the inspiratory muscles are increased. Whether impaired respiratory muscle function impacts morbidity and mortality in interstitial lung disease patients needs to be investigated in future studies.

  6. Interstitial cells in the musculature of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    , the ultrastructure and light microscopic morphology, as well as the functions and the development of ICC and of neighboring fibroblast-like cells (FLC), are critically reviewed. Directions for future research are considered and a unifying concept of mesenchymal cells, either KIT positive (the "ICC") or KIT negative......Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component...... "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells...

  7. About the presence of interstitial cells of Cajal outside the musculature of the gastrointestinal tract.

    Science.gov (United States)

    Huizinga, Jan D; Faussone-Pellegrini, Maria-Simonetta

    2005-01-01

    Santiago Ramon y Cajal observed a special cell type that appeared to function as endstructures of the intrinsic nervous system in several organs. These cells were structurally and functionally further characterized in the gut musculature and named interstitial cells of Cajal (ICC). In recent years, interstitial cells have been identified in the vasculature, urinary tract, glands and other organs. Their morphologies and functions are just beginning to be clarified. It is likely that amongst them, subtypes will be discovered that warrant the classification of interstitial cells of Cajal. This "point of view" continues the discussion on the criteria that should be used to identify ICC outside the musculature of the gut.

  8. Advanced sickle cell associated interstitial lung disease presenting with cor pulmonale in a Nigerian.

    Science.gov (United States)

    Fawibe, Ademola Emmanuel; Kolo, Philip Manman; Ogunmodede, James Ayodele; Desalu, Olufemi Olumuyiwa; Salami, Kazeem Alakija

    2012-04-01

    Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by pulmonary hypertension and cor pulmonale.

  9. Interstitial cells in the musculature of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    , the ultrastructure and light microscopic morphology, as well as the functions and the development of ICC and of neighboring fibroblast-like cells (FLC), are critically reviewed. Directions for future research are considered and a unifying concept of mesenchymal cells, either KIT positive (the "ICC") or KIT negative...... "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells...

  10. Effects of Electroacupuncture on Interstitial Cells of Cajal (ICC) Ultrastructure and Connexin 43 Protein Expression in the Gastrointestinal Tract of Functional Dyspepsia (FD) Rats.

    Science.gov (United States)

    Zhang, Guoshan; Xie, Shen; Hu, Wei; Liu, Yuer; Liu, Mailan; Liu, Mi; Chang, Xiaorong

    2016-06-14

    BACKGROUND Gastrointestinal motility disorder is the main clinical manifestation in functional dyspepsia (FD) patients. Electroacupuncture is effective in improving gastrointestinal motility disorder in FD; however, the underlying mechanism remains unclear. It has been demonstrated that interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal tract, and the pacemaker potential is transmitted to nearby cells through gap junctions between ICC or ICC and the smooth muscle. Therefore, this study aimed to assess the effects of electroacupuncture on ICC ultrastructure and expression of the gap junction protein connexin 43 (Cx43) in FD rats. MATERIAL AND METHODS The animals were randomized into 3 groups: control, model, and electroacupuncture. Electroacupuncture was applied at Zusanli (ST36) in the electroacupuncture group daily for 10 days, while no electroacupuncture was applied to model group animals. RESULTS Ultrastructure of ICC recovered normally in gastric antrum and small intestine specimens was improved, with Cx43 expression levels in these tissues significantly increased in the electroacupuncture group compared with the model group. CONCLUSIONS These findings indicated that electroacupuncture is effective in alleviating ICC damage and reduces Cx43 levels in FD rats, and suggest that ICC and Cx43 are involved in electroacupuncture treatment in rats with FD to improve gastrointestinal motility disorders.

  11. CD34-positive interstitial cells of the human detrusor

    DEFF Research Database (Denmark)

    Rasmussen, Helle; Hansen, Alastair; Smedts, Frank

    2007-01-01

    Interstitial cells of Cajal (ICC) are well described in the bowel wall. They are c-kit positive and play a role as pacemaker cells. Similar c-kit-positive cells have recently been described in the human bladder. The aim of this study was to characterize interstitial cells of the bladder detrusor...... using a panel of antibodies directed against CD117/c-kit, CD34, CD31, S100, tryptase, neurofilament, NSE, Factor-VIII and GFAP. A striking finding was an interstitial type of cell which is CD34 immunoreactive (CD34-ir) but CD117/c-kit negative. The cells have a tentacular morphology, enveloping...... and intermingling with individual muscle fasicles. Morphologically and immunohistochemically, they show no neurogenic, endothelial or mast cell differentiation. Transmission electron microscopy (TEM) showed the presence of interstitial cells with a round-to-oval nucleus, sparse perinuclear cytoplasm and long...

  12. The Mystery of the Interstitial Cells in the Urinary Bladder.

    Science.gov (United States)

    Koh, Sang Don; Lee, Haeyeong; Ward, Sean M; Sanders, Kenton M

    2018-01-06

    Intrinsic mechanisms to restrain smooth muscle excitability are present in the bladder, and premature contractions during filling indicate a pathological phenotype. Some investigators have proposed that c-Kit + interstitial cells (ICs) are pacemakers and intermediaries in efferent and afferent neural activity, but recent findings suggest these cells have been misidentified and their functions have been misinterpreted. Cells reported to be c-Kit + cells colabel with vimentin antibodies, but vimentin is not a specific marker for c-Kit + cells. A recent report shows that c-Kit + cells in several species coexpress mast cell tryptase, suggesting that they are likely to be mast cells. In fact, most bladder ICs labeled with vimentin antibodies coexpress platelet-derived growth factor receptor α (PDGFRα). Rather than an excitatory phenotype, PDGFRα + cells convey inhibitory regulation in the detrusor, and inhibitory mechanisms are activated by purines and stretch. PDGFRα + cells restrain premature development of contractions during bladder filling, and overactive behavior develops when the inhibitory pathways in these cells are blocked. PDGFRα + cells are also a prominent cell type in the submucosa and lamina propria, but little is known about their function in these locations. Effective pharmacological manipulation of bladder ICs depends on proper identification and further study of the pathways in these cells that affect bladder functions.

  13. Interstitial cells in the musculature of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells......Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component...

  14. Role of inflammation in bladder function and interstitial cystitis

    Science.gov (United States)

    Grover, Sonal; Srivastava, Abhishek; Lee, Richard; Tewari, Ashutosh K.; Te, Alexis E.

    2011-01-01

    Cystitis, or inflammation of the bladder, has a direct effect on bladder function. Interstitial cystitis is a syndrome characterized by urinary bladder pain and irritative symptoms of more than 6 months duration. It commonly occurs in young to middle-aged women with no known cause and in fact represents a diagnosis of exclusion. Many factors have been suggested, including chronic or subclinical infection, autoimmunity and genetic susceptibility, which could be responsible for initiating the inflammatory response. However, a central role of inflammation has been confirmed in the pathogenesis of interstitial cystitis. Patients with interstitial cystitis are usually managed with multimodal therapy to break the vicious cycle of chronic inflammation at every step. Patients who develop irreversible pathologies such as fibrosis are managed surgically, which is usually reserved for refractory cases. PMID:21789096

  15. Crohn's disease: ultrastructure of interstitial cells in colonic myenteric plexus

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johs.; Vanderwinden, Jean-Marie; Horn, Thomas

    2011-01-01

    -MP and other interstitial cells in the myenteric region of the colon are lacking for CD. In the present study, we characterized the ultrastructure of interstitial cells, nerves, and glial cells in the myenteric region in Crohn's colitis (CC). In comparison with controls, varicosities of the myenteric bundles...... were dilated and appeared to be empty. Lipid droplets and lipofuscin-bodies were prominent in glial cells and neurons. ICC-MP were scanty but, as in controls, had caveolae, prominent intermediate filaments, cytoplasmic dense bodies, and membrane-associated dense bands with a patchy basal lamina. ICC......The role of the interstitial cells of Cajal (ICC) in chronic inflammatory bowel disease, i.e., ulcerative colitis (UC) and Crohn's disease (CD), remains unclear. Ultrastructural alterations in ICC in the colonic myenteric plexus (ICC-MP) have been reported previously in UC, but descriptions of ICC...

  16. Interstitial cells in the musculature of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component (e...

  17. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity

    DEFF Research Database (Denmark)

    Huizinga, J D; Thuneberg, L; Klüppel, M

    1995-01-01

    The pacemaker activity in the mammalian gut is responsible for generating anally propagating phasic contractions. The cellular basis for this intrinsic activity is unknown. The smooth muscle cells of the external muscle layers and the innervated cellular network of interstitial cells of Cajal......, which is closely associated with the external muscle layers of the mammalian gut, have both been proposed to stimulate pacemaker activity. The interstitial cells of Cajal were identified in the last century but their developmental origin and function have remained unclear. Here we show...... of Cajal associated with Auerbach's nerve plexus and intestinal pacemaker activity....

  18. Ultrastructural and immunocytochemical characterization of interstitial cells in pre- and postnatal developing sheep pineal gland

    Directory of Open Access Journals (Sweden)

    E Redondo

    2009-12-01

    Full Text Available Pineal gland interstitial cells from 32 sheep embryos (from day 54 of gestation until birth and 18 sheep (from 1 month to >2 years were analysed using ultrastructural and immunohistochemical techniques. From day 98 of gestation and throughout postnatal development, a second cell type was observed in addition to pinealocytes; these cells displayed uniform ultrastructural features similar to those of CNS astrocytes. Ultrastructural homogeneity was not matched by the results of histochemical and immunohistochemical analysis. Expression of phosphotungstic acid hematoxylin, glial fibrillary acidic protein and vimentin indicates that the second cell population in the developing ovine pineal gland is, in fact, a combination of glial-astrocyte cells at varying stages of maturity. Pineal interstitial cells started to show signs of functional activity evident in vascular tropism; such activity, evident from around day 98 of gestation, appeared to relate to the exchange of substances between the pineal parenchyma and blood vessels and, though it continued throughout postnatal development, was most evident in animals slaughtered between 9 months and 2 years of age (group II. Morphologically, functional activi- ty in interstitial cells in this age-group was apparent in: 1, formation of specific contact sites between interstitial cells and nerve fibres in the perivascular space; and 2, the presence of numerous gap junctions between the bulbous endings of cytoplasmic processes.

  19. Interstitial cells of Cajal in human gut and gastrointestinal disease

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J

    1999-01-01

    This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastrointestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their fun...

  20. Respiratory and lower limb muscle function in interstitial lung disease.

    Science.gov (United States)

    Panagiotou, Marios; Polychronopoulos, Vlasis; Strange, Charlie

    2016-05-01

    Growing evidence suggests that respiratory and limb muscle function may be impaired in patients with interstitial lung disease (ILD). Importantly, muscle dysfunction could promote dyspnoea, fatigue and functional limitation all of which are cardinal features of ILD. This article examines the risk factors for skeletal muscle dysfunction in ILD, reviews the current evidence on overall respiratory and limb muscle function and focuses on the occurrence and implications of skeletal muscle dysfunction in ILD. Research limitations and pathways to address the current knowledge gaps are highlighted. © The Author(s) 2016.

  1. Interstitial cells of Cajal in the vermiform appendix in childhood.

    Science.gov (United States)

    Richter, A; Wit, C; Vanderwinden, J-M; Wit, J; Barthlen, W

    2009-02-01

    The interstitial cells of Cajal (ICC) have not yet been investigated in the vermiform appendix. They are important for the peristalsis of the gastrointestinal tract and have been found to be altered in various motility disorders. Motor disturbance has been suggested as a possible contributor in the unclear etiology of appendicitis. We wanted to examine the distribution of the ICC in the vermiform appendix. Furthermore we investigated whether ICC are altered in persons with appendicitis. We investigated the ICC distribution in 28 appendices of children using immunohistochemistry and anti-c-kit antibodies. Cells and processes were quantified in normal, acute and chronic inflamed appendices. IC(C)-CM and IC(C)-LM were found in the circular and longitudinal muscle layers, respectively. IC(C)-LM, however, were scarce and inhomogeneous in contrast to the IC(C)-CM. The functionally important subgroups of the colon, the IC(C)-SM and IC(C)-MP, however, could not be detected in the appendix with the used antibody. There was no difference in the distribution of detected ICC between normal and inflamed appendices. IC(C)-LM are altered and IC(C)-SM and IC(C)-MP are lost in the vermiform appendix with no differences between healthy and inflamed tissue and without a correlation to appendicitis. Thus, other factors must be considered in the etiology of appendicitis.

  2. Primary rat Sertoli and interstitial cells exhibit a differential response to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Clough, S.R.; Welsh, M.J.; Payne, A.H.; Brown, C.D.; Brabec, M.J. (Eastern Michigan Univ., Ypsilanti (USA))

    1990-01-01

    Two cell types central to the support of spermatogenesis, the Sertoli cell and the interstitial (Leydig) cell, were isolated from the same cohort of young male rats and challenged with cadmium chloride to compare their susceptibility to the metal. Both cell types were cultured under similar conditions, and similar biochemical endpoints were chosen to minimize experimental variability. These endpoints include the uptake of 109Cd, reduction of the vital tetrazolium dye MTT, incorporation of 3H-leucine, change in heat-stable cadmium binding capacity, and production of lactate. Using these parameters, it was observed that the Sertoli cell cultures were adversely affected in a dose-and time-dependent manner, while the interstitial cell cultures, treated with identical concentrations of CdCl2, were less affected. The 72-hr LC50's for Sertoli cells and interstitial cells were 4.1 and 19.6 microM CdCl2, respectively. Thus, different cell populations within the same tissue may differ markedly in susceptibility to a toxicant. These in vitro data suggest that the Sertoli cell, in relation to the interstitium, is particularly sensitive to cadmium. Because the Sertoli cell provides functional support for the seminiferous epithelium, the differential sensitivity of this cell type may, in part, explain cadmium-induced testicular dysfunction, particularly at doses that leave the vascular epithelium intact.

  3. Differential gene expression in the murine gastric fundus lacking interstitial cells of Cajal

    Directory of Open Access Journals (Sweden)

    Ward Sean M

    2003-06-01

    Full Text Available Abstract Background The muscle layers of murine gastric fundus have no interstitial cells of Cajal at the level of the myenteric plexus and only possess intramuscular interstitial cells and this tissue does not generate electric slow waves. The absence of intramuscular interstitial cells in W/WV mutants provides a unique opportunity to study the molecular changes that are associated with the loss of these intercalating cells. Method The gene expression profile of the gastric fundus of wild type and W/WV mice was assayed by murine microarray analysis displaying a total of 8734 elements. Queried genes from the microarray analysis were confirmed by semi-quantitative reverse transcription-polymerase chain reaction. Results Twenty-one genes were differentially expressed in wild type and W/WV mice. Eleven transcripts had 2.0–2.5 fold higher mRNA expression in W/WV gastric fundus when compared to wild type tissues. Ten transcripts had 2.1–3.9 fold lower expression in W/WV mutants in comparison with wild type animals. None of these genes have ever been implicated in any bowel motility function. Conclusions These data provides evidence that several important genes have significantly changed in the murine fundus of W/WV mutants that lack intramuscular interstitial cells of Cajal and have reduced enteric motor neurotransmission.

  4. Diabetes might adversely affect expression and function of interstitial cells in the urinary bladder and urethra in humans: a new mechanism in the development of diabetic lower urinary dysfunction?

    Science.gov (United States)

    Canda, Abdullah Erdem

    2011-05-01

    Diabetes is an important disease affecting many people worldwide which causes significant morbidity. In the lower urinary tract (LUT), diabetes causes LUT dysfunction in humans by leading to neuropathic bladder. In addition, diabetes can lead to functional and anatomical abnormalities of the external urethral sphincter. Diabetes was suggested to cause these complications by affecting autonomic or peripheral nerves or both. Cells having similar characteristics with interstitial cells of Cajal that are present in the gastrointestinal system have also been described in the human urinary tract. Interstitial cells (ICs) in the urinary tract were suggested to function as pacemaker cells, stretch or chemical sensors that might trigger detrusor contractions which work with close relationship with the nerves. In the human urethra, ICs were suggested to control the frequency of tonic contractions of the urethral smooth muscle. Therefore, ICs seem be playing a very important role in LUT function in humans. The hypothesis in this paper suggests that diabetes might also adversely affect IC expression and IC function in the human LUT which might play a significant role in the development of diabetic LUT dysfunction. A search of the English literature was performed by using Medline/PubMed in order to search this hypothesis and no particular study was found in humans. The information and evidence obtained following the investigation of this hypothesis might uncover the possible underlying mechanism of decreased IC expression or function in addition to neuropathy in the development of diabetic LUT dysfunction. Currently, no specific medical drug treatment or preventive measure exists targeting the cellular components of the LUT (i.e. ICs and nerves) which are in fact responsible for a normally functioning LUT. If the expression and distribution of ICs are adversely affected in the LUT of patients with diabetes, specific drugs might be developed as targeted therapy stimulating IC

  5. Ultrastructure of interstitial cells of Cajal associated with deep muscular plexus of human small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Mikkelsen, H B; Thuneberg, L

    1992-01-01

    Evidence showing that interstitial cells of Cajal have important regulatory functions in the gut musculature is accumulating. In the current study, the ultrastructure of the deep muscular plexus and associated interstial cells of Cajal in human small intestine were studied to provide a reference...... for identification and further physiological or pathological studies. The deep muscular plexus was sandwiched between a thin inner layer of smooth muscle (one to five cells thick) and the bulk of the circular muscle. Interstitial cells of Cajal in this region very much resembled smooth muscle cells (with...... distinguished from fibroblasts or macrophages in the region. They ramified in the inner zone of the outer division of circular muscle, penetrated the inner-most circular layer, and were also found at the submucosal border. They were in close, synapselike contact with nerve terminals of the deep muscular plexus...

  6. Perivascular Interstitial Cells of Cajal in Human ColonSummary

    Directory of Open Access Journals (Sweden)

    Yuan-An Liu

    2015-01-01

    Full Text Available Background & Aims: Interstitial cells of Cajal (ICC closely associate with nerves and smooth muscles to modulate gut motility. In the ICC microenvironment, although the circulating hormones/factors have been shown to influence ICC activities, the association between ICC and microvessels in the gut wall has not been described. We applied three-dimensional (3D vascular histology with c-kit staining to identify the perivascular ICC and characterize their morphologic and population features in the human colon wall. Methods: Full-thickness colons were obtained from colectomies performed for colorectal cancer. We targeted the colon wall away from the tumor site. Confocal microscopy with optical clearing (use of immersion solution to reduce scattering in optical imaging was performed to simultaneously reveal the ICC and vascular networks in space. 3D image rendering and projection were digitally conducted to illustrate the ICC–vessel contact patterns. Results: Perivascular ICC were identified in the submucosal border, myenteric plexus, and circular and longitudinal muscles via high-definition 3D microscopy. Through in-depth image projection, we specified two contact patterns—the intimate cell body-to-vessel contact (type I, 18% of ICC in circular muscle and the long-distance process-to-vessel contact (type II, 16%—to classify perivascular ICC. Particularly, type I perivascular ICC were detected with elevated c-kit staining levels and were routinely found in clusters, making them readily distinguishable from other ICC in the network. Conclusions: We propose a new subclass of ICC that closely associates with microvessels in the human colon. Our finding suggests a functional relationship between these mural ICC and microvessels based on the morphologic proximity. Keywords: 3D Histology, c-kit, ICC, Mural Cells

  7. Interstitial cells in the musculature of the gastrointestinal tract: Cajal and beyond

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    , the ultrastructure and light microscopic morphology, as well as the functions and the development of ICC and of neighboring fibroblast-like cells (FLC), are critically reviewed. Directions for future research are considered and a unifying concept of mesenchymal cells, either KIT positive (the "ICC") or KIT negative...... "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells...

  8. Interstitial cells of Cajal mediate mechanosensitive responses in the stomach

    Science.gov (United States)

    Won, Kyung-Jong; Sanders, Kenton M.; Ward, Sean M.

    2005-10-01

    Changes in motor activity are a basic response to filling of smooth muscle organs. Responses to gastric filling, for example, are thought to be regulated by neural reflexes. Here, we demonstrate a previously uncharacterized aspect of stretch-dependent responses in visceral smooth muscles that is mediated by mechanosensitive interstitial cells of Cajal. Length ramps were applied to the murine antral muscles while recording intracellular electrical activity and isometric force. Stretching muscles by an average of 27 ± 1% of resting length resulted in 5 mN of force. Increasing length caused membrane depolarization and increased slow-wave frequency. The responses were dependent on the rate of stretch. Stretch-dependent responses were not inhibited by neuronal antagonists or nifedipine. Increases in slow-wave frequency, but not membrane depolarization, were inhibited by reducing external Ca2+ (100 μM) and by Ni2+ (250 μM). Responses to stretch were inhibited by indomethacin (1 μM) and were absent in cyclooxygenase II-deficient mice, suggesting that cyclooxygenase II-derived eicosanoids may mediate these responses. Dual microelectrode impalements of muscle cells within the corpus and antrum showed that stretch-induced changes in slow-wave frequency uncoupled proximal-to-distal propagation of slow waves. This uncoupling could interfere with gastric peristalsis and impede gastric emptying. Stretch of antral muscles of W/WV mice, which lack intramuscular interstitial cells of Cajal, did not affect membrane depolarization or slow-wave frequency. These data demonstrate a previously uncharacterized nonneural stretch reflex in gastric muscles and provide physiological evidence demonstrating a mechanosensitive role for interstitial cells of Cajal in smooth muscle tissues. gastric compliance | pacemaker | stretch | slow waves | propagation

  9. Interstitial Fluid Flow: The Mechanical Environment of Cells and Foundation of Meridians

    Directory of Open Access Journals (Sweden)

    Wei Yao

    2012-01-01

    Full Text Available Using information from the deep dissection, microobservation, and measurement of acupoints in the upper and lower limbs of the human body, we developed a three-dimensional porous medium model to simulate the flow field using FLUENT software and to study the shear stress on the surface of interstitial cells (mast cells caused by interstitial fluid flow. The numerical simulation results show the following: (i the parallel nature of capillaries will lead to directional interstitial fluid flow, which may explain the long interstitial tissue channels or meridians observed in some experiments; (ii when the distribution of capillaries is staggered, increases in the velocity alternate, and the velocity tends to be uniform, which is beneficial for substance exchange; (iii interstitial fluid flow induces a shear stress, with magnitude of several Pa, on interstitial cell membranes, which will activate cells and lead to a biological response; (iv capillary and interstitial parameters, such as capillary density, blood pressure, capillary permeability, interstitial pressure, and interstitial porosity, affect the shear stress on cell surfaces. The numerical simulation results suggest that in vivo interstitial fluid flow constitutes the mechanical environment of cells and plays a key role in guiding cell activities, which may explain the meridian phenomena and the acupuncture effects observed in experiments.

  10. T Cell Interstitial Migration: Motility Cues from the Inflamed Tissue for Micro- and Macro-Positioning.

    Science.gov (United States)

    Gaylo, Alison; Schrock, Dillon C; Fernandes, Ninoshka R J; Fowell, Deborah J

    2016-01-01

    Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell's antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function.

  11. Ultrastructure of interstitial cells of Cajal in myenteric plexus of human colon

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johs.; Vanderwinden, Jean-Marie; Rasmussen, Helle

    2009-01-01

    The role of the interstitial cells of Cajal (ICC) associated with the myenteric plexus (ICC-MP) as regulators of the motility of the colonic external muscle remains unclear. Ultrastructural studies of myenteric interstitial cells are lacking in human colon. We therefore characterized the distinct......The role of the interstitial cells of Cajal (ICC) associated with the myenteric plexus (ICC-MP) as regulators of the motility of the colonic external muscle remains unclear. Ultrastructural studies of myenteric interstitial cells are lacking in human colon. We therefore characterized...

  12. Digital quantitative analysis of mast cell infiltration in interstitial cystitis.

    Science.gov (United States)

    Akiyama, Yoshiyuki; Maeda, Daichi; Morikawa, Teppei; Niimi, Aya; Nomiya, Akira; Yamada, Yukio; Igawa, Yasuhiko; Goto, Akiteru; Fukayama, Masashi; Homma, Yukio

    2018-02-01

    To evaluate the significance of mast cell infiltration in interstitial cystitis (IC) by comparison with equally inflamed controls using a digital quantification technique. Bladder biopsy specimens from 31 patients with Hunner type IC and 38 patients with non-Hunner type IC were analyzed. Bladder biopsy specimens from 37 patients without IC, including 19 non-specific chronic cystitis ("non-IC cystitis") specimens and 18 non-inflamed bladder ("normal bladder") specimens, were used as controls. Mast cell tryptase-, CD3-, CD20-, and CD138-immunoreactive cells were quantified using digital image analysis software to evaluate both mast cell and lymphoplasmacytic cell densities. Mast cell and lymphoplasmacytic cell densities were counted independently in the entire lamina propria and detrusor areas and compared among the four groups. In the lamina propria, there were no significant differences in mast cell and lymphoplasmacytic cell densities between Hunner type IC and non-IC cystitis or between non-Hunner type IC and normal bladder specimens. In the detrusor, the mast cell densities were not significantly different among the four groups. Mast cell density was correlated with lymphoplasmacytic cell density, but not with clinical parameters. Mast cell density is not significantly different between IC specimens and non-IC control specimens with a similar degree of background inflammation. The intensity of mast cell infiltration generally correlated with that of lymphoplasmacytic cells. We conclude that mast cell count is of no value in the differential diagnosis between IC and other etiologies. © 2017 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

  13. Lipoprotein(a Induces Human Aortic Valve Interstitial Cell Calcification

    Directory of Open Access Journals (Sweden)

    Bin Yu, PhD

    2017-08-01

    Full Text Available Lipoprotein(a, or Lp(a, significantly increased alkaline phosphatase activity, release of phosphate, calcium deposition, hydroxyapatite, cell apoptosis, matrix vesicle formation, and phosphorylation of signal transduction proteins; increased expression of chondro-osteogenic mediators; and decreased SOX9 and matrix Gla protein (p < 0.001. Inhibition of MAPK38 and GSK3β significantly reduced Lp(a-induced calcification of human aortic valve interstitial cells (p < 0.001. There was abundant presence of Lp(a and E06 immunoreactivity in diseased human aortic valves. The present study demonstrates a causal effect for Lp(a in aortic valve calcification and suggests that interfering with the Lp(apathway could provide a novel therapeutic approach in the management of this debilitating disease.

  14. Eplerenone-Mediated Aldosterone Blockade Prevents Renal Fibrosis by Reducing Renal Inflammation, Interstitial Cell Proliferation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Hui Chen

    2013-11-01

    Full Text Available Background/Aims: Prolonged elevation of serum aldosterone leads to renal fibrosis. Inflammation also plays a role in the pathogenesis of renal disease. We used a rat model of interstitial renal fibrosis to test the hypothesis that eplerenone-mediated aldosterone blockade prevents renal fibrosis due to its anti-inflammatory and anti-proliferative effects. Methods: Eplerenone (a selective aldosterone blocker or vehicle (control, was given to male Wistar rats (50 mg/kg, twice daily for 7 days before unilateral ureteral obstruction (UUO and for an additional 28 days after surgery. Body weight, blood pressure, renal histo-morphology, immune-staining for macrophages, monocyte chemotactic protein-1, proliferating cell nuclear antigen, α-smooth muscle actin, and serum and urine markers of renal function and oxidative stress were determined for both groups on 7, 14, and 28 days after surgery. Results: Epleronone had no effect on body weight or blood pressure. However, eplerenone inhibited the development of renal fibrosis, inflammation (macrophage and monocyte infiltration, interstitial cell proliferation, and activation of interstitial cells (α-SMA expression. Epleronone also reduced oxidative stress. Conclusion: The anti-fibrotic effect of eplerenone appears to be unrelated to its effect on blood pressure. Eplerenone inhibits renal inflammation, interstitial cell proliferation, phenotypic changes of interstitial cells, and reduces oxidative stress.

  15. Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction

    Science.gov (United States)

    Livingston, Man J.; Ding, Han-Fei; Huang, Shuang; Hill, Joseph A.; Yin, Xiao-Ming; Dong, Zheng

    2016-01-01

    ABSTRACT Renal fibrosis is the final, common pathway of end-stage renal disease. Whether and how autophagy contributes to renal fibrosis remains unclear. Here we first detected persistent autophagy in kidney proximal tubules in the renal fibrosis model of unilateral ureteral obstruction (UUO) in mice. UUO-associated fibrosis was suppressed by pharmacological inhibitors of autophagy and also by kidney proximal tubule-specific knockout of autophagy-related 7 (PT-Atg7 KO). Consistently, proliferation and activation of fibroblasts, as indicated by the expression of ACTA2/α-smooth muscle actin and VIM (vimentin), was inhibited in PT-Atg7 KO mice, so was the accumulation of extracellular matrix components including FN1 (fibronectin 1) and collagen fibrils. Tubular atrophy, apoptosis, nephron loss, and interstitial macrophage infiltration were all inhibited in these mice. Moreover, these mice showed a specific suppression of the expression of a profibrotic factor FGF2 (fibroblast growth factor 2). In vitro, TGFB1 (transforming growth factor β 1) induced autophagy, apoptosis, and FN1 accumulation in primary proximal tubular cells. Inhibition of autophagy suppressed FN1 accumulation and apoptosis, while enhancement of autophagy increased TGFB1-induced-cell death. These results suggest that persistent activation of autophagy in kidney proximal tubules promotes renal interstitial fibrosis during UUO. The profibrotic function of autophagy is related to the regulation on tubular cell death, interstitial inflammation, and the production of profibrotic factors. PMID:27123926

  16. Turnover time of Leydig cells and other interstitial cells in testes of adult rats

    NARCIS (Netherlands)

    Teerds, K. J.; de rooij, D. G.; Rommerts, F. F.; van der Tweel, I.; Wensing, C. J.

    1989-01-01

    The aim of this study was to investigate the turnover of Leydig cells and other interstitial cells in the adult rat testis. Normal adult rats received injections of [3H]thymidine at 9:00 and 21:00 for 2, 5, or 8 days. The percentage of labeled Leydig cells, which was initially low (0.8% +/- 0.2%),

  17. Roles of interstitial fluid pH in diabetes mellitus: Glycolysis and mitochondrial function

    Science.gov (United States)

    Marunaka, Yoshinori

    2015-01-01

    The pH of body fluids is one the most important key factors regulating various cell function such as enzyme activity and protein-protein interaction via modification of its binding affinity. Therefore, to keep cell function normal, the pH of body fluids is maintained constant by various systems. Insulin resistance is one of the most important, serious factors making the body condition worse in diabetes mellitus. I have recently found that the pH of body (interstitial) fluids is lower in diabetes mellitus than that in non-diabetic control, and that the lowered pH is one of the causes producing insulin resistance. In this review article, I introduce importance of body (interstitial) fluid pH in regulation of body function, evidence on abnormal regulation of body fluid pH in diabetes mellitus, and relationship between the body fluid pH and insulin resistance. Further, this review proposes perspective therapies on the basis of regulation of body fluid pH including propolis (honeybee product) diet. PMID:25685283

  18. Interstitial cells of Cajal and Auerbach's plexus. A scanning electron microscopical study of guinea-pig small intestine

    DEFF Research Database (Denmark)

    Jessen, Harry; Thuneberg, Lars

    1991-01-01

    Anatomy, interstitial cells of Cajal, myenteric plexus, small intestine, guinea-pig, scanning electron microscopy......Anatomy, interstitial cells of Cajal, myenteric plexus, small intestine, guinea-pig, scanning electron microscopy...

  19. Are mast cells still good biomarkers for bladder pain syndrome/interstitial cystitis?

    Science.gov (United States)

    Gamper, Marianne; Regauer, Sigrid; Welter, JoEllen; Eberhard, Jakob; Viereck, Volker

    2015-06-01

    ESSIC identifies mast cell infiltrates of detrusor muscle as a diagnostic criterion for bladder pain syndrome/interstitial cystitis. However, an increased mast cell count is also characteristic of overactive bladder syndrome. The lack of uniformity in mast cell detection methods hampers data comparison. Using state-of-the-art techniques we investigated whether mast cells differ among bladder conditions. We analyzed bladder biopsies from 56 patients, including 31 with bladder pain syndrome/interstitial cystitis with (12) or without (19) Hunner lesions, 13 with overactive bladder syndrome and 12 without bladder symptoms to determine the quantity, location, distribution and activation of mast cells using immunohistochemistry with anti-mast cell tryptase. Patients were allocated to study groups by key bladder symptoms commonly used to define conditions (pain and major urgency). Subepithelial mast cell localization (p interstitial cystitis with Hunner lesions. The optimal cutoff of 32 detrusor mast cells per mm(2) achieved only 68% accuracy with 38% positive predictive value. No difference was observed between bladder pain syndrome/interstitial cystitis without Hunner lesions and overactive bladder syndrome. Patient groups differed in lymphocyte infiltration (p = 0.001), nodular lymphocyte aggregates (p interstitial cystitis with Hunner lesions. Detrusor mastocytosis had poor predictive value for bladder pain syndrome/interstitial cystitis. Mast cell assessment did not distinguish bladder pain syndrome/interstitial cystitis without Hunner lesions from overactive bladder syndrome. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. Appearance of interstitial cells of Cajal in the human midgut.

    Science.gov (United States)

    Abramovic, Mirjana; Radenkovic, Goran; Velickov, Aleksandra

    2014-04-01

    Several subtypes of the interstitial cells of Cajal (ICC) form networks that play a role in gastrointestinal motor control. ICC express c-kit and depend on signaling via Kit receptors for development and phenotype maintenance. At 7-8 weeks of development, c-kit-immunoreactive (c-kit-IR) cells are present in the human oesophagus, stomach and proximal duodenum wall. In the remaining small and large bowel, c-kit-IR cells appear later. The object of the present study is to determine the timing of the appearance of c-kit-IR ICC in the parts of the digestive tube originating from the midgut (distal duodenum, jejunum, ileum and proximal colon). Specimens were obtained from eight human embryos and 11 fetuses at 7-12 weeks of gestational age. The specimens were exposed to anti-c-kit antibodies to investigate ICC differentiation. The differentiation of enteric neurons and smooth muscle cells was immunohistochemically examined by using anti-PGP9,5 and anti-desmin antibodies, respectively. In the distal duodenum, jejunum and ileum, c-kit-IR cells emerged at week 9 at the level of the myenteric plexus in the form of a thin row of cells encircling the inception of the ganglia. These cells were multipolar or spindle-shaped with two long processes and corresponded to the ICC of the myenteric plexus. In the proximal colon, c-kit-IR cells emerged at week 9-10 in the form of two parallel belts of cells extending at the submucosal plexus and the myenteric plexus levels. We conclude that ICC develop following two different patterns in the human midgut.

  1. Plexus muscularis profundus and associated interstitial cells. I. Light microscopical studies of mouse small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Thuneberg, L

    1982-01-01

    interstitial cells (ICC-II) in the subserous layer. (2) Auerbach's plexus with an associated extensive plexus of interstitial cells (ICC-I) in close contact with tertiary fasciculi. (3) Nerve fasciculi of the outer division of the circular muscle layer. These formed a nerve plexus in a well-defined plane...... in the outermost cell layers (plexus muscularis superficialis), with few fasciculi located internal to this plexus. A few bipolar interstitial cells (ICC-IV) were associated with nerve fasciculi of this region. (4) A nerve plexus located in the region between the two subdivisions of the circular muscle, plexus...

  2. Pulmonary function vascular index predicts prognosis in idiopathic interstitial pneumonia

    NARCIS (Netherlands)

    Corte, Tamera J.; Wort, Stephen J.; MacDonald, Peter S.; Edey, Anthony; Hansell, David M.; Renzoni, Elisabetta; Maher, Toby M.; Nicholson, Andrew G.; Bandula, Steven; Bresser, Paul; Wells, Athol U.

    2012-01-01

    Background and objective: Pulmonary hypertension (PH) is associated with increased mortality in fibrotic idiopathic interstitial pneumonia (IIP). We hypothesize that baseline KCO (diffusing capacity of carbon monoxide/alveolar volume) and 6-month decline in KCO reflect PH, thus predicting mortality

  3. Stem Cell Therapy for Interstitial Cystitis/Bladder Pain Syndrome.

    Science.gov (United States)

    Kim, Aram; Shin, Dong-Myung; Choo, Myung-Soo

    2016-01-01

    Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disease characterized by pelvic pain, usually with urinary frequency. These symptoms make patients suffer from a poor quality of life. However, there is still a lack of consensus on the pathophysiology and curable treatment of IC/BPS. We have reviewed several candidates for the pathophysiology of this disease and also treatments that have been used. Although several oral medications, bladder instillation therapies, fulguration for Hunner's lesion, and hydrodistention have been tried as IC/BPS treatments, their outcomes have not been satisfactory. As the application of stem cell therapy is expanding into the urologic field, innovative strategies have been tested with animal models of IC/BPS and have shown promising therapeutic effects for reversing the symptoms of this disorder. Although several concerns about stem cell sources and their safety should be addressed before initiating human clinical trials, we introduce stem cell therapy as a valuable future treatment approach for IC/BPS.

  4. Identification of interstitial cells of Cajal. Significance for studies of human small intestine and colon

    DEFF Research Database (Denmark)

    Rumessen, J J

    1994-01-01

    Interstitial cells of Cajal (ICC) were described a century ago by Ramón y Cajal a.o. as primitive neurons in the intestines. In the period 1900-1960 a large number of light microscopical studies of ICC were published, in which ICC were identified by heir characteristic morphology. After 1960...... muscle. These studies strongly suggested that ICC were fundamental regulators of external muscle function. These hypotheses have since been supported by independent morphological and electrophysiological evidence, strongly suggesting a pacemaker role of some ICC populations as well as other regulatory...

  5. The Glycoprofile Patterns of Endothelial Cells in Usual Interstitial Pneumonia

    Directory of Open Access Journals (Sweden)

    A Barkhordari

    2014-09-01

    Full Text Available [THIS ARTICLE HAS BEEN RETRACTED FOR DUPLICATE PUBLICATION] Background: The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. Objective: To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP compared to those found in normal tissue. Methods: Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. Results: High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc and Wisteria floribunda (GalNAc as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. Conclusion: These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically.

  6. Valvular interstitial cells suppress calcification of valvular endothelial cells

    NARCIS (Netherlands)

    Hjortnaes, Jesper; Shapero, Kayle; Goettsch, Claudia; Hutcheson, Joshua D; Keegan, Joshua; Kluin, J; Mayer, John E; Bischoff, Joyce; Aikawa, Elena

    BACKGROUND: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes

  7. Acute pergolide exposure stiffens engineered valve interstitial cell tissues and reduces contractility in vitro.

    Science.gov (United States)

    Capulli, Andrew K; MacQueen, Luke A; O'Connor, Blakely B; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the US market in 1997 and pergolide, a Parkinson's disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market and continued use of similar drugs reaffirm the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 h) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness, but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Acute Pergolide Exposure Stiffens Engineered Valve Interstitial Cell Tissues and Reduces Contractility In Vitro

    Science.gov (United States)

    Capulli, Andrew K.; MacQueen, Luke A.; O’Connor, Blakely B.; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the U.S. market in 1997 and pergolide, a Parkinson’s disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market, and continued use of similar drugs, reaffirms the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 hr) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. PMID:27174867

  9. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

    Directory of Open Access Journals (Sweden)

    David Vansthertem

    2010-01-01

    Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

  10. Subclinical interstitial lung involvement in rheumatic diseases. Correlations of high-resolution Computed Tomography patterns with functional and cytologic findings

    International Nuclear Information System (INIS)

    Salaffi, F.; Baldelli, S.

    1999-01-01

    The aims of this study were to quantify the severity and extent of subclinical interstitial lung disease as depicted on HRCT and to study the relationship between the patterns of lung disease quantified by HRCT and the functional parameters and bronchoalveolar lavage findings in patients with rheumatic diseases. The results confirm that HRCT is a sensitive tool in detecting interstitial lung disease in patients with rheumatic diseases with no signs and symptoms of pulmonary involvement. The relationship between the different HRCT patterns and bronchoalveolar lavage cell profiles can identify patients at higher risk of developing irreversible lung fibrosis. A long-term, prospective follow-up study is needed to determine whether these patients will develop over pulmonary disease [it

  11. Gastrointestinal peristalsis: joint action of enteric nerves, smooth muscle, and interstitial cells of Cajal.

    Science.gov (United States)

    Huizinga, J D

    1999-11-15

    Peristalsis is a propulsive motor pattern orchestrated by neuronal excitation and inhibition in cooperation with intrinsic muscular control mechanisms, including those residing in interstitial cells of Cajal (ICC). Interstitial cells of Cajal form a network of cells in which electrical slow waves originate and then propagate into the musculature initiating rhythmic contractile activity upon excitaton by enteric nerves. Interstitial cells of Cajal have now been isolated and their intrinsic properties reveal the presence of rhythmic inward currents not found in smooth muscle cells. In tissues where classical slow waves are not present, enteric cholinergic excitation will evoke slow wave-like activity that forces action potentials to occur in a rhythmic manner. Intrinsic and induced slow wave activity directs many of the peristaltic motor patterns in the gut. Copyright 1999 Wiley-Liss, Inc.

  12. Interstitial cells of Cajal in the striated musculature of the mouse esophagus

    DEFF Research Database (Denmark)

    Rumessen, J J; de Kerchove d'Exaerde, A; Mignon, S

    2001-01-01

    Interstitial cells of Cajal (ICC) are important regulatory cells in the smooth muscle coats of the digestive tract. Expression of the Kit receptor tyrosine kinase was used in this study as a marker to study their distribution and development in the striated musculature of the mouse esophagus...... scarce in both muscle layers of the thoracic esophagus, while their number increased steeply toward the cardia in the striated portion of the intraabdominal esophagus. They did not form networks and had no relationship with intrinsic myenteric ganglia and motor end-plates. They were often close to nerve...... but absent in adult ICC-deficient KitW-lacZ/KitWv mice. Interstitial cells of Cajal were identified by electron microscopy by their ultrastructure in the striated muscle of the esophagus and exhibited Xgal labeling, while fibroblasts and muscle cells were unlabeled. Interstitial cells of Cajal are scattered...

  13. The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy.

    Science.gov (United States)

    Zhou, Jerry; O'Connor, Michael D; Ho, Vincent

    2017-09-26

    Effective digestion requires propagation of food along the entire length of the gastrointestinal tract. This process involves coordinated waves of peristalsis produced by enteric neural cell types, including different categories of interstitial cells of Cajal (ICC). Impaired food transport along the gastrointestinal tract, either too fast or too slow, causes a range of gut motility disorders that affect millions of people worldwide. Notably, loss of ICC has been shown to affect gut motility. Patients that suffer from gut motility disorders regularly experience diarrhoea and/or constipation, insomnia, anxiety, attention lapses, irritability, dizziness, and headaches that greatly affect both physical and mental health. Limited treatment options are available for these patients, due to the scarcity of human gut tissue for research and transplantation. Recent advances in stem cell technology suggest that large amounts of rudimentary, yet functional, human gut tissue can be generated in vitro for research applications. Intriguingly, these stem cell-derived gut organoids appear to contain functional ICC, although their frequency and functional properties are yet to be fully characterised. By reviewing methods of gut organoid generation, together with what is known of the molecular and functional characteristics of ICC, this article highlights short- and long-term goals that need to be overcome in order to develop ICC-based therapies for gut motility disorders.

  14. The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Jerry Zhou

    2017-09-01

    Full Text Available Effective digestion requires propagation of food along the entire length of the gastrointestinal tract. This process involves coordinated waves of peristalsis produced by enteric neural cell types, including different categories of interstitial cells of Cajal (ICC. Impaired food transport along the gastrointestinal tract, either too fast or too slow, causes a range of gut motility disorders that affect millions of people worldwide. Notably, loss of ICC has been shown to affect gut motility. Patients that suffer from gut motility disorders regularly experience diarrhoea and/or constipation, insomnia, anxiety, attention lapses, irritability, dizziness, and headaches that greatly affect both physical and mental health. Limited treatment options are available for these patients, due to the scarcity of human gut tissue for research and transplantation. Recent advances in stem cell technology suggest that large amounts of rudimentary, yet functional, human gut tissue can be generated in vitro for research applications. Intriguingly, these stem cell-derived gut organoids appear to contain functional ICC, although their frequency and functional properties are yet to be fully characterised. By reviewing methods of gut organoid generation, together with what is known of the molecular and functional characteristics of ICC, this article highlights short- and long-term goals that need to be overcome in order to develop ICC-based therapies for gut motility disorders.

  15. Modulation of Pacemaker Potentials by Pyungwi-San in Interstitial Cells of Cajal from Murine Small Intestine - Pyungwi-San and Interstitial Cells of Cajal -

    Directory of Open Access Journals (Sweden)

    Kim Jung Nam

    2013-03-01

    Full Text Available Objective: Pyungwi-san (PWS plays a role in a number of physiologic and pharmacologic functions in many organs. Interstitial cells of Cajal (ICCs are pacemaker cells that generate slow waves in the gastrointestinal (GI tract. We aimed to investigate the beneficial effects of PWS in mouse small-intestinal ICCs. Methods: Enzymatic digestion was used to dissociate ICCs from the small intestine of a mouse. The wholecell patch-clamp configuration was used to record membrane potentials from the cultured ICCs. Results: ICCs generated pacemaker potentials in the GI tract. PWS produced membrane depolarization in the current clamp mode. Pretreatment with a Ca2+-free solution and a thapsigargin, a Ca2+-ATPase, inhibitor in the endoplasmic reticulum, eliminated the generation of pacemaker potentials. However, only when the thapsigargin was applied in a bath solution, the membrane depolarization was not produced by PWS. Furthermore, the membrane depolarizations due to PWS were inhibited not by U-73122, an active phospholipase C inhibitor, but by chelerythrine and calphostin C, protein kinase C inhibitors. Conclusions: These results suggest that PWS might affect GI motility by modulating the pacemaker activity in the ICCs.

  16. Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease.

    Science.gov (United States)

    Hamada, Tsutomu; Samukawa, Takuya; Kumamoto, Tomohiro; Hatanaka, Kazuhito; Tsukuya, Go; Yamamoto, Masuki; Machida, Kentaro; Watanabe, Masaki; Mizuno, Keiko; Higashimoto, Ikkou; Inoue, Yoshikazu; Inoue, Hiromasa

    2015-09-30

    Interstitial lung diseases (ILDs) are common in patients with connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell-activating factor belonging to the tumour necrosis factor family (BAFF) plays a crucial role in B cell development, survival, and antibody production. We examined serum levels of BAFF, surfactant protein D (SP-D), and Krebs von den Lungen-6 (KL-6) in 33 patients with CTD-ILD, 16 patients with undifferentiated CTD-ILD, 19 patients with CFIP, and 26 healthy volunteers. And we analysed the relationship between serum BAFF levels and pulmonary function, as well as the expression of BAFF in the lung tissue of patients with CTD-ILD. Serum levels of BAFF were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. However, there were no significant differences in serum levels of SP-D and KL-6. Furthermore, serum BAFF levels in CTD-ILD patients were inversely correlated with pulmonary function. BAFF was strongly expressed in the lungs of CTD-ILD patients, but weakly in normal lungs. This is the first study to demonstrate that serum BAFF levels were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. Furthermore, serum BAFF levels were correlated with pulmonary function. We consider that serum BAFF levels in patients with CTD-ILD reflect the presence of ILDs disease activity and severity. These finding suggest that BAFF may be a useful marker for distinguishing CTD-ILD from CFIP.

  17. Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient

    Directory of Open Access Journals (Sweden)

    Ibrahim Azar

    2017-01-01

    Full Text Available Sunitinib, a multitargeted tyrosine Kkinase inhibitor (TKI, is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS, and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN, in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF by either TKI (sunitinib and sorafenib or antibodies (bevacizumab suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

  18. Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

    Science.gov (United States)

    Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

    2017-01-01

    Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

  19. Inherent rhythmcity and interstitial cells of Cajal in a frog vein

    Indian Academy of Sciences (India)

    Interstitial cells of Cajal are responsible for rhythmic contractions of the musculature of the gastrointestinal tract and blood vessels. The existence of these cells and spontaneous rhythmicity were noticed in amphibian vein and the findings are reported in this paper. The postcaval vein was identified in the frog, Rana tigrina ...

  20. Inherent rhythmcity and interstitial cells of Cajal in a frog vein

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    substance(s), which depolarizes the smooth muscle cells of the blood vessel. While the role of the ICC ... Interstitial cells of Cajal are responsible for rhythmic contractions of the musculature of the gastrointestinal tract and blood vessels. ... decreased, while warm Ringer increased, the rate of contraction. Adrenaline caused ...

  1. Interstitial cells of Cajal in the striated musculature of the mouse esophagus

    DEFF Research Database (Denmark)

    Rumessen, J J; de Kerchove d'Exaerde, A; Mignon, S

    2001-01-01

    Interstitial cells of Cajal (ICC) are important regulatory cells in the smooth muscle coats of the digestive tract. Expression of the Kit receptor tyrosine kinase was used in this study as a marker to study their distribution and development in the striated musculature of the mouse esophagus. Sec...

  2. Ultrastructure of interstitial cells of Cajal at the colonic submuscular border in patients with ulcerative colitis

    DEFF Research Database (Denmark)

    Rumessen, J J

    1996-01-01

    Submuscular interstitial cells of Cajal (ICC) are putative pacemaker cells of the colonic external muscle. Although motility disturbances and smooth muscle dysfunction are prevalent in patients with ulcerative colitis (UC), ICC have never been studied in this disease. The aim of this study...... was to examine the ultrastructure of submuscular ICC in UC....

  3. Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal

    OpenAIRE

    Janevska, Vesna; Qerimi, Adelina; Basheska, Neli; Stojkova, Elena; Janevski, Vlado; Jovanovic, Rubens; Zhivadinovik, Julija; Spasevska, Liljana

    2015-01-01

    Objective: Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. Materials and methods...

  4. Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Elham Vali Khojeini

    2014-01-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

  5. Clinical role in biopsy after interstitial irradiation to squamous cell carcinoma of tongue

    International Nuclear Information System (INIS)

    Sato, Tomoichi

    1995-01-01

    The clinical role of biopsy after interstitial irradiation therapy was evaluated in 44 patients with squamous cell carcinoma of tongue on which biopsy was done in our hospital. More residual tumors were observed in the induration-positive groups compared to those of the induration-negative groups. No tumor was histologically observed in 71.4% of the induration-positive groups. On the adjacent and covering mucous membranes, epithelial dysplasia was detected in 15 patients, 1 of them was Grade III and 9 were Grade IV. Two patients had recurrence. In the initial stage of interstitial irradiation, reaction of stoma showed decrease of edema, inflammatory cell infiltration, regeneration and dilation of vessels after 6 weeks. The regeneration of collagen fiber increased within 3-14 weeks after irradiation, followed by decrease of its activity. After interstitial irradiation, 2 of 9 Grade IIb patients treated by surgery and 2 by re-interstitial irradiation survived. One of 3 Grade III patients manifested recurrence and was treated by surgery. All patients were alive. Fourteen of 17 Grade IV patients under careful observation were still alive. Eleven of 15 patients treated by total neck dissection after interstitial irradiation survived. Four Grade IV patients showed recurrence. Two-year primary lesion control rate was 91.2% and the survival rate for 5 year was 74.0%. (S.Y.). 54 refs

  6. Biochemical and morphological changes in endothelial cells in response to hypoxic interstitial edema

    Directory of Open Access Journals (Sweden)

    Miserocchi Giuseppe

    2006-01-01

    Full Text Available Abstract Background A correlation between interstial pulmonary matrix disorganization and lung cellular response was recently documented in cardiogenic interstitial edema as changes in the signal-cellular transduction platforms (lipid microdomains: caveoale and lipid rafts. These findings led to hypothesize a specific "sensing" function by lung cells resulting from a perturbation in cell-matrix interaction. We reason that the cell-matrix interaction may differ between the cardiogenic and the hypoxic type of lung edema due to the observed difference in the sequential degradation of matrix proteoglycans (PGs family. In cardiogenic edema a major fragmentation of high molecular weight PGs of the interfibrillar matrix was found, while in hypoxia the fragmentation process mostly involved the PGs of the basement membrane controlling microvascular permeability. Based on these considerations, we aim to describe potential differences in the lung cellular response to the two types of edema. Methods We analysed the composition of plasma membrane and of lipid microdomains in lung tissue samples from anesthetized rabbits exposed to mild hypoxia (12 % O2 for 3–5 h causing interstitial lung edema. Lipid analysis was performed by chromatographic techniques, while protein analysis by electrophoresis and Western blotting. Lipid peroxidation was assessed on total plasma membranes by a colorimetric assay (Bioxytech LPO-586, OxisResearch. Plasma membrane fluidity was also assessed by fluorescence. Lipid microdomains were isolated by discontinuous sucrose gradient. We also performed a morphometric analysis on lung cell shape on TEM images from lung tissue specimen. Results After hypoxia, phospholipids content in plasma membranes remained unchanged while the cholesterol/phospholipids ratio increased significantly by about 9% causing a decrease in membrane fluidity. No significant increase in lipid peroxidation was detected. Analysis of lipid microdomains showed a

  7. Recruitment of Bone Marrow-Derived Valve Interstitial Cells is a Normal Homeostatic Process

    Science.gov (United States)

    Hajdu, Zoltan; Romeo, Stephen J.; Fleming, Paul A.; Markwald, Roger R.; Visconti, Richard P.; Drake, Christopher J.

    2011-01-01

    Advances in understanding of the maintenance of the cardiac valves during normal cardiac function and response to injury have lead to several novel findings, including that there is contribution of extra-cardiac cells to the major cellular population of the valve: the valve interstitial cell (VIC). While suggested to occur in human heart studies, we have been able to experimentally demonstrate, using a mouse model, that cells of bone marrow hematopoietic stem cell origin engraft into the valves and synthesize collagen type I. Based on these initial findings, we sought to further characterize this cell population in terms of its similarity to VICs and begin to elucidate its contribution to valve homeostasis. To accomplish this, chimeric mice whose bone marrow was repopulated with enhanced green fluorescent protein (EGFP) expressing total nucleated bone marrow cells were used to establish a profile of EGFP+ valve cells in terms of their expression of hematopoietic antigens, progenitor markers, fibroblast- and myofibroblast-related molecules, as well as their distribution within the valves. Using this profile, we show that normal (non-irradiated, non-transplanted) mice have BM-derived cell populations that exhibit identical morphology and phenotype to those observed in transplanted mice. Collectively, our findings establish that the engraftment of bone marrow-derived cells occurs as part of normal valve homeostasis. Further, our efforts demonstrate that the use of myeloablative irradiation, which is commonly employed in studies involving bone marrow transplantation, does not elicit changes in the bone marrow-derived VIC phenotype in recipient mice. PMID:21871458

  8. Impaired Na+/K+-ATPase Function in Patients with Interstitial Cystitis/Painful Bladder Syndrome

    Science.gov (United States)

    Lee, Ming-Huei

    2016-01-01

    Na+/K+-ATPase (NKA) is abundantly expressed in the basolateral membrane of epithelial cells, which is necessary for tight junction formation. The tight junction is an urothelial barrier between urine and the underlying bladder. Impairment of tight junctions allows migration of urinary solutes in patients with interstitial cystitis/painful bladder syndrome (IC/PBS). We evaluated NKA expression and activity in bladder samples from patients with IC/PBS. The study group consisted of 85 patients with IC/PBS, and the control group consisted of 20 volunteers. Bladder biopsies were taken from both groups. We determined the expression and distribution of NKA using NKA activity assays, immunoblotting, immunohistochemical staining, and immunofluorescent staining. The protein levels and activity of NKA in the study group were significantly lower than the control group (1.08 ± 0.06 vs. 2.39 ± 0.29 and 0.60 ± 0.04 vs. 1.81 ± 0.18 µmol ADP/mg protein/hour, respectively; P < 0.05). Additionally, immunofluorescent staining for detection of CK7, a marker of the bladder urothelium, predominantly colocalized with NKA in patients in the study group. Our results demonstrated the expression and activity of NKA were decreased in bladder biopsies of patients with IC/PBS. These findings suggest that NKA function is impaired in the bladders from patients with IC/PBS. PMID:26839484

  9. Impaired Na(+)/K(+)-ATPase Function in Patients with Interstitial Cystitis/Painful Bladder Syndrome.

    Science.gov (United States)

    Lee, Jane-Dar; Yang, Wen-Kai; Lee, Ming-Huei

    2016-02-01

    Na(+)/K(+)-ATPase (NKA) is abundantly expressed in the basolateral membrane of epithelial cells, which is necessary for tight junction formation. The tight junction is an urothelial barrier between urine and the underlying bladder. Impairment of tight junctions allows migration of urinary solutes in patients with interstitial cystitis/painful bladder syndrome (IC/PBS). We evaluated NKA expression and activity in bladder samples from patients with IC/PBS. The study group consisted of 85 patients with IC/PBS, and the control group consisted of 20 volunteers. Bladder biopsies were taken from both groups. We determined the expression and distribution of NKA using NKA activity assays, immunoblotting, immunohistochemical staining, and immunofluorescent staining. The protein levels and activity of NKA in the study group were significantly lower than the control group (1.08 ± 0.06 vs. 2.39 ± 0.29 and 0.60 ± 0.04 vs. 1.81 ± 0.18 µmol ADP/mg protein/hour, respectively; P < 0.05). Additionally, immunofluorescent staining for detection of CK7, a marker of the bladder urothelium, predominantly colocalized with NKA in patients in the study group. Our results demonstrated the expression and activity of NKA were decreased in bladder biopsies of patients with IC/PBS. These findings suggest that NKA function is impaired in the bladders from patients with IC/PBS.

  10. Ultrastructure of Cajal-like interstitial cells in the human detrusor

    DEFF Research Database (Denmark)

    Rasmussen, Helle; Rumessen, Jüri J; Hansen, Alastair

    2009-01-01

    The aim of this ultrastructural study was to examine the human detrusor for interstitial cells of Cajal (ICC)-like cells (ICC-L) by conventional transmission electron microscopy (TEM) and immuno-transmission electron microscopy (I-TEM) with antibodies directed towards CD117 and CD34. Two main types...... of interstitial cells were identified by TEM: ICC-L and fibroblast-like cells (FLC). ICC-L were bipolar with slender (0.04 microm) flattened dendritic-like processes, frequently forming a branching labyrinth network. Caveolae and short membrane-associated dense bands were present. Mitochondria, rough endoplasmic...... reticulum and Golgi apparatus were observed in the cell somata and cytoplasmic processes. Intermediate filaments were abundant but no thick filaments were found. ICC-L were interconnected by close appositions, gap junctions and peg-and-socket junctions (PSJ) but no specialised contacts to smooth muscle...

  11. Distribution and ultrastructure of interstitial cells of Cajal in the mouse colon, using antibodies to Kit and Kit(W-lacZ) mice

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J; Bernex, F

    2000-01-01

    The roles of the interstitial cells of Cajal in the stomach and intestine are becoming increasingly clear. Interstitial cells of Cajal in the colon are less well known, however. We studied the development and distribution of the interstitial cells of Cajal in the mouse colon, using the tyrosine k...

  12. Dynamic Heterogeneity of the Heart Valve Interstitial Cell Population in Mitral Valve Health and Disease

    Directory of Open Access Journals (Sweden)

    Tori E. Horne

    2015-08-01

    Full Text Available The heart valve interstitial cell (VIC population is dynamic and thought to mediate lay down and maintenance of the tri-laminar extracellular matrix (ECM structure within the developing and mature valve throughout life. Disturbances in the contribution and distribution of valve ECM components are detrimental to biomechanical function and associated with disease. This pathological process is associated with activation of resident VICs that in the absence of disease reside as quiescent cells. While these paradigms have been long standing, characterization of this abundant and ever-changing valve cell population is incomplete. Here we examine the expression pattern of Smooth muscle α-actin, Periostin, Twist1 and Vimentin in cultured VICs, heart valves from healthy embryonic, postnatal and adult mice, as well as mature valves from human patients and established mouse models of disease. We show that the VIC population is highly heterogeneous and phenotypes are dependent on age, species, location, and disease state. Furthermore, we identify phenotypic diversity across common models of mitral valve disease. These studies significantly contribute to characterizing the VIC population in health and disease and provide insights into the cellular dynamics that maintain valve structure in healthy adults and mediate pathologic remodeling in disease states.

  13. Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures.

    Directory of Open Access Journals (Sweden)

    Moon Young Lee

    Full Text Available Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC, which serve as slow-wave electrical pacemakers for gastrointestinal (GI smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies.

  14. Thermal analysis of laser interstitial thermotherapy in ex vivo fibro-fatty tissue using exponential functions

    Energy Technology Data Exchange (ETDEWEB)

    Salas, Nelson Jr. [Biomedical Optics and Laser Laboratory, Department of Biomedical Engineering, University of Miami College of Engineering, PO Box 248294, Coral Gables, FL 33124 (United States); Manns, Fabrice [Biomedical Optics and Laser Laboratory, Department of Biomedical Engineering, University of Miami College of Engineering, PO Box 248294, Coral Gables, FL 33124 (United States); Milne, Peter J [Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami School of Medicine, 1638 NW 10th Ave, McKnight Bldg, Miami, FL 33136 (United States); Denham, David B [Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami School of Medicine, 1638 NW 10th Ave, McKnight Bldg, Miami, FL 33136 (United States); Minhaj, Ahmed M [Biomedical Optics and Laser Laboratory, Department of Biomedical Engineering, University of Miami College of Engineering, PO Box 248294, Coral Gables, FL 33124 (United States); Parel, Jean-Marie [Biomedical Optics and Laser Laboratory, Department of Biomedical Engineering, University of Miami College of Engineering, PO Box 248294, Coral Gables, FL 33124 (United States); Robinson, David S [Center for Breast Care, St Luke' s Hospital of Kansas City, 4400 Broadway, Suite 509, Kansas City, MO 64111 (United States)

    2004-05-07

    A therapeutic procedure to treat small, surface breast tumours up to 10 mm in radius plus a 5 mm margin of healthy, surrounding tissue using laser interstitial thermotherapy (LITT) is currently being investigated. The purpose of this study is to analyse and model the thermal and coagulative response of ex vivo fibro-fatty tissue, a model for breast tissue, during experimental laser interstitial thermotherapy at 980 nm. Laser radiation at 980 nm was delivered interstitially through a diffusing tip optical fibre inserted into a fibro-fatty tissue model to produce controlled heating at powers ranging from 3.2 to 8.0 W. Tissue temperature was measured with thermocouples placed at 15 positions around the fibre. The induced coagulation zone was measured on gross anatomical sections. Thermal analysis indicates that a finite sum of exponential functions is an approximate solution to the heat conduction equation that more accurately predicts the time-temperature dependence in tissue prior to carbonization (T < 100 deg. C) during LITT than the traditional model using a single exponential function. Analysis of the ellipsoid coagulation volume induced in tissue indicates that the 980 nm wavelength does not penetrate deep enough in fibro-fatty tissue to produce a desired 30 mm diameter (14.1 x 10{sup 3} mm{sup 3}) coagulation volume without unwanted tissue liquefaction and carbonization.

  15. Interstitial mononuclear cell infiltrates in chronic rejection of the kidney and correlation with peripheral blood.

    OpenAIRE

    Jeong, H. J.; Hong, S. W.; Kim, Y. S.; Kim, M. S.; Choi, I. H.; Park, K.; Choi, I. J.

    1996-01-01

    To investigate the characteristics of interstitial inflammatory cells and possible involvement of nudelta T cells, 16 renal allograft biopsies showing chronic rejection were stained by immunohistochemical method and correlated with the data of peripheral blood evaluated by flow cytometry. For immunophenotyping, fresh frozen sections were stained with monoclonal antibodies against CD3, CD4, CD8, CD68, CD56, TCRdelta1 and HLA DR. Paraffin embedded tissue was stained with CD45RO, CD20-Cy and CD6...

  16. The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy

    OpenAIRE

    Jerry Zhou; Michael D. O’Connor; Vincent Ho

    2017-01-01

    Effective digestion requires propagation of food along the entire length of the gastrointestinal tract. This process involves coordinated waves of peristalsis produced by enteric neural cell types, including different categories of interstitial cells of Cajal (ICC). Impaired food transport along the gastrointestinal tract, either too fast or too slow, causes a range of gut motility disorders that affect millions of people worldwide. Notably, loss of ICC has been shown to affect gut motility. ...

  17. Peripheral-type benzodiazepine receptors in bronchoalveolar lavage cells of patients with interstitial lung disease

    International Nuclear Information System (INIS)

    Branley, Howard M.; Bois, Roland M. du; Wells, Athol U.; Jones, Hazel A.

    2007-01-01

    Introduction: PK11195 is a ligand with high affinity for peripheral benzodiazepine receptors (PBRs), which are present in large numbers in macrophages. PBRs play a role in antioxidant pathways and apoptosis, key factors in control of lung health. Intrapulmonary PBRs, assessed in vivo by positron emission tomography (PET), are decreased in interstitial lung disease (ILD) despite increased macrophage numbers. We wished to ascertain whether the observed decrease in in vivo expression of PBRs in the PET scans could be accounted for by a reduction in PBRs per cell by saturation-binding assays of R-PK11195 in cells obtained by bronchoalveolar lavage (BAL). Methods: We performed receptor saturation-binding assays with [ 3 H]-R-PK11195 on a mixed population of cells recovered by BAL to quantify the number of R-PK11195 binding sites per macrophage in 10 subjects with ILD and 10 normal subjects. Results: Receptor affinity [dissociation constant (Kd)] was similar in ILD patients and controls. However, R-PK11195 binding sites per cell [(maximal binding sites available (B max )] were decreased in macrophages obtained by BAL from subjects with ILD compared to normal (P<.0005). Microautoradiography confirmed localization of R-PK11195 to macrophages in a mixed inflammatory cell population obtained by BAL. Conclusion: These results demonstrate that in vitro PBR expression per cell on macrophages obtained by BAL is reduced in patients with ILD indicating a potentially functionally different macrophage phenotype. As PBRs are involved in the orchestration of lung inflammatory responses, this finding offers further insight into the role of macrophages in the pathogenesis of ILDs and offers a potential avenue for pharmacological strategy

  18. Changes in Sexual Behavior of Orchidectomized Rats Under Influence of Allotransplantation of Testicular Interstitial Cell Suspension.

    Science.gov (United States)

    Deng, Bo; Bondarenko, Tatyana; Pakhomov, Oleksandr

    2017-05-09

    Transplantation of hormone-producing cells is an experimental endocrine dysfunction treatment. The present study investigated the effects of orchidectomy (OE) and transplantation of interstitial cell suspension (ICS) on rat sexual behavior. Adult experimental animals were divided into two populations. One of these populations had sexual experience before the experiment and the other did not. Each population was divided into three groups: control group and two orchidectomized groups. One of the orchidectomized groups was treated with ICS, and the other was treated with the vehicle. The changes in the sexual behavior were investigated on the following parameters: mount latency (ML), intromission latency (IL), ejaculation latency (EL), mount frequency (MF), intromission frequency (IF), copulatory efficacy (CE), and IF/EL ratio. The investigation of these changes lasted 4 weeks after ICS transplantation. The parameters of sexual behavior reflected a decrease in sexual function after OE at the beginning of the observation, especially for the animals that did not have a sexual experience. However, it was shown that sexual activity increased in the following 4 weeks. We have indicated that the loss of gonads attenuated the capacity to acquire sexual experience; nonetheless, it did not mean that the animals completely lost this capacity. Transplantation of ICS facilitated the maintenance of male sexual behavior after OE, fractionally enlarged the size of regressed seminal vesicles of the animals, and increased the free testosterone (T) level. These findings suggest the ICS can be considered as a temporal source of androgens, which can facilitate a restoration of sexual activity.

  19. Thermal analysis of laser interstitial thermotherapy in ex vivo fibro-fatty tissue using exponential functions

    International Nuclear Information System (INIS)

    Salas, Nelson Jr.; Manns, Fabrice; Milne, Peter J; Denham, David B; Minhaj, Ahmed M; Parel, Jean-Marie; Robinson, David S

    2004-01-01

    A therapeutic procedure to treat small, surface breast tumours up to 10 mm in radius plus a 5 mm margin of healthy, surrounding tissue using laser interstitial thermotherapy (LITT) is currently being investigated. The purpose of this study is to analyse and model the thermal and coagulative response of ex vivo fibro-fatty tissue, a model for breast tissue, during experimental laser interstitial thermotherapy at 980 nm. Laser radiation at 980 nm was delivered interstitially through a diffusing tip optical fibre inserted into a fibro-fatty tissue model to produce controlled heating at powers ranging from 3.2 to 8.0 W. Tissue temperature was measured with thermocouples placed at 15 positions around the fibre. The induced coagulation zone was measured on gross anatomical sections. Thermal analysis indicates that a finite sum of exponential functions is an approximate solution to the heat conduction equation that more accurately predicts the time-temperature dependence in tissue prior to carbonization (T 3 mm 3 ) coagulation volume without unwanted tissue liquefaction and carbonization

  20. Ulcerative colitis: ultrastructure of interstitial cells in myenteric plexus

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johs.; Vanderwinden, J-M; Horn, T

    2010-01-01

    degenerative changes, such as lipid droplets and irregular vacuoles. Nerve terminals often appeared swollen and empty. Glial cells, muscle cells, and fibroblast-like cells (FLC) showed no alterations. FLC enclosed macrophages (MLC), which were in close contact with naked axon terminals. The organization...

  1. An Interstitial Network of Podoplanin-Expressing Cells in the Human Endolymphatic Duct

    Science.gov (United States)

    Mayerl, Christina; Rubin, Kristofer; Wick, Georg; Rask-Andersen, Helge

    2006-01-01

    The human endolymphatic duct (ED) with encompassing interstitial connective tissue (CT) is believed to be important for endolymph resorption and fluid pressure regulation of the inner ear. The periductal CT cells are interconnected via numerous cellular extensions, but do not form vessel structures. Here we report that the periductal CT is populated by two distinct cell phenotypes; one expressing podoplanin, a protein otherwise found on lymph endothelia and on epithelia involved in fluid fluxes, and a second expressing a fibroblast marker. A majority of the interstitial cells expressed podoplanin but not the lymphatic endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial growth factor receptor-3 (VEGFR-3). The fibroblast marker positive cells were found close to the ED epithelium. In the mid- and distal parts of the ED, these cells were enriched under folded epithelia. Furthermore, subepithelial CT cells were found to express activated platelet derived growth factor (PDGF)-β receptors. Cultured CT cells from human inner ear periductal and perisaccular explant tissues were identified as fibroblasts. These cells compacted a three-dimensional collagen lattice by a process that could be promoted by PDGF-BB, a factor involved in interstitial fluid pressure regulation. Our results are compatible with the notion that the periductal CT cells are involved in the regulation of inner ear fluid pressure. By active compaction of the periductal CT and by the formation of villous structures, the CT cells could modulate fluid fluxes over the ED epithelium as well as the longitudinal flow of endolymph in the ED. PMID:16408168

  2. Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal.

    Science.gov (United States)

    Janevska, Vesna; Qerimi, Adelina; Basheska, Neli; Stojkova, Elena; Janevski, Vlado; Jovanovic, Rubens; Zhivadinovik, Julija; Spasevska, Liljana

    2015-01-01

    Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. We analyzed 8 cases of superficial leiomyomas and one deep leiomyoma, received in our institutions as endoscopically or surgically obtained material. The tumor sections were immunohistochemicaly stained with CD117, CD34, NF, S100, αSMA, desmin, caldesmon and mast cell antigen. All leiomyomas showed diffuse positivity for αSMA, caldesmon and desmin. All of them had CD117 and CD34 positive cells morphologically identical to the interstitial cells of Cajal between smooth muscle fibers, 5 had S-100 and NF positive cells and 2 showed positivity for GFAP. The cells were found in different quantity; they were usually diffusely scattered through the tumors without predilection site, forming small groups in some areas. CD177, CD34, S-100 and NF positive cells are present in superficial leiomyomas and they may suggest common origin of GI stromal tumors.

  3. Proliferation of Interstitial Cells in the Cyclophosphamide-Induced Cystitis and the Preventive Effect of Imatinib

    OpenAIRE

    Sancho, Maria; Triguero, Domingo; Lafuente-Sanchis, Aranzazu; Garcia-Pascual, Angeles

    2017-01-01

    Cyclophosphamide- (CYP-) induced cystitis in the rat is a well-known model of bladder inflammation that leads to an overactive bladder, a process that appears to involve enhanced nitric oxide (NO) production. We investigated the changes in the number and distribution of interstitial cells (ICs) and in the expression of endothelial NO synthase (eNOS) in the bladder and urethra of rats subjected to either intermediate or chronic CYP treatment. Pronounced hyperplasia and hypertrophy of ICs were ...

  4. Interstitial cells of Cajal as targets for pharmacological intervention in gastrointestinal motor disorders

    DEFF Research Database (Denmark)

    Huizinga, J D; Thuneberg, L; Vanderwinden, J M

    1997-01-01

    Interstitial cells of Cajal (ICCs) have recently been identified as the pacemaker cells for contractile activity of the gastrointestinal tract. These cells generate the electrical 'slow-wave' activity that determines the characteristic frequency of phasic contractions of the stomach, intestine...... through the gut organs. Here Jan Huizinga, Lars Thuneberg, Jean-Marie Vanderwinden and Jüri Rumessen, suggest that, as ICCs are unique to the gut, they might be ideal targets for pharmacological intervention in gastrointestinal motility disorders, which are very common and costly....

  5. Interstitial interfaces show marked differences in regenerating tubules, matured tubules, and the renal stem/progenitor cell niche.

    Science.gov (United States)

    Minuth, Will W; Denk, Lucia

    2012-05-01

    Stem/progenitor cells are promising candidates for the regeneration of parenchyma in acute and chronic renal failure. After an implantation stem/progenitor cells must migrate through the interstitial space to concentrate at the site of damage. However, information is lacking to what extent the interstitial interface is influencing the development of stem/progenitor cells into nephron structures. In consequence, tubule regeneration within an artificial polyester interstitium was analyzed by electron microscopy in comparison with the interstitial interface of matured tubules and the interstitium within the renal stem/progenitor cell niche. The experiments demonstrate that fixation of specimens with glutaraldehyde (GA) is leading in all cases to inconspicuously looking interstitial interfaces. In contrast, fixation of regenerating tubules in GA containing ruthenium red and tannic acid shows a dense network of fibers lining along the basal lamina. In contrast, matured tubules reveal after ruthenium red label an extremely thickened basal lamina, while only a punctate pattern is obtained after tannic acid treatment. Finally, within the renal stem/progenitor cell niche ruthenium red and tannic acid label reveals large amounts of extracellular matrix spanning through the interstitium. Thus, fixation of tissue in GA containing ruthenium red and tannic acid exhibits an unexpectedly regional heterogeneity of the renal interstitial interface. This fact has to be considered for an optimal therapeutic repair of parenchyma, since contacts between stem/progenitor cells with the interstitial interface influence further development. Copyright © 2012 Wiley Periodicals, Inc.

  6. Influence of 125I seed interstitial brachytherapy on recovery of facial nerve function

    International Nuclear Information System (INIS)

    Song Tieli; Zheng Lei; Zhang Jie; Cai Zhigang; Yang Zhaohui; Yu Guangyan; Zhang Jianguo

    2010-01-01

    Objective: To study the influence of 125 I seed interstitial brachytherapy in parotid region on the recovery of facial nerve function. Methods: A total of the data of 21 patients with primary parotid carcinoma were treated with resection and 125 I interstitial brachytherapy. All the patients had no facial palsy before operation and the prescribed dose was 60 Gy. During 4 years of follow-up, the House-Brackmann grading scales and ENoG were used to evaluate the function of facial nerve. According to the modified regional House-Brackmann grading scales, the facial nerve branches of patients in affected side were divided into normal and abnormal groups, and were compared with those in contra-lateral side. Results: Post-operation facial palsy occurred in all the patients, but the facial palsy recovered within 6 months. The latency time differences between affected side and contralateral side were statistically significant in abnormal group from 1 week to 6 months after treatment (t=2.362, P=0.028), and were also different in normal group 1 week after treatment (t=2.522, P=0.027). Conclusions: 125 I interstitital brachytherapy has no influence on recovery of facial nerve function after tumor resection and no delayed facial nerve damage. (authors)

  7. Interstitial cystitis antiproliferative factor (APF as a cell-cycle modulator

    Directory of Open Access Journals (Sweden)

    Zhang Chen-Ou

    2004-04-01

    Full Text Available Abstract Background Interstitial cystitis (IC is a chronic bladder disorder of unknown etiology. Antiproliferative factor (APF, a peptide found in the urine of IC patients, has previously been shown to decrease incorporation of thymidine by normal bladder epithelial cells. This study was performed to determine the effect of APF on the cell cycle of bladder epithelial cells so as to better understand its antiproliferative activity. Methods Explant cultures from normal bladder biopsy specimens were exposed to APF or mock control. DNA cytometry was performed using an automated image analysis system. Cell cycle phase fractions were calculated from the DNA frequency distributions and compared by two-way analysis of variance (ANOVA. Results APF exposure produced statistically significant increases in the proportion of tetraploid and hypertetraploid cells compared to mock control preparations, suggesting a G2 and/or M phase cell cycle block and the production of polyploidy. Conclusions APF has a specific effect on cell cycle distributions. The presence of a peptide with this activity may contribute to the pathogenesis of interstitial cystitis through disruption of normal urothelial proliferation and repair processes.

  8. Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal.

    Science.gov (United States)

    Zhu, Mei Hong; Sung, In Kyung; Zheng, Haifeng; Sung, Tae Sik; Britton, Fiona C; O'Driscoll, Kate; Koh, Sang Don; Sanders, Kenton M

    2011-09-15

    Interstitial cells of Cajal (ICC) provide pacemaker activity and functional bridges between enteric motor nerve terminals and gastrointestinal smooth muscle cells. The ionic conductance(s) in ICC that are activated by excitatory neural inputs are unknown. Transgenic mice (Kit(copGFP/+)) with constitutive expression of a bright green fluorescent protein were used to investigate cellular responses of ICC to cholinergic stimulation. ICC displayed spontaneous transient inward currents (STICs) under voltage clamp that corresponded to spontaneous transient depolarizations (STDs) under current clamp. STICs reversed at 0 mV when E(Cl) = 0 mV and at -40 mV when E(Cl) was -40 mV, suggesting the STICs were due to a chloride conductance. Carbachol (CCh, 100 nm and 1 μm) induced a sustained inward current (depolarization in current clamp) and increased the amplitude and frequency of STICs and STDs. CCh responses were blocked by atropine (10 μm) or 4-DAMP (100 nm), an M(3) receptor antagonist. STDs were blocked by niflumic acid and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (both 100 μm), and CCh had no effect in the presence of these drugs. The responses of intact circular muscles to CCh and stimulation of intrinsic excitatory nerves by electrical field stimulation (EFS) were also compared. CCh (1 μm) caused atropine-sensitive depolarization and increased the maximum depolarization of slow waves. Similar atropine-sensitive responses were elicited by stimulation of intrinsic excitatory neurons. Niflumic acid (100 μm) blocked responses to EFS but had minor effect on responses to exogenous CCh. These data suggest that different ionic conductances are responsible for electrical responses elicited by bath-applied CCh and cholinergic nerve stimulation.

  9. Muscarinic activation of Ca2+-activated Cl− current in interstitial cells of Cajal

    Science.gov (United States)

    Zhu, Mei Hong; Sung, In Kyung; Zheng, Haifeng; Sung, Tae Sik; Britton, Fiona C; O'Driscoll, Kate; Koh, Sang Don; Sanders, Kenton M

    2011-01-01

    Abstract Interstitial cells of Cajal (ICC) provide pacemaker activity and functional bridges between enteric motor nerve terminals and gastrointestinal smooth muscle cells. The ionic conductance(s) in ICC that are activated by excitatory neural inputs are unknown. Transgenic mice (KitcopGFP/+) with constitutive expression of a bright green fluorescent protein were used to investigate cellular responses of ICC to cholinergic stimulation. ICC displayed spontaneous transient inward currents (STICs) under voltage clamp that corresponded to spontaneous transient depolarizations (STDs) under current clamp. STICs reversed at 0 mV when ECl = 0 mV and at –40 mV when ECl was –40 mV, suggesting the STICs were due to a chloride conductance. Carbachol (CCh, 100 nm and 1 μm) induced a sustained inward current (depolarization in current clamp) and increased the amplitude and frequency of STICs and STDs. CCh responses were blocked by atropine (10 μm) or 4-DAMP (100 nm), an M3 receptor antagonist. STDs were blocked by niflumic acid and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (both 100 μm), and CCh had no effect in the presence of these drugs. The responses of intact circular muscles to CCh and stimulation of intrinsic excitatory nerves by electrical field stimulation (EFS) were also compared. CCh (1 μm) caused atropine-sensitive depolarization and increased the maximum depolarization of slow waves. Similar atropine-sensitive responses were elicited by stimulation of intrinsic excitatory neurons. Niflumic acid (100 μm) blocked responses to EFS but had minor effect on responses to exogenous CCh. These data suggest that different ionic conductances are responsible for electrical responses elicited by bath-applied CCh and cholinergic nerve stimulation. PMID:21768263

  10. Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

    Science.gov (United States)

    Steiner, Clara; Gevaert, Thomas; Ganzer, Roman; De Ridder, Dirk; Neuhaus, Jochen

    2018-02-20

    Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM + /PDGFRα + and ≥ 90% were VIM + /TRPA1 + . In human and pig ≥ 74% of ULP ICs were VIM + /αSMA + , while in GP the percentage differed significantly with only 37% VIM + /αSMA + ICs. Additionally, over 90% of αSMA + ICs were also TRPA1 + and PDGFRα + in human, GP and pig. In all three species, TRPA1 + and PDGFRα + ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

  11. HGF Expressing Stem Cells in Usual Interstitial Pneumonia Originate from the Bone Marrow and Are Antifibrotic.

    Directory of Open Access Journals (Sweden)

    Amiq Gazdhar

    Full Text Available Pulmonary fibrosis may result from abnormal alveolar wound repair after injury. Hepatocyte growth factor (HGF improves alveolar epithelial wound repair in the lung. Stem cells were shown to play a major role in lung injury, repair and fibrosis. We studied the presence, origin and antifibrotic properties of HGF-expressing stem cells in usual interstitial pneumonia.Immunohistochemistry was performed in lung tissue sections and primary alveolar epithelial cells obtained from patients with usual interstitial pneumonia (UIP, n = 7. Bone marrow derived stromal cells (BMSC from adult male rats were transfected with HGF, instilled intratracheally into bleomycin injured rat lungs and analyzed 7 and 14 days later.In UIP, HGF was expressed in specific cells mainly located in fibrotic areas close to the hyperplastic alveolar epithelium. HGF-positive cells showed strong co-staining for the mesenchymal stem cell markers CD44, CD29, CD105 and CD90, indicating stem cell origin. HGF-positive cells also co-stained for CXCR4 (HGF+/CXCR4+ indicating that they originate from the bone marrow. The stem cell characteristics were confirmed in HGF secreting cells isolated from UIP lung biopsies. In vivo experiments showed that HGF-expressing BMSC attenuated bleomycin induced pulmonary fibrosis in the rat, indicating a beneficial role of bone marrow derived, HGF secreting stem cells in lung fibrosis.HGF-positive stem cells are present in human fibrotic lung tissue (UIP and originate from the bone marrow. Since HGF-transfected BMSC reduce bleomycin induced lung fibrosis in the bleomycin lung injury and fibrosis model, we assume that HGF-expressing, bone-marrow derived stem cells in UIP have antifibrotic properties.

  12. Morphometry and morphology of nucleus of the Sertoli and interstitial cells of the tambaqui Colossoma macropomum (Cuvier, 1881) (Pisces: Characidae) during the reproductive cycle.

    Science.gov (United States)

    Nakaghi, L S O; Mitsuiki, D; Santos, H S L; Pacheco, M R; Ganeco, L N

    2003-02-01

    This study allowed the characterization of the tambaqui Colossoma macropomum testes structural organization, emphasizing Sertoli and interstitial cells and analyzing morphometrically the Sertoli cell nucleus diameter and the interstitial tissue area during the reproductive cycle. Fragments of tambaqui testes were collected in the following reproductive cycle stages: immature, resting, maturation I and II, mature, and regression, and were histologically processed. The Sertoli cells were found at the periphery of the cysts of germinative lineage cells and the nuclei were shown to be smaller as these cells developed. The interstitial cells were better observed between the seminiferous lobules next to vessels in the interstitial tissue of maturing testes.

  13. Identification of Interstitial Cajal-Like Cells in the Human Thoracic Duct

    DEFF Research Database (Denmark)

    Briggs Boedtkjer, Donna; Rumessen, Jüri; Baandrup, Ulrik

    2012-01-01

    were used to identify ICLCs in live tissue. Methylene blue stained cells with morphology suggestive of ICLCs in the TD. Immunoreactivity localized the ICLC protein markers c-kit, CD34 and vimentin to many cells and processes associated with smooth muscle cells (SMCs): coexpression of c...... spindle shapes. Confocal imaging with calcium-dependent fluorophores corroborated cell morphology and localization observed in fixed tissues. Lymphatic ICLCs thus constitute a significant cell type of the human TD and physically interact with lymphatic SMCs.......Interstitial Cajal-like cells (ICLCs) are speculated to be pacemakers in smooth muscle tissues. While the human thoracic duct (TD) is spontaneously active, the origin of this activity is unknown. We hypothesized that ICLCs could be present in the TD and using histological techniques...

  14. Mesenchymal stromal stem cell therapy in advanced interstitial lung disease - Anaphylaxis and short-term follow-up

    Directory of Open Access Journals (Sweden)

    Balamugesh Thangakunam

    2015-01-01

    Full Text Available There are limited treatment options for advanced interstitial lung disease (ILD. We describe a patient of ILD treated with mesenchymal stromal stem cell infusion. The index patient had end-stage ILD due to a combination of insults including treatment with radiotherapy and a tyrosine kinase inhibitor Erlotinib. He was oxygen-dependent and this was hampering his quality of life. He tolerated the first infusion stem cells without any problem. During the second infusion he developed anaphylactic shock, which was appropriately managed. At 6-months follow-up he had no improvement in oxygenation, pulmonary function or CT scan parameters. In view of anaphylaxis, further infusions of MSC were withheld. A longer follow-up may reveal long-term benefits or side effects, if any. However the occurrence of anaphylaxis is of concern suggesting that further trials should be conducted with intensive monitoring.

  15. Passivation of interstitial and vacancy mediated trap-states for efficient and stable triple-cation perovskite solar cells

    Science.gov (United States)

    Mahmud, Md Arafat; Elumalai, Naveen Kumar; Upama, Mushfika Baishakhi; Wang, Dian; Gonçales, Vinicius R.; Wright, Matthew; Xu, Cheng; Haque, Faiazul; Uddin, Ashraf

    2018-04-01

    The current work reports the concurrent passivation of interstitial and oxygen vacancy mediated defect states in low temperature processed ZnO electron transport layer (ETL) via Ultraviolet-Ozone (UVO) treatment for fabricating highly efficient (maximum efficiency: 16.70%), triple cation based MA0.57FA0.38Rb0.05PbI3 (MA: methyl ammonium, FA: formamidinium, Rb: rubidium) perovskite solar cell (PSC). Under UV exposure, ozone decomposes to free atomic oxygen and intercalates into the interstitial and oxygen vacancy induced defect sites in the ZnO lattice matrix, which contributes to suppressed trap-assisted recombination phenomena in perovskite device. UVO treatment also reduces the content of functional hydroxyl group on ZnO surface, that increases the inter-particle connectivity and grain size of perovskite film on UVO treated ZnO ETL. Owing to this, the perovskite film atop UVO treated ZnO film exhibits reduced micro-strain and dislocation density values, which contribute to the enhanced photovoltaic performance of PSC with modified ZnO ETL. The modified PSCs exhibit higher recombination resistance (RRec) ∼40% compared to pristine ZnO ETL based control devices. Adding to the merit, the UVO treated ZnO PSC also demonstrates superior device stability, retaining about 88% of its initial PCE in the course of a month-long, systematic degradation study.

  16. Voids in silicon as a sink for interstitial iron: a density functional study

    Science.gov (United States)

    Al-Ani, Oras A.; Goss, J. P.; Al-Hadidi, Meaad; Briddon, P. R.; Rayson, M. J.; Cowern, N. E. B.

    2017-06-01

    Transition metals, and in particular iron, are deleterious when contaminating electronic grade silicon. The gettering of these impurities to less important regions of devices is therefore a key mechanism in the optimisation of materials for applications such as photovoltaics. Voids are one potential gettering site for iron, and we present the results of a density function study on the binding of interstitial iron at such a location. We find a binding energy of around 2 eV, with the various sites at the model void lead to a wide range of binding energies. Perhaps surprisingly, we find that the most stable site lies just outside the void, which may explain the experimental observation that only a single layer of iron forms at voids. The direct relationship between binding energy and strain that caused by segregate iron atom at the sites that provided by the void structure are also presented.

  17. Increased CXCR3 Expression of Infiltrating Plasma Cells in Hunner Type Interstitial Cystitis

    Science.gov (United States)

    Akiyama, Yoshiyuki; Morikawa, Teppei; Maeda, Daichi; Shintani, Yukako; Niimi, Aya; Nomiya, Akira; Nakayama, Atsuhito; Igawa, Yasuhiko; Fukayama, Masashi; Homma, Yukio

    2016-01-01

    An up-regulated CXCR3 pathway and affluent plasma cell infiltration are characteristic features of Hunner type interstitial cystitis (HIC). We further examined these two features using bladder biopsy samples taken from 27 patients with HIC and 15 patients with non-IC cystitis as a control. The number of CD3-positive T lymphocytes, CD20-positive B lymphocytes, CD138-positive plasma cells, and CXCR3-positive cells was quantified by digital image analysis. Double-immunofluorescence for CXCR3 and CD138 was used to detect CXCR3 expression in plasma cells. Correlations between CXCR3 positivity and lymphocytic and plasma cell numbers and clinical parameters were explored. The density of CXCR3-positive cells showed no significant differences between HIC and non-IC cystitis specimens. However, distribution of CXCR3-positivity in plasma cells indicated co-localization of CXCR3 with CD138 in HIC specimens, but not in non-IC cystitis specimens. The number of CXCR3-positive cells correlated with plasma cells in HIC specimens alone. Infiltration of CXCR3-positive cells was unrelated to clinical parameters of patients with HIC. These results suggest that infiltration of CXCR3-positive plasma cells is a characteristic feature of HIC. The CXCR3 pathway and specific immune responses may be involved in accumulation/retention of plasma cells and pathophysiology of the HIC bladder. PMID:27339056

  18. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration

    DEFF Research Database (Denmark)

    Lammermann, Tim; Renkawitz, Jorg; Wu, Xunwei

    2009-01-01

    proteolysis. Instead, the protrusive flow of the actin cytoskeleton directly drives a basal mode of locomotion that is occasionally supported by actomyosin contractions at the trailing edge to propel the cell's rigid nucleus. We here delete the small GTPase Cdc42 in DCs and find that actin flow and actomyosin......Mature dendritic cells (DCs) moving from the skin to the lymph node are a prototypic example of rapidly migrating amoeboid leukocytes. Interstitial DC migration is directionally guided by chemokines, but independent of specific adhesive interactions with the tissue as well as pericellular...... contraction are still initiated in response to chemotactic cues. Accordingly, the cells are able to polarize and form protrusions. However, in the absence of Cdc42 the protrusions are temporally and spatially dysregulated which leads to impaired leading edge coordination. While this defect still allows...

  19. Image-guided Interstitial Photodynamic Therapy for Squamous Cell Carcinomas: Preclinical investigation

    Science.gov (United States)

    Sajisevi, Mirabelle; Rigual, Nestor R; Bellnier, David A.; Seshadri, Mukund

    2014-01-01

    Objective Photodynamic therapy (PDT) is a clinically approved minimally invasive treatment for cancer. In this preclinical study, using an imaging-guided approach, we examined the potential utility of PDT in the management of bulky squamous cell carcinomas (SCCs). Methods To mimic bulky oropharyngeal cancers seen in the clinical setting, intramuscular SCCs were established in six-to-eight week old female C3H mice. Animals were injected with the photosensitizer, 2-[hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH; 0.4 μmol/kg, i.v.) and tumors were illuminated 24 hours post injection with 665 nm light. PDT as a single treatment modality was administered by surface illumination or by interstitial placement of fibers (iPDT). Magnetic resonance imaging was used to guide treatment and assess tumor response to PDT along with correlative histopathologic assessment. Results Interstitial HPPH-PDT resulted in a marked change on T2 maps 24 hours post treatment compared to untreated controls or transcutaneous illumination. Corresponding apparent diffusion coefficient maps also showed hyperintense areas in tumors following iPDT suggestive of effective photodynamic cell kill. Histologic sections (H&E) confirmed presence of extensive tumor necrosis following iPDT. Conclusions These results highlight the potential utility of PDT in the treatment of bulky oropharyngeal cancers. The findings of our study also demonstrate the utility of MRI as a non-invasive tool for mapping of early tissue response to PDT. PMID:25750858

  20. Therapeutic effect of urine-derived stem cells for protamine/lipopolysaccharide-induced interstitial cystitis in a rat model.

    Science.gov (United States)

    Li, Jia; Luo, Hui; Dong, Xingyou; Liu, Qian; Wu, Chao; Zhang, Teng; Hu, Xiaoyan; Zhang, Yuanyuan; Song, Bo; Li, Longkun

    2017-05-08

    Interstitial cystitis (IC) is a chronic inflammation disorder mainly within the submucosal and muscular layers of the bladder. As the cause of IC remains unknown, no effective treatments are currently available. Administration of stem cell provides a potential for treatment of IC. This study was conducted using urine-derived stem cells (USCs) for protamine/lipopolysaccharide (PS/LPS)-induced interstitial cystitis in a rodent model. In total, 60 female Sprague-Dawley rats were randomized into three experimental groups (n = 5/group): sham controls; IC model alone; and IC animals intravenously treated with USCs (1.2 × 10 6 suspended in 0.2 ml phosphate-buffered saline (PBS). Our data showed that the bladder micturition function was significantly improved in IC animals intravenously treated with USCs compared to those in the IC model alone group. The amount of antioxidants and antiapoptotic protein biomarkers heme oxygenase (HO)-1, NAD(P)H quinine oxidoreductase (NQO)-1, and Bcl-2 within the bladder tissues were significantly higher in IC animals intravenously treated with USCs and lower in the sham controls group as assessed by Western blot and immunofluorescent staining. In addition, the expression of autophagy-related protein LC3A was significantly higher in the IC model alone group than that in IC animals intravenously treated with USCs. Inflammatory biomarkers and apoptotic biomarkers (interleukin (IL)-6, tumor necrosis factor (TNF)α, nuclear factor (NF)-κB, caspase 3, and Bax) and the downstream inflammatory and oxidative stress biomarkers (endoplasmic reticulum stress and autophagy-related protein (GRP78, LC3, Beclin1)) in the bladder tissue revealed statistically different results between groups. USCs restored the bladder function and histological construction via suppressing oxidative stress, inflammatory reaction, and apoptotic processes in a PS/LPS-induced IC rodent model, which provides potential for treatment of patients with IC.

  1. The human trigeminal ganglion: c-kit positive neurons and interstitial cells.

    Science.gov (United States)

    Rusu, M C; Pop, F; Hostiuc, S; Dermengiu, D; Lală, A I; Ion, D A; Mănoiu, V S; Mirancea, N

    2011-10-20

    The presence of c-kit positive neurons in sensory ganglia has been verified in various species but not in humans. Our aim has been to identify whether human primary trigeminal neurons label with c-kit/CD117 and thus, whether data gathered in animal studies can be extrapolated to humans. We also intended to establish whether, and which non-neuronal cells also label with c-kit in the trigeminal ganglion. Human adult trigeminal ganglia from eight cadavers were processed for immunohistochemistry on paraffin embedded samples using monoclonal antibodies for CD117/c-kit, and three additional trigeminal ganglia were used for transmission electron microscopy (TEM). To evaluate which neuronal type (A or B) was labeled with c-kit, we evaluated the same neurons on adjacent sections labeled with antibodies for neurofilaments (NF). c-kit has labeled trigeminal neurons (TNs), mast cells and interstitial cells (ICs) within the trigeminal ganglion. c-kit+TNs were NF-and thus were strongly presumed to be nociceptive, as such neurons are known to be NF-poor. c-kit+ICs with long and moniliform processes intermingled with the satellite glial cells (SGCs) of the neuronal envelopes. TEM evaluations confirmed this mixed composition of the neuronal envelopes and demonstrated that the perineuronal ICs are in fact interstitial Cajal-like cells (ICLCs) and/or telocytes. c-kit+TNs were objectified in humans and strongly presumed to be nociceptive. TNs envelopes mostly consist of SGCs, but are also combined with ICLCs/telocytes. Copyright © 2011 Elsevier GmbH. All rights reserved.

  2. CD34+ cells in human intestine are fibroblasts adjacent to, but distinct from, interstitial cells of Cajal

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J; De Laet, M H

    1999-01-01

    Interstitial cells of Cajal (ICC) generate the pacemaker component of the gut and play important roles in the control of gut motility. The tyrosine kinase receptor Kit is an established marker for ICC. Recently, it has been reported that immunoreactivity for the sialomucin CD34 may be present...... and confocal microscopy. CD34 immunoreactivity identified previously unrecognized cells closely adjacent to, but distinct from, the Kit immunoreactive ICC. These CD34 immunoreactive cells expressed the fibroblast marker prolyl 4-hydroxylase-whereas ICC did not-and were also distinct from smooth muscle cells......, glial cells, and macrophages. In the human gut, CD34 immunoreactivity is not expressed by ICC but by a population of fibroblasts, likely corresponding to the "fibroblast-like cells" described in previous ultrastructural studies. Our findings also challenge the hypothesis that stromal tumors originate...

  3. A technique for in vitro culture of canine valvular interstitial cells.

    Science.gov (United States)

    Heaney, Allison M; Bulmer, Barret J; Ross, Christopher R; Schermerhorn, Thomas

    2009-06-01

    To develop a method for in vitro culture of canine valvular interstitial cells (VICs). Canine VICs were isolated from the distal third of the anterior mitral valve leaflet using an explant technique and maintained in cell culture. Molecular phenotyping of the cultured cells was performed using reverse transcription polymerase chain reaction and immunocytochemistry. Cells resembling fibroblasts migrated from canine mitral valve explants and were maintained in culture for up to eight passages. Establishment of the valve explant required collagen but once established, subsequent passages grew on non-coated plastic plates. At confluence the cultured cells exhibited the characteristic whorled pattern of fibroblasts in culture. The isolated valve cells expressed vimentin but not platelet endothelial cell adhesion molecule or von Willebrand's factor, consistent with the molecular phenotype of VICs. VICs can be readily isolated from canine mitral valve leaflets and successfully maintained in culture using standard culture techniques. The described techniques permit the study of bioactive VICs in a controlled environment and may be a useful in vitro model for investigation of cellular and molecular alterations associated with canine chronic degenerative valve disease.

  4. Characterization of epicardial-derived cardiac interstitial cells: differentiation and mobilization of heart fibroblast progenitors.

    Directory of Open Access Journals (Sweden)

    Adrián Ruiz-Villalba

    Full Text Available The non-muscular cells that populate the space found between cardiomyocyte fibers are known as 'cardiac interstitial cells' (CICs. CICs are heterogeneous in nature and include different cardiac progenitor/stem cells, cardiac fibroblasts and other cell types. Upon heart damage CICs soon respond by initiating a reparative response that transforms with time into extensive fibrosis and heart failure. Despite the biomedical relevance of CICs, controversy remains on the ontogenetic relationship existing between the different cell kinds homing at the cardiac interstitium, as well as on the molecular signals that regulate their differentiation, maturation, mutual interaction and role in adult cardiac homeostasis and disease. Our work focuses on the analysis of epicardial-derived cells, the first cell type that colonizes the cardiac interstitium. We present here a characterization and an experimental analysis of the differentiation potential and mobilization properties of a new cell line derived from mouse embryonic epicardium (EPIC. Our results indicate that these cells express some markers associated with cardiovascular stemness and retain part of the multipotent properties of embryonic epicardial derivatives, spontaneously differentiating into smooth muscle, and fibroblast/myofibroblast-like cells. Epicardium-derived cells are also shown to initiate a characteristic response to different growth factors, to display a characteristic proteolytic expression profile and to degrade biological matrices in 3D in vitro assays. Taken together, these data indicate that EPICs are relevant to the analysis of epicardial-derived CICs, and are a god model for the research on cardiac fibroblasts and the role these cells play in ventricular remodeling in both ischemic or non/ischemic myocardial disease.

  5. Leukocyte compartments in the mouse lung: distinguishing between marginated, interstitial, and alveolar cells in response to injury.

    Science.gov (United States)

    Barletta, Kathryn E; Cagnina, R Elaine; Wallace, Kori L; Ramos, Susan I; Mehrad, Borna; Linden, Joel

    2012-01-31

    We developed a flow cytometry-based assay to simultaneously quantify multiple leukocyte populations in the marginated vascular, interstitial, and alveolar compartments of the mouse lung. An intravenous injection of a fluorescently labeled anti-CD45 antibody was used to label circulating and marginated vascular leukocytes. Following vascular flushing to remove non-adherent cells and collection of broncho-alveolar lavage (BAL) fluid, lungs were digested and a second fluorescent anti-CD45 antibody was added ex vivo to identify cells not located in the vascular space. In the naïve mouse lung, we found about 11 million CD45+ leukocytes, of which 87% (9.5 million) were in the vascular marginated compartment, consisting of 17% NK cells, 17% neutrophils, 57% mononuclear myeloid cells (monocytes, macrophage precursors and dendritic cells), and 10% T cells (CD4+, CD8+, and invariant NKT cells). Non-vascular compartments including the interstitial compartment contained 7.7×10(5)cells, consisting of 49% NK cells, 25% dendritic cells, and 16% other mononuclear myeloid cells. The alveolar compartment was overwhelmingly populated by macrophages (5.63×10(5)cells, or 93%). We next studied leukocyte margination and extravasation into the lung following acid injury, a model of gastric aspiration. At 1 h after injury, neutrophils were markedly elevated in the blood while all other circulating leukocytes declined by an average of 79%. At 4 h after injury, there was a peak in the numbers of marginated neutrophils, NK cells, CD4+ and CD8+ T cells and a peak in the number of alveolar NK cells. Most interstitial cells consisted of DCs, neutrophils, and CD4+ T cells, and most alveolar compartment cells consisted of macrophages, neutrophils, and NK cells. At 24 h after injury, there was a decline in the number of all marginated and interstitial leukocytes and a peak in alveolar neutrophils. In sum, we have developed a novel assay to study leukocyte margination and trafficking following

  6. Conditioned medium derived from mesenchymal stem cells culture as a intravesical therapy for cystitis interstitials.

    Science.gov (United States)

    Adamowicz, Jan; Pokrywczyńska, Marta; Drewa, Tomasz

    2014-06-01

    The treatment of Interstinal Cystitisis (IC) is still challenge for urologist. Available therapies do not result in long-term control of symptoms and do not provide pain relive to patients. Unique abilities of mesenchymal stem cells (MSC) could be used to develop new treatment approaches for Interstitial Cystitis. Conditioned Medium (CM) derived from MSC culture is rich in plenty of growth factors, cytokines and trophic agents which were widely reported to enhance regeneration of urinary bladder in different conditions. This ready mixture of growth factors could be used to develop intravesical therapy for patients with IC. MSC-CM has anti-apoptotic, anti-inflammatory, supportive, angiogenic, immunosuppressive and immunomodulative properties and seems to be ideal substance to prevent IC recurrence and to create favorable environment for regeneration of damaged bladder wall. Copyright © 2014. Published by Elsevier Ltd.

  7. Effects of Raloxifene on the Proliferation and Apoptosis of Human Aortic Valve Interstitial Cells

    Directory of Open Access Journals (Sweden)

    Zhimin Fu

    2016-01-01

    Full Text Available We aimed to explore the effects of raloxifene (RAL on the proliferation and apoptosis of human aortic valve interstitial cells (AVICs. Different concentrations of RAL were used to act on AVICs. MTS kit is used to test the effects of different concentrations of RAL on the proliferation of AVICs. Cell cycle and apoptosis test used flow cytometry after seven-day treatment. The relative expression levels of caspase-3 and caspase-8 are tested with RT-qPCR and Western blot. The results of MTS testing revealed that the absorbance value (OD value of the cells in the concentration groups of 10 and 100 nmol/L RAL at a wavelength of 490 nm at five, seven, and nine days significantly decreased compared with that in the control group. Meanwhile, the results of flow cytometry of the cells collected after seven days showed that the ratio of the S stage and the cell apoptosis rate of AVICs can be significantly reduced by RAL in the concentration groups of 10 and 100 nmol/L. The mRNA and protein expressions of caspase-3 and caspase-8 were significantly decreased compared with those in the control group. This study laid the foundation for further treatment of aortic valve disease by using RAL.

  8. Improved pulmonary function following pirfenidone treatment in a patient with progressive interstitial lung disease associated with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Zarir F Udwadia

    2015-01-01

    Full Text Available Pirfenidone is an anti-fibrotic drug which has been approved for the management of patients with Idiopathic Pulmonary Fibrosis (IPF. However, its role in interstitial lung disease (ILD due to other causes such as systemic sclerosis (SSc is not clear. We present a case of a patient with SSc associated ILD who showed a subjective as well as objective improvement in lung function with pirfenidone.

  9. Probing the mystery of Chinese medicine meridian channels with special emphasis on the connective tissue interstitial fluid system, mechanotransduction, cells durotaxis and mast cell degranulation

    Directory of Open Access Journals (Sweden)

    Fung Peter

    2009-05-01

    Full Text Available Abstract This article hypothesizes that the Chinese medicine meridian system is a special channel network comprising of skin with abundant nerves and nociceptive receptors of various types, and deeper connective tissues inside the body with the flowing interstitial fluid system. These meridian channels provide efficient migratory tracks mainly due to durotaxis (also including chemotaxis for mast cells, fibroblasts and other cells to migrate and carry out a number of physiological functions. Acupuncture acting on meridian channel causes cytoskeletal remodeling through mechanotransduction, leading to regulation of gene expression and the subsequent production of related proteins. Also, stimulation on cell surface can trigger Ca2+ activities, resulting in a cascade of intra- and inter-cellular signaling. Moreover, nerve endings in the meridian channels interact with mast cells and induce the degranulation of these cells, leading to the release of many specific biomolecules needed for homeostasis, immune surveillance, wound healing and tissue repair. Acupoint along a meridian channel is a functional site to trigger the above functions with specificity and high efficiency.

  10. Proliferative potential of malignant glioma cells before and after interstitial brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kunishiro, Katsuzo; Matsumoto, Kengo; Higashi, Hisato; Adachi, Hisashi; Tamiya, Takashi; Furuta, Tomohisa; Ohtomo, Takashi [Okayama Univ. (Japan). School of Medicine

    1999-05-01

    The viability of tumor cells in radionecrotic tissue after interstitial brachytherapy (BRTX) was evaluated using immunohistochemical markers of proliferative potential in primary and recurrent tumors. Tumor specimens from 30 patients with malignant gliomas (14 anaplastic astrocytomas, 16 glioblastomas) taken before and after BRTX were examined using MIB-1 monoclonal antibody. Histological examinations of specimens obtained by craniotomy or stereotactic biopsy after BRTX revealed tumor recurrence in 18 patients and radionecrosis in 12 patients including two with pure radionecrosis and 10 with a mixture of both tumor and radionecrosis. The MIB-1 index of the tumors with radionecrosis was 7.6{+-}5.5%, and that of the primary tumors was 17.0{+-}11.2%, showing a significant difference (p<0.05). There was no significant difference between the MIB-1 index of the primary tumors with local recurrence after BRTX and the primary tumors which underwent radionecrosis. Although morphologically viable tumor cells were found in the radionecrotic tissue, BRTX causes a reduction in the proliferative potential of these tumor cells. (author)

  11. Exogenous serotonin regulates proliferation of interstitial cells of Cajal in mouse jejunum through 5-HT2B receptors

    OpenAIRE

    Wouters, Mira; Gibbons, Simon J; Roeder, Jaime L; Distad, Marne; Ou, Yijun; Strege, Peter R; Szurszewski, Joseph H; Farrugia, Gianrico

    2007-01-01

    BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) are required for normal gastrointestinal motility. Loss of ICC is associated with several motility disorders. The mechanisms modulating ICC survival and proliferation are poorly understood. This study aimed to establish whether 5-hydroxytryptamine (5-HT) plays a role in regulating ICC proliferation. METHODS: Expression of 5-HT receptor mRNA was investigated in muscle strips, in purified populations of ICC, and in identified single cells. Th...

  12. Histamine-enhanced contractile responses of gastric smooth muscle via interstitial cells of Cajal in the Syrian hamster.

    Science.gov (United States)

    Naganuma, S; Shiina, T; Yasuda, S; Suzuki, Y; Shimizu, Y

    2017-11-21

    Gastric motility is controlled by the autonomic and enteric nervous systems and by interstitial cells of Cajal (ICCs). Although histamine is known to be released from enterochromaffin-like cells in the gastric mucosa, its regulatory roles in gastric motility are still controversial. Therefore, we investigated the functional roles of histamine in gastric motility. Stomach preparations from hamsters were used because the stomach of hamsters can be easily separated into the forestomach and the glandular stomach. A whole preparation of the stomach was mounted in a Magnus tube, and mechanical responses were recorded using a force transducer. Exogenous application of histamine had little effect on contractile activity of the glandular stomach. In contrast, the monoamine evoked regular, periodic contractions in the forestomach. An H1 receptor agonist reproduced the contractile responses and an H1 receptor antagonist blocked histamine-evoked contractions. Atropine and tetrodotoxin did not affect the histamine-evoked contractions. Pretreatment with drugs that inhibit the activity of ICCs abolished the effects of histamine. The findings suggest that histamine regulates gastric motility by acting on ICCs via H1 receptors in the hamster. The remarkable ability of histamine to induce rhythmic contractions would be useful for treatment of gastric dysmotility. © 2017 John Wiley & Sons Ltd.

  13. Incidence of interstitial pneumonia after hyperfractionated total body irradiation before autologous bone marrow/stem cell transplantation

    International Nuclear Information System (INIS)

    Lohr, F.; Schraube, P.; Wenz, F.; Flentje, M.; Kalle, K. von; Haas, R.; Hunstein, W.; Wannenmacher, M.

    1995-01-01

    Purpose/Objectives Interstitial pneumonia (IP) is a severe complication after allogenic bone marrow transplantation (BMT) with incidence rates between 10 % and 40 % in different series. It is a polyetiologic disease that occurs depending on age, graft vs. host disease (GvHD), CMV-status, total body irradiation (TBI) and immunosuppressive therapy after BMT. The effects of fractionation and dose rate are not entirely clear. This study evaluates the incidence of lethal IP after hyperfractionated TBI for autologous BMT or stem cell transplantation. Materials and Methods Between 1982 and 1992, 182 patients (60 % male, 40 % female) were treated with hyperfractionated total body irradiation (TBI) before autologous bone marrow transplantation. Main indications were leukemias and lymphomas (53 % AML, 21 % ALL, 22 % NHL, 4 % others) Median age was 30 ys (15 - 55 ys). A total dose of 14.4 Gy was applied using lung blocks (12 fractions of 1.2 Gy in 4 days, dose rate 7-18 cGy/min, lung dose 9 - 9.5 Gy). TBI was followed by cyclophosphamide (200 mg/kg). 72 % were treated with bone marrow transplantation, 28 % were treated with stem cell transplantation. Interstitial pneumonia was diagnosed clinically, radiologically and by autopsy. Results 4 patients died most likely of interstitial pneumonia. For another 12 patients interstitial pneumonia was not the most likely cause of death but could not be excluded. Thus, the incidence of lethal IP was at least 2.2 % but certainly below 8.8 %. Conclusion Lethal interstitial pneumonia is a rare complication after total body irradiation before autologous bone marrow transplantation in this large, homogeously treated series. In the autologous setting, total doses of 14.4 Gy can be applied with a low risk for developing interstitial pneumonia if hyperfractionation and lung blocks are used. This falls in line with data from series with identical twins or t-cell depleted marrow and smaller, less homogeneous autologous transplant studies. Thus

  14. Urothelial Functional Protein and Sensory Receptors in Patients With Interstitial Cystitis/Bladder Pain Syndrome With and Without Hunner's Lesion.

    Science.gov (United States)

    Jhang, Jia-Fong; Hsu, Yung-Hsiang; Kuo, Hann-Chorng

    2016-12-01

    To investigate the urothelium function and sensory receptors difference between interstitial cystitis/bladder pain syndrome (IC/BPS) patients with or without Hunner's lesion. Fourteen female IC/BPS patients with Hunner's lesion (Hunner IC) and 14 age-matched IC/BPS patients without Hunner's lesions (non-Hunner IC) were enrolled. Bladder mucosa biopsies were obtained. Bladder inflammation, eosinophil infiltration, and urothelial denudation were graded on a 4-point scale after staining with hematoxylin and eosin. Adhesive protein E-cadherin, tryptase, and zonula occuldens-1 in the bladder tissues were assessed with immunofluorescence staining. Urothelial muscarinic receptors M2, M3, endothelial nitric oxide synthase (eNOS), and purinergic receptor P2X3 were evaluated by Western blotting. Hunner IC patients had a significantly higher mean visual analog scale pain score and smaller cystometric bladder capacity than non-Hunner IC patients. The Hunner IC bladder specimens showed more severe or moderate eosinophilic infiltration and urothelial denudation than the non-Hunner IC bladder specimens did. The E-cadherin expression was significantly lower, and eNOS expression was significantly higher in the Hunner IC bladder samples than in the non-Hunner IC samples. The other functional proteins or sensory receptors did not differ between groups. Bladder inflammation and urothelial cell adhesion defects were more severe in the Hunner IC than that in the non-Hunner IC patients. eNOS was significantly higher in the Hunner IC than in the non-Hunner IC bladder samples, suggesting that eNOS expression difference may implicate different pathogenesis in 2 types of IC. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The Role of Interstitial Cells of Cajal in Acute Cholecystitis in Guinea Pig Gallbladder.

    Science.gov (United States)

    Huang, Zhen-Peng; Qiu, Hu; Yang, Yan; Zhang, Li; Yang, Bin; Lin, Meng-Juan; Yu, Bao-Ping

    2016-01-01

    Acute cholecystitis is common in gallbladder motility disorder. Interstitial cells of Cajal (ICCs) in the gallbladder are involved in the regulation of gallbladder motility. The aim of this study was to explore the change of gallbladder ICCs in acute cholecystitis. Thirty adult guinea pigs were randomly divided into 3 groups: a sham-operated group (healthy controls) and 2 study groups. The animals in the study group were subjected to bile duct ligation and then to laparotomy and cholecystectomy at 24 and 48 hours after surgery. Immunohistochemistry, immunohistofluorescence, and laser confocal microscopy were performed to observe the shape, size, morphology, and density of gallbladder ICCs. Western blot and real-time PCR were performed to detect stem cell factor and c-kit protein and mRNA expression, respectively. There were no differences in the shape, size, and morphology of the gallbladder ICCs in the control and the two acute cholecystitis groups. Density of gallbladder ICCs, SCF level, and c-kit protein and mRNA expression all decreased in the acute cholecystitis groups. Further, SCF level and c-kit protein and mRNA expression decreased with progress of acute cholecystitis (all P cholecystitis can decrease ICCs through repression of SCF and c-kit expression and that ICCs loss play a role in acute cholecystitis. © 2016 The Author(s) Published by S. Karger AG, Basel.

  16. Recombination Cross Section for Interstitials and Vacancies as a Function of Vacancy Concentration

    DEFF Research Database (Denmark)

    Leffers, Torben; Singh, Bachu Narain

    1981-01-01

    the actual recombination event. This makes it possible to cover the range of vacancy concentrations from very high values down to 10−6 and to include the case where interstitials and vacancies are equally mobile. We are therefore in a position to establish the dependence of Ziv, on the various relevant...

  17. Differentiation of interstitial cells of Cajal in the human distal colon.

    Science.gov (United States)

    Radenkovic, Goran; Abramovic, Mirjana

    2012-01-01

    At the end of the embryonic period of human development, interstitial cells of Cajal (ICC) are present in the esophagus, stomach, and proximal duodenum, around the inception of the myenteric plexus (MP) ganglia. In the small and large bowel, ICC appear later. The object of the present study was to determine the timing of appearance and pattern of distribution of ICC in the human embryonic and fetal distal colon. Human distal colon specimens were obtained from 8 embryos and 14 fetuses without gastrointestinal disorders. The specimens were 7-16 weeks of gestational age. The specimens were exposed to anti-c-kit antibodies to investigate ICC differentiation. Enteric plexuses were immunohistochemically examined using anti-neuron-specific enolase, and the differentiation of smooth muscle cells was studied with anti-desmin antibodies. In the distal colon, ICC emerged at weeks 10-11 of the fetal period in the form of two parallel belts of densely packed cells extending at the submucous plexus (SMP) and the MP level. These cells correspond to ICC of the SMP (ICC-SMP) and ICC of the MP (ICC-MP). The simultaneous appearance of ICC at the SMP and MP level in the distal colon can be explained by the fact that there are differences in the migration of neural crest cells in particular portions of the digestive tube. In conclusion, in humans, there was a difference in the patterns of development of ICC in the distal colon compared to the rest of the gut. Copyright © 2012 S. Karger AG, Basel.

  18. Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages

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    Meyerhans Andreas

    2010-09-01

    Full Text Available Abstract Background Investigations on pulmonary macrophages (MΦ mostly focus on alveolar MΦ (AM as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM, are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. Methods Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. Results IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG. Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6. Conclusion AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response.

  19. Interstitial lung diseases in children

    Directory of Open Access Journals (Sweden)

    N. S. Lev

    2014-01-01

    Full Text Available The paper deals with interstitial lung diseases in children. It gives an update and the results of the authors’ observations of different forms of interstitial lung diseases. Particular emphasis is placed on hypersensitive pneumonitis as the most common nosological entity among childhood interstitial lung diseases. The authors followed up 186 children with hypersensitive pneumonitis. They present the most important clinical, functional, radiological, and immunological diagnostic signs of this disease and consider its prognosis. In addition, there is evidence for other rare forms of interstitial lung diseases (idiopathic interstitial pneumonia, idiopathic pulmonary hemosiderosis, etc. in children. 

  20. Nephron progenitor cell death elicits a limited compensatory response associated with interstitial expansion in the neonatal kidney

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    Sree Deepthi Muthukrishnan

    2018-01-01

    Full Text Available The final nephron number in an adult kidney is regulated by nephron progenitor cell availability and collecting duct branching in the fetal period. Fetal environmental perturbations that cause reductions in cell numbers in these two compartments result in low nephron endowment. Previous work has shown that maternal dietary factors influence nephron progenitor cell availability, with both caloric restriction and protein deprivation leading to reduced cell numbers through apoptosis. In this study, we evaluate the consequences of inducing nephron progenitor cell death on progenitor niche dynamics and on nephron endowment. Depletion of approximately 40% of nephron progenitor cells by expression of diphtheria toxin A at embryonic day 15 in the mouse results in 10-20% nephron reduction in the neonatal period. Analysis of cell numbers within the progenitor cell pool following induction of apoptosis reveals a compensatory response in which surviving progenitor cells increase their proliferation and replenish the niche. The proliferative response is temporally associated with infiltration of macrophages into the nephrogenic zone. Colony stimulating factor 1 (CSF1 has a mitogenic effect on nephron progenitor cells, providing a potential explanation for the compensatory proliferation. However, CSF1 also promotes interstitial cell proliferation, and the compensatory response is associated with interstitial expansion in recovering kidneys which can be pharmacologically inhibited by treatment with clodronate liposomes. Our findings suggest that the fetal kidney employs a macrophage-dependent compensatory regenerative mechanism to respond to acute injury caused by death of nephron progenitor cells, but that this regenerative response is associated with neonatal interstitial expansion.

  1. Interstitial cell tumor in a black-and-white ruffed lemur (Varecia variegatus variegatus).

    Science.gov (United States)

    Neiffer, D L; Klein, E C

    2001-06-01

    A 14.5-yr-old, male black-and-white ruffed lemur (Varecia variegatus variegatus) presented for acute enlargement of the left testicle and hemiscrotum. Physical examination also revealed poor pelage quality with short guard hairs, sparse undercoat, and areas of alopecia. Increased aggression was also reported. A unilateral, open orchiectomy was performed, with the left testicle, epidydymis, associated vaginal tunic, and attached spermatic cord removed. Microscopic evaluation was consistent with an interstitial cell tumor, with many morphologic features similar to this neoplasm in people. No overt histopathologic criteria of malignancy were present. Following orchiectomy, gradual improvement in pelage quality was noted and was considered almost normal by 5 mo postoperative. In contrast with the aggressive preoperative behavior, the lemur was extremely submissive for 3 mo following the surgery. Gradual return to normal behavior and social status occurred over the next 2 mo. Multiple follow-up examinations and radiographs revealed no evidence of metastasis, and biopsy of the remaining testicle 4 mo later revealed no evidence of neoplasia. Serial measurements of testosterone and estradiol revealed levels within the range of those for other ruffed lemurs, as were repeated measurements taken of the remaining testicle. At 19 mo postoperative, the lemur had a coat quality considered nearly normal and maintained its historical social position in the lemur group without abnormal aggressive behavior.

  2. Biophysically-based modelling of the interstitial cells of Cajal: Current status and future perspectives

    Directory of Open Access Journals (Sweden)

    Rachel eLees-Green

    2011-07-01

    Full Text Available Gastrointestinal motility research is progressing rapidly, leading to significant advances in the last 15 years in understanding the cellular mechanisms underlying motility, following the discovery of the central role played by the interstitial cells of Cajal (ICC. As experimental knowledge of ICC physiology has expanded, biophysically-based modelling has become a valuable tool for integrating experimental data, for testing hypotheses on ICC pacemaker mechanisms, and for applications in in silico studies including in multiscale models. This review is focused on the cellular electrophysiology of ICC. Recent evidence from both experimental and modelling domains have called aspects of the existing pacemaker theories into question. Therefore, current experimental knowledge of ICC pacemaker mechanisms is examined in depth, and current theories of ICC pacemaking are evaluated and further developed. Existing biophysically-based ICC models and their physiological foundations are then critiqued in light of the recent advances in experimental knowledge, and opportunities to improve these models are identified. The review concludes by examining several potential clinical applications of biophysically-based ICC modelling from the subcellular through to the organ level, including ion channelopathies and ICC network degradation.

  3. Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks

    Directory of Open Access Journals (Sweden)

    James N. Warnock

    2011-01-01

    Full Text Available The study aimed to identify mechanosensitive pathways and gene networks that are stimulated by elevated cyclic pressure in aortic valve interstitial cells (VICs and lead to detrimental tissue remodeling and/or pathogenesis. Porcine aortic valve leaflets were exposed to cyclic pressures of 80 or 120 mmHg, corresponding to diastolic transvalvular pressure in normal and hypertensive conditions, respectively. Linear, two-cycle amplification of total RNA, followed by microarray was performed for transcriptome analysis (with qRT-PCR validation. A combination of systems biology modeling and pathway analysis identified novel genes and molecular mechanisms underlying the biological response of VICs to elevated pressure. 56 gene transcripts related to inflammatory response mechanisms were differentially expressed. TNF-α, IL-1α, and IL-1β were key cytokines identified from the gene network model. Also of interest was the discovery that pentraxin 3 (PTX3 was significantly upregulated under elevated pressure conditions (41-fold change. In conclusion, a gene network model showing differentially expressed inflammatory genes and their interactions in VICs exposed to elevated pressure has been developed. This system overview has detected key molecules that could be targeted for pharmacotherapy of aortic stenosis in hypertensive patients.

  4. Proliferation of Interstitial Cells in the Cyclophosphamide-Induced Cystitis and the Preventive Effect of Imatinib

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    Maria Sancho

    2017-01-01

    Full Text Available Cyclophosphamide- (CYP- induced cystitis in the rat is a well-known model of bladder inflammation that leads to an overactive bladder, a process that appears to involve enhanced nitric oxide (NO production. We investigated the changes in the number and distribution of interstitial cells (ICs and in the expression of endothelial NO synthase (eNOS in the bladder and urethra of rats subjected to either intermediate or chronic CYP treatment. Pronounced hyperplasia and hypertrophy of ICs were evident within the lamina propria and in the muscle layer. IC immunolabeling with CD34, PDGFRα, and vimentin was enhanced, as reflected by higher colocalization indexes of the distinct pairs of markers. Moreover, de novo expression of eNOS was evident in vimentin and CD34 positive ICs. Pretreatment with the receptor tyrosine kinase inhibitor Imatinib prevented eNOS expression and ICs proliferation, as well as the increased voiding frequency and urinary tract weight provoked by CYP. As similar results were obtained in the urethra, urethritis may contribute to the uropathology of CYP-induced cystitis.

  5. Squamous Cell Carcinoma of the Bladder Mimicking Interstitial Cystitis and Voiding Dysfunction

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    Colton Prudnick

    2013-01-01

    Full Text Available Squamous cell carcinoma (SCC of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.

  6. Distribution of Interstitial Cells of Cajal in the Esophagus of Fetal Rats with Esophageal Atresia

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    Caner Isbir

    2016-04-01

    Full Text Available Aim: Scarcity of the interstitial cells of Cajal (ICC is related to motility disorders. In the study, we aimed to evaluate the number and density of ICCs in the fetal rat esophagus in the adriamycin - esophageal atresia (EA model. Material and Method: Rat fetuses were divided into three groups as a control, adriamycin group without EA and adriamycin group with EA. Four doses of adriamycin, 2 mg/kg each, were injected intraperitoneally to the adriamycin group rats between on 6 and 9 days of gestation. The presence of ICCs in the esophagus of the rat fetuses was determined by using an immunohistochemistry technique (c-kit, CD117. The average numbers of ICCs were calculated with microscopic evaluation by using a visual scoring system (range1 to 3. Results: Seven fetuses were included in each group. The ICCs score 3 distributions of fetuses were 5 (72% fetuses in the control group, 3 (43% fetuses in the adriamycin group without EA, 1 (14% fetus in the adriamycin group with EA. It have been found that there was a marked reduction of ICCs distribution in the adriamycin group with EA compared to control group (p 0.05. Discussion: ICCs density was significantly decreased in the rat fetuses with EA compared to the fetuses without EA. These findings support the idea that ICCs density may be congenitally abnormal in EA. This may be led to dismotility seen in the operated esophagus due to EA.

  7. Immunohistochemical studies of the enteric nervous system and interstitial cells of Cajal in the canine stomach

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    Colin Musara

    2013-03-01

    Full Text Available The distribution of interstitial cells of Cajal (ICC, the probable pacemakers in gastrointestinal motility, was investigated using an antigenic marker of gastric ICC known as C-Kit. Antiserum raised against the general neuronal marker protein gene peptide 9.5 (PGP as well as the nitrergic neuronal marker neuronal nitric oxide synthase (nNOS were used to investigate the distribution of gastric nerves. Polyclonal goat anti-human C-Kit was reliable in labelling ICC in the stomach. Two classes of ICC were identified according to their distribution: ICC-MY distributed around the periphery of myenteric ganglia and ICC-IM in the circular and longitudinal muscle layers. The neuronal marker PGP was reliably consistent in revealing the density and distribution of the enteric nervous system. Density of nerve fibres was higher in circular smooth muscle than in longitudinal smooth muscle. From nNOS immunohistochemistry, it is evident that inhibitory (nitrergic nerves constitute a substantial fraction of the enteric nervous system.

  8. Caffeine inhibits nonselective cationic currents in interstitial cells of Cajal from the murine jejunum.

    Science.gov (United States)

    Jin, Nan Ge; Koh, Sang Don; Sanders, Kenton M

    2009-10-01

    Interstitial cells of Cajal (ICC) discharge unitary potentials in gastrointestinal muscles that constitute the basis for pacemaker activity. Caffeine has been used to block unitary potentials, but the ionic conductance responsible for unitary potentials is controversial. We investigated currents in cultured ICC from murine jejunum that may underlie unitary potentials and studied the effects of caffeine. Networks of ICC generated slow wave events under current clamp, and these events were blocked by caffeine in a concentration-dependent manner. Single ICC generated spontaneous transient inward currents (STICs) under voltage clamp at -60 mV and noisy voltage fluctuations in current clamp. STICs were unaffected when the equilibrium potential for Cl- (ECl) was set to -60 mV (excluding Cl- currents) and reversed at 0 mV, demonstrating that a nonselective cationic conductance, and not a Cl- conductance, is responsible for STICs in ICC. Caffeine inhibited STICs in a concentration-dependent manner. Reduced intracellular Ca2+ and calmidazolium (CMZ; 1 microM) activated persistent inward, nonselective cation currents in ICC. Currents activated by CMZ and by dialysis of cells with 10 mM BAPTA were also inhibited by caffeine. Excised inside-out patches contained channels that exhibited spontaneous openings, and resulting currents reversed at 0 mV. Channel openings were increased by reducing Ca2+ concentration from 10(-6) M to 10(-8) M. CMZ (1 microM) also increased openings of nonselective cation channels. Spontaneous currents and channels activated by CMZ were inhibited by caffeine (5 mM). The findings demonstrate that the Ca2+-inhibited nonselective cation channels that generate STICs in ICC are blocked directly by caffeine. STICs are responsible for unitary potentials in intact muscles, and the block of these events by caffeine is consistent with the idea that a nonselective cation conductance underlies unitary potentials in ICC.

  9. Mesenchymal Stem Cell Therapy Alleviates Interstitial Cystitis by Activating Wnt Signaling Pathway

    Science.gov (United States)

    Song, Miho; Lim, Jisun; Yu, Hwan Yeul; Park, Junsoo; Chun, Ji-Youn; Jeong, Jaeho; Heo, Jinbeom; Kang, Hyunsook; Kim, YongHwan; Cho, Yong Mee; Kim, Seong Who; Oh, Wonil; Choi, Soo Jin; Jang, Sung-Wuk; Park, Sanghyeok

    2015-01-01

    Interstitial cystitis (IC) is a syndrome characterized by urinary urgency, frequency, pelvic pain, and nocturia in the absence of bacterial infection or identifiable pathology. IC is a devastating disease that certainly decreases quality of life. However, the causes of IC remain unknown and no effective treatments or cures have been developed. This study evaluated the therapeutic potency of using human umbilical cord-blood-derived mesenchymal stem cells (UCB-MSCs) to treat IC in a rat model and to investigate its responsible molecular mechanism. IC was induced in 10-week-old female Sprague–Dawley rats via the instillation of 0.1 M HCl or phosphate-buffered saline (PBS; sham). After 1 week, human UCB-MSC (IC+MSC) or PBS (IC) was directly injected into the submucosal layer of the bladder. A single injection of human UCB-MSCs significantly attenuated the irregular and decreased voiding interval in the IC group. Accordingly, denudation of the epithelium and increased inflammatory responses, mast cell infiltration, neurofilament production, and angiogenesis observed in the IC bladders were prevented in the IC+MSC group. The injected UCB-MSCs successfully engrafted to the stromal and epithelial tissues and activated Wnt signaling cascade. Interference with Wnt and epidermal growth factor receptor activity by small molecules abrogated the benefits of MSC therapy. This is the first report that provides an experimental evidence of the therapeutic effects and molecular mechanisms of MSC therapy to IC using an orthodox rat animal model. Our findings not only provide the basis for clinical trials of MSC therapy to IC but also advance our understanding of IC pathophysiology. PMID:25745847

  10. Hydrogen Passivation of Interstitial Zn Defects in Heteroepitaxial InP Cell Structures and Influence on Device Characteristics

    Science.gov (United States)

    Ringel, S. A.; Chatterjee, B.

    2004-01-01

    Hydrogen passivation of heteroepitaxial InP solar cells is of recent interest for deactivation of dislocations and other defects caused by the cell/substrate lattice mismatch that currently limit the photovoltaic performance of these devices. In this paper we present strong evidence that, in addition to direct hydrogen-dislocation interactions, hydrogen forms complexes with the high concentration of interstitial Zn defects present within the p(+) Zn-doped emitter of MOCVD-grown heteroepitaxial InP devices, resulting in a dramatic increase of the forward bias turn-on voltage by as much as 280 mV, from 680 mV to 960 mV. This shift is reproducible and thermally reversible and no such effect is observed for either n(+)p structures or homoepitaxial p(+)n structures grown under identical conditions. A combination of photoluminescence (PL), electrochemical C-V dopant profiling, SIMS and I-V measurements were performed on a set of samples having undergone a matrix of hydrogenation and post-hydrogenation annealing conditions to investigate the source of this voltage enhancement and confirm the expected role of interstitial Zn and hydrogen. A precise correlation between all measurements is demonstrated which indicates that Zn interstitials within the p(+) emitter and their interaction with hydrogen are indeed responsible for this device behavior.

  11. Inflammation induced by mast cell deficiency rather than the loss of interstitial cells of Cajal causes smooth muscle dysfunction in W/Wv mice

    Science.gov (United States)

    Winston, John H.; Chen, Jinghong; Shi, Xuan-Zheng; Sarna, Sushil K.

    2014-01-01

    The initial hypothesis suggested that the interstitial cells of Cajal (ICC) played an essential role in mediating enteric neuronal input to smooth muscle cells. Much information for this hypothesis came from studies in W/Wv mice lacking ICC. However, mast cells, which play critical roles in regulating inflammation in their microenvironment, are also absent in W/Wv mice. We tested the hypothesis that the depletion of mast cells in W/Wv mice generates inflammation in fundus muscularis externa (ME) that impairs smooth muscle reactivity to Ach, independent of the depletion of ICC. We performed experiments on the fundus ME from wild type (WT) and W/Wv mice before and after reconstitution of mast cells by bone marrow transplant. We found that mast cell deficiency in W/Wv mice significantly increased COX-2 and iNOS expression and decreased smooth muscle reactivity to Ach. Mast cell reconstitution or concurrent blockade of COX-2 and iNOS restored smooth muscle contractility without affecting the suppression of c-kit in W/Wv mice. The expression of nNOS and ChAT were suppressed in W/Wv mice; mast cell reconstitution did not restore them. We conclude that innate inflammation induced by mast cell deficiency in W/Wv mice impairs smooth muscle contractility independent of ICC deficiency. The impairment of smooth muscle contractility and the suppression of the enzymes regulating the synthesis of Ach and NO in W/Wv mice need to be considered in evaluating the role of ICC in regulating smooth muscle and enteric neuronal function in W/Wv mice. PMID:24550836

  12. Inflammation induced by mast cell deficiency rather than the loss of interstitial cells of Cajal causes smooth muscle dysfunction in W/W(v) mice.

    Science.gov (United States)

    Winston, John H; Chen, Jinghong; Shi, Xuan-Zheng; Sarna, Sushil K

    2014-01-01

    The initial hypothesis suggested that the interstitial cells of Cajal (ICC) played an essential role in mediating enteric neuronal input to smooth muscle cells. Much information for this hypothesis came from studies in W/W(v) mice lacking ICC. However, mast cells, which play critical roles in regulating inflammation in their microenvironment, are also absent in W/W(v) mice. We tested the hypothesis that the depletion of mast cells in W/W(v) mice generates inflammation in fundus muscularis externa (ME) that impairs smooth muscle reactivity to Ach, independent of the depletion of ICC. We performed experiments on the fundus ME from wild type (WT) and W/W(v) mice before and after reconstitution of mast cells by bone marrow transplant. We found that mast cell deficiency in W/W(v) mice significantly increased COX-2 and iNOS expression and decreased smooth muscle reactivity to Ach. Mast cell reconstitution or concurrent blockade of COX-2 and iNOS restored smooth muscle contractility without affecting the suppression of c-kit in W/W(v) mice. The expression of nNOS and ChAT were suppressed in W/W(v) mice; mast cell reconstitution did not restore them. We conclude that innate inflammation induced by mast cell deficiency in W/W(v) mice impairs smooth muscle contractility independent of ICC deficiency. The impairment of smooth muscle contractility and the suppression of the enzymes regulating the synthesis of Ach and NO in W/W(v) mice need to be considered in evaluating the role of ICC in regulating smooth muscle and enteric neuronal function in W/W(v) mice.

  13. Interstitial Cystitis

    Science.gov (United States)

    ... bathroom at scheduled times and using relaxation techniques. Physical therapy. People who have interstitial cystitis may have painful spasms of pelvic floor muscles. If you have muscle spasms, you can ...

  14. Interstitial nephritis

    Science.gov (United States)

    ... Allergic reaction to a drug (acute interstitial allergic nephritis). Autoimmune disorders, such as antitubular basement membrane disease, Kawasaki disease, Sjögren syndrome, systemic lupus erythematosus, or Wegener granulomatosis. Infections. Long-term use ...

  15. Total Glucosides of Paeony Promote Intestinal Motility in Slow Transit Constipation Rats through Amelioration of Interstitial Cells of Cajal

    Science.gov (United States)

    Zhu, Feiye; Xu, Shan; Zhang, Yongsheng; Chen, Fangming; Ji, Jinjun; Xie, Guanqun

    2016-01-01

    Objectives Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment of STC and the possible mechanisms. Study Design A prospective experimental animal study. Methods The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated. Meanwhile, the colorimetric method and enzyme linked immunosorbent assay (ELISA) were employed to determine the changes of nitric oxide (NO), nitric oxide synthase (NOS), vasoative intestinal peptide (VIP) and the P substance (SP) in the serum, respectively. The protein expressions of c-kit and stem cell factor (SCF) were assessed by immunohistochemical analysis and western blot, respectively, and the mRNA level of c-kit was measured by a reverse transcription polymerase chain reaction (RT-PCR). Results The TGP attenuated STC responses in terms of an increase in the fecal volume and moisture content, an enhancement of intestinal transit rate and the reduction of NO, NOS and VIP in the serum. In addition, the c-kit, a labeling of interstitial cells of Cajal (ICC) increased at both protein and mRNA levels. SCF, which serves as a ligand of c-kit also increased at protein level. Conclusion The analysis of our data indicated that the TGP could obviously attenuate STC through improving the function of ICC and blocking the inhibitory neurotransmitters such as NO, NOS and VIP. PMID:27478893

  16. Total Glucosides of Paeony Promote Intestinal Motility in Slow Transit Constipation Rats through Amelioration of Interstitial Cells of Cajal.

    Directory of Open Access Journals (Sweden)

    Feiye Zhu

    Full Text Available Using an atropine-diphenoxylate-induced slow transit constipation (STC model, this study explored the effects of the total glucosides of paeony (TGP in the treatment of STC and the possible mechanisms.A prospective experimental animal study.The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated. Meanwhile, the colorimetric method and enzyme linked immunosorbent assay (ELISA were employed to determine the changes of nitric oxide (NO, nitric oxide synthase (NOS, vasoative intestinal peptide (VIP and the P substance (SP in the serum, respectively. The protein expressions of c-kit and stem cell factor (SCF were assessed by immunohistochemical analysis and western blot, respectively, and the mRNA level of c-kit was measured by a reverse transcription polymerase chain reaction (RT-PCR.The TGP attenuated STC responses in terms of an increase in the fecal volume and moisture content, an enhancement of intestinal transit rate and the reduction of NO, NOS and VIP in the serum. In addition, the c-kit, a labeling of interstitial cells of Cajal (ICC increased at both protein and mRNA levels. SCF, which serves as a ligand of c-kit also increased at protein level.The analysis of our data indicated that the TGP could obviously attenuate STC through improving the function of ICC and blocking the inhibitory neurotransmitters such as NO, NOS and VIP.

  17. Impact of the alterations in the interstitial cells of Cajal on intestinal motility in post-infection irritable bowel syndrome.

    Science.gov (United States)

    Yang, Bo; Zhou, Xu-Chun; Lan, Cheng

    2015-04-01

    The interstitial cells of Cajal (ICC) are basic components of gastrointestinal motility. However, changes in ICC and their role in post‑infection irritable bowel syndrome (PI‑IBS) remain to be elucidated. To observe the impact of alterations in the ICC on intestinal motility in a PI‑IBS mouse model, female C57BL\\6 mice were infected by the oral administration of 400 Trichinella spiralis larvae. The abdominal withdrawal reflex, intestine transportation time (ITT), grain numbers, Bristol scores, wet/dry weights and the percentage water content of the mice feces every 2 h were used to assess changes in the intestinal motor function. The intestines were excised and sectioned for pathological and histochemical examination. These intestines were also used to quantify the protein and mRNA expression of c‑kit. The C57BL\\6 mouse can act as a PI‑IBS model at day 56 post‑infection. Compared with the control mice, the ITT was shorter, the grain numbers, Bristol scores, wet weights and water contents of the mice feces were higher and the dry weights were unchanged in the PI‑IBS mice. The protein and mRNA expression levels of c‑kit were upregulated in the entire PI‑IBS mouse intestines. Following immunohistochemical staining, the increased number of c‑kit‑positive cells were detected predominantly in the submucosa and myenteron. These results suggested that the alterations of the ICC resulted in the changes of the intestinal motility patterns in the PI‑IBS mouse models induced by Trichinella spiralis infection, which may be the main mechanism underlying intestinal motility disorders in PI‑IBS.

  18. The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

    Science.gov (United States)

    Yasuda, Yuichiro; Hattori, Yoshihiro; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Urata, Yoshiko; Nogami, Munenobu; Takenaka, Daisuke; Negoro, Shunichi; Satouchi, Miyako

    2018-01-01

    The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  19. Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

    Directory of Open Access Journals (Sweden)

    Daniel Antunes Silva Pereira

    2015-04-01

    Full Text Available OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD. METHODS: This was a retrospective study of patients with interstitial lung disease (ILD, positive antinuclear antibody (ANA results (≥ 1/320, with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD. RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89% and anti-SSA (anti-Ro, 27%. The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05. Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

  20. YKL-40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis

    DEFF Research Database (Denmark)

    Richter, Benedikte; Roslind, A.; Hesse, U.

    2010-01-01

    Aims: Bladder pain syndrome/interstitial cystitis (BPS/IC), diagnosed according to the new 2008 criteria of the European Society for the Study of Interstitial Cystitis (ESSIC), may lead to detrusor fibrosis. In some inflammatory diseases, fibrosis is related to YKL-40. The aims were to examine YKL......-40 antigenic expression in bladder tissue and levels in serum and urine in BPS/IC and to evaluate whether YKL-40 could be a non-invasive, prognostic biomarker for bladder fibrogenesis and treatment intensity. Methods and results: Immunohistochemistry, immunoelectron microscopy and enzyme...... of detrusor fibrosis with YKL-40-positive cells (P = 0.001), mast cells (P = 0.014) and urine YKL-40 (P = 0.009). Bladder capacity correlated inversely with YKL-40-positive cells (P Treatment intensity was not associated with YKL-40. Conclusion: Serum and urine levels...

  1. [Modern Views on Children's Interstitial Lung Disease].

    Science.gov (United States)

    Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

    2015-01-01

    Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.

  2. Intragraft Tubular Vimentin and CD44 Expression Correlate With Long-Term Renal Allograft Function and Interstitial Fibrosis and Tubular Atrophy

    NARCIS (Netherlands)

    Kers, Jesper; Xu-Dubois, Yi-Chun; Rondeau, Eric; Claessen, Nike; Idu, Mirza M.; Roelofs, Joris J. T. H.; Bemelman, Fréderike J.; ten Berge, Ineke J. M.; Florquin, Sandrine

    2010-01-01

    Background. Development of interstitial fibrosis and tubular atrophy (IF/TA) is the main histologic feature involved in renal allograft deterioration. The aim of this study was to validate whether de novo tubular expression of CD44 (transmembrane glycoprotein) and vimentin (mesenchymal cell marker),

  3. Tumor interstitial fluid

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J.

    2013-01-01

    Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical secr...

  4. Mast Cell Function

    Science.gov (United States)

    da Silva, Elaine Zayas Marcelino; Jamur, Maria Célia

    2014-01-01

    Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role. PMID:25062998

  5. Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation.

    Directory of Open Access Journals (Sweden)

    Kyung Min Kim

    Full Text Available Shear stress activates cellular signaling involved in cellular proliferation, differentiation, and migration. However, the mechanisms of mesenchymal stem cell (MSC differentiation under interstitial flow are not fully understood. Here, we show the increased osteogenic differentiation of MSCs under exposure to constant, extremely low shear stress created by osmotic pressure-induced flow in a microfluidic chip. The interstitial level of shear stress in the proposed microfluidic system stimulated nuclear localization of TAZ (transcriptional coactivator with PDZ-binding motif, a transcriptional modulator of MSCs, activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic differentiation. TAZ-depleted cells showed defects in shear stress-induced osteogenic differentiation. In shear stress induced cellular signaling, Rho signaling pathway was important forthe nuclear localization of TAZ. Taken together, these results suggest that TAZ is an important mediator of interstitial flow-driven shear stress signaling in osteoblast differentiation of MSCs.

  6. FDG-PET/CT in the prediction of pulmonary function improvement in nonspecific interstitial pneumonia. A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Jacquelin, V. [AP-HP, Hosp. Avicenne, Department of Nuclear Medicine, Bobigny (France); Mekinian, A. [AP-HP, Hosp. Saint-Antoine, Department of Internal Medicine and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris (France); Brillet, P.Y. [AP-HP, Hosp. Avicenne, Department of Radiology, Bobigny (France); Univ. Paris 13, Sorbonne Paris Cité, Bobigny (France); Nunes, H. [AP-HP, Hosp. Avicenne, Department of Pneumology, Bobigny (France); Univ. Paris 13, Sorbonne Paris Cité, Bobigny (France); Fain, O. [AP-HP, Hosp. Saint-Antoine, Department of Internal Medicine and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris (France); Valeyre, D. [AP-HP, Hosp. Avicenne, Department of Pneumology, Bobigny (France); Univ. Paris 13, Sorbonne Paris Cité, Bobigny (France); Soussan, M., E-mail: michael.soussan@aphp.fr [AP-HP, Hosp. Avicenne, Department of Nuclear Medicine, Bobigny (France); Univ. Paris 13, Sorbonne Paris Cité, Bobigny (France)

    2016-12-15

    Purpose: Our study aimed to analyse the characteristics of nonspecific interstitial pneumonia (NSIP) using FDG-PET/CT (PET) and to evaluate its ability to predict the therapeutic response. Procedures: Eighteen NSIP patients were included. Maximum standardized uptake value (SUV{sub max}), FDG uptake extent (in percentage of lung volume), high resolution CT scan (HRCT) elementary lesions, and HRCT fibrosis score were recorded. The predictive value of the parameters for lung function improvement was evaluated using logistic regression and Receiver Operating Characteristic (ROC) curve analysis (n = 13/18). Results: All patients had an increased pulmonary FDG uptake (median SUV{sub max} = 3.1 [2–7.6]), with a median extent of 19% [6–67]. Consolidations, ground-glass opacities, honeycombing and reticulations showed uptake in 90%, 89%, 85% and 76%, respectively. FDG uptake extent was associated with improvement of pulmonary function under treatment (increase in forced vital capacity > 10%, p = 0.03), whereas SUV{sub max} and HRCT fibrosis score were not (p > 0.5). For FDG uptake extent, ROC analysis showed an area under the curve at 0.85 ± 0.11 and sensitivity/specificity was 88%/80% for a threshold fixed at 21%. Conclusions: Increased FDG uptake was observed in all NSIP patients, both in inflammatory and fibrotic HRCT lesions. The quantification of FDG uptake extent might be useful to predict functional improvement under treatment.

  7. FDG-PET/CT in the prediction of pulmonary function improvement in nonspecific interstitial pneumonia. A Pilot Study

    International Nuclear Information System (INIS)

    Jacquelin, V.; Mekinian, A.; Brillet, P.Y.; Nunes, H.; Fain, O.; Valeyre, D.; Soussan, M.

    2016-01-01

    Purpose: Our study aimed to analyse the characteristics of nonspecific interstitial pneumonia (NSIP) using FDG-PET/CT (PET) and to evaluate its ability to predict the therapeutic response. Procedures: Eighteen NSIP patients were included. Maximum standardized uptake value (SUV max ), FDG uptake extent (in percentage of lung volume), high resolution CT scan (HRCT) elementary lesions, and HRCT fibrosis score were recorded. The predictive value of the parameters for lung function improvement was evaluated using logistic regression and Receiver Operating Characteristic (ROC) curve analysis (n = 13/18). Results: All patients had an increased pulmonary FDG uptake (median SUV max = 3.1 [2–7.6]), with a median extent of 19% [6–67]. Consolidations, ground-glass opacities, honeycombing and reticulations showed uptake in 90%, 89%, 85% and 76%, respectively. FDG uptake extent was associated with improvement of pulmonary function under treatment (increase in forced vital capacity > 10%, p = 0.03), whereas SUV max and HRCT fibrosis score were not (p > 0.5). For FDG uptake extent, ROC analysis showed an area under the curve at 0.85 ± 0.11 and sensitivity/specificity was 88%/80% for a threshold fixed at 21%. Conclusions: Increased FDG uptake was observed in all NSIP patients, both in inflammatory and fibrotic HRCT lesions. The quantification of FDG uptake extent might be useful to predict functional improvement under treatment.

  8. Feasibility of pig and human-derived aortic valve interstitial cells seeding on fixative-free decellularized animal pericardium.

    Science.gov (United States)

    Santoro, Rosaria; Consolo, Filippo; Spiccia, Marco; Piola, Marco; Kassem, Samer; Prandi, Francesca; Vinci, Maria Cristina; Forti, Elisa; Polvani, Gianluca; Fiore, Gianfranco Beniamino; Soncini, Monica; Pesce, Maurizio

    2016-02-01

    Glutaraldehyde-fixed pericardium of animal origin is the elective material for the fabrication of bio-prosthetic valves for surgical replacement of insufficient/stenotic cardiac valves. However, the pericardial tissue employed to this aim undergoes severe calcification due to chronic inflammation resulting from a non-complete immunological compatibility of the animal-derived pericardial tissue resulting from failure to remove animal-derived xeno-antigens. In the mid/long-term, this leads to structural deterioration, mechanical failure, and prosthesis leaflets rupture, with consequent need for re-intervention. In the search for novel procedures to maximize biological compatibility of the pericardial tissue into immunocompetent background, we have recently devised a procedure to decellularize the human pericardium as an alternative to fixation with aldehydes. In the present contribution, we used this procedure to derive sheets of decellularized pig pericardium. The decellularized tissue was first tested for the presence of 1,3 α-galactose (αGal), one of the main xenoantigens involved in prosthetic valve rejection, as well as for mechanical tensile behavior and distensibility, and finally seeded with pig- and human-derived aortic valve interstitial cells. We demonstrate that the decellularization procedure removed the αGAL antigen, maintained the mechanical characteristics of the native pig pericardium, and ensured an efficient surface colonization of the tissue by animal- and human-derived aortic valve interstitial cells. This establishes, for the first time, the feasibility of fixative-free pericardial tissue seeding with valve competent cells for derivation of tissue engineered heart valve leaflets. © 2015 Wiley Periodicals, Inc.

  9. Action potential generation in the small intestine of W mutant mice that lack interstitial cells of Cajal

    DEFF Research Database (Denmark)

    Malysz, J; Thuneberg, L; Mikkelsen, Hanne Birte

    1996-01-01

    The small intestine of W/Wv mice lacks both the network of interstitial cells of Cajal (ICC), associated with Auerbach's plexus, and pacemaker activity, i.e., it does not generate slow-wave-type action potentials. The W/Wv muscle preparations showed a wide variety of electrical activities, ranging...... from total quiescence to generation of action potentials at regular or irregular frequency with or without periods of quiescence. The action potentials consisted of a slow component with superimposed spikes, preceded by a slowly developing depolarization and followed by a transient hyperpolarization....... The action potentials were completely abolished by L-type Ca2+ channel blockers. W/Wv mice responded to K+ channel blockade (0.5 mM Ba2+ or 10 mM tetraethylammonium chloride) with effects on amplitude, frequency, rate of rise, and duration of the action potentials. In quiescent tissues from W/Wv mice, K...

  10. Abnormal distribution of the interstitial cells of cajal in an adult patient with pseudo-obstruction and megaduodenum

    DEFF Research Database (Denmark)

    Boeckxstaens, Guy E; Rumessen, Jüri J; de Wit, Laurens

    2002-01-01

    Interstitial cells of Cajal (ICC) are fundamental regulators of GI motility. Here, we report the manometrical abnormalities and abnormalities of ICC distribution and ultrastructure encountered in a 30-yr-old patient with megaduodenum and pseudo-obstruction. Full thickness biopsies taken during...... laparoscopic placement of a jejunostomy showed vacuolated myocytes and fibrosis predominantly in the outer third of the circular muscle layer of the duodenum, suggestive for visceral myopathy. The distribution of ICC was also strikingly abnormal: by light microscopy, ICC surrounding the myenteric plexus were...... lacking in the megaduodenum, whereas ICC were normally present in the duodenal circular muscle and in the jejunum. By electron microscopy, very few ICC were identified around the duodenal myenteric plexus. These findings suggest that abnormalities in ICC may contribute to the disturbed motility in some...

  11. Umbilical cord-derived mesenchymal stem cells alleviated inflammation and inhibited apoptosis in interstitial cystitis via AKT/mTOR signaling pathway.

    Science.gov (United States)

    Xie, Juncong; Liu, Bolong; Chen, Jialiang; Xu, Yuancheng; Zhan, Hailun; Yang, Fei; Li, Wenbiao; Zhou, Xiangfu

    2018-01-01

    Interstitial cystitis (IC) is a bladder syndrome characterized by pelvic pain and urinary frequency without infection or other identifiable pathology. There are no effective treatments to cure IC. This study investigated the effects of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) injection on IC rat model. Furthermore, we used a coculture system to find the possible molecular mechanism on the human uroepithelial cells (SV-HUC-1), which was the cell model of IC. A rat model of IC was established via systemic injection with cyclophosphamide (CYP) and a cell model of IC was induced by being exposed to tumor necrosis factor (TNF)-α (10 ng/ml). After one week, UC-MSCs injection significantly ameliorated the bladder voiding function in IC rat model. And the Histo- and immunohistochemical analyses showed that UC-MSCs can repair impaired bladder, reduce mast cell infiltration and inhibit apoptosis of urothelium. ELISA results showed that UC-MSCs can decrease IL-1β, IL-6 and TNF-α in bladder. In the coculture system, UC-MSCs can promote proliferation of impaired SV-HUC-1 cells, and inhibit apoptosis. However, while knocked down EGF secreted by UC-MSCs with siRNA, the effects would be weaken. Western blot showed that UC-MSCs increase protein expression levels of p-AKT and p-mTOR in SV-HUC-1 cells, and decrease the levels of cleaved caspase-3. Taken together, we provide evidence that UC-MSCs therapy can successfully alleviate IC in a preclinical animal Model and cell model by alleviating inflammation, promoting proliferation and inhibiting apoptosis. In addition, we demonstrate that the AKT/mTOR signaling pathway was activated. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Interstitial flow promotes vascular fibroblast, myofibroblast, and smooth muscle cell motility in 3-D collagen I via upregulation of MMP-1

    Science.gov (United States)

    Shi, Zhong-Dong; Ji, Xin-Ying; Qazi, Henry

    2009-01-01

    Neointima formation often occurs in regions where the endothelium has been damaged and the transmural interstitial flow is elevated. Vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts (FBs/MFBs) contribute to intimal thickening by migrating from the media and adventitia into the site of injury. In this study, for the first time, the direct effects of interstitial flow on SMC and FB/MFB migration were investigated in an in vitro three-dimensional system. Collagen I gels were used to mimic three-dimensional extracellular matrix (ECM) for rat aortic SMCs and FBs/MFBs. Exposure to interstitial flow induced by 1 cmH2O pressure differential (shear stress, ∼0.05 dyn/cm2; flow velocity, ∼0.5 μm/s; and Darcy permeability, ∼10−11 cm2) substantially enhanced cell motility. Matrix metalloproteinase (MMP) inhibitor (GM-6001) abolished flow-induced migration augmentation, which suggested that the enhanced motility was MMP dependent. The upregulation of MMP-1 played a critical role for the flow-enhanced motility, which was further confirmed by silencing MMP-1 gene expression. Longer exposures to higher flows suppressed the number of migrated cells, although MMP-1 gene expression remained high. This suppression was a result of both flow-induced tissue inhibitor of metalloproteinase-1 upregulation and increased apoptotic and necrotic cell death. Interstitial flow did not affect MMP-2 gene expression or activity in the collagen I gel for any cell type. Our findings shed light on the mechanism by which vascular SMCs and FBs/MFBs contribute to intimal thickening in regions of vascular injury where interstitial flow is elevated. PMID:19465549

  13. Interstitial Cystitis Association

    Science.gov (United States)

    ... frequency? You may have IC. Get The Facts Interstitial Cystitis Association The Interstitial Cystitis Association (ICA) is the ... news and events. Please leave this field empty Interstitial Cystitis Association 7918 Jones Branch Drive, Suite 300 McLean, ...

  14. Generation of a tenascin-C-CreER2 knockin mouse line for conditional DNA recombination in renal medullary interstitial cells.

    Directory of Open Access Journals (Sweden)

    Wenjuan He

    Full Text Available Renal medullary interstitial cells (RMIC are specialized fibroblast-like cells that exert important functions in maintaining body fluid homeostasis and systemic blood pressure. Here, we generated a RMIC specific tenascin-C promoter driven inducible CreER2 knockin mouse line with an EGFP reporter. Similar as endogenous tenascin-C expression, the reporter EGFP expression in the tenascin-C-CreER2(+/- mice was observed in the inner medulla of the kidney, and co-localized with COX2 but not with AQP2 or AQP1, suggesting selective expression in RMICs. After recombination (tenascin-C-CreER2(+/-/ROSA26-lacZ(+/- mice + tamoxifen, β-gal activity was restricted to the cells in the inner medulla of the kidney, and didn't co-localize with AQP2, consistent with selective Cre recombinase activity in RMICs. Cre activity was not obvious in other major organs or without tamoxifen treatment. This inducible RMIC specific Cre mouse line should therefore provide a novel tool to manipulate genes of interest in RMICs.

  15. The Effects of Diabetes Induction on the Rat Heart: Differences in Oxidative Stress, Inflammatory Cells, and Fibrosis between Subendocardial and Interstitial Myocardial Areas

    Directory of Open Access Journals (Sweden)

    Maria C. Guido

    2017-01-01

    Full Text Available Diabetic cardiomyopathy (DCM is characterized by cardiac remodeling and impaired diastolic function that may lead to heart failure. The aim of this study was to evaluate oxidative stress, inflammatory cells, and fibrosis in both subendocardial (SEN and interstitial (INT areas of the myocardium. Male Wistar rats were allocated to 2 groups of 9 animals, a control (CT group and streptozotocin-induced diabetes (DM. After 8 weeks, echocardiography morphometry, protein expression, and confocal microscopy in SEN and INT areas of the left ventricle (LV were performed. The echocardiographic analysis showed that diabetes induction leads to cardiac dilation, hypertrophy, and LV diastolic dysfunction. As compared to CT, the induction of diabetes increased inflammatory cells and fibrosis in both SEN and INT areas of DM myocardium and increased ROS generation only in SEN. Comparing the SEN and INT areas in the DM group, inflammatory cells and fibrosis in SEN were greater than in INT. In conclusion, diabetic myocardium SEN area, wherein oxidative stress was more pronounced, is more susceptible to cardiac dysfunction than INT area. This finding can be important for the understanding of the heart remodeling process occurring in DCM and perhaps to engender targeted therapies to attenuate or revert DCM-related diastolic dysfunction.

  16. New insights into canted spiro carbon interstitial in graphite

    Science.gov (United States)

    EL-Barbary, A. A.

    2017-12-01

    The self-interstitial carbon is the key to radiation damage in graphite moderator nuclear reactor, so an understanding of its behavior is essential for plant safety and maximized reactor lifetime. The density functional theory is applied on four different graphite unit cells, starting from of 64 carbon atoms up to 256 carbon atoms, using AIMPRO code to obtain the energetic, athermal and mechanical properties of carbon interstitial in graphite. This study presents first principles calculations of the energy of formation that prove its high barrier to athermal diffusion (1.1 eV) and the consequent large critical shear stress (39 eV-50 eV) necessary to shear graphite planes in its presence. Also, for the first time, the gamma surface of graphite in two dimensions is calculated and found to yield the critical shear stress for perfect graphite. Finally, in contrast to the extensive literature describing the interstitial of carbon in graphite as spiro interstitial, in this work the ground state of interstitial carbon is found to be canted spiro interstitial.

  17. Correlation between HRCT findings, pulmonary function tests and bronchoalveolar lavage cytology in interstitial lung disease associated with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Biederer, J.; Muhle, C.; Heller, M.; Reuter, M.; Schnabel, A.; Gross, W.L.

    2004-01-01

    A prospective study correlating high-resolution computed tomography (HRCT), lung function tests (PFT) and bronchoalveolar lavage (BAL) cytology in patients with interstitial lung disease (ILD) associated with rheumatoid arthritis (RA). Fifty-three RA patients with suspected ILD (19 men, 34 women) underwent 71 HRCT (14 of 53 with sequential HRCT, mean follow-up 24.3 months). The HRCT evaluation by two observers on consensus included a semi-quantitative characterisation of lesion pattern and profusion on representative anatomical levels. Fifty-two HRCT were followed by PFT and BAL. Agreement or discordance of HRCT-, PFT- and BAL findings were analysed with Pearson's correlation, κ score and McNemar's test. Tobacco-fume exposure was estimated in pack years. Smoking/non-smoking groups were compared with Student's t test. In 49 of 53 patients, HRCT was suggestive of ILD associated with RA (66 of 71 HRCT). Reticular lesions were found in 40 of 53 patients, in 15 of 40 presenting as mixed pattern with ground-glass opacities (GGO). Pure reticular patterns predominated in patients with long duration of ILD (p>0.01). Pure GGO were not observed. Lesion profusion was highly variable and correlated moderately negative with diffusion capacity (mean 88.2% (SD±20.9%); r=-0.54; p 0.2), but not towards lymphocytosis (κ=0.10; p=0.23; McNemar test p>0.2). Differences in smoking history were not significant (p>0.1). The HRCT appears most appropriate for the detection and follow-up of ILD associated with RA. The PFT and BAL correlate only partially with lesion profusion or grading on HRCT, but they contribute valuable information about dynamic lung function and differential diagnoses (pneumonia, medication side effects). (orig.)

  18. Toward a Concept of Stretch Coupling in Smooth Muscle: A Thesis by Lars Thuneberg on Contractile Activity in Neonatal Interstitial Cells of Cajal

    DEFF Research Database (Denmark)

    Huizinga, Jan D; Lammers, Wim J E P; Mikkelsen, Hanne B

    2010-01-01

    The hypothesis was put forward by Thuneberg that rhythmically contracting interstitial cells of Cajal (ICC) were sensing stretch of the musculature and that this information was transmitted to smooth muscle cells via peg and socket contacts. The present study provides the evidence for the contrac...... amongst the physiological properties of the ICC networks of the gut musculature. Anat Rec, 2010. (c) 2010 Wiley-Liss, Inc....

  19. The carbon-substitutional-carbon-interstitial (CsCi) defect pair in silicon from hybrid functional calculations

    CSIR Research Space (South Africa)

    Ouma, CNM

    2016-06-01

    Full Text Available as metastable (bistable) defects [1–6]. The reason why metastable defects pose a challenge when one attempts to model them theoretically can be attributed to the fact that the two configurations of the defect being close energy thus the formation energy..., Identification of a bistable defect in silicon: The carbon interstitial-carbon substitutional pair, Appl. Phys. Lett. 51 (1987) 1155. doi:10.1063/1.98717. [4] L. Song, X. Zhan, B. Benson, G. Watkins, Bistable defect in silicon: The interstitial...

  20. Short-Term Pulmonary Function Trends Are Predictive of Mortality in Interstitial Lung Disease Associated With Systemic Sclerosis.

    Science.gov (United States)

    Goh, Nicole S; Hoyles, Rachel K; Denton, Christopher P; Hansell, David M; Renzoni, Elisabetta A; Maher, Toby M; Nicholson, Andrew G; Wells, Athol U

    2017-08-01

    To determine the prognostic value of pulmonary function test (PFT) trends at 1 and 2 years in interstitial lung disease (ILD) associated with systemic sclerosis (SSc). The prognostic significance of PFT trends at 1 year (n = 162) and 2 years (n = 140) was examined against 15-year survival in patients with SSc-associated ILD. PFT trends, expressed as continuous change and as categorical change in separate analyses, were examined against mortality in univariate and multivariate models. SSc-associated ILD was defined at presentation as either limited lung fibrosis or extensive lung fibrosis, using the United Kingdom Raynaud's and Scleroderma Association severity staging system. One-year PFT trends were predictive of mortality only in patients with extensive lung fibrosis: categorical change in the forced vital capacity (FVC), alone or in combination with categorical change in the diffusing capacity for carbon monoxide (DLco), had greater prognostic significance than continuous change in the FVC or trends in other PFT variables. Taking into account both prognostic value and sensitivity to change, the optimal definition of progression for trial purposes was an FVC and DLco composite end point, consisting of either an FVC decline from baseline of ≥10% or an FVC decline of 5-9% in association with a DLco decline of ≥15%. At 2 years, gas transfer trends had the greatest prognostic significance, in the whole cohort and in those with limited lung fibrosis. However, in patients with extensive lung fibrosis, the above-defined FVC and DLco composite end point was the strongest prognostic determinant. Larger changes in the FVC:DLco ratio than in the carbon monoxide transfer coefficient were required to achieve prognostic significance. Based on linkages to long-term outcomes, these findings provide support for use of routine spirometry and gas transfer monitoring in patients with SSc-associated ILD, with further evaluation of a composite FVC and DLco end point

  1. Digital Clubbing Is Associated with Higher Serum KL-6 Levels and Lower Pulmonary Function in Patients with Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Kazushige Shiraishi

    2018-01-01

    Full Text Available Background. Although digital clubbing is a common presentation in patients with interstitial lung disease (ILD, little has been reported regarding its role in assessing patients with ILD. This study evaluated patients with ILD for the presence of clubbing and investigated its association with clinical data. Methods. We evaluated patients with ILD who visited the teaching hospital at which the study was conducted, between October 2014 and January 2015. Clubbing, evaluated using a Vernier caliper for individual patients, was defined as a phalangeal depth ratio > 1. We examined the association of clubbing with clinical data. Results. Of 102 patients with ILD, we identified 17 (16.7% with clubbing. The partial pressure of oxygen in arterial blood was lower (65.2 ± 5.9 mmHg versus 80.2 ± 3.1 mmHg; p=0.03, serum Krebs von den Lugen-6 (KL-6 levels were higher (1495.0 ± 277.4 U/mL versus 839.1 ± 70.2 U/mL; p=0.001, and the percent predicted diffusing capacity of carbon monoxide was lower (50.0 ± 6.0 versus 73.5 ± 3.1; p=0.002 in these patients with clubbing. Conclusions. Patients with clubbing had lower oxygen levels, higher serum KL-6 levels, and lower pulmonary function than those without clubbing.

  2. Smoking-related interstitial lung diseases

    International Nuclear Information System (INIS)

    Marten, K.

    2007-01-01

    The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis

  3. Interstitial Granulomatous Dermatitis (IGD

    Directory of Open Access Journals (Sweden)

    Tiberiu Tebeica

    2017-07-01

    Full Text Available We report the case of a 42 years old male patient suffering from skin changes , which appeared in the last 7-8 years.  Two biopsies were performed during the evolution of the lesion. Both showed similar findings that consisted in a busy dermis with interstitial, superficial and deep infiltrates of lymphocytes and histiocytes dispersed among collagen bundles, with variable numbers of neutrophils scattered throughout. Some histiocytes were clustered in poorly formed granuloma that included rare giant cells, with discrete Palisades and piecemeal collagen degeneration, but without mucin deposition or frank necrobiosis of collagen. The clinical and histologic findings were supportive for interstitial granulomatous dermatitis. Interstitial granulomatous dermatitis (IGD is a poorly understood entity that was regarded by many as belonging to the same spectrum of disease or even synonym with palisaded and neutrophilic granulomatous dermatitis (PNGD. Although IGD and PNGD were usually related to connective tissue disease, mostly rheumatoid arthritis, some patients with typical histologic findings of IGD never develop autoimmune disorders, but they have different underlying conditions, such as metabolic diseases, lymphoproliferative disorders or other malignant tumours. These observations indicate that IGD and PNGD are different disorders with similar manifestations.

  4. Interstitial cells of Cajal, enteric neurons, and smooth muscle and myoid cells of the murine gastrointestinal tract express full-length dystrophin.

    Science.gov (United States)

    Vannucchi, Maria-Giuliana; Zardo, Claudio; Corsani, Letizia; Faussone-Pellegrini, Maria-Simonetta

    2002-12-01

    A gene located on the X chromosome is responsible for the transcription of several mRNA and related dystrophin isoforms. Lack or truncated expression of the 427-kDa, full-length isoform in skeletal muscle results in Duchenne muscular dystrophy (DMD). Patients with DMD, as well as mdx mice, a mutant strain also lacking this isoform, show gastrointestinal dismotilities. The present aim was to identify the cell types that express full-length dystrophin in the gastrointestinal tract. An immunohistochemical study was performed using an antibody specific for this isoform, and double labelings were made for interstitial cells of Cajal (ICC) identification and to verify whether all neurons express full-length dystrophin. Three different fixation procedures were used. The results showed that ICC, enteric neurons, and smooth muscle and myoid cells expressed full-length dystrophin. In ICC and neurons, dystrophin-immunoreactive patches were irregularly distributed at the cell contour and within the cytoplasm. In smooth muscle and myoid cells, regularly spaced dystrophin-immunoreactive bars were located along the cell contour. Labeling intensity varied according to fixation procedure. The different subcellular distributions of dystrophin immunoreactivity might reflect diverse roles played by full-length isoforms in each cell type. Dystrophin loss in cells involved in gastrointestinal motility might explain the gastrointestinal symptomatology affecting DMD patients and mdx mice.

  5. Analysis of gene expression in prostate cancer epithelial and interstitial stromal cells using laser capture microdissection

    International Nuclear Information System (INIS)

    Gregg, Jennifer L; Brown, Kathleen E; Mintz, Eric M; Piontkivska, Helen; Fraizer, Gail C

    2010-01-01

    The prostate gland represents a multifaceted system in which prostate epithelia and stroma have distinct physiological roles. To understand the interaction between stroma and glandular epithelia, it is essential to delineate the gene expression profiles of these two tissue types in prostate cancer. Most studies have compared tumor and normal samples by performing global expression analysis using a mixture of cell populations. This report presents the first study of prostate tumor tissue that examines patterns of differential expression between specific cell types using laser capture microdissection (LCM). LCM was used to isolate distinct cell-type populations and identify their gene expression differences using oligonucleotide microarrays. Ten differentially expressed genes were then analyzed in paired tumor and non-neoplastic prostate tissues by quantitative real-time PCR. Expression patterns of the transcription factors, WT1 and EGR1, were further compared in established prostate cell lines. WT1 protein expression was also examined in prostate tissue microarrays using immunohistochemistry. The two-step method of laser capture and microarray analysis identified nearly 500 genes whose expression levels were significantly different in prostate epithelial versus stromal tissues. Several genes expressed in epithelial cells (WT1, GATA2, and FGFR-3) were more highly expressed in neoplastic than in non-neoplastic tissues; conversely several genes expressed in stromal cells (CCL5, CXCL13, IGF-1, FGF-2, and IGFBP3) were more highly expressed in non-neoplastic than in neoplastic tissues. Notably, EGR1 was also differentially expressed between epithelial and stromal tissues. Expression of WT1 and EGR1 in cell lines was consistent with these patterns of differential expression. Importantly, WT1 protein expression was demonstrated in tumor tissues and was absent in normal and benign tissues. The prostate represents a complex mix of cell types and there is a need to analyze

  6. Changes in the Interstitial Cells of Cajal and Immunity in Chronic Psychological Stress Rats and Therapeutic Effects of Acupuncture at the Zusanli Point (ST36

    Directory of Open Access Journals (Sweden)

    Mucang Liu

    2016-01-01

    Full Text Available Now, chronic psychological stress (CPS related diseases are increasing. Many CPS patients have gastrointestinal complaints, immune suppression, and immune imbalance. Increasing evidence is indicating that acupuncture (AP at the Zusanli point (ST36 can alleviate functional gastrointestinal disorders (FGID, immune suppression, and immune imbalance. However, few studies have investigated the potential mechanisms. In this study, CPS rat models were established, and electroacupuncture (EA at ST36 was done for CPS rats. Daily food intake, weight, intestinal sensitivity, the morphology of interstitial cell of Cajal (ICC in the small intestine, and serum indexes were measured. The study found that, in CPS rats, EA at ST36 could improve food intake, weight, visceral hypersensitivity, and immunity; in CPS rats, in small intestine, the morphology of ICCs was abnormal and the number was decreased, which may be part causes of gastrointestinal motility dysfunction. EA at ST36 showed useful therapeutic effects. The mechanisms may be partially related to its repairing effects on ICCs damages; in CPS rats, there were immune suppression and immune imbalance, which may be part causes of visceral hypersensitivity. EA at ST36 showed useful therapeutic effects. The mechanisms may be partially related to its regulation on immunity.

  7. Elucidating the Molecular-Level Events in Valvular Interstitial Cell Calcification to Improve the Design of Tissue-Engineered Heart Valves

    Science.gov (United States)

    Gu, Xiaoxiao

    Calcification is the leading cause of native and bioprosthetic heart valve failure, yet its etiology and progression remain poorly understood. Total valve replacement, which is both invasive and accompanied by numerous shortcomings, is commonly performed to replace stenotic valves, but there are currently no medical agents that are FDA-approved for the prevention of aortic valve disease progression. Tissue engineering offers an attractive alternative to current valve replacement options. Thus, there is a pressing need to: (1) better understand the progression of valve calcification, (2) develop more options for prevention and treatment of valve calcification, and (3) define the properties of appropriate scaffold environments that will support the growth of engineered valve tissue. In this thesis, we describe our plan to bring together these goals in cardiovascular medicine: we aim to identify differences between calcifying and non-calcifying valve cultures and then use this information to discover potential calcification inhibitors and define biomaterial environments that can be used to support either healthy or diseased valvular interstitial cell function.

  8. [Interstitial lung diseases].

    Science.gov (United States)

    Junker, K; Brasch, F

    2008-11-01

    Interstitial lung diseases comprise a heterogeneous group of about 200 entities. In the classification of these diseases, diffuse parenchymal lung diseases with known cause, granulomatous diseases, and other specific interstitial lung diseases are separated from the important group of idiopathic interstitial pneumonias, which are classified according to the 2002 ATS/ERS consensus classification. Concerning the histological pattern, this classification differentiates between "usual interstitial pneumonia" (UIP), "nonspecific interstitial pneumonia" (NSIP), "organising pneumonia" (COP), "diffuse alveolar damage" (DAD), "respiratory bronchiolitis" (RB), "desquamative interstitial pneumonia" (DIP), "lymphocytic interstitial pneumonia" (LIP) and "unclassifiable interstitial pneumonias". A key message of this classification is that the pathologist will give the diagnosis of a histological pattern, whereas the final clinicopathologic diagnosis can be made only by the clinical pulmonologist after careful correlation with the clinical and radiologic features, which is essential in the diagnosis of interstitial lung diseases.

  9. Loss of interstitial cells of Cajal after pulsating electromagnetic field (PEMF) in gastrointestinal tract of the rats.

    Science.gov (United States)

    Kaszuba-Zwoińska, J; Gil, K; Ziomber, A; Zaraska, W; Pawlicki, R; Królczyk, G; Matyja, A; Thor, P J

    2005-09-01

    Exposure to the magnetic field has remarkably increased lately due to fast urbanization and widely available magnetic field in diagnosis and treatment. However, biological effects of the magnetic field are not well recognized. The myoelectric activity recorded from the gastrointestinal and urinary systems is generated by specialized electrically active cells called interstitial cells of Cajal (ICCs). Thus it seems rational that ICC have significant vulnerability to physical factors like an electromagnetic field. The aim of this study was to evaluate the influence of pulsating electromagnetic field (PEMF) (frequency 10 kHz, 30ms, 300 muT burst, with frequency 1Hz) on ICCs density in the rat gastrointestinal tract. Rats were divided into two groups (n=32). The first group was exposed to PEMF continuously for 1, 2, 3, and 4 weeks (n = 16), and the second group (n=16) served as a control. Tissue samples of the rat stomach, duodenum and proximal colon were fixed and paraffin embedded. The tangential sections of 5 microm thickness were stained immunohistochemically with anti-c-Kit (sc-168) antibody and visualized finally by DAB as chromogen (brown end product). C-Kit positive branched ICC-like cells were detected under the light microscope, distinguished from the c-kit-negative non-branched smooth muscle cells and from the c-kit positive but non-branched mast cells and quantitatively analyzed by MultiScan computer program. Apoptosis detection was performed with rabbit anti-Bax polyclonal antibody (Calbiochem, Germany) and LSAB 2 visualization system. The surface of c-Kit immunopositive cells decreased after exposure to PEMF in each part of the gastrointestinal tract. Reduced density of ICCs was related to exposure time. The most sensitive to PEMF were ICCs in the fundus of the stomach and in the duodenum, less sensitive were ICCs in the colon and pacemaker areas of the stomach. No marked changes in ICC density in the pyloric part of the stomach were observed. We

  10. Valve interstitial cell culture: Production of mature type I collagen and precise detection

    Czech Academy of Sciences Publication Activity Database

    Lišková, Jana; Hadraba, Daniel; Filová, Elena; Koňařík, M.; Pirk, J.; Jelen, K.; Bačáková, Lucie

    2017-01-01

    Roč. 80, č. 8 (2017), s. 936-942 ISSN 1059-910X R&D Projects: GA MŠk(CZ) LM2015062; GA MZd(CZ) NV15-29153A; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : ascorbic acid * cell culture * collagen * fluorescent microscopy * porcine VIC * second harmonic generation Subject RIV: EI - Biotechnology ; Bionics OBOR OECD: Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction) Impact factor: 1.147, year: 2016

  11. Bladder wall injection of mesenchymal stem cells ameliorates bladder inflammation, overactivity, and nociception in a chemically induced interstitial cystitis-like rat model.

    Science.gov (United States)

    Furuta, Akira; Yamamoto, Tokunori; Igarashi, Taro; Suzuki, Yasuyuki; Egawa, Shin; Yoshimura, Naoki

    2018-03-06

    We investigated the effects of bladder wall injection of mesenchymal stem cells (MSCs) on bladder tissues, function, and nociceptive behavior in a chemically induced interstitial cystitis-like rat model. Chemical cystitis of female rats was induced by intravesical instillation of 0.1 N hydrochloride (HCl) once a week for 2 weeks. Bladders were harvested 1, 2, 3, and 4 weeks after the second application for histological examination. Adipose-derived MSCs (HCl + MSCs) or phosphate-buffered saline (HCl + PBS) was injected into the bladder wall at the time of the second application of HCl. Histological examination, nociceptive behavior, and cystometrograms were evaluated 2 weeks after the injection compared with controls, which received instillation and injection of PBS into the bladder (sham + PBS). The number of mast cells and expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) were significantly increased at 1 and 2 weeks, and expression of collagen fibers was significantly increased from 2-4 weeks after the second application of HCl. Significantly increased nociceptive behavior, number of mast cells, expression of TNF-α, TGF-β, and collagen fibers were observed in HCl + PBS compared with sham + PBS, whereas these changes were significantly decreased in HCl + MSCs compared with HCl + PBS. In addition, bladder capacity and voiding threshold pressures were significantly decreased in HCl + PBS but not in HCl + MSCs compared with sham + PBS. The results suggest that bladder injection of MSCs ameliorates inflammation and fibrosis in bladder tissues, bladder overactivity, and nociception in a rat model of chemically induced cystitis.

  12. Intracellular Ca(2+) release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal.

    Science.gov (United States)

    Zhu, Mei Hong; Sung, Tae Sik; O'Driscoll, Kate; Koh, Sang Don; Sanders, Kenton M

    2015-04-15

    Interstitial cells of Cajal (ICC) provide pacemaker activity in gastrointestinal muscles that underlies segmental and peristaltic contractions. ICC generate electrical slow waves that are due to large-amplitude inward currents resulting from anoctamin 1 (ANO1) channels, which are Ca(2+)-activated Cl(-) channels. We investigated the hypothesis that the Ca(2+) responsible for the stochastic activation of ANO1 channels during spontaneous transient inward currents (STICs) and synchronized activation of ANO1 channels during slow wave currents comes from intracellular Ca(2+) stores. ICC, obtained from the small intestine of Kit(+/copGFP) mice, were studied under voltage and current clamp to determine the effects of blocking Ca(2+) uptake into stores and release of Ca(2+) via inositol 1,4,5-trisphosphate (IP3)-dependent and ryanodine-sensitive channels. Cyclocpiazonic acid, thapsigargin, 2-APB, and xestospongin C inhibited STICs and slow wave currents. Ryanodine and tetracaine also inhibited STICs and slow wave currents. Store-active compounds had no direct effects on ANO1 channels expressed in human embryonic kidney-293 cells. Under current clamp, store-active drugs caused significant depolarization of ICC and reduced spontaneous transient depolarizations (STDs). After block of ryanodine receptors with ryanodine and tetracaine, repolarization did not restore STDs. ANO1 expressed in ICC has limited access to cytoplasmic Ca(2+) concentration, suggesting that pacemaker activity depends on Ca(2+) dynamics in restricted microdomains. Our data from studies of isolated ICC differ somewhat from studies on intact muscles and suggest that release of Ca(2+) from both IP3 and ryanodine receptors is important in generating pacemaker activity in ICC. Copyright © 2015 the American Physiological Society.

  13. Intracellular Ca2+ release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal

    Science.gov (United States)

    Zhu, Mei Hong; Sung, Tae Sik; O'Driscoll, Kate; Koh, Sang Don

    2015-01-01

    Interstitial cells of Cajal (ICC) provide pacemaker activity in gastrointestinal muscles that underlies segmental and peristaltic contractions. ICC generate electrical slow waves that are due to large-amplitude inward currents resulting from anoctamin 1 (ANO1) channels, which are Ca2+-activated Cl− channels. We investigated the hypothesis that the Ca2+ responsible for the stochastic activation of ANO1 channels during spontaneous transient inward currents (STICs) and synchronized activation of ANO1 channels during slow wave currents comes from intracellular Ca2+ stores. ICC, obtained from the small intestine of Kit+/copGFP mice, were studied under voltage and current clamp to determine the effects of blocking Ca2+ uptake into stores and release of Ca2+ via inositol 1,4,5-trisphosphate (IP3)-dependent and ryanodine-sensitive channels. Cyclocpiazonic acid, thapsigargin, 2-APB, and xestospongin C inhibited STICs and slow wave currents. Ryanodine and tetracaine also inhibited STICs and slow wave currents. Store-active compounds had no direct effects on ANO1 channels expressed in human embryonic kidney-293 cells. Under current clamp, store-active drugs caused significant depolarization of ICC and reduced spontaneous transient depolarizations (STDs). After block of ryanodine receptors with ryanodine and tetracaine, repolarization did not restore STDs. ANO1 expressed in ICC has limited access to cytoplasmic Ca2+ concentration, suggesting that pacemaker activity depends on Ca2+ dynamics in restricted microdomains. Our data from studies of isolated ICC differ somewhat from studies on intact muscles and suggest that release of Ca2+ from both IP3 and ryanodine receptors is important in generating pacemaker activity in ICC. PMID:25631870

  14. Melatonin treatment further improves adipose-derived mesenchymal stem cell therapy for acute interstitial cystitis in rat.

    Science.gov (United States)

    Chen, Yen-Ta; Chiang, Hsin-Ju; Chen, Chih-Hung; Sung, Pei-Hsun; Lee, Fan-Yen; Tsai, Tzu-Hsien; Chang, Chia-Lo; Chen, Hong-Hwa; Sun, Cheuk-Kwan; Leu, Steve; Chang, Hsueh-Wen; Yang, Chih-Chao; Yip, Hon-Kan

    2014-10-01

    This study tests the hypothesis that combined melatonin and adipose-derived mesenchymal stem cell (ADMSC, 1.2 × 10(6) given intravenously) treatment offer superior protection against cyclophosphamide (CYP 150 mg/kg)-induced acute interstitial cystitis (AIC) in rats. Male adult Sprague-Dawley rats were treated as follows: sham controls, AIC alone, AIC + melatonin, AIC + ADMSC, and AIC + melatonin +ADMSC. When melatonin was used, it was given as follows: 20 mg/kg at 30 min after CYP and 50 mg/kg at 6 and 18 hr after CYP. Twenty-four-hour urine volume, urine albumin level, and severity of hematuria were highest in AIC rats and lowest in the controls; likewise urine volume was higher in AIC + melatonin rats than in AIC + ADMSC and AIC + melatonin + ADMSC treated rats; in all cases, P < 0.001. The numbers of CD14+, CD74+, CD68+, MIP+, Cox-2+, substance P+, cells and protein expression of IL-6, IL-12, RANTES, TNF-α, NF-κB, MMP-9, iNOS (i.e. inflammatory biomarkers), glycosaminoglycan level, expression of oxidized protein, and protein expression of reactive oxygen species (NOX-1, NOX-2, NOX-4) in the bladder tissue exhibited an identical pattern compared with that of hematuria among the five groups (all P < 0.0001). The integrity of epithelial layer and area of collagen deposition displayed an opposite pattern compared to that of hematuria among all groups (P < 0.0001). The cellular expressions of antioxidants (GR, GPx, HO-1, NQO 1) showed a significant progressive increase form controls to AIC + melatonin + ADMSC (all P < 0.0001). Combined regimen of melatonin and ADMSC was superior to either alone in protecting against CYP-induced AIC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Lack of pyloric interstitial cells of Cajal explains distinct peristaltic motor patterns in stomach and small intestine.

    Science.gov (United States)

    Wang, Xuan-Yu; Lammers, Wim J E P; Bercik, Premysl; Huizinga, Jan D

    2005-09-01

    The frequency and propagation velocity of distension-induced peristaltic contractions in the antrum and duodenum are distinctly different and depend on activation of intrinsic excitatory motoneurons as well as pacemaker cells, the interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP). Because ICC are critical for coordination of motor activities along the long axis of many regions in the gut, the role of ICC in antroduodenal coordination was investigated. We used immunohistochemistry, electron microscopy, simultaneous multiple electrical recordings in vitro, and videofluoroscopy in vivo in mice and rats. A strongly reduced number of ICC-AP with loss of network characteristics was observed in a 4-mm area in the rat and a 1-mm area in the mouse pyloric region. The pyloric region showed a slow wave-free gap of 4.1 mm in rats and 1.3 mm in mice. Between antrum and duodenum, there was no interaction of electrical activities and in the absence of gastric emptying, there was no coordination of motor activities. When the pyloric sphincter opened, 2.4 s before the front of the antral wave reached the pylorus, the duodenum distended after receiving gastric content and aboral duodenal peristalsis was initiated, often disrupting other motor patterns. The absence of ICC-AP and slow wave activity in the pyloric region allows the antrum and duodenum to have distinct uncoordinated motor activities. Coordination of aborally propagating peristaltic antral and duodenal activity is initiated by opening of the pylorus, which is followed by distention-induced duodenal peristalsis. Throughout this coordinated motor activity, the pacemaker systems in antrum and duodenum remain independent.

  16. Plexus muscularis profundus and associated interstitial cells. I. Light microscopical studies of mouse small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Thuneberg, L

    1982-01-01

    muscularis profundus (PMP). PMP was revealed throughout the small intestine as a continuous network of elongated, circularly oriented meshes. The pattern of connections between PMP and the other enteric plexuses was studied stereoscopically. Ganglion cells intrinsic to PMP occurred widely scattered...

  17. Epimorphin expression in interstitial pneumonia

    Directory of Open Access Journals (Sweden)

    Suga Moritaka

    2005-01-01

    Full Text Available Abstract Epimorphin modulates epithelial morphogenesis in embryonic mouse organs. We previously suggested that epimorphin contributes to repair of bleomycin-induced pulmonary fibrosis in mice via epithelium-mesenchyme interactions. To clarify the role of epimorphin in human lungs, we evaluated epimorphin expression and localization in normal lungs, lungs with nonspecific interstitial pneumonia (NSIP, and lungs with usual interstitial pneumonia (UIP; we also studied the effect of recombinant epimorphin on cultured human alveolar epithelial cells in vitro. Northern and Western blotting analyses revealed that epimorphin expression in NSIP samples were significantly higher than those in control lungs and lungs with UIP. Immunohistochemistry showed strong epimorphin expression in mesenchymal cells of early fibrotic lesions and localization of epimorphin protein on mesenchymal cells and extracellular matrix of early fibrotic lesions in the nonspecific interstitial pneumonia group. Double-labeled fluorescent images revealed expression of matrix metalloproteinase 2 in re-epithelialized cells overlying epimorphin-positive early fibrotic lesions. Immunohistochemistry and metalloproteinase activity assay demonstrated augmented expression of metalloproteinase induced by recombinant epimorphin in human alveolar epithelial cells. These findings suggest that epimorphin contributes to repair of pulmonary fibrosis in nonspecific interstitial pneumonia, perhaps partly by inducing expression of matrix metalloproteinase 2, which is an important proteolytic factor in lung remodeling.

  18. Nestin expression is upregulated in the fibrotic rat heart and is localized in collagen-expressing mesenchymal cells and interstitial CD31(+- cells.

    Directory of Open Access Journals (Sweden)

    Vanessa Hertig

    Full Text Available Renal and lung fibrosis was characterized by the accumulation of collagen-immunoreactive mesenchymal cells expressing the intermediate filament protein nestin. The present study tested the hypothesis that nestin expression was increased in the hypertrophied/fibrotic left ventricle of suprarenal abdominal aorta constricted adult male Sprague-Dawley rats and induced in ventricular fibroblasts by pro-fibrotic peptide growth factors. Nestin protein levels were upregulated in the pressure-overloaded left ventricle and expression positively correlated with the rise of mean arterial pressure. In sham and pressure-overloaded hearts, nestin immunoreactivity was detected in collagen type I(+-and CD31(+-cells identified in the interstitium and perivascular region whereas staining was absent in smooth muscle α-actin(+-cells. A significantly greater number of collagen type I(+-cells co-expressing nestin was identified in the left ventricle of pressure-overloaded rats. Moreover, an accumulation of nestin(+-cells lacking collagen, CD31 and smooth muscle α-actin staining was selectively observed at the adventitial region of predominantly large calibre blood vessels in the hypertrophied/fibrotic left ventricle. Angiotensin II and TGF-β1 stimulation of ventricular fibroblasts increased nestin protein levels via phosphatidylinositol 3-kinase- and protein kinase C/SMAD3-dependent pathways, respectively. CD31/eNOS(+-rat cardiac microvascular endothelial cells synthesized/secreted collagen type I, expressed prolyl 4-hydroxylase and TGF-β1 induced nestin expression. The selective accumulation of adventitial nestin(+-cells highlighted a novel feature of large vessel remodelling in the pressure-overloaded heart and increased appearance of collagen type I/nestin(+-cells may reflect an activated phenotype of ventricular fibroblasts. CD31/collagen/nestin(+-interstitial cells could represent displaced endothelial cells displaying an unmasked mesenchymal phenotype

  19. Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis

    Science.gov (United States)

    Hadley, Jill A.; Hall, Joseph C.; O'Brien, Ami; Ball, Richard

    1992-01-01

    The effect of simulated microgravity on the structure and function of the testis and epididymis cells was investigated in rats subjected to 7 days of tail suspension. Results of a histological examination revealed presence of disorganized seminiferous tubules and accumulation of large multinucleated cells and spermatids in the lumen of the epididymis. In addition, decreases in the content of testis protein and in testosterone levels in the testis, the interstitial fluid, and the epididymis were observed.

  20. A morphological and quantitative immunohistochemical study of the interstitial cells of Cajal in the normal equine intestinal tracts.

    Science.gov (United States)

    Pavone, S; Mandara, M T

    2010-05-01

    The interstitial cells of Cajal (ICC) play a key role in the control of intestinal motility and have been implicated in several human gastrointestinal dysmotility syndromes, in equine grass sickness and in other intestinal disorders where a significant reduction in ICC density was observed. To investigate the density of ICC in clinically normal horses, ICC c-Kit expression was evaluated by image analysis in order to obtain numerical data. Intestinal samples from the jejunum to small colon from 5 clinically normal horses were studied. Immunohistochemical labelling of ICC was performed using an anti-c-Kit antibody. Density of ICC was calculated using image analysis software. In the equine intestinal tract 2 types of ICC were observed: intramuscular ICC, i.e. ICC in the internal circular layer (IC-CM) and ICC in the external longitudinal layer (IC-LM), and myenteric ICC (IC-MY). The density of IC-MY was found to be higher throughout the small intestine. IC-MY density in the large intestine appeared to be greatest in the right ventral colon and in the small colon. IC-MY density in the ileocaecal junction showed an intermediate value compared to the small and large intestine. On the other hand, the density of IC-CM was found to be higher in the ileocaecal junction, whereas the caecum, left ventral colon and the left dorsal colon showed the lowest c-Kit immunoreactivity. The ileal tract and the ileocaecal junction showed an appreciable IC-LM density. Image analysis is a rapid and reproducible method to establish the density of ICC in the normal equine intestinal tract. This study corroborates the findings of previous studies and provides a platform for further future pathological investigations of the equine intestine by supplying usable numerical data as comparative elements.

  1. Neurotrophin 3 upregulates proliferation and collagen production in human aortic valve interstitial cells: a potential role in aortic valve sclerosis.

    Science.gov (United States)

    Yao, Qingzhou; Song, Rui; Ao, Lihua; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong

    2017-06-01

    Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves overexpress growth factor neurotrophin 3 (NT3). In the present study, we tested the hypothesis that NT3 is a profibrogenic factor to human AVICs. AVICs isolated from normal human aortic valves were cultured in M199 growth medium and treated with recombinant human NT3 (0.10 µg/ml). An exposure to NT3 induced AVIC proliferation, upregulated the production of collagen and matrix metalloproteinase (MMP), and augmented collagen deposition. These changes were abolished by inhibition of the Trk receptors. NT3 induced Akt phosphorylation and increased cyclin D1 protein levels in a Trk receptor-dependent fashion. Inhibition of Akt abrogated the effect of NT3 on cyclin D1 production. Furthermore, inhibition of either Akt or cyclin D1 suppressed NT3-induced cellular proliferation and MMP-9 and collagen production, as well as collagen deposition. Thus, NT3 upregulates cellular proliferation, ECM protein production, and collagen deposition in human AVICs. It exerts these effects through the Trk-Akt-cyclin D1 cascade. NT3 is a profibrogenic mediator in human aortic valve, and overproduction of NT3 by aortic valve tissue may contribute to the mechanism of valvular sclerosis. Copyright © 2017 the American Physiological Society.

  2. Acute interstitial nephritis in T-cell leukemia in a pediatric patient.

    Science.gov (United States)

    Biro, Erika; Szikszay, Edit; Pethő-Orosz, Petronella; Bigida, László; Balla, György; Szabó, Tamás

    2016-09-01

    Acute lymphoid leukemia is the most frequently occurring malignancy in childhood, but acute tubulointerstitial nephritis with associated acute renal failure as the leading manifestation of leukemia is extremely rare. Only a few pediatric cases have been described in the literature. We present a surprising case in which physical examination and initial investigation were not typical for leukemia. Ultrasound showed only modest kidney enlargement while laboratory results indicated acute renal failure. Renal biopsy indicated tubulointerstitial nephritis, and subsequent steroid treatment led to sudden clinical improvement. One month later, however, the patient returned with typical clinical features of leukemia. Re-evaluation of the original kidney biopsy block indicated T-cell acute lymphoid leukemia. The present case highlights the importance of renal biopsy. © 2016 Japan Pediatric Society.

  3. Interstitial Lung Diseases

    Science.gov (United States)

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...

  4. YKL-40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis

    DEFF Research Database (Denmark)

    Richter, Benedikte; Roslind, A.; Hesse, U.

    2010-01-01

    Aims: Bladder pain syndrome/interstitial cystitis (BPS/IC), diagnosed according to the new 2008 criteria of the European Society for the Study of Interstitial Cystitis (ESSIC), may lead to detrusor fibrosis. In some inflammatory diseases, fibrosis is related to YKL-40. The aims were to examine YKL...

  5. Normalization of proliferation and tight junction formation in bladder epithelial cells from patients with interstitial cystitis/painful bladder syndrome by d-proline and d-pipecolic acid derivatives of antiproliferative factor.

    Science.gov (United States)

    Keay, Susan; Kaczmarek, Piotr; Zhang, Chen-Ou; Koch, Kristopher; Szekely, Zoltan; Barchi, Joseph J; Michejda, Christopher

    2011-06-01

    Interstitial cystitis/painful bladder syndrome is a chronic bladder disorder with epithelial thinning or ulceration, pain, urinary frequency and urgency, for which there is no reliably effective therapy. We previously reported that interstitial cystitis/painful bladder syndrome bladder epithelial cells make a glycopeptide antiproliferative factor or 'APF' (Neu5Acα2-3Galβ1-3GalNAcα-O-TVPAAVVVA) that induces abnormalities in normal cells similar to those in interstitial cystitis/painful bladder syndrome cells in vitro, including decreased proliferation, decreased tight junction formation, and increased paracellular permeability. We screened inactive APF derivatives for their ability to block antiproliferative activity of asialylated-APF ('as-APF') in normal bladder cells and determined the ability of as-APF-blocking derivatives to normalize tight junction protein expression, paracellular permeability, and/or proliferation of interstitial cystitis/painful bladder syndrome cells. Only two of these derivatives [Galβ1-3GalNAcα-O-TV-(d-pipecolic acid)-AAVVVA and Galβ1-3GalNAcα-O-TV-(d-proline)-AAVVVA] blocked as-APF antiproliferative activity in normal cells (p PCR; 2) normalized interstitial cystitis/painful bladder syndrome epithelial cell tight junction protein expression and tight junction formation by confocal immunofluorescence microscopy; and 3) decreased paracellular permeability of (14) C-mannitol and (3) H-inulin between confluent interstitial cystitis/painful bladder syndrome epithelial cells on Transwell plates, suggesting that these potent APF antagonists may be useful for the development as interstitial cystitis/painful bladder syndrome therapies. Published 2011. This article is a US Government work and is in the public domain in the USA.

  6. Interstitial cystitis: painful bladder syndrome

    Directory of Open Access Journals (Sweden)

    R F Sholan

    2018-02-01

    Full Text Available Interstitial cystitis, or painful bladder syndrome, is a chronic inflammatory disease of a bladder of unknown etiology. It negatively affects the quality of life, causes depressive disorders, anxiety, and sexual dysfunction. Despite numerous studies, the etiology of interstitial cystitis is still unclear and it’s considered as painful bladder syndrome with multifactorial origin. According to the US National Health and Nutrition Examination Survey, 470/100 000 people (60/100 000 men, 850/100 000 women are diagnosed with interstitial cystitis. Diagnosis of the disease is difficult and is substantially based on clinical symptoms. Pelvic pain, urinary urgency, frequency and nocturia are the basic complaints in this pathology. The diagnosis requires exclusion of diseases with similar manifestations. So interstitial cystitis is frequently misdiagnosed as urinary tract infection, overactive bladder, urethral obstruction or diverticulosis, chronic prostatitis, bladder cancer, vulvodynia, endometriosis, and chronic pelvic pain. Etiopathogenesis of the disease is uncertain, which makes etiologic treatment impossible. Currently scientific discussions on the causes of disease continue as well as different treatment regimens are offered, but are often ineffective, palliative and temporary. The treatment for intersticial cystitis should focus on restoring normal bladder function, prevention of relapse of symptoms and improvement of patients’ quality of life. The literature review presents current view on the terminology, epidemiology, diagnosis and treatment of interstitial cystitis.

  7. Changes in sexual function of women with refractory interstitial cystitis/bladder pain syndrome after intravesical therapy with a hyaluronic acid solution.

    Science.gov (United States)

    Hung, Man-Jung; Su, Tsung-Hsien; Lin, Yi-Hao; Huang, Wen-Chu; Lin, Tzu-Yin; Hsu, Chun-Shuo; Chuang, Fei-Chi; Tsai, Ching-Pei; Shen, Pao-Sheng; Chen, Gin-Den

    2014-09-01

    Intravesical instillation with a hyaluronic acid (HA) solution is an effective treatment for interstitial cystitis/bladder pain syndrome (IC/BPS), but its impact on sexual functioning of patients is not known. The aim of this study was to evaluate the changes in sexual function of women with refractory IC/BPS who underwent a second-line intravesical HA therapy. A total of 103 women diagnosed with refractory IC/BPS were enrolled in this prospective, multicenter study. Sexual function was evaluated using the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-9). Bladder-related symptoms and bother were assessed by the Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), and a pain visual analog scale (VAS), respectively. Data were analyzed with univariate methods or multivariate logistic regression analysis accordingly. Changes in PISQ-9, ICSI, ICPI, and pain VAS scores after treatment were assessed. Mean age and duration of symptoms was 43.6 ± 11.8 and 5.1 ± 5.0 years, respectively. ICSI, ICPI, and pain VAS scores were significantly (P < 0.001) improved after 1 month and 6 months of treatment. Of the 87 (84.5%) sexually active women evaluated, PISQ-9 total scores improved significantly (P < 0.001) from the baseline (mean 18.9 ± 6.4), after 1 month (20.4 ± 5.8), and 6-months (21.5 ± 5.6) of treatment. Significantly improved PISQ-9 items included "dyspareunia" (P < 0.001) and "negative reactions" (P = 0.015) during sexual intercourse, and "intensity" (P < 0.001) of sexual orgasms. After a logistic regression analysis, we found that a baseline PISQ-9 score was negatively correlated with the duration of IC/BPS symptoms (P = 0.022). Meanwhile, the changes in PISQ-9 scores were positively correlated with the reduction in ICSI scores after treatment (P = 0.045). Intravesical HA is an effective treatment for refractory IC/BPS. A longer

  8. Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis.

    Science.gov (United States)

    Hauser, Paul J; VanGordon, Samuel B; Seavey, Jonathan; Sofinowski, Troy M; Ramadan, Mohammad; Abdullah, Shivon; Buffington, C A Tony; Hurst, Robert E

    2015-08-01

    We analyzed the urothelium of cats diagnosed with feline interstitial cystitis to determine whether abnormalities in protein expression patterns could be detected and whether the expression pattern was similar to that in patients with human interstitial cystitis/bladder pain syndrome. The proteins analyzed are involved in cell adhesion and barrier function, comprise the glycosaminoglycan layer or are differentiation markers. Formalin fixed biopsies from 8 cats with feline interstitial cystitis and from 7 healthy control cats were labeled by immunohistochemistry and scored with a modified version of a system previously used for human samples. Cluster analysis was performed to investigate relationships between markers and samples. Of the feline interstitial cystitis bladders 89% showed abnormal protein expression and chondroitin sulfate patterns while only 27% of normal tissues showed slight abnormalities. Abnormalities were found in most feline interstitial cystitis samples, including biglycan in 87.5%, chondroitin sulfate, decorin, E-cadherin and keratin-20 in 100%, uroplakin in 50% and ZO-1 in 87.5%. In feline interstitial cystitis bladders about 75% of chondroitin sulfate, biglycan and decorin samples demonstrated absent luminal staining or no staining. Cluster analysis revealed that feline interstitial cystitis and normal samples could be clearly separated into 2 groups, showing that the urothelium of cats with feline interstitial cystitis is altered from normal urothelium. Feline interstitial cystitis produces changes in luminal glycosaminoglycan and several proteins similar to that in patients, suggesting some commonality in mechanism. Results support the use of feline interstitial cystitis as a model of human interstitial cystitis. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Abnormal Akt signalling in bladder epithelial cell explants from patients with interstitial cystitis/bladder pain syndrome can be induced by antiproliferative factor treatment of normal bladder cells.

    Science.gov (United States)

    Keay, Susan K; Zhang, Chen-Ou

    2016-07-01

    To determine whether protein kinase B (Akt) signalling and secretion of specific downstream effector proteins are abnormal in specific cell fractions of bladder epithelial cells from patients with interstitial cystitis/bladder pain syndrome (IC/BPS), as explanted bladder epithelial cells from patients with IC/BPS produce a frizzled 8-related glycopeptide antiproliferative factor (APF) that inhibits normal bladder epithelial cell proliferation and expression of several proteins known to be regulated by Akt signalling. A related secondary objective was to determine whether treatment of normal bladder epithelial cells with active synthetic asialo-antiproliferative factor (as-APF) induces similar changes in Akt signalling and specific downstream effector proteins/mRNAs. Cell proteins were extracted into four subcellular fractions from primary bladder epithelial explants of six patients who fulfilled modified National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) criteria for IC/BPS and six age- and gender-matched controls. Total and/or phosphorylated cellular Akt, glycogen synthase kinase 3β (GSK3β), and β-catenin; total cellular JunB; and secreted matrix metalloproteinase 2 (MMP2) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) levels were determined by Western blot. MMP2, JunB, p53, uroplakin 3 (UPK3), and β-actin mRNAs were quantified by quantitative reverse transcriptase-polymerase chain reaction. Akt activity was determined by nonradioactive assay. IC/BPS cells had lower Akt activity, along with lower Akt ser473- and GSK3β ser9-phosphorylation and higher β-catenin ser33,37/thr41-phosphorylation in specific fractions as compared with matched control cells. IC/BPS explants also had evidence of additional downstream abnormalities compared with control cells, including lower nuclear JunB; lower secreted MMP2 and HB-EGF; plus lower MMP2, JunB, and UPK3 mRNAs but higher p53 mRNA relative to β-actin. Each of these IC

  10. The behavior of interstitials in irradiated graphite

    International Nuclear Information System (INIS)

    Pedraza, D.F.

    1991-01-01

    A computer model is developed to simulate the behavior of self-interstitials with particular attention to clustering. Owing to the layer structure of graphite, atomistic simulations can be performed using a large parallelepipedic supercell containing a few layers. In particular, interstitial clustering is studied here using a supercell that contains two basal planes only. Frenkel pairs are randomly produced. Interstitials are placed at sites between the crystal planes while vacancies are distributed in the two crystal planes. The size of the computational cell is 20000 atoms and periodic boundary conditions are used in two dimensions. Vacancies are assumed immobile whereas interstitials are given a certain mobility. Two point defect sinks are considered, direct recombination of Frenkel pairs and interstitial clusters. The clusters are assumed to be mobile up to a certain size where they are presumed to become loop nuclei. Clusters can shrink by emission of singly bonded interstitials or by recombination of a peripheral interstitial with a neighboring vacancy. The conditions under which interstitial clustering occurs are reported. It is shown that when clustering occurs the cluster size population gradually shifts towards the largest size cluster. The implications of the present results for irradiation growth and irradiation-induced amorphization are discussed

  11. Interstitial guidance of cancer invasion.

    Science.gov (United States)

    Gritsenko, Pavlo G; Ilina, Olga; Friedl, Peter

    2012-01-01

    Cancer cell invasion into healthy tissues develops preferentially along pre-existing tracks of least resistance, followed by secondary tissue remodelling and destruction. The tissue scaffolds supporting or preventing guidance of invasion vary in structure and molecular composition between organs. In the brain, the guidance is provided by myelinated axons, astrocyte processes, and blood vessels which are used as invasion routes by glioma cells. In the human breast, containing interstitial collagen-rich connective tissue, disseminating breast cancer cells preferentially invade along bundled collagen fibrils and the surface of adipocytes. In both invasion types, physical guidance prompted by interfaces and space is complemented by molecular guidance. Generic mechanisms shared by most, if not all, tissues include (i) guidance by integrins towards fibrillar interstitial collagen and/or laminins and type IV collagen in basement membranes decorating vessels and adipocytes, and, likely, CD44 engaging with hyaluronan; (ii) haptotactic guidance by chemokines and growth factors; and likely (iii) physical pushing mechanisms. Tissue-specific, resticted guidance cues include ECM proteins with restricted expression (tenascins, lecticans), cell-cell interfaces, and newly secreted matrix molecules decorating ECM fibres (laminin-332, thrombospondin-1, osteopontin, periostin). We here review physical and molecular guidance mechanisms in interstitial tissue and brain parenchyma and explore shared principles and organ-specific differences, and their implications for experimental model design and therapeutic targeting of tumour cell invasion. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  12. [Apoptosis of interstitial cells of Cajal in deep muscular layer of small intestine in rats with multiple organ dysfunction syndrome].

    Science.gov (United States)

    Xie, Mingzheng; Qi, Qinghui

    2015-06-01

    To observe the apoptosis of interstitial cells of Cajal in deep muscular layer (ICC-DMP) of small intestine in rats with multiple organ dysfunction syndrome (MODS) as a result of bacterial peritonitis, and the expression of c-kit (an ICC phenotype marker) and Bax/Bcl-2, in order to investigate the mechanism of gastrointestinal motility dysfunction in MODS. According to the random number table, 40 Wistar rats were randomly divided into two groups: control group (n=20) and MODS group (n=20). The MODS model in rats was reproduced by intraperitoneal injection of 8×10(8) cfu/mL Escherichia coli suspension 1 mL, and the control group was given the same amount of normal saline. After 24 hours, the upper small intestine was harvested for examination. Ultrastructure of ICC-DMP was observed using electron microscope. The network structure of ICC-DMP and the expression of c-kit and Bax/Bcl-2 were observed and determined with immunofluorescence and laser scanning confocal microscope. Macroscopic observation revealed that the gastrointestinal motility of rats was normal in the control group. Compared with the control group, gastro intestine was significantly expanded with parulytic ileus in MODS group. It was shown by transmission electron microscopy that intermediate filament structure of ICC-DMP was clear without swelling of mitochondria; chromatin distributed uniformly with small amounts of heterochromatin aggregated in perinuclear. Compared with the control group, intermediate filament structure of ICC-DMP was fuzzy, and mitochondria were swollen obviously in MODS group; chromatin was assembled in nucleus centre. It was shown by laser scanning confocal microscope that the network structure of ICC-DMP was clear, the expression of c-kit and Bcl-2 was strongly and overlapping; the expression of Bax was weak and scatter distributed. Compared with control group, ICC-DMP quantity in MODS group was significantly reduced (cells/HP: 15.80±2.30 vs. 25.70±3.97, t=6.819, P=0

  13. Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells Enhance Endogenous Repair of Injured Porcine Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Fiona C. Lewis, BSc, PhD

    2017-12-01

    Full Text Available Skeletal muscle-derived PW1pos/Pax7neg interstitial cells (PICs express and secrete a multitude of proregenerative growth factors and cytokines. Utilizing a porcine preclinical skeletal muscle injury model, delivery of allogeneic porcine PICs (pPICs significantly improved and accelerated myofiber regeneration and neocapillarization, compared with saline vehicle control-treated muscles. Allogeneic pPICs did not contribute to new myofibers or capillaries and were eliminated by the host immune system. In conclusion, allogeneic pPIC transplantation stimulated the endogenous stem cell pool to bring about enhanced autologous skeletal muscle repair and regeneration. This allogeneic cell approach is considered a cost-effective, easy to apply, and readily available regenerative therapeutic strategy.

  14. TGF-β/MAPK signaling mediates the effects of bone marrow mesenchymal stem cells on urinary control and interstitial cystitis after urinary bladder transplantation.

    Science.gov (United States)

    Xiao, Ya; Song, Ya-Jun; Song, Bo; Huang, Chi-Bing; Ling, Qing; Yu, Xiao

    2017-01-01

    This study aimed to explore the role of the transforming growth factor-β/mitogen activated protein kinase (TGF-β/MAPK) signaling pathway in the effects of bone marrow mesenchymal stem cells (BMSCs) on urinary control and interstitial cystitis in a rat model of urinary bladder transplantation. A urinary bladder transplantation model was established using Sprague-Dawley rats. Rats were assigned to normal (blank control), negative control (phosphate-buffered saline injection), BMSCs (BMSC injection), sp600125 (MAPK inhibitor injection), or protamine sulfate (protamine sulfate injection) groups. Immunohistochemistry, urodynamic testing, hematoxylin-eosin staining, Western blotting, enzyme-linked immunosorbent assay, and MTT assay were used to assess BMSC growth, the kinetics of bladder urinary excretion, pathological changes in bladder tissue, bladder tissue ultrastructure, the expression of TGF-β/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and the effects of antiproliferative factor on cell proliferation. Compared with normal, negative control, BMSCs, and sp600125 groups, rats in the PS group exhibited decreased discharge volume, maximal micturition volume, contraction interval, and bladder capacity but increased residual urine volume, bladder pressure, bladder peak pressure, expression of TGF-β/MAPK signaling pathway-related proteins, levels of inflammatory cytokines, and growth inhibition rate. Levels of inflammatory cytokines and the growth inhibition rate were positively correlated with the expression of TGF-β/MAPK signaling pathway-related proteins. Our findings demonstrate that the TGF-β/MAPK signaling pathway mediates the beneficial effects of BMSCs on urinary control and interstitial cystitis.

  15. Potassium and ANO1/TMEM16A chloride channel profiles distinguish atypical and typical smooth muscle cells from interstitial cells in the mouse renal pelvis

    Science.gov (United States)

    Iqbal, Javed; Tonta, Mary A; Mitsui, Retsu; Li, Qun; Kett, Michelle; Li, Jinhua; Parkington, Helena C; Hashitani, Hikaru; Lang, Richard J

    2012-01-01

    BACKGROUND AND PURPOSE Although atypical smooth muscle cells (SMCs) in the proximal renal pelvis are thought to generate the pacemaker signals that drive pyeloureteric peristalsis, their location and electrical properties remain obscure. EXPERIMENTAL APPROACH Standard patch clamp, intracellular microelectrode and immunohistochemistry techniques were used. To unequivocally identify SMCs, transgenic mice with enhanced yellow fluorescent protein (eYFP) expressed in cells containing α-smooth muscle actin (α-SMA) were sometimes used. KEY RESULTS Atypical SMCs were distinguished from typical SMCs by the absence of both a transient 4-aminopyridine-sensitive K+ current (IKA) and spontaneous transient outward currents (STOCs) upon the opening of large-conductance Ca2+-activated K+ (BK) channels. Many typical SMCs displayed a slowly activating, slowly decaying Cl- current blocked by niflumic acid (NFA). Immunostaining for KV4.3 and ANO1/ TMEM16A Cl- channel subunits co-localized with α-SMA immunoreactive product predominately in the distal renal pelvis. Atypical SMCs fired spontaneous inward currents that were either selective for Cl- and blocked by NFA, or cation-selective and blocked by La3+. α-SMA- interstitial cells (ICs) were distinguished by the presence of a Xe991-sensitive KV7 current, BK channel STOCs and Cl- selective, NFA-sensitive spontaneous transient inward currents (STICs). Intense ANO1/ TMEM16A and KV7.5 immunostaining was present in Kit-α-SMA- ICs in the suburothelial and adventitial regions of the renal pelvis. CONCLUSIONS AND IMPLICATIONS We conclude that KV4.3+α-SMA+ SMCs are typical SMCs that facilitate muscle wall contraction, that ANO1/ TMEM16A and KV7.5 immunoreactivity may be selective markers of Kit- ICs and that atypical SMCs which discharge spontaneous inward currents are the pelviureteric pacemakers. PMID:22014103

  16. Interstitial cystitis intravesical therapy.

    Science.gov (United States)

    Ha, Tanya; Xu, Jie Hua

    2017-07-01

    Interstitial cystitis (IC) is a progressive bladder disorder that presents with symptoms of bladder urgency, frequency and pain. The aetiology of the disease remains uncertain, but it is postulated that there is an initial infective insult which damages the glycosaminoglycan (GAG) layer of the bladder urothelium. This defect allows an influx of ions, particularly potassium, which initiates an inflammatory reaction in the bladder wall, which incites the symptoms described above. Treatment initially involves behavioural and oral medication, with second line being intravesical instillation therapy. Treatment strategies focus on restoring lower urinary tract epithelial function, inhibiting neural activation, controlling allergies and relieving symptoms. In this review, current intravesical therapy will be discussed, as well as what lies on the horizon for intravesical therapy in IC.

  17. Urinary Monocyte Chemoattractant Protein-1 Levels and Interstitial Changes in the Renal Cortex and Their Relationship with Loss of Renal Function in Renal Transplant Patients with Delayed Graft Function

    Directory of Open Access Journals (Sweden)

    Miguel Moyses Neto

    2015-01-01

    Full Text Available Background: Inflammatory cell infiltration and residual areas of fibrosis in kidneys after renal transplantation can lead to functional abnormalities with long-term implications. Objectives: The aim of this study was to determine urinary monocyte chemoattractant protein-1 (uMCP-1 levels, relative cortical interstitial area (RCIA, and cortical tubulointerstitial macrophage infiltration in renal transplant patients with delayed graft function (DGF and their possible correlation with graft outcome. Design: Patients were followed after biopsies for one year, and their renal function and structure were evaluated, as well as parameters of inflammatory process. Setting: Clinical Hospital of the School of Medicine of Ribeirão Preto. Patients: Twenty-two cadaveric kidney transplant recipients with DGF were followed for one year. Measurements: Renal function, RCIA, macrophages infiltration and uMCP-1 levels were evaluated. Methods: Renal function was evaluated by plasma creatinine levels. RCIA was determined by morphometry. Immunohistochemical staining of macrophages was performed using an anti-CD68 monoclonal antibody. uMCP-1 levels were determined using a human MCP-1/CCL2 immunoassay kit. Results: There was a significant increase in uMCP-1 levels in transplant patients compared with controls ( p < 0.001. RCIA was 7.1% (6.4 to 9.2; median and 25th to 75th percentiles in controls and 37.1% (28.1 to 43.7 in patients with kidney transplants ( p < 0.001. The patients who presented with a higher RCIA in the first biopsy showed higher levels of plasma creatinine one year after transplantation (r = 0.44; p < 0.05. The number of tubulointerstitial macrophages per 0.10 mm 2 grid field was higher in the renal cortex of transplant patients compared with the controls (19.4 (9.0 to 47.1 vs. 2.5 (1.8 to 3.4, p < 0.001. There was also a positive correlation between the RCIA and the number of tubulointerstitial macrophages in the renal cortex of these patients (r = 0

  18. Tumor interstitial fluid - a treasure trove of cancer biomarkers.

    Science.gov (United States)

    Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J; Timmermans-Wielenga, Vera; Talman, Mai-Lis; Serizawa, Reza R; Moreira, José M A

    2013-11-01

    Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical secretion, non-classical secretion, secretion via exosomes and membrane protein shedding. Consequently, the interstitial aqueous phase of solid tumors is a highly promising resource for the discovery of molecules associated with pathological changes in tissues. Firstly, it allows one to delve deeper into the regulatory mechanisms and functions of secretion-related processes in tumor development. Secondly, the anomalous secretion of molecules that is innate to tumors and the tumor microenvironment, being associated with cancer progression, offers a valuable source for biomarker discovery and possible targets for therapeutic intervention. Here we provide an overview of the features of tumor-associated interstitial fluids, based on recent and updated information obtained mainly from our studies of breast cancer. Data from the study of interstitial fluids recovered from several other types of cancer are also discussed. This article is a part of a Special Issue entitled: The Updated Secretome. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Treatment Approaches for Interstitial Cystitis: Multimodality Therapy

    Science.gov (United States)

    Evans, Robert J

    2002-01-01

    Interstitial cystitis is an increasingly common disease characterized by urgency, frequency, and pelvic pain. Its etiology is poorly understood but is likely to be multifactorial. A proposed pathophysiology describing a cascade of events, including epithelial dysfunction, mast cell activation, and neurogenic inflammation, is presented. Using this model, multimodality therapy regimens have been developed that treat all components of this cascade. Multimodality therapy appears more effective than single agents in the treatment of interstitial cystitis. PMID:16986029

  20. Two Days of Calorie Deprivation Induced by Underfeeding and Aerobic Exercise Degrades Mood and Lowers Interstitial Glucose but Does Not Impair Cognitive Function in Young Adults.

    Science.gov (United States)

    Lieberman, Harris R; Bukhari, Asma S; Caldwell, John A; Wilson, Marques A; Mahoney, Caroline R; Pasiakos, Stefan M; McClung, James P; Smith, Tracey J

    2017-01-01

    In studies assessing the effects of acute undernutrition on cognitive function, volunteers are sedentary and findings are equivocal, even though glucose concentrations fall substantially. However, military personnel and endurance athletes often are underfed when physical demands, and consequently energy expenditure, are substantial. The objective of this study was to determine whether 2 d of near-total calorie deprivation combined with aerobic exercise degraded cognitive performance and mood. A double-blind, placebo-controlled, crossover design was used. Twenty-three volunteers [17 men (mean ± SD age: 20.5 ± 0.7 y) and 6 women (mean ± SD age: 23.3 ± 1.4 y); mean ± SD body mass index (in kg/m 2 ): 25 ± 3] participated for 68 h, including a 51-h inpatient phase in a calorie-deprived or fully fed state during which behavioral testing was conducted and interstitial glucose was monitored continuously. Mood and cognitive performance, including psychomotor and visual vigilance, visual match-to-sample, repeated acquisition (motor learning), N-back (working memory), and grammatical reasoning, were repeatedly assessed. During each condition, individual daily energy intake and expenditure were controlled. During calorie deprivation, volunteers consumed 266 ± 61 kcal/d; during full feeding, they consumed 3935 ± 769 kcal/d. Participants engaged in identical exercise sessions for 4 h/d at 40-65% of peak volume of oxygen uptake attained. Calorie deprivation did not affect any aspect of cognitive performance, but produced robust effects on mood measured by the Profile of Mood States, including increased tension (P mood disturbance (from -0.80 ± 5.1 to 20.1 ± 6.1; P mood, but not cognition, in spite of substantial reductions in interstitial glucose concentrations. This trial was registered at clinicaltrials.gov as NCT01603550. © 2017 American Society for Nutrition.

  1. Porcine Skeletal Muscle-Derived Multipotent PW1pos/Pax7neg Interstitial Cells: Isolation, Characterization, and Long-Term Culture

    Science.gov (United States)

    Lewis, Fiona C.; Henning, Beverley J.; Marazzi, Giovanna; Sassoon, David

    2014-01-01

    Developing effective strategies for the regeneration of solid tissue requires an understanding of the biology underlying the tissue’s endogenous repair mechanisms. PW1/Peg3pos/Pax7neg skeletal muscle-derived interstitial progenitor cells (PICs) were first identified recently in the interstitium of murine skeletal muscle and shown to contribute to muscle fiber regeneration in vivo. PICs, therefore, represent a novel candidate resident progenitor cell for muscle regeneration. To explore the potential of these cells for clinical translation, we must ascertain the presence of PICs in larger mammalian species and identify criteria to successfully isolate and expand this population. In this study, we report the isolation, characterization, and maintenance of multipotent PICs from juvenile porcine skeletal muscle. We show that porcine PICs can be reproducibly isolated from skeletal muscle, express stem/progenitor cell markers, and have a stable phenotype and karyotype through multiple passages. Furthermore, porcine PICs are clonogenic and multipotent, giving rise to skeletal myoblast/myotubes, smooth muscle, and endothelial cells. In addition, PICs can be induced to differentiate into cardiomyocyte-like cells. These results demonstrate, in an animal model with size and physiology extrapolatable to the human, that porcine skeletal muscle-derived PW1pos/Pax7neg PICs are a source of stem/progenitor cells. These findings open new avenues for a variety of solid tissue engineering and regeneration using a single multipotent stem cell type isolated from an easily accessible source, such as skeletal muscle. PMID:24744394

  2. Alpha8 Integrin (Itga8 Signalling Attenuates Chronic Renal Interstitial Fibrosis by Reducing Fibroblast Activation, Not by Interfering with Regulation of Cell Turnover.

    Directory of Open Access Journals (Sweden)

    Ines Marek

    Full Text Available The α8 integrin (Itga8 chain contributes to the regulation of cell proliferation and apoptosis in renal glomerular cells. In unilateral ureteral obstruction Itga8 is de novo expressed in the tubulointerstitium and a deficiency of Itga8 results in more severe renal fibrosis after unilateral ureteral obstruction. We hypothesized that the increased tubulointerstitial damage after unilateral ureteral obstruction observed in mice deficient for Itga8 is associated with altered tubulointerstitial cell turnover and apoptotic mechanisms resulting from the lack of Itga8 in cells of the tubulointerstitium. Induction of unilateral ureteral obstruction was achieved by ligation of the right ureter in mice lacking Itga8. Unilateral ureteral obstruction increased proliferation and apoptosis rates of tubuloepithelial and interstitial cells, however, no differences were observed in the tubulointerstitium of mice lacking Itga8 and wild type controls regarding fibroblast or proliferating cell numbers as well as markers of endoplasmic reticulum stress and apoptosis after unilateral ureteral obstruction. In contrast, unilateral ureteral obstruction in mice lacking Itga8 led to more pronounced tubulointerstitial cell activation i.e. to the appearance of more phospho-SMAD2/3-positive cells and more α-smooth muscle actin-positive cells in the tubulointerstitium. Furthermore, a more severe macrophage and T-cell infiltration was observed in these animals compared to controls. Thus, Itga8 seems to attenuate tubulointerstitial fibrosis in unilateral ureteral obstruction not via regulation of cell turnover, but via regulation of TGF-β signalling, fibroblast activation and/or immune cell infiltration.

  3. Changes in the interstitial cells of Cajal and neuronal nitric oxide synthase positive neuronal cells with aging in the esophagus of F344 rats.

    Science.gov (United States)

    Kim, Hee Jin; Kim, Nayoung; Kim, Yong Sung; Nam, Ryoung Hee; Lee, Sun Min; Park, Ji Hyun; Choi, Daeun; Hwang, Young-Jae; Lee, Jongchan; Lee, Hye Seung; Kim, Min-Seob; Lee, Moon Young; Lee, Dong Ho

    2017-01-01

    The aging-associated cellular and molecular changes in esophagus have not been established, yet. Thus we evaluated histological structure, interstitial cells of Cajal (ICCs), neuronal nitric oxide synthase (nNOS)-positive cells, and contractility in the esophagus of Fischer 344 rat at different ages (6-, 31-, 74-weeks, and 2-years). The lamina propria thickness and endomysial area were calculated. The immunoreactivity of c-Kit, nNOS and protein gene product (PGP) 9.5 was counted after immunohistochemistry. Expression of c-Kit, stem cell factor (SCF), nNOS and PGP 9.5 mRNA was measured by real-time PCR, and expression of c-Kit and nNOS protein was detected by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The lamina propria thickness increased (6 week vs 2 year, P = 0.005) and the endomysial area of longitudinal muscle decreased with aging (6 week vs 2 year, Paging (6 week vs 2 year; Pchange of PGP 9.5-immunopositiviy. The expressions of nNOS, c-Kit and SCF mRNA also reduced with aging (6 week vs 2 year; P = 0.006, P = 0.001 and P = 0.006, respectively), while the change of PGP 9.5 mRNA expression was not significant. Western blot showed the significant decreases of nNOS and c-Kit protein expression with aging (6 week vs 2 year; P = 0.008 and P = 0.012, respectively). The EFS-induced esophageal contractions significantly decreased in 2-yr-old rat compared with 6-wk-old rats, however, L-NG-Nitroarginine methylester did not significantly increase the spontaneous and EFS-induced contractions in the 6-wk- and 2-yr-old rat esophagus. In conclusion, an increase of lamina propria thickness, a decrease of endomysial area, c-Kit, SCF and NOS expression with preserved total enteric neurons, and contractility in aged rat esophagus may explain the aging-associated esophageal dysmotility.

  4. Diabetes and Stem Cell Function

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2015-01-01

    Full Text Available Diabetes mellitus is one of the most common serious metabolic diseases that results in hyperglycemia due to defects of insulin secretion or insulin action or both. The present review focuses on the alterations to the diabetic neuronal tissues and skeletal muscle, including stem cells in both tissues, and the preventive effects of physical activity on diabetes. Diabetes is associated with various nervous disorders, such as cognitive deficits, depression, and Alzheimer’s disease, and that may be caused by neural stem cell dysfunction. Additionally, diabetes induces skeletal muscle atrophy, the impairment of energy metabolism, and muscle weakness. Similar to neural stem cells, the proliferation and differentiation are attenuated in skeletal muscle stem cells, termed satellite cells. However, physical activity is very useful for preventing the diabetic alteration to the neuronal tissues and skeletal muscle. Physical activity improves neurogenic capacity of neural stem cells and the proliferative and differentiative abilities of satellite cells. The present review proposes physical activity as a useful measure for the patients in diabetes to improve the physiological functions and to maintain their quality of life. It further discusses the use of stem cell-based approaches in the context of diabetes treatment.

  5. Mild pulmonary emphysema a risk factor for interstitial lung disease when using cetuximab for squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Okamoto, Isaku; Tsukahara, Kiyoaki; Sato, Hiroki; Motohashi, Ray; Yunaiyama, Daisuke; Shimizu, Akira

    2017-12-01

    Interstitial lung disease (ILD) is an occasionally fatal adverse event associated with cetuximab (Cmab) therapy. Our objective was to clarify to what degree pulmonary emphysema is a risk factor in the treatment of head and neck cancer with Cmab through a retrospective analysis. Subjects were 116 patients who were administered Cmab for head and neck squamous cell carcinoma. The degree of pulmonary emphysema before initiating treatment with Cmab was visually assessed retrospectively, with scoring according to the Goddard classification used in Japanese chronic obstructive pulmonary disease (COPD) guidelines for chest computed tomography (CT). Scoring was conducted by two diagnostic radiologists and mean scores were used. Cutoffs for the development and nondevelopment of ILD were examined by receiver operating characteristic (ROC) analysis and Fisher's exact test. Values of p emphysema would represent a risk factor for ILD when using Cmab.

  6. Study of the relationship of dyspnea with depression and functional status in patients with interstitial lung disease

    Directory of Open Access Journals (Sweden)

    Hoda A. Abu Youssef

    2015-01-01

    Conclusion: Dyspnea is common in ILD and is strongly correlated with functional status and psychiatric disorders. Dyspnea score, functional status and psychiatric disorders are more affected in ILD with PHTN than in ILD without PHTN. Accordingly, routine screening for mental disorders is recommended for patients with ILD, and should be accompanied by accurate assessment of patient’s symptoms, particularly in patients with high levels of functional impairment.

  7. Acute Tubular Necrosis and Interstitial Nephritis during Pemetrexed Therapy

    Directory of Open Access Journals (Sweden)

    Judith Michels

    2009-03-01

    Full Text Available We report a patient with unknown primary undifferentiated carcinoma who developed acute renal failure associated with interstitial fibrosis following pemetrexed therapy. Despite drug withdrawal, renal function remained altered and the patient experienced chronic renal insufficiency. Pemetrexed disodium (Alimta™ is a multitargeted antifolate agent approved by the Food and Drug Administration (FDA for patients diagnosed with mesothelioma and non-small cell lung cancer. This drug is almost exclusively cleared by renal excretion [1]. The most common side effects are hematologic dose-limiting toxicities and nonhematologic toxicities including fatigue, diarrhea, nausea, mucositis and rash. Although few cases of renal failure have been published, no study has reported on the renal pathological findings in this setting. We present a case of acute tubular necrosis associated with interstitial fibrosis after pemetrexed therapy.

  8. Acute interstitial nephritis due to proton pump inhibitors

    Directory of Open Access Journals (Sweden)

    K Sampathkumar

    2013-01-01

    Full Text Available Proton pump inhibitors (PPI are commonly prescribed for dyspepsia and acid peptic disease. Acute interstitial nephritis (AIN is an uncommon though important side-effect of these classes of drugs. We describe four cases: three females and one male. PPIs implicated were pantoprazole in two, omeprazole and esomeprazole in one each. AIN developed after an average period of 4 weeks of drug therapy. The symptoms were vomiting, loin pain, and oliguria. Minimal proteinuria with pyuria were seen and the mean serum creatinine was 4.95 ± 4 mg/dl. Two patients required hemodialysis. Renal biopsy showed interstitial mononuclear, plasma cell and eosinophilic infiltrates in all cases. PPI was stopped and steroids were started in all. Renal recovery was total in two and partial in two. A high index of suspicion is required to diagnose PPI induced AIN. Renal biopsy for confirmation followed up by prompt steroid therapy results in renal functional improvement.

  9. DFT STUDY REVISES INTERSTITIAL CONFIGURATIONS IN HCP Zr

    Energy Technology Data Exchange (ETDEWEB)

    Samolyuk, German D [ORNL; Golubov, Stanislav I [ORNL; Osetskiy, Yury N [ORNL; Stoller, Roger E [ORNL

    2012-06-01

    Analysis of experimental result on microstructure evolution in irradiated Zr and alloys has demonstrated that available knowledge on self-interstitial defects in Zr is in contradiction. We therefore have initiated an extensive theoretical and modeling program to clarify this issue. In this report we present first ab initio calculations results of single SIA configurations in Zr. We demonstrate importance of simulations cell size, applied exchange-correlation functional and simulated c/a ratio. The results obtained demonstrate clearly that the most stable configurations are in basal plane and provide some evidences for enhanced interstitial transport along basal planes. The results obtained will be used in generation a new interatomic potential for Zr to be used in large-scale atomistic modeling of mechanisms relevant for radiation-induced microstructure evolution.

  10. Smoking-related interstitial lung diseases; Interstitielle Lungenerkrankungen bei Rauchern

    Energy Technology Data Exchange (ETDEWEB)

    Marten, K. [Technische Univ. Muenchen (Germany). Klinikum rechts der Isar, Inst. fuer Roentgendiagnostik

    2007-03-15

    The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis.

  11. Acute interstitial pneumonia

    International Nuclear Information System (INIS)

    Cuervo M, Francisco; Carrillo Bayona, Jorge; Ojeda, Paulina

    2004-01-01

    The paper refers to a 71 year-old patient, to who is diagnosed acute interstitial pneumonia; with square of 20 days of evolution of cough dry emetizant, fever, general uneasiness, migraine, progressive dyspnoea and lost of weight

  12. Interstitial Lung Disease

    Science.gov (United States)

    ... grouped together under the label of idiopathic interstitial pneumonias, the most common and deadly of which is idiopathic pulmonary fibrosis. Risk factors Factors that may make you more susceptible to ...

  13. Hunner-Type (Classic Interstitial Cystitis: A Distinct Inflammatory Disorder Characterized by Pancystitis, with Frequent Expansion of Clonal B-Cells and Epithelial Denudation.

    Directory of Open Access Journals (Sweden)

    Daichi Maeda

    Full Text Available Interstitial cystitis (IC is a chronic bladder disease with urinary frequency, bladder discomfort or bladder pain of unknown etiology. Based on cystoscopic findings, patients with IC are classified as either Hunner-type/classic IC (HIC, presenting with a specific Hunner lesion, or non-Hunner-type IC (NHIC, presenting with no Hunner lesion, but post-hydrodistension mucosal bleeding. Inflammatory cell infiltration, composed predominantly of lymphocytes, plasma cells and epithelial denudation, has in the past been documented as a major pathological IC finding. However, the significance of the pathological evaluation of IC, especially with regard to the difference between HIC and NHIC, has been downplayed in recent years. In this study, we performed immunohistochemical quantification of infiltrating T-lymphocytes, B-lymphocytes and plasma cells, and measured the amount of residual epithelium in urinary bladder biopsy specimens taken from patients with HIC and NHIC, and those with no IC, using image analysis software. In addition, in situ hybridization of the light chains was performed to examine clonal B-cell expansion. Lymphoplasmacytic infiltration was significantly more severe in HIC specimens than in NHIC specimens (P <0.0001. Substantial lymphoplasmacytic inflammation (≥200 cells/mm2 was observed in 93% of HIC specimens, whereas only 8% of NHIC specimens were inflamed. Plasmacytic infiltration was more prominent in HIC specimens compared with NHIC and non-IC cystitis specimens (P <0.005. Furthermore, expansion of light-chain-restricted B-cells was observed in 31% of cases of HIC. The amount of residual epithelium was decreased in HIC specimens compared with NHIC specimens and non-IC cystitis specimens (P <0.0001. These results suggest that NHIC and HIC are distinct pathological entities, with the latter characterized by pancystitis, frequent clonal B-cell expansion and epithelial denudation. An abnormality in the B-cell population may be

  14. Hunner-Type (Classic) Interstitial Cystitis: A Distinct Inflammatory Disorder Characterized by Pancystitis, with Frequent Expansion of Clonal B-Cells and Epithelial Denudation

    Science.gov (United States)

    Morikawa, Teppei; Kunita, Akiko; Ota, Yasunori; Katoh, Hiroto; Niimi, Aya; Nomiya, Akira; Ishikawa, Shumpei; Goto, Akiteru; Igawa, Yasuhiko; Fukayama, Masashi; Homma, Yukio

    2015-01-01

    Interstitial cystitis (IC) is a chronic bladder disease with urinary frequency, bladder discomfort or bladder pain of unknown etiology. Based on cystoscopic findings, patients with IC are classified as either Hunner-type/classic IC (HIC), presenting with a specific Hunner lesion, or non-Hunner-type IC (NHIC), presenting with no Hunner lesion, but post-hydrodistension mucosal bleeding. Inflammatory cell infiltration, composed predominantly of lymphocytes, plasma cells and epithelial denudation, has in the past been documented as a major pathological IC finding. However, the significance of the pathological evaluation of IC, especially with regard to the difference between HIC and NHIC, has been downplayed in recent years. In this study, we performed immunohistochemical quantification of infiltrating T-lymphocytes, B-lymphocytes and plasma cells, and measured the amount of residual epithelium in urinary bladder biopsy specimens taken from patients with HIC and NHIC, and those with no IC, using image analysis software. In addition, in situ hybridization of the light chains was performed to examine clonal B-cell expansion. Lymphoplasmacytic infiltration was significantly more severe in HIC specimens than in NHIC specimens (P <0.0001). Substantial lymphoplasmacytic inflammation (≥200 cells/mm2) was observed in 93% of HIC specimens, whereas only 8% of NHIC specimens were inflamed. Plasmacytic infiltration was more prominent in HIC specimens compared with NHIC and non-IC cystitis specimens (P <0.005). Furthermore, expansion of light-chain-restricted B-cells was observed in 31% of cases of HIC. The amount of residual epithelium was decreased in HIC specimens compared with NHIC specimens and non-IC cystitis specimens (P <0.0001). These results suggest that NHIC and HIC are distinct pathological entities, with the latter characterized by pancystitis, frequent clonal B-cell expansion and epithelial denudation. An abnormality in the B-cell population may be involved in the

  15. Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

    Directory of Open Access Journals (Sweden)

    Tada Harue

    2009-08-01

    Full Text Available Abstract Background In Japan, high incidences of interstitial lung disease (ILD and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC. We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. Findings We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0. ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%, of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD. Conclusion The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

  16. Lung structure-respiratory function relationships in experimentally-induced bronchiolitis, bronchopneumonia and interstitial pneumonia in rats

    International Nuclear Information System (INIS)

    Mauderly, J.L.; Madron, E. de; Harkema, J.R.

    1988-01-01

    Histopathology and respiratory function of rats with three different types and distributions of lower lung inflammation were compared to better understand lung structure-function relationships. Rats were exposed 21 h/day for 7 days to 0.8 ppm ozone (O 3 ), sham-exposed as controls, or given 5 mg/kg bacterial endotoxin either intratracheally (ITE) or intraperitoneally (IPE). Respiratory function was measured 24 h after the end of treatment, than the rats were sacrificed and the distribution of inflammation was evaluated morphometrically. Chronic centriacinar inflammation with formation of new respiratory bronchioles caused an obstructive functional impairment in the O 3 rats, which was clearly distinguished from the restrictive impairments resulting from acute inflammation in ITE and IPE rats. Only the magnitudes of changes related to the distribution of inflammation differentiated the ITE and IPE groups. Flow parameters previously thought sensitive to large airway resistance were changed in the O 3 rats. Alveolar luminal inflammatory exudate affected quasistatic compliance more than septal inflammation in ITE and IPE rats. Quasistatic chord compliance was the most sensitive of three indices of pressure-volume relationships. The findings in this study improve the basis for interpreting respiratory function changes of rats. (author)

  17. Chronic interstitial pneumonia with honeycombing in coal workers

    Energy Technology Data Exchange (ETDEWEB)

    Brichet, A.; Tonnel, A.B.; Brambilla, E.; Devouassoux, G.; Remy-Jardin, M.; Copin, M.C.; Wallaert, B. [A. Calmette Hospital, Lille (France)

    2002-10-01

    Coal worker's pneumoconiosis (CWP) results from coal mine dust inhalation. The paper reports the presence of a chronic interstitial pneumonia (CIP) with honeycombing in 38 cases of coal miners, with or without CWP. The 38 patients were selected on the basis of clinical criteria which are unusual in CWP, i.e. fine inspiratory crackles and severe dyspnea. There were 37 men and one woman; mean age was 67.5 {+-} 9.1 years. Thirty-two were smokers. Duration of exposure was 26.7 {+-} 9.9 years. All the patients had clinical examination, chest radiography, computed tomography (CT), lung function, laboratory investigations, wedged fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). In eight cases, lung specimens were obtained. Seventeen out of 38 had finger clubbing. 17 had radiological signs of CWP limited to the upper lobes or diffusely distributed. CT showed honeycombing (36 cases), and/or ground glass opacities (30 cases) with traction bronchiectasis (8 cases) predominant in the lower lobes. BAL analysis demonstrated an increased percentage of neutrophils (9.4% {+-} 6). Lung function showed a restrictive pattern associated with a decreased DLCO and hypoxemia. Lung specimens demonstrated in 2 cases a homogenous interstitial fibrosis of intra-alveolar septum with an accumulation of immune and inflammatory cells without temporal variation and with obvious honeycombing. The 6 other cases showed features of usual interstitial pneumonia. These cases, should alert other clinicians to a possible association between CIP with honeycombing and coal dust exposure, with or without associated CWP.

  18. Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal.

    Science.gov (United States)

    Durnin, Leonie; Lees, Andrea; Manzoor, Sheerien; Sasse, Kent C; Sanders, Kenton M; Mutafova-Yambolieva, Violeta N

    2017-11-01

    Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα + ) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit W /Kit W-v ( W/W v ) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD + )/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5'-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/W v , Nos1 -/- , and Prkg1 -/- mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/W v mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/W v mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric

  19. Involvement of MAPKs and PLC Pathways in Modulation of Pacemaking Activity by So-Cheong-Ryong-Tang in Interstitial Cells of Cajal from Murine Small Intestine

    Directory of Open Access Journals (Sweden)

    Min Woo Hwang

    2013-01-01

    Full Text Available Purpose. Interstitial cells of Cajal (ICCs are the pacemaker cells that generate slow waves in the gastrointestinal (GI tract. We have aimed to investigate the effects of Socheongryong-Tang (SCRT in ICCs from mouse’s small intestine. Methods. The whole-cell patch-clamp configuration was used to record membrane potentials from cultured ICCs. Intracellular Ca2+ ([Ca2+]i increase was studied in cultured ICCs using fura-2 AM. Results. ICCs generated pacemaker potentials in mouse’s small intestine. SCRT produced membrane depolarization in current clamp mode. Y25130 (5-HT3 receptor antagonist and RS39604 (5-HT4 receptor antagonist blocked SCRT-induced membrane depolarizations, whereas SB269970 (5-HT7 receptor antagonist did not. When GDP-β-S (1 mM was in the pipette solution, SCRT did not induce the membrane depolarizations. [Ca2+]i analysis showed that SCRT increased [Ca2+]i. In the presence of PD98059 (p42/44 MAPK inhibitor, SCRT did not produce membrane depolarizations. In addition, SB203580 (p38 MAPK inhibitor and JNK inhibitors blocked the depolarizations by SCRT in pacemaker potentials. Furthermore, the membrane depolarizations by SCRT were not inhibited by U-73122, an active phospholipase C (PLC inhibitor, but by U-73343, an inactive PLC inhibitor. Conclusion. These results suggest that SCRT might affect GI motility by the modulation of pacemaker activity through MAPKs and PLC pathways in the ICCs.

  20. Regulation of tumor invasion by interstitial fluid flow

    Science.gov (United States)

    Shieh, Adrian C.; Swartz, Melody A.

    2011-02-01

    The importance of the tumor microenvironment in cancer progression is undisputed, yet the significance of biophysical forces in the microenvironment remains poorly understood. Interstitial fluid flow is a nearly ubiquitous and physiologically relevant biophysical force that is elevated in tumors because of tumor-associated angiogenesis and lymphangiogenesis, as well as changes in the tumor stroma. Not only does it apply physical forces to cells directly, but interstitial flow also creates gradients of soluble signals in the tumor microenvironment, thus influencing cell behavior and modulating cell-cell interactions. In this paper, we highlight our current understanding of interstitial fluid flow in the context of the tumor, focusing on the physical changes that lead to elevated interstitial flow, how cells sense flow and how they respond to changes in interstitial flow. In particular, we emphasize that interstitial flow can directly promote tumor cell invasion through a mechanism known as autologous chemotaxis, and indirectly support tumor invasion via both biophysical and biochemical cues generated by stromal cells. Thus, interstitial fluid flow demonstrates how important biophysical factors are in cancer, both by modulating cell behavior and coupling biophysical and biochemical signals.

  1. Action potential generation in the small intestine of W mutant mice that lack interstitial cells of Cajal

    DEFF Research Database (Denmark)

    Malysz, J; Thuneberg, L; Mikkelsen, Hanne Birte

    1996-01-01

    + channel blockade evoked the typical spikelike action potentials. Electron microscopy identified few methylene blue-positive cells in the W/Wv small intestine associated with Auerbach's plexus as individual ICC. Numbers of resident macrophage-like cells (MLC) and fibroblast-like cells (FLC) were...

  2. Effect of Wortmannin on the repair profiles of DNA double-strand breaks in the whole genome and in interstitial telomeric sequences of Chinese hamster cells

    International Nuclear Information System (INIS)

    Losada, Raquel; Rivero, Maria Teresa; Slijepcevic, Predrag; Goyanes, Vicente; Fernandez, Jose Luis

    2005-01-01

    The DNA breakage detection-fluorescence in situ hybridization (DBD-FISH) procedure was applied to analyze the effect of Wortmannin (WM) in the rejoining kinetics of ionizing radiation-induced DNA double-strand breaks (DSBs) in the whole genome and in the long interstitial telomeric repeat sequence (ITRS) blocks from Chinese hamster cell lines. The results indicate that the ITRS blocks from wild-type Chinese hamster cell lines, CHO9 and V79B, exhibit a slower initial rejoining rate of ionizing radiation-induced DSBs than the genome overall. Neither Rad51C nor the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) activities, involved in homologous recombination (HR) and in non-homologous end-joining (NHEJ) pathways of DSB repair respectively, influenced the rejoining kinetics within ITRS in contrast to DNA sequences in the whole genome. Nevertheless, DSB removal rate within ITRS was decreased in the absence of Ku86 activity, though at a lower affectation level than in the whole genome, thus homogenizing both rejoining kinetics rates. WM treatment slowed down the DSB rejoining kinetics rate in ITRS, this effect being more pronounced in the whole genome, resulting in a similar pattern to that of the Ku86 deficient cells. In fact, no WM effect was detected in the Ku86 deficient Chinese hamster cells, so probably WM does not add further impairment in DSB rejoining than that resulted as a consequence of absence of Ku activity. The same slowing effect was also observed after treatment of Rad51C and DNA-PKcs defective hamster cells by WM, suggesting that: (1) there is no potentiation of the HR when the NHEJ is impaired by WM, either in the whole genome or in the ITRS, and (2) that this impairment may probably involve more targets than DNA-PKcs. These results suggest that there is an intragenomic heterogeneity in DSB repair, as well as in the effect of WM on this process

  3. Regulation of tumor invasion by interstitial fluid flow

    International Nuclear Information System (INIS)

    Shieh, Adrian C; Swartz, Melody A

    2011-01-01

    The importance of the tumor microenvironment in cancer progression is undisputed, yet the significance of biophysical forces in the microenvironment remains poorly understood. Interstitial fluid flow is a nearly ubiquitous and physiologically relevant biophysical force that is elevated in tumors because of tumor-associated angiogenesis and lymphangiogenesis, as well as changes in the tumor stroma. Not only does it apply physical forces to cells directly, but interstitial flow also creates gradients of soluble signals in the tumor microenvironment, thus influencing cell behavior and modulating cell–cell interactions. In this paper, we highlight our current understanding of interstitial fluid flow in the context of the tumor, focusing on the physical changes that lead to elevated interstitial flow, how cells sense flow and how they respond to changes in interstitial flow. In particular, we emphasize that interstitial flow can directly promote tumor cell invasion through a mechanism known as autologous chemotaxis, and indirectly support tumor invasion via both biophysical and biochemical cues generated by stromal cells. Thus, interstitial fluid flow demonstrates how important biophysical factors are in cancer, both by modulating cell behavior and coupling biophysical and biochemical signals

  4. Atomic displacements due to interstitial hydrogen in Cu and Pd

    Indian Academy of Sciences (India)

    Abstract. The density functional theory (DFT) is used to study the atomic interac- tions in transition metal-based interstitial alloys. The strain field is calculated in the discrete lattice model using Kanzaki method. The total energy and hence atomic forces between interstitial hydrogen and transition metal hosts are calculated ...

  5. Involvement of cyclic nucleotide-gated channels in spontaneous activity generated in isolated interstitial cells of Cajal from the rabbit urethra.

    Science.gov (United States)

    Sancho, Maria; Bradley, Eamonn; Garcia-Pascual, Angeles; Triguero, Domingo; Thornbury, Keith D; Hollywood, Mark A; Sergeant, Gerard P

    2017-11-05

    Cyclic nucleotide-gated (CNG) channels are non-selective cation channels that mediate influx of extracellular Na + and Ca 2+ in various cell types. L-cis-Diltiazem, a CNG channel blocker, inhibits contraction of urethral smooth muscle (USM), however the mechanisms underlying this effect are still unclear. We investigated the possibility that CNG channels contribute to spontaneous pacemaker activity in freshly isolated interstitial cells of Cajal (ICC) isolated from the rabbit urethra (RUICC). Using immunocytochemistry, we found intense CNG1-immunoreactivity in vimentin-immunoreactive RUICC, mainly within patches of the cellular body and processes. In contrast, α-actin immunoreactive smooth muscle cells (SMC) did not show significant reactivity to a specific CNGA1 antibody. Freshly isolated RUICC, voltage clamped at -60mV, developed spontaneous transient inward currents (STICs) that were inhibited by L-cis-Diltiazem (50µM). Similarly, L-cis-Diltiazem (50µM) also inhibited Ca 2+ waves in isolated RUICC, recorded using a Nipkow spinning disk confocal microscope. L-cis-Diltiazem (50µM) did not affect caffeine (10mM)-induced Ca 2+ transients, but significantly reduced phenylephrine-evoked Ca 2+ oscillations and inward currents in in RUICC. L-type Ca 2+ current amplitude in isolated SMC was reduced by ~18% in the presence of L-cis-Diltiazem (50µM), however D-cis-Diltiazem, a recognised L-type Ca 2+ channel blocker, abolished L-type Ca 2+ current but did not affect Ca 2+ waves or STICs in RUICC. These results indicate that the effects of L-cis-diltiazem on rabbit USM could be mediated by inhibition of CNG1 channels that are present in urethral ICC and therefore CNG channels contribute to spontaneous activity in these cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells.

    Science.gov (United States)

    Thé, Torriceli Souza; Portella, Renata Siqueira; Guerreiro, Marcos Lázaro; Andrade, Sonia Gumes

    2013-09-01

    Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH) has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs) in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

  7. Interstitial Cystitis / Painful Bladder Syndrome

    Science.gov (United States)

    ... Vesicoureteral Reflux The Urinary Tract & How It Works Interstitial Cystitis (Painful Bladder Syndrome) View or Print All Sections Definition & Facts Interstitial cystitis (IC) is a chronic, or long-lasting, condition ...

  8. Sexual Dysfunction in Interstitial Cystitis.

    Science.gov (United States)

    Tonyali, Senol; Yilmaz, Mehmet

    2017-11-01

    Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a debilitating disease characterized with urgency, frequency, and pelvic pain affecting especially women. Sexual dysfunction in female patients with IC/BPS consists of dyspareunia, altered sexual desire and orgasm frequency and insufficient lubrication is reported to negatively affect the patient's quality of life. In the present study, we aimed to determine the association between IC/BPS and sexual dysfunction and improvement in sexual dysfunction related to given treatments. A PubMed/Medline and EMBASE search was conducted using keywords: "interstitial cystitis", "sexual dysfunction", and "bladder pain syndrome". Several studies have been conducted to determine the relation between IC/BPS and sexual dysfunction. And also limited studies focusing on IC/BPS specific treatments reported significant improvements in sexual function after either oral or intravesical treatment. However, given the used different questionnaires, study protocols, patient characteristics, previous treatments and follow-up period, it is not possible to make a head-to-head comparison of the treatment effects on sexual function. Further, randomized controlled studies are needed to confirm these results and make a comparison between effects of various treatment modalities on sexual functioning in IC/BPS.

  9. Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia

    Czech Academy of Sciences Publication Activity Database

    Bolar, N. A.; Golzio, C.; Živná, M.; Hayot, G.; Van Hemelrijk, C.; Schepers, D.; Vandeweyer, G.; Hoischen, A.; Huyghe, J. R.; Raes, A.; Matthys, E.; Sys, E.; Azou, M.; Gubler, M. C.; Praet, M.; Van Camp, G.; McFadden, K.; Pediaditakis, I.; Přistoupilová, A.; Hodaňová, K.; Vyleťal, P.; Hartmannová, H.; Stránecký, V.; Hůlková, H.; Barešová, V.; Jedličková, I.; Sovová, J.; Hnízda, Aleš; Kidd, K.; Bleyer, A. J.; Spong, R. S.; Vande Walle, J.; Mortier, G.; Brunner, H.; Van Laer, L.; Kmoch, S.; Katsanis, N.; Loeys, B. L.

    2016-01-01

    Roč. 99, č. 1 (2016), s. 174-187 ISSN 0002-9297 R&D Projects: GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : Sec61 * tubulo-interstitial kidney disease * rare disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.025, year: 2016 http://www.sciencedirect.com/science/article/pii/S0002929716301999

  10. Interstitial granulomatous dermatitis (IGD)

    NARCIS (Netherlands)

    Tebeica, Tiberiu; Voicu, Cristiana; Patterson, James W.; Mangarov, Hristo; Lotti, T.; Wollina, Uwe; Lotti, Jacopo; França, Katlein; Batashki, Atanas; Tchernev, Georgi

    2017-01-01

    We report the case of a 42 years old male patient suffering from skin changes, which appeared in the last 7-8 years. Two biopsies were performed during the evolution of the lesion. Both showed similar findings that consisted in a busy dermis with interstitial, superficial and deep infiltrates of

  11. Role of mitochondria in modulation of spontaneous Ca2+ waves in freshly dispersed interstitial cells of Cajal from the rabbit urethra.

    Science.gov (United States)

    Sergeant, Gerard P; Bradley, Eamonn; Thornbury, Keith D; McHale, Noel G; Hollywood, Mark A

    2008-10-01

    Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit pacemaker activity that results from spontaneous Ca(2+) waves. The purpose of this study was to investigate if this activity was influenced by Ca(2+) uptake into mitochondria. Spontaneous Ca(2+) waves were recorded using a Nipkow spinning disk confocal microscope and spontaneous transient inward currents (STICs) were recorded using the whole-cell patch clamp technique. Disruption of the mitochondrial membrane potential with the electron transport chain inhibitors rotenone (10 microm) and antimycin A (5 microm) abolished Ca(2+) waves and increased basal Ca(2+) levels. Similar results were achieved when mitochondria membrane potential was collapsed using the protonophores FCCP (0.2 microm) and CCCP (1 microm). Spontaneous Ca(2+) waves were not inhibited by the ATP synthase inhibitor oligomycin (1 microm), suggesting that these effects were not attributable to an effect on ATP levels. STICs recorded under voltage clamp at -60 mV were also inhibited by CCCP and antimycin A. Dialysis of cells with the mitochondrial uniporter inhibitor RU360 (10 microm) also inhibited STICS. Stimulation of Ca(2+) uptake into mitochondria using the plant flavonoid kaempferol (10 microm) induced a series of propagating Ca(2+) waves. The kaempferol-induced activity was inhibited by application of caffeine (10 mm) or removal of extracellular Ca(2+), but was not significantly affected by the IP(3) receptor blocker 2-APB (100 microm). These data suggest that spontaneous Ca(2+) waves in urethral ICC are regulated by buffering of cytoplasmic Ca(2+) by mitochondria.

  12. Role of mitochondria in modulation of spontaneous Ca2+ waves in freshly dispersed interstitial cells of Cajal from the rabbit urethra

    Science.gov (United States)

    Sergeant, Gerard P; Bradley, Eamonn; Thornbury, Keith D; McHale, Noel G; Hollywood, Mark A

    2008-01-01

    Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit pacemaker activity that results from spontaneous Ca2+ waves. The purpose of this study was to investigate if this activity was influenced by Ca2+ uptake into mitochondria. Spontaneous Ca2+ waves were recorded using a Nipkow spinning disk confocal microscope and spontaneous transient inward currents (STICs) were recorded using the whole-cell patch clamp technique. Disruption of the mitochondrial membrane potential with the electron transport chain inhibitors rotenone (10 μm) and antimycin A (5 μm) abolished Ca2+ waves and increased basal Ca2+ levels. Similar results were achieved when mitochondria membrane potential was collapsed using the protonophores FCCP (0.2 μm) and CCCP (1 μm). Spontaneous Ca2+ waves were not inhibited by the ATP synthase inhibitor oligomycin (1 μm), suggesting that these effects were not attributable to an effect on ATP levels. STICs recorded under voltage clamp at −60 mV were also inhibited by CCCP and antimycin A. Dialysis of cells with the mitochondrial uniporter inhibitor RU360 (10 μm) also inhibited STICS. Stimulation of Ca2+ uptake into mitochondria using the plant flavonoid kaempferol (10 μm) induced a series of propagating Ca2+ waves. The kaempferol-induced activity was inhibited by application of caffeine (10 mm) or removal of extracellular Ca2+, but was not significantly affected by the IP3 receptor blocker 2-APB (100 μm). These data suggest that spontaneous Ca2+ waves in urethral ICC are regulated by buffering of cytoplasmic Ca2+ by mitochondria. PMID:18703577

  13. Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease

    Science.gov (United States)

    Wallace, Darren P.; White, Corey; Savinkova, Lyudmyla; Nivens, Emily; Reif, Gail A.; Pinto, Cibele S.; Raman, Archana; Parnell, Stephen C.; Conway, Simon J.; Fields, Timothy A.

    2013-01-01

    In renal cystic diseases, sustained enlargement of fluid-filled cysts is associated with severe interstitial fibrosis and progressive loss of functioning nephrons. Periostin, a matricellular protein, is highly overexpressed in cyst-lining epithelial cells of autosomal dominant polycystic disease kidneys (ADPKD) compared to normal tubule cells. Periostin accumulates in situ within the matrix subjacent to ADPKD cysts, binds to αVβ3- and αVβ5-integrins and stimulates the integrin-linked kinase to promote cell proliferation. We knocked out periostin (Postn) in pcy/pcy mice, an orthologous model of nephronophthisis type 3, to determine whether periostin loss reduces PKD progression in a slowly progressive model of renal cystic disease. At 20 weeks of age, pcy/pcy: Postn−/− mice had a 34% reduction in kidney weight/body weight, a reduction in cyst number and total cystic area, a 69% reduction in phosphorylated S6, a downstream component of the mTOR pathway, and fewer proliferating cells in the kidneys compared to pcy/pcy: Postn+/+ mice. The pcy/pcy Postn knockout mice also had less interstitial fibrosis with improved renal function at 20 weeks and significantly longer survival (51.4 compared to 38.0 weeks). Thus, periostin adversely modifies the progression of renal cystic disease by promoting cyst epithelial cell proliferation, cyst enlargement and interstitial fibrosis, all contributing to the decline in renal function and premature death. PMID:24284511

  14. Influence of interstitial Mn on magnetism in room-temperature ferromagnet Mn(1+delta)Sb

    OpenAIRE

    Taylor, A. E.; Berlijn, T.; Hahn, S. E.; May, A. F.; Williams, T. J.; Poudel, L.; Calder, S.; Fishman, R. S.; Stone, M. B.; Aczel, A. A.; Cao, H. B.; Lumsden, M. D.; Christianson, A. D.

    2015-01-01

    We report elastic and inelastic neutron scattering measurements of the high-TC ferromagnet Mn(1+delta)Sb. Measurements were performed on a large, TC=434 K, single crystal with interstitial Mn content of delta~0.13. The neutron diffraction results reveal that the interstitial Mn has a magnetic moment, and that it is aligned antiparallel to the main Mn moment. We perform density functional theory calculations including the interstitial Mn, and find the interstitial to be magnetic in agreement w...

  15. Effects of new-generation TMEM16A inhibitors on calcium-activated chloride currents in rabbit urethral interstitial cells of Cajal.

    Science.gov (United States)

    Fedigan, Stephen; Bradley, Eamonn; Webb, Timothy; Large, Roddy J; Hollywood, Mark A; Thornbury, Keith D; McHale, Noel G; Sergeant, Gerard P

    2017-11-01

    Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit Ca 2+ -activated Cl - currents (I ClCa ) that are important for the development of urethral tone. Here, we examined if TMEM16A (ANO1) contributed to this activity by examining the effect of "new-generation" TMEM16A inhibitors, CACC inh -A01 and T16A inh -A01, on I ClCa recorded from freshly isolated rabbit urethral ICC (RUICC) and on contractions of intact strips of rabbit urethra smooth muscle. Real-time quantitative PCR experiments demonstrated that TMEM16A was highly expressed in rabbit urethra smooth muscle, in comparison to TMEM16B and TMEM16F. Single-cell RT-PCR experiments revealed that only TMEM16A was expressed in freshly isolated RUICC. Depolarization-evoked I ClCa in isolated RUICC, recorded using voltage clamp, were inhibited by CACC inh -A01 and T16A inh -A01 with IC 50 values of 1.2 and 3.4 μM, respectively. Similarly, spontaneous transient inward currents (STICs) recorded from RUICC voltage clamped at -60 mV and spontaneous transient depolarizations (STDs), recorded in current clamp, were also inhibited by CACC inh -A01 and T16A inh -A01. In contrast, spontaneous Ca 2+ waves in isolated RUICC were only partially reduced by CACC inh -A01 and T16A inh -A01. Finally, neurogenic contractions of strips of rabbit urethra smooth muscle (RUSM), evoked by electric field stimulation (EFS), were also significantly reduced by CACC inh -A01 and T16A inh -A01. These data are consistent with the idea that TMEM16A is involved with CACCs in RUICC and in contraction of rabbit urethral smooth muscle.

  16. The protective effects of total phenols in magnolia officinalix rehd. et wils on gastrointestinal tract dysmotility is mainly based on its influence on interstitial cells of cajal

    Science.gov (United States)

    Tian, Hui; Huang, Dazhi; Li, Tao; Huang, Lihua; Zheng, Xingguang; Tang, Danxia; Zhang, Lu; Wang, Jian

    2015-01-01

    Magnolia officinalix Rehd. et Wils is a kind of herb which is widely used for gastrointestinal tract mobility disorder in Asian countries. In this study, we investigated whether the total phenols of Magnolia officinalix Rehd. et Wils (TPM) treatment improves gastrointestinal tract dysmobility induced by intraperitoneal injection of atropine (5 mg/kg) in rats. Rats were randomly grouped into three units: TPM-pretreated/atropine-treated group, atropinetreated group and control group. TPM were administrated for 7 days. Gastric residual rate and intestinal transit were measured 20 min after atropine injected, and gastrointestinal hormones (including: gastrin (GAS), motilin (MTL), somatostatin (SS) and p substance (PS) levels in serum were also measured by ELISA kits. The number and distribution of interstitial cells of Cajal (ICCs) in stomach were detected by immunohistochemistry analysis, while c-kit and stem cell factor (SCF) expressions in stomach were also measured by western blotting. We found that TPM pretreatment significantly improved atropine-induced gastric residual rate increase, while had no significantly effects on intestinal transit; it also significantly normalized GAS, MTL and PS serum levels. Atropine-induced ICCs numbers decreased in both sinuses ventriculi and body of stomach, which is improved by TPM pretreatment. Western blotting results showed the expressions of c-kit and SCF were down-regulated after atropine injection, which can be reversed with TPM pretreatment. These results above indicates that TPM treatment can significantly protected atropine-induced gastric dysmoblility, which may owed to its regulation on c-kit/SCF signing pathway. PMID:26884941

  17. 3-D illustration of network orientations of interstitial cells of Cajal subgroups in human colon as revealed by deep-tissue imaging with optical clearing.

    Science.gov (United States)

    Liu, Yuan-An; Chung, Yuan-Chiang; Pan, Shien-Tung; Hou, Yung-Chi; Peng, Shih-Jung; Pasricha, Pankaj J; Tang, Shiue-Cheng

    2012-05-15

    Morphological changes of interstitial cells of Cajal (ICC) have been proposed to characterize motility disorders. However, a global view of the network orientations of ICC subgroups has not been established to illustrate their three-dimensional (3-D) architectures in the human colon. In this research, we integrate c-kit immunostaining, 3-D microscopy with optical clearing, and image rendering to present the location-dependent network orientations with high definition. Full-depth colonic tissues were obtained from colectomies performed for nonobstructing carcinoma. Specimens of colon wall were prepared away from the tumor site. C-kit and nuclear fluorescent staining were used to identify the ICC processes and cell body. Optical clearing was used to generate transparent colon specimens, which led to panoramic visualization of the fluorescence-labeled ICC networks at the myenteric plexus (ICC-MY), longitudinal (ICC-LM) and circular (ICC-CM) muscles, and submucosal boundary (ICC-SM) up to 300 μm in depth via confocal microscopy with subcellular level resolution. We observed four distinct network patterns: 1) periganglionic ICC-MY that connect with ICC-LM and ICC-CM, 2) plexuses of ICC-LM within the longitudinal muscle and extending toward the serosa, 3) repetitive and organized ICC-CM layers running parallel to the circular muscle axis and extending toward the submucosa, and 4) a condensed ICC-SM layer lining the submucosal border. Among the four patterns, the orderly aligned ICC-CM layers provide an appropriate target for quantitation. Our results demonstrate the location-dependent network orientations of ICC subgroups and suggest a practical approach for in-depth imaging and quantitative analysis of ICC in the human colon specimen.

  18. Basement membrane and interstitial proteoglycans produced by MDCK cells correspond to those expressed in the kidney cortex

    DEFF Research Database (Denmark)

    Erickson, A C; Couchman, J R

    2001-01-01

    ) cells has been utilized. Proteoglycans were prepared from conditioned medium by DEAE anion exchange chromatography. The eluted PGs were treated with heparitinase or chondroitinase ABC (cABC), separately or combined, followed by SDS-PAGE. Western blot analysis, using antibodies specific for various PG...

  19. [Signaling network-based functional cell design].

    Science.gov (United States)

    Ju, Jianqi; Wei, Ping

    2017-03-25

    Cellular signaling networks act as the central processor to deal with environmental signals and regulate cell function, and determine cell fate. Using synthetic biology approach to engineer cell signaling networks is crucial for ultimately constructing man-made "cell machines". Cellular signaling networks can encode sophisticated cell information by processing quantitatively signaling dynamics, which enables multi-dimensional regulation of functional sub-circuits. Here, we first review the research progresses on the signaling coding mechanisms; and then elaborate the methodologies and applications of cells signaling engineering; finally, we envision that signaling-based cell engineering are important for the increasingly-complicated next generation synthetic biology.

  20. PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells.

    Science.gov (United States)

    Juliano, Celina E; Reich, Adrian; Liu, Na; Götzfried, Jessica; Zhong, Mei; Uman, Selen; Reenan, Robert A; Wessel, Gary M; Steele, Robert E; Lin, Haifan

    2014-01-07

    PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) are found in animal germlines and are essential for fertility, but their functions outside of the gonad are not well understood. The cnidarian Hydra is a simple metazoan with well-characterized stem/progenitor cells that provides a unique model for analysis of PIWI function. Here we report that Hydra has two PIWI proteins, Hydra PIWI (Hywi) and Hydra PIWI-like (Hyli), both of which are expressed in all Hydra stem/progenitor cells, but not in terminally differentiated cells. We identified ∼15 million piRNAs associated with Hywi and/or Hyli and found that they exhibit the ping-pong signature of piRNA biogenesis. Hydra PIWI proteins are strictly cytoplasmic and thus likely act as posttranscriptional regulators. To explore this function, we generated a Hydra transcriptome for piRNA mapping. piRNAs map to transposons with a 25- to 35-fold enrichment compared with the abundance of transposon transcripts. By sequencing the small RNAs specific to the interstitial, ectodermal, and endodermal lineages, we found that the targeting of transposons appears to be largely restricted to the interstitial lineage. We also identified putative nontransposon targets of the pathway unique to each lineage. Finally we demonstrate that hywi function is essential in the somatic epithelial lineages. This comprehensive analysis of the PIWI-piRNA pathway in the somatic stem/progenitor cells of a nonbilaterian animal suggests that this pathway originated with broader stem cell functionality.

  1. Interventional MR: interstitial therapy

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J.; Mack, M.G.; Straub, R.; Engelmann, K.; Eichler, K. [Dept. of Diagnostic and Interventional Radiology, Johann Wolfgang Goethe University, Frankfurt am Main (Germany); Mueller, P.K. [Department of Radiology, Virchow, Humboldt Univ. of Berlin (Germany)

    1999-10-01

    The rationale and results for interstitial therapies via interventional MRI in the treatment of tumors in various regions are presented. Different interstitial treatment techniques are presented based on varying technologies both for tumor ablation and treatment monitoring. Data are presented based on 335 patients, 29-84 years of age (mean age 59 years, 196 men and 139 women) with a total of 932 liver tumors, 16 head and neck tumors and 14 abdominal recurrent pelvic and lymphatic tumors. All lesions had been treated with MR-guided laser-induced interstitial thermotherapy (LITT) via 2516 laser applications and 1856 cannulations. Data in the literature are extremely varying depending on author experience, treatment technique, and the included patient material. In our patient material we were able to achieve a local tumor control of 96.7 % depending on the size of the tumorous lesion, the topographical relationship, and the applied laser parameters. The overall cumulative survival rate of patients with liver metastases was 45.74 months (median 40.97 months, 95 % confidence interval 31.42-50.52). The cumulative survival rate of the patient group with hepatic metastases of colorectal carcinoma was 42.71 months (median 39.33 months, 95 % confidence interval 33.26-45.37). In patients with head and neck tumors a relevant reduction in clinically relevant symptoms such as pain, swallowing disorders, or nervous compression was achieved in 11 of 15 patients treated with LITT. In 14 soft tissue tumors, such as pelvic tumor recurrence and lymph node metastases, a local tumor control was obtained in 68 % of lesions. Interstitial therapies under interventional MRI guidance, such as LITT, results in a high local tumor control with an improved survival rate. (orig.) With 7 figs., 28 refs.

  2. Are interstitial cells of Cajal involved in mechanical stress-induced gene expression and impairment of smooth muscle contractility in bowel obstruction?

    Directory of Open Access Journals (Sweden)

    Chester C Wu

    Full Text Available The network of interstitial cells of Cajal (ICC is altered in obstructive bowel disorders (OBD. However, whether alteration in ICC network is a cause or consequence of OBD remains unknown. This study tested the hypothesis that mechanical dilation in obstruction disrupts the ICC network and that ICC do not mediate mechanotranscription of COX-2 and impairment of smooth muscle contractility in obstruction.Medical-grade silicon bands were wrapped around the distal colon to induce partial obstruction in wild-type and ICC deficient (W/W(v mice.In wild-type mice, colon obstruction led to time-dependent alterations of the ICC network in the proximal colon segment. Although unaffected on days 1 and 3, the ICC density decreased markedly and the network was disrupted on day 7 of obstruction. COX-2 expression increased, and circular muscle contractility decreased significantly in the segment proximal to obstruction. In W/W(v control mice, COX-2 mRNA level was 4.0 (±1.1-fold higher (n=4 and circular muscle contractility was lower than in wild-type control mice. Obstruction further increased COX-2 mRNA level in W/W(v mice to 7.2 (±1.0-fold vs. W/W(v controls [28.8 (±4.1-fold vs. wild-type controls] on day 3. Obstruction further suppressed smooth muscle contractility in W/W(v mice. However, daily administration of COX-2 inhibitor NS-398 significantly improved muscle contractility in both W/W(v sham and obstruction mice.Lumen dilation disrupts the ICC network. ICC deficiency has limited effect on stretch-induced expression of COX-2 and suppression of smooth muscle contractility in obstruction. Rather, stretch-induced COX-2 plays a critical role in motility dysfunction in partial colon obstruction.

  3. Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease.

    Science.gov (United States)

    Kashiwabara, Kosuke; Semba, Hiroshi; Fujii, Shinji; Tsumura, Shinsuke

    2017-04-01

    Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome. We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not. EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5 mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5 months, p = 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone. EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.

  4. Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in Patients with Juvenile Dermatomyositis.

    Science.gov (United States)

    Kobayashi, Norimoto; Kobayashi, Ichiro; Mori, Masaaki; Sato, Shinji; Iwata, Naomi; Shigemura, Tomonari; Agematsu, Kazunaga; Yokota, Shumpei; Koike, Kenichi

    2015-12-01

    Rapidly progressive interstitial lung disease (RP-ILD) is an intractable and fatal complication of juvenile dermatomyositis (JDM). This study evaluated serum levels of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in JDM patients with complicating ILD, and their association with ILD phenotypes, clinical variables, and anti-melanoma differentiation-associated gene 5 (MDA5). We measured the levels of BAFF, APRIL, and anti-MDA5 in the sera of 23 JDM patients with ILD [8 in the RP-ILD group and 15 in the chronic ILD (C-ILD) group], 17 JDM patients without ILD (non-ILD group), and 10 age-matched controls, using the ELISA method. ILD was identified by high-resolution computed tomography. Serum BAFF titers were significantly higher in the JDM patients with RP-ILD versus those with C-ILD (p = 0.011) and in healthy controls (p = 0.0004). The C-ILD group had significantly higher levels of BAFF versus controls (p ≤ 0.0001). Serum APRIL was markedly elevated in the RP-ILD group as compared with the C-ILD group (p = 0.003) and controls (p = 0.006). In patients with ILD, both BAFF and APRIL levels were correlated with serum Krebs von den Lungen-6 and interleukin 18. Subjects with high titer anti-MDA5 (> 200 U) had higher levels of BAFF and APRIL than those with low titer anti-MDA5 (< 100 U; p = 0.019 and p = 0.0029, respectively), which may have been due to a relationship between RP-ILD and high anti-MDA5 titer. Our findings of markedly elevated levels of BAFF and APRIL in patients with RP-ILD JDM suggest the potential importance of these cytokines in the diagnosis and treatment of RP-ILD accompanying JDM.

  5. Correlation between pretreatment or follow-up CT findings and therapeutic effect of autologous peripheral blood stem cell transplantation for interstitial pneumonia associated with systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Yabuuchi, Hidetake, E-mail: yabuuchi@shs.kyushu-u.ac.jp [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Matsuo, Yoshio [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tsukamoto, Hiroshi [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sunami, Shunya; Kamitani, Takeshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sakai, Shuji [Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hatakenaka, Masamitsu [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Nagafuji, Koji; Horiuchi, Takahiko; Harada, Mine; Akashi, Koichi [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2011-08-15

    Purpose: To evaluate what is useful among various parameters including CT findings, laboratory parameters (%VC, %DLco, KL-6), patients related data (age, sex, duration of disease) to discriminate between responder and non-responder in patients who received autologous peripheral blood stem cell transplantation (auto-PBSCT) for interstitial pneumonia (IP) with systemic sclerosis (SSc). Method: Auto-PBSCT and follow-up of at least one year by chest CT, serum KL-6, %VC, and %DLco were performed in 15 patients for IP with SSc. Analyzed CT findings included extent of ground-glass opacity (GGO), intralobular reticular opacity, number of segments that showed traction bronchiectasis, and presence of honeycombing. We regarded the therapeutic response of patients as responders when TLC or VC increase over 10% or DLco increase more than 15%, otherwise we have classified as non-responder. We applied univariate and multivariate analyses to find the significant indicators to discriminate responders from non-responders. P < 0.05 was considered statistically significant. Results: Univariate and multivariate analyses showed that the significant parameter to discriminate responders from non-responders were pretreatment KL-6, presence of honeycombing, extent of GGO, and early change in extent of GGO. Among them, extent of GGO and early change in extent of GGO were the strongest discriminators between responders and non-responders (P = 0.001, 0.001, respectively). Conclusion: Several CT findings and pretreatment KL-6 may be useful to discriminate between responder and non-responder in patients who received auto-PBSCT for IP with SSc.

  6. Autopsy findings in a case of a small cell lung cancer complicated by radiotherapy induced acute interstitial pneumonia

    International Nuclear Information System (INIS)

    Umeki, Shigenori; Hirokawa, Mitsuyoshi

    1993-01-01

    The authors describe the case of a 71-year-old man who had been referred to his hospital because of a dry cough and an associated abnormality that had been detected by x-ray. Based on chest x-ray evaluations and the endoscopic bronchial biopsy findings the diagnosis was a small cell lung cancer. The patient thus received a 2 time regimen of cisplatin chemotherapy and subsequent radiotherapy (40 Gy). Two weeks after this radiotherapy, however the patient complained of an increasing dyspnea. Two days later, he was readmitted to hospital because of pneumonia and severe dyspnea, but died of respiratory failure on the same day. The autopsy findings revealed diffuse organized alveolar duct damage that had been induced by radiotherapy directed toward a relatively large area that included the right lower lung and the mediastinum. (author)

  7. Interstitial line: sonographic finding in interstitial (cornual) ectopic pregnancy.

    Science.gov (United States)

    Ackerman, T E; Levi, C S; Dashefsky, S M; Holt, S C; Lindsay, D J

    1993-10-01

    To evaluate the relationship of the endometrial canal and decidua vera to the interstitial gestational sac and to determine if this relationship can be used to increase the predictive value of ultrasound (US) in the diagnosis of interstitial ectopic pregnancy. The US findings in 12 patients with interstitial ectopic pregnancy were reviewed. Radiologists also reviewed the cases of 40 patients with various diagnoses to assess the accuracy of the interstitial line sign. US showed a definite gestational sac in four of the 12 patients (33%); the rest had a heterogeneous mass in the cornual region. Thinning of the myometrial mantle was seen in these four patients. The gestational sac appeared eccentric in three of these but in only three of 12 (25%) overall. The endometrial canal or interstitial portion of the tube was identified in 11 of 12 patients (92%). The interstitial line had better sensitivity (80%) and specificity (98%) than eccentric gestational sac location (sensitivity, 40%; specificity, 88%) and myometrial thinning (sensitivity, 40%; specificity, 93%) for the diagnosis of interstitial ectopic pregnancy. The interstitial line sign is a useful diagnostic sign of interstitial ectopic pregnancy.

  8. Magnetic effects of interstitial hydrogen in nickel

    Energy Technology Data Exchange (ETDEWEB)

    León, Andrea [Departamento de Física, Universidad Técnica Federico Santa María, Valparaíso (Chile); Velásquez, E.A. [Facultad de Física y Centro de Investigación en Nanotecnología y Materiales Avanzados CIEN-UC, Pontificia Universidad Católica de Chile, Santiago (Chile); Centro para el Desarrollo de la Nanociencia y la Nanotecnología CEDENNA, Santiago (Chile); Grupo de Investigación en Modelamiento y Simulación Computacional, Universidad de San Buenaventura Sec. Medellín, Medellín (Colombia); Mazo-Zuluaga, J. [Grupo de Instrumentación Científica y Microelectrónica, Grupo de Estado Sólido, IF-FCEN, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín (Colombia); Mejía-López, J. [Facultad de Física y Centro de Investigación en Nanotecnología y Materiales Avanzados CIEN-UC, Pontificia Universidad Católica de Chile, Santiago (Chile); Centro para el Desarrollo de la Nanociencia y la Nanotecnología CEDENNA, Santiago (Chile); Florez, J.M. [Departamento de Física, Universidad Técnica Federico Santa María, Valparaíso (Chile); and others

    2017-01-01

    Hydrogen storage in materials is among the most relevant fields when thinking about energy conversion and storage. In this work we present a study that responds to a couple of questions concerning induced electronic changes that H produces in ferromagnetic nickel (Ni) host. We calculate and explain the change of magnetic properties of Ni with different concentrations of H. Density functional theory calculations (DFT) were performed for super-cells of fcc Ni with interstitial H in octahedral sites at different concentrations. In order to physically explain the effect of magnetization diminishing as the hydrogen concentration increases, we propose a simple Stoner type of model to describe the influence of the H impurity on the magnetic properties of Ni. The exchange splitting reduction, as shown in first principles calculations, is clearly explained within this physical model. Using a paramagnetic Ni fcc band with variable number of electrons and a Stoner model allow us to obtain the correct trend for the magnetic moment of the system as a function of the H concentration. - Highlights: • We calculate and explain the change of magnetic properties of Ni with different concentrations of H. • We propose a simple Stoner type of model to describe the influence of the H impurity on the magnetic properties of Ni. • The band exchange splitting reduction as the H concentration increases, is a consequence of the competition between the band energy term (kinetic energy) and the ferromagnetic energy term (Weiss field).

  9. Engineering Cell Shape and Function

    Science.gov (United States)

    Singhvi, Rahul; Kumar, Amit; Lopez, Gabriel P.; Stephanopoulos, Gregory N.; Wang, Daniel I. C.; Whitesides, George M.; Ingber, Donald E.

    1994-04-01

    An elastomeric stamp, containing defined features on the micrometer scale, was used to imprint gold surfaces with specific patterns of self-assembled monolayers of alkanethiols and, thereby, to create islands of defined shape and size that support extracellular matrix protein adsorption and cell attachment. Through this technique, it was possible to place cells in predetermined locations and arrays, separated by defined distances, and to dictate their shape. Limiting the degree of cell extension provided control over cell growth and protein secretion. This method is experimentally simple and highly adaptable. It should be useful for applications in biotechnology that require analysis of individual cells cultured at high density or repeated access to cells placed in specified locations.

  10. Comparison of an interstitial cystitis/bladder pain syndrome clinical cohort with symptomatic community women from the RAND Interstitial Cystitis Epidemiology study.

    Science.gov (United States)

    Konkle, Katy S; Berry, Sandra H; Elliott, Marc N; Hilton, Lara; Suttorp, Marika J; Clauw, Daniel J; Clemens, J Quentin

    2012-02-01

    The RAND Interstitial Cystitis Epidemiology survey estimated that 2.7% to 6.5% of United States women have urinary symptoms consistent with a diagnosis of interstitial cystitis/bladder pain syndrome. We describe the demographic and clinical characteristics of the symptomatic community based RAND Interstitial Cystitis Epidemiology cohort, and compare them with those of a clinically based interstitial cystitis/bladder pain syndrome cohort. Subjects included 3,397 community women who met the criteria for the RAND Interstitial Cystitis Epidemiology high sensitivity case definition, and 277 women with an interstitial cystitis/bladder pain syndrome diagnosis recruited from specialist practices across the United States (clinical cohort). Questions focused on demographic information, symptom severity, quality of life indicators, concomitant diagnoses and treatment. Average symptom duration for both groups was approximately 14 years. Women in the clinical cohort reported worse baseline pain and maximum pain, although the absolute differences were small. Mean Interstitial Cystitis Symptom Index scores were approximately 11 for both groups, but mean Interstitial Cystitis Problem Index scores were 9.9 and 13.2 for the clinical cohort and the RAND Interstitial Cystitis Epidemiology cohort, respectively (p Interstitial Cystitis Epidemiology subjects were more likely to be uninsured. The RAND Interstitial Cystitis Epidemiology community cohort was remarkably similar to an interstitial cystitis/bladder pain syndrome clinical cohort with respect to demographics, symptoms and quality of life measures. In contrast to other chronic pain conditions for which clinical cohorts typically report worse symptoms and functional status than population based samples, our data suggest that many measures of symptom severity and functional impact are similar, and sometimes worse, in the RAND Interstitial Cystitis Epidemiology cohort. These findings suggest that interstitial cystitis/bladder pain

  11. Interstitial pregnancy: role of MRI

    International Nuclear Information System (INIS)

    Filhastre, M.; Lesnik, A.; Dechaud, H.; Taourel, P.

    2005-01-01

    We report the MRI features of two cases of interstitial pregnancy. In both cases, MRI was able to localize the ectopic pregnancy by showing a gestational structure surrounded by a thick wall in the upper part of the uterine wall separated from the endometrium by an uninterrupted junctional zone. Because US may confuse angular and interstitial pregnancies and because interstitial pregnancy has a particular evolutive course, MR imaging may play a key role in the diagnosis and management of women with interstitial pregnancy. (orig.)

  12. Regulation of satellite cell function in sarcopenia

    Directory of Open Access Journals (Sweden)

    Stephen E Alway

    2014-09-01

    Full Text Available The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell function that is impacted by the environment (niche of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia, and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration. While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function.

  13. Regulation of Satellite Cell Function in Sarcopenia

    Science.gov (United States)

    Alway, Stephen E.; Myers, Matthew J.; Mohamed, Junaith S.

    2014-01-01

    The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell) function that is impacted by the environment (niche) of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse, or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins, and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration). While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function. PMID:25295003

  14. Desquamative interstitial pneumonia: A case report

    Directory of Open Access Journals (Sweden)

    Lovrenski Aleksandra

    2014-01-01

    Full Text Available Introduction. Desquamative interstitial pneumonia is one of the rarest idiopathic interstitial pneumonias and the rarest form of smoking-related interstitial lung diseases. It was first described by Liebow in 1965. Histologically, it is characterized by the presence of eosinophilic macrophages uniformly filling airspaces which often contain a finely granular light-brown pigment that does not stain for hemosiderin. The alveolar walls are usually mildly thickened by fibrous tissue and infiltrated by a moderate number of lymphocytes. Case Outline. Our patient was a 56-year-old male, heavy smoker, with bilateral lung infiltrations of unknown etiology and several months of discomfort in the form of dry cough and shortness of breath. Lung function tests showed a moderate restrictive ventilation disorder and a severe reduction of diffusing capacity. Since bronchoscopic specimens did not reveal lung lesion etiology, an open lung biopsy of the lower left pulmonary lobe was performed, and based on the obtained surgical material the pathohistologically diagnosis of desquamative interstitial pneumonia was established. The patient was started on corticosteroid and immunosuppressive therapy, and he ceased smoking. At the last control examination, two years after the onset of symptoms, the patient was feeling well, and high-resolution computed tomography (HRCT scan of the thorax showed regression of pathological changes. Conclusion. Although, as in our case, the majority of DIP patients improve on treatment, some patients still develop progressive irreversible fibrosis despite therapy.

  15. Generation of functional eyes from pluripotent cells.

    Directory of Open Access Journals (Sweden)

    Andrea S Viczian

    2009-08-01

    Full Text Available Pluripotent cells such as embryonic stem (ES and induced pluripotent stem (iPS cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision.

  16. Determination of the population of octahedral and tetrahedral interstitials in zirconium hydrides

    International Nuclear Information System (INIS)

    Fedorov, V.M.; Gogava, V.V.; Shilo, S.I.; Biryukova, E.A.

    1983-01-01

    Results of neutron investigations of ZrHsub(1.66), ZrHsub(1.75) and ZrHsub(1.98) zirconium hydrides are presented. Investigations were conducted using plane polycrystal samples by multidetector system of scattered neutron detection. Neutron diffraction method was used to determine the number of interstitial hydrogen atoms in interstitials of the lattice cell in the case of statistic atom distribution. The numbers of interstitial atoms in octahedral interstitials for zirconium hydrides were determined experimentally; the difference of potential energies of hydrogen atoms in octa- and tetrahedral interstitials was determined as well. It is shown that experimentally determined difference of potential energies of hydrogen atoms, occupying octa- and tetrahedral positions in investigated zirconium hydrides results at room temperature in the pretailing occupation of tetrahedral interstitials by hydrogen atoms (85-90%); the occupation number grows with temperature decrease and the ordering of interstitial vacancies with formation of hydrogen superstructure takes place at low temperatures

  17. Absence of peristalsis in the ileum of W/W(V) mutant mice that are selectively deficient in myenteric interstitial cells of Cajal.

    Science.gov (United States)

    Nakagawa, Tadashi; Misawa, Hiromi; Nakajima, Yoshiyuki; Takaki, Miyako

    2005-06-01

    It is well known that the enteric nervous system plays a key role in the generation of gastrointestinal peristaltic movements. Recently, the networks of interstitial cells of Cajal (ICC) have been found to be essential in the generation of spontaneous gastrointestinal movements. However, the role of ICC in the mechanisms involved in the generation of peristaltic movements is still controversial. The aim of the present study was to reveal how pacemaker myenteric ICC (ICC-MY) and the enteric nervous system contribute to the mechanisms involved in the generation of intestinal peristalsis. We compared spontaneous peristaltic movements of the ileum in wild type (WT) mice with those in W/W(V) mutant mice which are selectively deficient in ICC-MY. Simultaneous recordings were made from both the circular and longitudinal muscle of a 4-cm long segment of ileum under hydrostatic pressure of 0--0.5 cm H(2)O. Mechanical activity and continuous video-images of the ileum were compared between WT and W/W(V) mutant mice under control conditions, in the presence of N-nitro-L-arginine methyl ester (L-NAME) and after tetrodotoxin (TTX). In the WT mouse ileum, peristaltic waves to propagate from the oral to the anal end were frequently observed. The frequency of these peristaltic waves and their associated synchronous longitudinal and circular muscle contractions was increased by L-NAME. The peristaltic waves were abolished by TTX. In the W/W(V) mutant mouse ileum, no peristaltic waves to propagate from the oral to the anal end were observed in control and even after L-NAME, although the local spontaneously generated longitudinal and circular muscle contractions were enhanced by L-NAME. These local contractions were not abolished by TTX. The results presented here suggested that ICC-MY are essential for the generation of spontaneous intestinal peristaltic movements. It is conceivable that ICC-MY may determine the polarity of the excitation of the intestine such that longitudinal and

  18. REGULATORY T–CELLS: ORIGIN AND FUNCTION

    Directory of Open Access Journals (Sweden)

    I. S. Freidlin

    2005-01-01

    Full Text Available Abstract. Over the past decade a population of so–called “regulatory T cells” (Treg cells has been linked to the prevention of autoimmunity. In this review we discuss the molecular mechanisms of Treg cells development and function including the identification of the unique molecular marker of Treg cells – the transcription factor Foxp3. We discuss also the mechanisms of suppression, which include the direct cell contact through binding of cell surface molecules CTLA–4 on Treg cells to CD80/CD86 molecules of effector T cells and the local secretion of cytokines (IL–10, TGFβ. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. These cells are a good target for designing ways to induce or abrogate immunological tolerance to self and non–self antigens. (Med. Immunol., 2005, vol.7, № 4, pp. 347–354

  19. Role of Polyamines in Immune Cell Functions

    Directory of Open Access Journals (Sweden)

    Rebecca S. Hesterberg

    2018-03-01

    Full Text Available The immune system is remarkably responsive to a myriad of invading microorganisms and provides continuous surveillance against tissue damage and developing tumor cells. To achieve these diverse functions, multiple soluble and cellular components must react in an orchestrated cascade of events to control the specificity, magnitude and persistence of the immune response. Numerous catabolic and anabolic processes are involved in this process, and prominent roles for l-arginine and l-glutamine catabolism have been described, as these amino acids serve as precursors of nitric oxide, creatine, agmatine, tricarboxylic acid cycle intermediates, nucleotides and other amino acids, as well as for ornithine, which is used to synthesize putrescine and the polyamines spermidine and spermine. Polyamines have several purported roles and high levels of polyamines are manifest in tumor cells as well in autoreactive B- and T-cells in autoimmune diseases. In the tumor microenvironment, l-arginine catabolism by both tumor cells and suppressive myeloid cells is known to dampen cytotoxic T-cell functions suggesting there might be links between polyamines and T-cell suppression. Here, we review studies suggesting roles of polyamines in normal immune cell function and highlight their connections to autoimmunity and anti-tumor immune cell function.

  20. Mitochondria, endothelial cell function, and vascular diseases.

    Science.gov (United States)

    Tang, Xiaoqiang; Luo, Yu-Xuan; Chen, Hou-Zao; Liu, De-Pei

    2014-01-01

    Mitochondria are perhaps the most sophisticated and dynamic responsive sensing systems in eukaryotic cells. The role of mitochondria goes beyond their capacity to create molecular fuel and includes the generation of reactive oxygen species, the regulation of calcium, and the activation of cell death. In endothelial cells, mitochondria have a profound impact on cellular function under both healthy and diseased conditions. In this review, we summarize the basic functions of mitochondria in endothelial cells and discuss the roles of mitochondria in endothelial dysfunction and vascular diseases, including atherosclerosis, diabetic vascular dysfunction, pulmonary artery hypertension, and hypertension. Finally, the potential therapeutic strategies to improve mitochondrial function in endothelial cells and vascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants and calorie restriction.

  1. Mitochondria, Endothelial Cell Function and Vascular Diseases

    Directory of Open Access Journals (Sweden)

    Xiaoqiang eTang

    2014-05-01

    Full Text Available Mitochondria are perhaps the most sophisticated and dynamic responsive sensing systems in eukaryotic cells. The role of mitochondria goes beyond their capacity to create molecular fuel and includes the generation of reactive oxygen species, the regulation of calcium, and the activation of cell death. In endothelial cells, mitochondria have a profound impact on cellular function under both healthy and diseased conditions. In this review, we summarize the basic functions of mitochondria in endothelial cells and discuss the roles of mitochondria in endothelial dysfunction and vascular diseases, including atherosclerosis, diabetic vascular dysfunction, pulmonary artery hypertension and hypertension. Finally, the potential therapeutic strategies to improve mitochondrial function in endothelial cells and vascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants and calorie restriction.

  2. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Juan Antonio Guadix

    2017-12-01

    Full Text Available Summary: Human pluripotent stem cells (hPSCs are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA and bone morphogenetic protein 4 (BMP4 promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (proepicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (proepicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (proepicardial-like cells displaying functional properties (adhesion and spreading over the myocardium of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (proepicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. : The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair. Keywords: human pluripotent stem cells, proepicardium, progenitor cells, cardiovascular, differentiation

  3. In vitro functional gut-like organ formation from mouse embryonic stem cells.

    Science.gov (United States)

    Yamada, Takatsugu; Yoshikawa, Masahide; Takaki, Miyako; Torihashi, Shigeko; Kato, Yoko; Nakajima, Yoshiyuki; Ishizaka, Shigeaki; Tsunoda, Yukio

    2002-01-01

    Embryonic stem (ES) cells have a pluripotent ability to differentiate into a variety of cell lineages in vitro. We have recently found that ES cells can give rise to a functional gut-like unit, which forms a three-dimensional dome-like structure with lumen and exhibits mechanical activity, such as spontaneous contraction and peristalsis. The aim of the present study was to investigate the electrophysiological and morphological properties of ES cell-derived contracting clusters. Electrical activity was examined by an extracellular recording. Morphology and cellular components were investigated by immunohistochemistry and electron microscopy. Clusters with rhythmic contractions displayed electrical slow waves at a regular rhythm, and clusters with highly coordinated peristalsis showed regular slow waves and spontaneous spike action potentials. Immunoreactivity for c-Kit, a marker of interstitial cells of Cajal (ICC), was observed in dense network structures. Neuronal marker PGP9.5 immunoreactivity was observed only in clusters with peristalsis. The topographical structure of the wall was organized by an inner epithelial layer and outer smooth muscle layer. The smooth muscle layer was provided with an ICC network and innervated with enteric neurons. ES cells can differentiate into a functional gut-like organ in vitro that exhibits physiological and morphological properties characteristic of the gastrointestinal (GI) tract. This ES cell-derived gut provides a powerful tool for studying GI motility and gut development in vitro, and has potential for elucidating and treating a variety of motility disorders.

  4. Induction of Functional Hair-Cell-Like Cells from Mouse Cochlear Multipotent Cells

    Directory of Open Access Journals (Sweden)

    Quanwen Liu

    2016-01-01

    Full Text Available In this paper, we developed a two-step-induction method of generating functional hair cells from inner ear multipotent cells. Multipotent cells from the inner ear were established and induced initially into progenitor cells committed to the inner ear cell lineage on the poly-L-lysine substratum. Subsequently, the committed progenitor cells were cultured on the mitotically inactivated chicken utricle stromal cells and induced into hair-cell-like cells containing characteristic stereocilia bundles. The hair-cell-like cells exhibited rapid permeation of FM1-43FX. The whole-cell patch-clamp technique was used to measure the membrane currents of cells differentiated for 7 days on chicken utricle stromal cells and analyze the biophysical properties of the hair-cell-like cells by recording membrane properties of cells. The results suggested that the hair-cell-like cells derived from inner ear multipotent cells were functional following differentiation in an enabling environment.

  5. Functions of proteoglycans at the cell surface

    DEFF Research Database (Denmark)

    Höök, M; Woods, A; Johansson, S

    1986-01-01

    Proteoglycans (primarily heparan sulphate proteoglycans) are found at the surface of most adherent eukaryotic cells. Earlier studies suggest that these molecules can be associated with the cell surface principally by two different mechanisms. Proteoglycans may occur as membrane......-intercalated glycoproteins, where the core protein of the proteoglycan is anchored in the lipid interior of the plasma membrane, or they may be bound via the polysaccharide components of the molecule to specific anchoring proteins present at the cell surface. A number of functions have been proposed for cell surface......-associated proteoglycans, including: regulation of cell-substrate adhesion; regulation of cell proliferation; participation in the binding and uptake of extracellular components; and participation in the regulation of extracellular matrix formation. Evidence is discussed suggesting that the cell-associated heparan...

  6. Gallium interstitial contributions to diffusion in gallium arsenide

    Science.gov (United States)

    Schick, Joseph T.; Morgan, Caroline G.

    2011-09-01

    A new diffusion path is identified for gallium interstitials, which involves lower barriers than the barriers for previously identified diffusion paths [K. Levasseur-Smith and N. Mousseau, J. Appl. Phys. 103, 113502 (2008), P. A. Schultz and O. A. von Lilienfeld, Modelling and Simulation in Materials Science and Engineering 17, 084007 (2009)] for the charge states which dominate diffusion over most of the available range of Fermi energies. This path passes through the ⟨110⟩ gallium-gallium split interstitial configuration, and has a particularly low diffusion barrier of 0.35 eV for diffusion in the neutral charge state. As a part of this work, the character of the charge states for the gallium interstitials which are most important for diffusion is investigated, and it is shown that the last electron bound to the neutral interstitial occupies a shallow hydrogenic bound state composed of conduction band states for the hexagonal interstitial and both tetrahedral interstitials. How to properly account for the contributions of such interstitials is discussed for density-functional calculations with a k-point mesh not including the conduction band edge point. Diffusion barriers for gallium interstitials are calculated in all the charge states which can be important for a Fermi level anywhere in the gap, q = 0, +1, +2, and +3, for diffusion via the ⟨110⟩ gallium-gallium split interstitial configuration and via the hexagonal interstitial configuration. The lowest activation enthalpies over most of the available range of Fermi energies are found to correspond to diffusion in the neutral or singly positive state via the ⟨110⟩ gallium-gallium split interstitial configuration. It is shown that several different charge states and diffusion paths contribute significantly for Fermi levels within 0.2 eV above the valence band edge, which may help to explain some of the difficulties [H. Bracht and S. Brotzmann, Phys. Rev. B 71, 115216 (2005)] which have been

  7. Gallium interstitial contributions to diffusion in gallium arsenide

    Directory of Open Access Journals (Sweden)

    Joseph T. Schick

    2011-09-01

    Full Text Available A new diffusion path is identified for gallium interstitials, which involves lower barriers than the barriers for previously identified diffusion paths [K. Levasseur-Smith and N. Mousseau, J. Appl. Phys. 103, 113502 (2008, P. A. Schultz and O. A. von Lilienfeld, Modelling and Simulation in Materials Science and Engineering 17, 084007 (2009] for the charge states which dominate diffusion over most of the available range of Fermi energies. This path passes through the ⟨110⟩ gallium-gallium split interstitial configuration, and has a particularly low diffusion barrier of 0.35 eV for diffusion in the neutral charge state. As a part of this work, the character of the charge states for the gallium interstitials which are most important for diffusion is investigated, and it is shown that the last electron bound to the neutral interstitial occupies a shallow hydrogenic bound state composed of conduction band states for the hexagonal interstitial and both tetrahedral interstitials. How to properly account for the contributions of such interstitials is discussed for density-functional calculations with a k-point mesh not including the conduction band edge point. Diffusion barriers for gallium interstitials are calculated in all the charge states which can be important for a Fermi level anywhere in the gap, q = 0, +1, +2, and +3, for diffusion via the ⟨110⟩ gallium-gallium split interstitial configuration and via the hexagonal interstitial configuration. The lowest activation enthalpies over most of the available range of Fermi energies are found to correspond to diffusion in the neutral or singly positive state via the ⟨110⟩ gallium-gallium split interstitial configuration. It is shown that several different charge states and diffusion paths contribute significantly for Fermi levels within 0.2 eV above the valence band edge, which may help to explain some of the difficulties [H. Bracht and S. Brotzmann, Phys. Rev. B 71, 115216 (2005] which

  8. Oxidative atom-transfer to a trimanganese complex to form Mn6(μ6-E) (E = O, N) clusters featuring interstitial oxide and nitride functionalities.

    Science.gov (United States)

    Fout, Alison R; Zhao, Qinliang; Xiao, Dianne J; Betley, Theodore A

    2011-10-26

    Utilizing a hexadentate ligand platform, a trinuclear manganese complex of the type ((H)L)Mn(3)(thf)(3) was synthesized and characterized ([(H)L](6-) = [MeC(CH(2)N(C(6)H(4)-o-NH))(3)](6-)). The pale-orange, formally divalent trimanganese complex rapidly reacts with O-atom transfer reagents to afford the μ(6)-oxo complex ((H)L)(2)Mn(6)(μ(6)-O)(NCMe)(4), where two trinuclear subunits bind the central O-atom and the ((H)L) ligands cooperatively bind both trinuclear subunits. The trimanganese complex ((H)L)Mn(3)(thf)(3) rapidly consumes inorganic azide ([N(3)]NBu(4)) to afford a dianionic hexanuclear nitride complex [((H)L)(2)Mn(6)(μ(6)-N)](NBu(4))(2), which subsequently can be oxidized with elemental iodine to ((H)L)(2)Mn(6)(μ(6)-N)(NCMe)(4). EPR and alkylation of the interstitial light atom substituent were used to distinguish the nitride from the oxo complex. The oxo and oxidized nitride complexes give rise to well-defined Mn(II) and Mn(III) sites, determined by bond valence summation, while the dianionic nitride shows a more symmetric complex, giving rise to indistinguishable ion oxidation states based on crystal structure bond metrics.

  9. Interstitial cystitis: painful bladder syndrome

    OpenAIRE

    R F Sholan; G Sh Garaev; G M Nasrullaeva

    2018-01-01

    Interstitial cystitis, or painful bladder syndrome, is a chronic inflammatory disease of a bladder of unknown etiology. It negatively affects the quality of life, causes depressive disorders, anxiety, and sexual dysfunction. Despite numerous studies, the etiology of interstitial cystitis is still unclear and it’s considered as painful bladder syndrome with multifactorial origin. According to the US National Health and Nutrition Examination Survey, 470/100 000 people (60/100 000 men, 850/100 0...

  10. Cell functional enviromics: Unravelling the function of environmental factors

    Directory of Open Access Journals (Sweden)

    Alves Paula M

    2011-06-01

    Full Text Available Abstract Background While functional genomics, focused on gene functions and gene-gene interactions, has become a very active field of research in molecular biology, equivalent methodologies embracing the environment and gene-environment interactions are relatively less developed. Understanding the function of environmental factors is, however, of paramount importance given the complex, interactive nature of environmental and genetic factors across multiple time scales. Results Here, we propose a systems biology framework, where the function of environmental factors is set at its core. We set forth a "reverse" functional analysis approach, whereby cellular functions are reconstructed from the analysis of dynamic envirome data. Our results show these data sets can be mapped to less than 20 core cellular functions in a typical mammalian cell culture, while explaining over 90% of flux data variance. A functional enviromics map can be created, which provides a template for manipulating the environmental factors to induce a desired phenotypic trait. Conclusion Our results support the feasibility of cellular function reconstruction guided by the analysis and manipulation of dynamic envirome data.

  11. Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functions via epigenetic modulation of Sca-1 and Pw1 promoters.

    Science.gov (United States)

    Smeriglio, Piera; Alonso-Martin, Sonia; Masciarelli, Silvia; Madaro, Luca; Iosue, Ilaria; Marrocco, Valeria; Relaix, Frédéric; Fazi, Francesco; Marazzi, Giovanna; Sassoon, David A; Bouché, Marina

    2016-04-01

    Understanding the regulation of the stem cell fate is fundamental for designing novel regenerative medicine strategies. Previous studies have suggested that pharmacological treatments with small molecules provide a robust and reversible regulation of the stem cell program. Previously, we showed that treatment with a vanadium compound influences muscle cell fatein vitro In this study, we demonstrate that treatment with the phosphotyrosine phosphatase inhibitor bisperoxovanadium (BpV) drives primary muscle cells to a poised stem cell stage, with enhanced function in muscle regenerationin vivofollowing transplantation into injured muscles. Importantly, BpV-treated cells displayed increased self-renewal potentialin vivoand replenished the niche in both satellite and interstitial cell compartments. Moreover, we found that BpV treatment induces specific activating chromatin modifications at the promoter regions of genes associated with stem cell fate, includingSca-1andPw1 Thus, our findings indicate that BpV resets the cell fate program by specific epigenetic regulations, such that the committed myogenic cell fate is redirected to an earlier progenitor cell fate stage, which leads to an enhanced regenerative stem cell potential.-Smeriglio, P., Alonso-Martin, S., Masciarelli, S., Madaro, L., Iosue, I., Marrocco, V., Relaix, F., Fazi, F., Marazzi, G., Sassoon, D. A., Bouché, M. Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functionsviaepigenetic modulation of Sca-1 and Pw1 promoters. © FASEB.

  12. Interstitial lung diseases in children

    Directory of Open Access Journals (Sweden)

    Clement Annick

    2010-08-01

    Full Text Available Abstract Interstitial lung disease (ILD in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. These disorders are characterized by inflammatory and fibrotic changes that affect alveolar walls. Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange. Many pathological situations can impair gas exchange and, therefore, may contribute to progressive lung damage and ILD. Consequently, diagnosis approach needs to be structured with a clinical evaluation requiring a careful history paying attention to exposures and systemic diseases. Several classifications for ILD have been proposed but none is entirely satisfactory especially in children. The present article reviews current concepts of pathophysiological mechanisms, etiology and diagnostic approaches, as well as therapeutic strategies. The following diagnostic grouping is used to discuss the various causes of pediatric ILD: 1 exposure-related ILD; 2 systemic disease-associated ILD; 3 alveolar structure disorder-associated ILD; and 4 ILD specific to infancy. Therapeutic options include mainly anti-inflammatory, immunosuppressive, and/or anti-fibrotic drugs. The outcome is highly variable with a mortality rate around 15%. An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy.

  13. Functions of proteoglycans at the cell surface

    DEFF Research Database (Denmark)

    Höök, M; Woods, A; Johansson, S

    1986-01-01

    sulphate helps to connect the intracellular cytoskeleton to the extracellular matrix in focal adhesions. This evidence includes: the co-localization of actin and heparan sulphate proteoglycan during the process of cell spreading, and in isolated focal adhesions; biochemical analyses of a hydrophobic......Proteoglycans (primarily heparan sulphate proteoglycans) are found at the surface of most adherent eukaryotic cells. Earlier studies suggest that these molecules can be associated with the cell surface principally by two different mechanisms. Proteoglycans may occur as membrane......-intercalated glycoproteins, where the core protein of the proteoglycan is anchored in the lipid interior of the plasma membrane, or they may be bound via the polysaccharide components of the molecule to specific anchoring proteins present at the cell surface. A number of functions have been proposed for cell surface...

  14. Interstitial integrals in the multiple-scattering model

    International Nuclear Information System (INIS)

    Swanson, J.R.; Dill, D.

    1982-01-01

    We present an efficient method for the evaluation of integrals involving multiple-scattering wave functions over the interstitial region. Transformation of the multicenter interstitial wave functions to a single center representation followed by a geometric projection reduces the integrals to products of analytic angular integrals and numerical radial integrals. The projection function, which has the value 1 in the interstitial region and 0 elsewhere, has a closed-form partial-wave expansion. The method is tested by comparing its results with exact normalization and dipole integrals; the differences are 2% at worst and typically less than 1%. By providing an efficient means of calculating Coulomb integrals, the method allows treatment of electron correlations using a multiple scattering basis set

  15. Stem cell-specific activation of an ancestral myc protooncogene with conserved basic functions in the early metazoan Hydra.

    Science.gov (United States)

    Hartl, Markus; Mitterstiller, Anna-Maria; Valovka, Taras; Breuker, Kathrin; Hobmayer, Bert; Bister, Klaus

    2010-03-02

    The c-myc protooncogene encodes a transcription factor (Myc) with oncogenic potential. Myc and its dimerization partner Max are bHLH-Zip DNA binding proteins controlling fundamental cellular processes. Deregulation of c-myc leads to tumorigenesis and is a hallmark of many human cancers. We have identified and extensively characterized ancestral forms of myc and max genes from the early diploblastic cnidarian Hydra, the most primitive metazoan organism employed so far for the structural, functional, and evolutionary analysis of these genes. Hydra myc is specifically activated in all stem cells and nematoblast nests which represent the rapidly proliferating cell types of the interstitial stem cell system and in proliferating gland cells. In terminally differentiated nerve cells, nematocytes, or epithelial cells, myc expression is not detectable by in situ hybridization. Hydra max exhibits a similar expression pattern in interstitial cell clusters. The ancestral Hydra Myc and Max proteins display the principal design of their vertebrate derivatives, with the highest degree of sequence identities confined to the bHLH-Zip domains. Furthermore, the 314-amino acid Hydra Myc protein contains basic forms of the essential Myc boxes I through III. A recombinant Hydra Myc/Max complex binds to the consensus DNA sequence CACGTG with high affinity. Hybrid proteins composed of segments from the retroviral v-Myc oncoprotein and the Hydra Myc protein display oncogenic potential in cell transformation assays. Our results suggest that the principal functions of the Myc master regulator arose very early in metazoan evolution, allowing their dissection in a simple model organism showing regenerative ability but no senescence.

  16. Macrophage Chemotaxis in Anti-tubular Basement Membrane-Induced Interstitial Nephritis in Guinea Pigs

    NARCIS (Netherlands)

    Kennedy, Thomas L.; Merrow, Martha; Phillips, S. Michael; Norman, Michael; Neilson, Eric G.

    1985-01-01

    Interstitial renal lesions containing T cells and macrophages develop after 14 days in guinea pigs immunized to produce anti-tubular basement membrane-induced interstitial nephritis. We serially examined the renal venous and systemic arterial sera from such animals to determine if chemotactic

  17. Hypoxia Activates Src and Promotes Endocytosis Which Decreases MMP-2 Activity and Aggravates Renal Interstitial Fibrosis.

    Science.gov (United States)

    Cheng, Zhengyuan; Liu, Lei; Wang, Zhi; Cai, Yingying; Xu, Qing; Chen, Pingsheng

    2018-02-15

    The aggravation of renal interstitial fibrosis in the advanced-stage of chronic kidney disease is related to decreased matrix metalloproteinase-2 (MMP-2) activity, which is induced by hypoxia in the kidney; however, the specific mechanism remains unclear. We previously demonstrated that inhibition of Caveolin-1, a key gene involved in endocytosis, increased MMP-2 activity in hypoxic HK-2 cells. It has been reported that activated Src (phospho-Src Tyr416) is a key molecule in multiple fibrotic pathways. However, whether Src functions on the regulation of Caveolin-1 and MMP-2 activity in hypoxic HK-2 cells remains poorly understood. To explore the underlying mechanism, a rat model of renal interstitial fibrosis was established, then we observed obvious hypoxia in fibrotic kidney tissue and the protein levels of phospho-Src and Caveolin-1 increased, while MMP-2 activity decreased. Next, we treated HK-2 cells with the phospho-Src inhibitor PP1. Compared with normal cells grown in hypoxia, in cells treated with PP1, the protein levels of phospho-Src and Caveolin-1 decreased, as did the protein levels of the MMP-2-activity-regulated molecules RECK (reversion-inducing-cysteine-rich protein with kazal motifs) and TIMP-2 (tissue inhibitor of metalloproteinase-2), while the protein level of MT1-MMP (membrane type 1-matrix metalloproteinase) increased and MMP-2 activity was enhanced. Therefore, hypoxia promotes the phosphorylation of Src and phospho-Src can enhance the endocytosis of HK-2 cells, which leads to decreased MMP-2 activity and aggravates renal interstitial fibrosis.

  18. Interstitial brachytherapy in carcinoma of the penis

    International Nuclear Information System (INIS)

    Chaudhary, A.J.; Ghosh, S.; Bhalavat, R.L.; Kulkarni, J.N.; Sequeira, B.V.E.

    1999-01-01

    Aim: Keeping in line with the increasing emphasis on organ preservation, we at the Tata Memorial Hospital have evaluated the role of Ir-192 interstitial implant as regards local control, functional and cosmetic outcome in early as well as locally recurrent carcinoma of the distal penis. Patients and Methods: From October 1988 to December 1996, 23 patients with histopathologically proven cancer of the penis were treated with radical radiation therapy using Ir-192 temporary interstitial implant. Our patients were in the age group of 20 to 60 years. The primary lesions were T1 and 7, T2 in 7 and recurrent in 9 patients. Only 7 patients had palpable groin nodes at presentation, all of which were pathologically negative. The median dose of implant was 50 Gy (range 40 to 60 Gy), using the LDR afterloading system and the Paris system of implant rules for dosimetry. Follow-up ranged from 4 to 117 months (median 24 months). Results: At last follow-up 18 of the 23 patients remained locally controlled with implant alone. Three patients failed only locally, 2 locoregionally and 1 only at the groin. Of the 5 patients who failed locally, 4 were successfully salvaged with partial penectomy and remained controlled when last seen. Local control with implant alone at 8 years was 70% by life table analysis. The patients had excellent functional and cosmetic outcome. We did not record any case of skin or softtissue necrosis. Only 2 patients developed meatal stenosis, both of which were treated endoscopically. Conclusion: Our results lead us to interpret that interstitial brachytherapy with Ir-192 offers excellent local control rates with preservation of organ and function. Penectomy can be reserved as a means for effective salvage. (orig.) [de

  19. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis

    2001-11-01

    Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

  20. Interstitial pneumonitis after acetylene welding: a case report.

    Science.gov (United States)

    Brvar, Miran

    2014-01-01

    Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume) and impaired diffusion capacity (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.

  1. Interstitial pneumonitis after acetylene welding: A case report

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2014-02-01

    Full Text Available Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume and impaired diffusion capacity (47% of predicted capacity. Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.

  2. Anatomically-specific intratubular and interstitial biominerals in the human renal medullo-papillary complex.

    Directory of Open Access Journals (Sweden)

    Ling Chen

    Full Text Available Limited information exists on the anatomically-specific early stage events leading to clinically detectable mineral aggregates in the renal papilla. In this study, quantitative multiscale correlative maps of structural, elemental and biochemical properties of whole medullo-papillary complexes from human kidneys were developed. Correlative maps of properties specific to the uriniferous and vascular tubules using high-resolution X-ray computed tomography, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, and immunolocalization of noncollagenous proteins (NCPs along with their association with anatomy specific biominerals were obtained. Results illustrated that intratubular spherical aggregates primarily form at the proximal regions distant from the papillary tip while interstitial spherical and fibrillar aggregates are distally located near the papillary tip. Biominerals at the papillary tip were closely localized with 10 to 50 μm diameter vasa recta immunolocalized for CD31 inside the medullo-papillary complex. Abundant NCPs known to regulate bone mineralization were localized within nanoparticles, forming early pathologic mineralized regions of the complex. Based on the physical association between vascular and urothelial tubules, results from light and electron microscopy techniques suggested that these NCPs could be delivered from vasculature to prompt calcification of the interstitial regions or they might be synthesized from local vascular smooth muscle cells after transdifferentiation into osteoblast-like phenotypes. In addition, results provided insights into the plausible temporal events that link the anatomically specific intratubular mineral aggregates with the interstitial biomineralization processes within the functional unit of the kidney.

  3. Progression of renal injury toward interstitial inflammation and glomerular sclerosis is dependent on abnormal protein filtration.

    Science.gov (United States)

    Zoja, Carlamaria; Abbate, Mauro; Remuzzi, Giuseppe

    2015-05-01

    Chronic proteinuric renal diseases, independent from the type of the initial insult, have in common a loss of selectivity of the glomerular barrier to protein filtration. Glomerular sclerosis is the progressive lesion affecting the glomerular capillary wall, the primary site at which the protein filtration is abnormally enhanced by disease. Dysfunction of podocytes, that serve to maintain the intact barrier, is a central event in lesion development. However, glomerular injury is signalled to tubular and interstitial structures largely in advance of nephron destruction. Glomerular ultrafiltration of excessive amounts of plasma-derived proteins and associated factors incites tubulointerstitial damage and might amplify an inherent susceptibility of the kidney to become dysfunctional in several disease conditions. Thus, noxious substances in the proteinuric ultrafiltrate promote apoptotic responses and multiple changes in the phenotype of tubule cells with generation of inflammatory and fibrogenic mediators. The severity of tubular interstitial damage has long been recognized to be highly correlated to the degree of deterioration of renal failure even better than glomerular lesions. This review focuses on pathways of tubular injury and apoptosis that in turn promote nephron-by-nephron degeneration and interstitial fibrosis during proteinuria contributing to multifaceted processes of kidney scarring and function loss. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  4. Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction.

    Directory of Open Access Journals (Sweden)

    Wilco P Pulskens

    Full Text Available Progressive renal disease is characterized by tubulo-interstitial injury with ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these pathophysiological processes through its canonical effects in cytokine maturation. Nlrp3 may additionally exert inflammasome-independent effects following tissue injury. Hence, in this study we investigated potential non-canonical effects of Nlrp3 following progressive renal injury by subjecting WT and Nlrp3-deficient (-/- mice to unilateral ureter obstruction (UUO. Our results revealed a progressive increase of renal Nlrp3 mRNA in WT mice following UUO. The absence of Nlrp3 resulted in enhanced tubular injury and dilatation and an elevated expression of injury biomarker NGAL after UUO. Moreover, interstitial edema was significantly elevated in Nlrp3-/- mice. This could be explained by increased intratubular pressure and an enhanced tubular and vascular permeability. In accordance, renal vascular leakage was elevated in Nlrp3-/- mice that associated with reduced mRNA expression of intercellular junction components. The decreased epithelial barrier function in Nlrp3-/- mice was not associated with increased apoptosis and/or proliferation of renal epithelial cells. Nlrp3 deficiency did not affect renal fibrosis or inflammation. Together, our data reveal a novel non-canonical effect of Nlrp3 in preserving renal integrity and protection against early tubular injury and interstitial edema following progressive renal injury.

  5. The role of interstitial changes in the progression of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Beata Sulikowska

    2015-07-01

    Full Text Available Interstitium – the renal tubulointerstitial compartment – is located between the renal tubule basement membrane and microcirculation vessels. Interstitial fibroblasts produce the extracellular matrix and constitute the structure’s cellular skeleton, regulating spatial relationships between its components (microenvironment.The tubular epithelium and endothelium cooperate within an integrated microenvironment. Structural or functional impairment of the extracellular matrix, microcirculation vessels or tubular epithelium results in disturbances of tubulointerstitial compartment components.In the course of glomerular kidney diseases, the intrarenal RAA system becomes activated and inflammatory mediators are released. Interstitial inflammation and microcirculatory disorders develop, inducing adverse consequences, manifested mainly through the process of hypoxia and inflammation.Inflammation-induced increase in interleukin-1 (TNF-α expression leads to increased concentrations of VEGF, ICAM-1, angiotensin II, IL-6 and IL-8. Cytokines activate fibroblasts, myofibroblasts and endothelial cells. Fibrosis is also triggered by HIF-1alpha pathway activation, resulting in vascular growth and fibroblast proliferation. This reaction likewise occurs through activation of NF-ĸβ, EPO, GLUT-1, IGF-1 and INOS.Interstitial fibrosis is one of the factors determining the clinical course of kidney diseases. Apart from inducing fibrosis, microcirculatory disorders lead to the progression of hypoxia.Angiogenesis is a part of the repair process accompanying fibrosis. Its determinant is the normal function and structure of endothelial cells manifested by their ability to migrate and proliferate in response to, inter alia, angiopoietins, VEGF and nitric oxide synthase.Administering a three-drug RAAS-inhibiting therapy to patients with chronic glomerulopathies improves tubular function, measured by the decrease in excretion of NAG and propeptide of type III

  6. Schwann cell myelination requires Dynein function

    Directory of Open Access Journals (Sweden)

    Langworthy Melissa M

    2012-11-01

    Full Text Available Abstract Background Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear. Results By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1, which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression. Conclusion Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.

  7. Validity of Ultrasound Lung Comets for Assessment of the Severity of Interstitial Pneumonia.

    Science.gov (United States)

    Asano, Mariko; Watanabe, Hiroyuki; Sato, Kazuhiro; Okuda, Yuji; Sakamoto, Sho; Hasegawa, Yukiyasu; Sudo, Kazuhisa; Takeda, Masahide; Sano, Masaaki; Kibira, Satoshi; Ito, Hiroshi

    2017-11-30

    Ultrasound (US) lung comets are often observed in patients with interstitial lung disease or congestive heart failure, but few studies have explored the clinical importance of US lung comets in patients with the former condition. We explored whether the US lung comet number could be used to assess the severity of interstitial pneumonia. Forty stable patients with interstitial pneumonia were examined. Lung comets evident on transthoracic US imaging in 12 selected regions of the posterior chest wall were analyzed. We defined lung comets accompanied by thickened and irregular pleural lines as interstitial US lung comets; these predominated in patients with interstitial pneumonia. The total number of interstitial US lung comets was correlated with the data from chest high-resolution computed tomography, pulmonary function tests, serologic tests, and the 6-minute walk test. The 40 patients included 16 with idiopathic pulmonary fibrosis and 24 with nonspecific interstitial pneumonia. Thirty-four patients had interstitial US lung comets, which were more common in the lower than the upper lung area. Good correlations were evident between the lung comet number and the extent of the reticular pattern on chest high-resolution computed tomography (r = 0.710; P comet number had a strong negative correlation with the percutaneous oxygen saturation level after the 6-minute walk test (r = -0.751; P comets evident on transthoracic US imaging may be a valuable marker of disease severity in patients with interstitial pneumonia. © 2017 by the American Institute of Ultrasound in Medicine.

  8. Smoking-related interstitial lung diseases: radiologic-pathologic correlation

    International Nuclear Information System (INIS)

    Hidalgo, Alberto; Franquet, Tomas; Gimenez, Ana; Pineda, Rosa; Madrid, Marta; Bordes, Ramon

    2006-01-01

    Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis. (orig.)

  9. Smoking-related interstitial lung diseases: radiologic-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Hidalgo, Alberto [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Hospital de la Santa Creu i Sant Pau, Thoracic Radiology, Department of Radiology, Barcelona (Spain); Franquet, Tomas; Gimenez, Ana; Pineda, Rosa; Madrid, Marta [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Bordes, Ramon [Universidad Autonoma de Barcelona, Department of Pathology, Hospital de Sant Pau, Barcelona (Spain)

    2006-11-15

    Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis. (orig.)

  10. Ultrasound in Rheumatologic Interstitial Lung Disease: A Case Report of Nonspecific Interstitial Pneumonia in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    A. Laria

    2015-01-01

    Full Text Available According to the American Thoracic Society (ATS/European Respiratory Society consensus classification, idiopathic interstitial pneumonias (IIPs include several clinic-radiologic-pathologic entities: idiopathic pulmonary fibrosis (IPF, usual interstitial pneumonia (UIP, nonspecific interstitial pneumonia (NSIP, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia. Ultrasound Lung Comets (ULCs are an echographic chest-sonography hallmark of pulmonary interstitial fibrosis. We describe the ultrasound (US findings in the follow-up of a NSIP’s case in rheumatoid arthritis (RA.

  11. Epidemiologic issues in interstitial cystitis

    NARCIS (Netherlands)

    Parsons, J. Kellogg; Kurth, Karlheinz; Sant, Grannum R.

    2007-01-01

    As a result of variations in disease definition and diagnostic criteria for interstitial cystitis (IC), the performance of epidemiologic studies has been challenging. Initial prevalence studies used physician-confirmed diagnoses of IC; more recent studies, which have incorporated the use of patient

  12. Thermotransport in interstitial solid solutions

    International Nuclear Information System (INIS)

    Fogel'son, R.L.

    1982-01-01

    On the basis of literature data the problem of thermotransport of impurities (H, N, O, C) in interstitial solid solutions is considered. It is shown that from experimental data on the thermotransport an important parameter of dissolved atoms can be found which characterizes atom state in these solutions-enthalpy of transport

  13. [Central lung embolism in chronic interstitial pneumopathy].

    Science.gov (United States)

    Mordasini, C; Hess, B; Zimmermann, A

    1998-04-15

    An 80 year old patient with known interstitial pneumopathy of unknown etiology was hospitalized because of acute onset and rapid deterioration of dyspnea at rest within days. A foregoing neurologic investigation including CT and EEG because of prior syncopes and cramp attacks had not revealed pathologic findings. Thorax X-ray at admission showed homogenous loss of transparency on the left side, calcified basal plaques on both sides and prominent central pulmonary vessels with jumping caliber. A punctate of the leftsided pleural effusion revealed lymphocytic exsudate, normal pH, low glucose and an elevated LDH. The patient died shortly after a collapse at a bowel visit and pulmonary embolism was suspected in accordance to results from arterial blood gas analysis, ECG and chest X-ray. Neurologic symptoms could be explained by recurrent pulmonary embolism. Pleural plaques together with the punctate suggested a malignant etiology. A mesothelioma was taken into consideration, although there were no anamnestic reports on an exposition to asbestos. Autopsy revealed almost complete central embolism of the left pulmonary artery with acute cor pulmonale thus confirming the clinical suspicion. The embolus showed components of different ages of origin. Besides bronchitic and emphysematous alteration histology of the pulmonary tissue revealed interstitial and septal fibrosis with focal tissue consolidation. In one giant cell a typical asbestos body was found (in 1 out of 10 sections). In spite of missing information on an exposition to asbestos an abnormally high exposition must be taken into consideration because of the finding of an asbestos particle in relation to the amount of tissue studied. Apart from interstitial fibrosis asbestos may also cause consolidation of pulmonary tissue. Histology of plaquelike lesions revealed mesothelioma of fibrous type. This finding supports the suspicion that a major part of the pulmonary lesions was due to exposition to asbestos.

  14. Renal extramedullary hematopoiesis: interstitial and glomerular pathology.

    Science.gov (United States)

    Alexander, Mariam P; Nasr, Samih H; Kurtin, Paul J; Casey, Edward T; Hernandez, Loren P Herrera; Fidler, Mary E; Sethi, Sanjeev; Cornell, Lynn D

    2015-12-01

    Renal extramedullary hematopoiesis is rarely recognized in the antemortem setting. We identified 14 patients with renal extramedullary hematopoiesis on antemortem specimens from 1994 to 2015. The mean age was 68 years (range 47-87 years); males predominated (M:F=9:5). All presented with renal insufficiency, including five (36%) with acute kidney injury. The mean serum creatinine at biopsy was 2.9 mg/dl (range 1.2-7.3 mg/dl). All had proteinuria (mean 7.9 g/24 h; range 0.5-28; n=13), including 9 with ≥3 g/24 h. Renal extramedullary hematopoiesis appeared histologically as an interstitial infiltrate (n=12) and/or a perirenal infiltrate (n=3) or mass-like lesion (n=1). Five were misdiagnosed as interstitial nephritis. Concurrent glomerular disease was prevalent and included fibrillary-like glomerulonephritis (n=3), chronic thrombotic microangiopathy (n=5), focal segmental glomerulosclerosis (n=6), and diabetic glomerulosclerosis (n=2). All patients had an underlying hematologic malignancy: primary myelofibrosis in 9, myeloproliferative neoplasm not otherwise specified in 1, essential thrombocythemia in 1, polycythemia vera in 1, and plasma cell myeloma in 2. Clinical follow-up was available in 12 patients, mean of 29 months (range 4-120 months). In 10 patients for whom treatment history could be obtained, 9 were treated with chemotherapy, and 1 was treated with steroids. The mean creatinine at last follow-up was 2 mg/dl (range 1.2-3.9 mg/dl) (n=9). Ten patients died in the follow-up period from their underlying hematological disease and had persistent renal disease. The two remaining patients had persistent chronic kidney disease. Renal extramedullary hematopoiesis should be considered in the differential diagnosis of interstitial infiltrates, particularly in the presence of a glomerulopathy and a hematologic malignancy.

  15. Interstitial impurity interactions and dislocation microdynamics in Mo crystals

    International Nuclear Information System (INIS)

    Kwok, D.N.

    1975-05-01

    The effects of interstitial impurities on the mechanical properties of molybdenum are explored by comparing results obtained for crystals of various interstitial contents controlled by ultra-high vacuum outgassing. Results show a modulus reduction for as-grown samples and for outgassed specimens at low applied stresses. As a function of plastic microstrain, the values of modulus defect for both as-grown and outgassed specimens saturate at the same value. Interstitial impurities act as pinning agents to dislocation bowing, but when all the easy dislocation loops have broken away from local interstitial pins, the modulus defect reaches a constant saturation value. Etch pitting techniques were used to correlate microstrain observations with dislocation generation and motion. It has been found that edge dislocation generation and movement are active in the microstrain region while screw dislocations are relatively inactive until the macrostrain region is reached. Dislocation velocities range from 10 -6 to 10 -3 cm/s and the average distance between interstitial impurity pinning points is found to be approximately 8 x 10 -4 cm. (U.S.)

  16. Acute ciprofloxacin-induced crystal nephropathy with granulomatous interstitial nephritis

    Directory of Open Access Journals (Sweden)

    R Goli

    2017-01-01

    Full Text Available Crystal-induced acute kidney injury (AKI is caused by the intratubular precipitation of crystals, which results in obstruction and kidney injury. Ciprofloxacin, a commonly used antibiotic, causes AKI secondary to immune-mediated interstitial injury. Rare mechanisms of ciprofloxacin-induced renal injury include crystalluria, rhabdomyolysis, and granulomatous interstitial nephritis. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy due to ciprofloxacin occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of ciprofloxacin-induced crystal nephropathy and granulomatous interstitial nephritis in a young patient with no other predisposing factors. The patient responded to conservative treatment without the need for glucocorticoids.

  17. Interstitial brachytherapy for eyelid carcinoma. Outcome analysis in 60 patients

    Energy Technology Data Exchange (ETDEWEB)

    Krengli, M.; Deantonio, L. [University Hospital ' ' Maggiore della Carita' ' , Division of Radiotherapy, Novara (Italy); University of ' ' Piemonte Orientale' ' , Department of Translational Medicine, Novara (Italy); Masini, L.; Filomeno, A.; Gambaro, G. [University Hospital ' ' Maggiore della Carita' ' , Division of Radiotherapy, Novara (Italy); Comoli, A.M. [University Hospital Maggiore della Carita, Ophthalmology, Novara (Italy); Negri, E. [University Hospital Maggiore della Carita, Medical Physics, Novara (Italy)

    2014-03-15

    Eyelid cancer is a therapeutic challenge due to the cosmetic and functional implications of this anatomical region and the objectives of therapy are tumor control, functional and cosmetic outcome. The present study was performed to analyze local control, toxicity, functional and cosmetic results in patients with eyelid carcinoma treated by interstitial brachytherapy. In this study 60 patients with eyelid carcinoma were treated by interstitial brachytherapy using iridium ({sup 192}Ir) wires with a linear activity of 1.2-1.7 mCi/cm. The prescription dose was 51-70 Gy (mean 65 Gy, median 66 Gy). Of the 60 patients 51 (85.0 %) had received no prior treatment, 4 (6.7 %) had received previous surgery with positive or close margins and 5 (8.3 %) had suffered local recurrence after surgery. Of the tumors 52 (86.7 %) were basal cell carcinoma, 7 (11.7 %) squamous cell carcinoma and 1 (1.7 %) Merkel cell carcinoma. Clinical stage of the 51 previously untreated tumors was 38 T1N0, 12 T2N0 and 1 T3N0. Mean follow-up was 92 months (range 6-253 months). Local control was maintained in 96.7 % of patients. Late effects higher than grade 2 were observed in 3.0 % of cases. Functional and cosmetic outcomes were optimal in 68.4 % of patients. Interstitial brachytherapy for carcinoma of the eyelid can achieve local control, cosmetic and functional results comparable to those of surgery. (orig.) [German] Das Karzinom des Augenlids stellt aufgrund der funktionellen und kosmetischen Beeintraechtigungen dieser anatomischen Region eine therapeutische Herausforderung dar. Ziele der Therapie sind sowohl die Tumorkontrolle als auch ein gutes funktionelles und kosmetisches Ergebnis. Lokale Kontrolle, Toxizitaet sowie funktionelle und kosmetische Ergebnisse bei Patienten mit Karzinom des Augenlids, die mit interstitieller Brachytherapie behandelt wurden, sollten analysiert werden. Sechzig Patienten mit Karzinom des Augenlids wurden mit interstitieller Brachytherapie mit Iridium-192-Draehten

  18. Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

    Directory of Open Access Journals (Sweden)

    Federica Novelli

    Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

  19. Development of a practical animal model of photodynamic therapy using a high concentration of extracellular talaporfin sodium in interstitial fluid: influence of albumin animal species on myocardial cell photocytotoxicity in vitro.

    Science.gov (United States)

    Ogawa, Emiyu; Arai, Tsunenori

    2017-12-01

    Photodynamic reaction-induced photocytotoxicity using talaporfin sodium is inhibited by serum proteins binding to talaporfin sodium. The serum albumin binding site for talaporfin sodium differs among animal species. To identify a practical animal therapeutic model, we studied the ability of human, canine, bovine, and porcine albumin to influence talaporfin sodium-induced photocytotoxicity in rat myocardial cells in vitro. Human, canine, bovine, and porcine serum albumins were used. The ratio of talaporfin sodium binding, which is strongly associated with photocytotoxicity, was measured by ultrafiltration with an albumin concentration of 0.5-20 mg/ml and 20 μg/ml talaporfin sodium to mimic interstitial fluid. Rat myocardial cell lethality was measured by the WST assay 2 h after samples were exposed to a radiant exposure of 20 J/cm 2 by a red diode laser (Optical Fuel™, Sony, Tokyo, Japan) with a wavelength of 663 nm. The binding ratio dependence on albumin concentration differed among the animal species. Bovine albumin exhibited the largest difference from human albumin, with a maximum difference of 31% at 2 mg/ml albumin. The cell lethality characteristic was similar between human and canine albumin. The cell lethality dependence on albumin was not in the same order as the binding ratio. Cell lethality was lowest for human albumin with higher albumin concentrations between 5 and 20 mg/ml. There were no significant differences in cell lethality between bovine and porcine albumin and between human and canine albumin. We suggest that the canine model may be a useful animal therapeutic model for evaluating photodynamic therapy using a high concentration of the photosensitizer in the extracellular space.

  20. Intravesical liposome therapy for interstitial cystitis.

    Science.gov (United States)

    Tyagi, Pradeep; Kashyap, Mahendra; Majima, Tsuyoshi; Kawamorita, Naoki; Yoshizawa, Tsuyoshi; Yoshimura, Naoki

    2017-04-01

    Over the past two decades, there has been lot of interest in the use of liposomes as lipid-based biocompatible carriers for drugs administered by the intravesical route. The lipidic bilayer structure of liposomes facilitates their adherence to the apical membrane surface of luminal cells in the bladder, and their vesicular shape allows them to co-opt the endocytosis machinery for bladder uptake after instillation. Liposomes have been shown to enhance the penetration of both water-soluble and insoluble drugs, toxins, and oligonucleotides across the bladder epithelium. Empty liposomes composed entirely of the endogenous phospholipid, sphingomyelin, could counter mucosal inflammation and promote wound healing in patients suffering from interstitial cystitis. Recent clinical studies have tested multilamellar liposomes composed entirely of sphingomyelin as a novel intravesical therapy for interstitial cystitis. In addition, liposomes have been used as a delivery platform for the instillation of botulinum toxin in overactive bladder patients. The present review discusses the properties of liposomes that are important for their intrinsic therapeutic effect, summarizes the recently completed clinical studies with intravesical liposomes and covers the latest developments in this field. © 2017 The Japanese Urological Association.

  1. Impaired Leydig cell function in infertile men

    DEFF Research Database (Denmark)

    Andersson, A-M; Jørgensen, N; Frydelund-Larsen, L

    2004-01-01

    To investigate whether an impaired Leydig cell function is present in severely oligospermic men, serum testosterone (T), LH, estradiol (E(2)), and SHBG levels in 357 idiopathic infertile men were compared with levels in 318 proven fertile men. In addition, the T/LH ratio, E(2)/T ratio, and calcul......To investigate whether an impaired Leydig cell function is present in severely oligospermic men, serum testosterone (T), LH, estradiol (E(2)), and SHBG levels in 357 idiopathic infertile men were compared with levels in 318 proven fertile men. In addition, the T/LH ratio, E(2)/T ratio......, and calculated free T index (cFT) were compared between the two groups.A shift toward lower serum T levels, cFT, and T/LH ratio and higher serum LH, E(2), and E(2)/T levels was observed in the group of infertile men. On average, the infertile men had 18, 26, and 34% lower serum T, cFT, and T/LH levels......, respectively, and 19, 18, and 33% higher serum LH, E(2), and E(2)/T levels, respectively, than the fertile men. Twelve percent of the infertile men had a serum T level that fell below the 2.5 percentile of the fertile levels, and 15% of the infertile men had a LH level that was above the 97.5 percentile...

  2. TMC function in hair cell transduction

    Science.gov (United States)

    Holt, Jeffrey R.; Pan, Bifeng; Koussa, Mounir A.; Asai, Yukako

    2014-01-01

    Transmembrane channel-like (TMC) proteins 1 and 2 are necessary for hair cell mechanotransduction but their precise function is controversial. A growing body of evidence supports a direct role for TMC1 and TMC2 as components of the transduction complex. However, a number of important questions remain and alternate hypotheses have been proposed. Here we present an historical overview of the identification and cloning of Tmc genes, a discussion of mutations in TMC1 that cause deafness in mice and humans and a brief review of other members of the Tmc gene superfamily. We also examine expression of Tmc mRNAs and localization of the protein products. The review focuses on potential functions of TMC proteins and the evidence from Beethoven mice that suggests a direct role for TMC1 in hair cell mechanotransduction. Data that support alternate interpretations are also considered. The article concludes with a discussion of outstanding questions and future directions for TMC research. This article is part of a Special Issue entitled “Annual Reviews 2014”. PMID:24423408

  3. Histamine regulates murine primary dendritic cell functions.

    Science.gov (United States)

    Schenk, Heiko; Neumann, Detlef; Kloth, Christina

    2016-10-01

    The modulation of antigen uptake and activation of dendritic cells (DCs) by histamine may function as a regulator of inflammation. Therefore, we sought to determine the impact of histamine on antigen uptake by and activation of murine DCs. DCs from spleen and lung were either identified by flow cytometry or were immunomagnetically enriched. Cells were stimulated with histamine, and the regulation of MHC-II and co-stimulatory molecule expression (CD80, CD86, and ICOS-L) and antigen uptake were quantified by flow cytometry. Individual contributions of the histamine receptor subtypes were determined by using the antagonists mepyramine (histamine H1-receptor: H1R), famotidine (H2R), and JNJ 7777120 (H4R). Histamine accelerated the uptake of soluble antigen via the H1R, H2R, and H4R in splenic DCs. Co-stimulatory molecule expression was enhanced already by enrichment procedures, thus, the analyses were performed in unseparated cell populations. Histamine enhanced the expression of CD86 and ICOS-L while expression of CD80 was unaffected. Antagonism at H1R, H2R, and H4R and at H1R and H4R reduced the histamine-induced enhanced expression of CD86 and ICOS-L, respectively. Histamine contributes to the regulation of the immunological synapse by stimulation of antigen uptake and activation of DCs via H1R, H2R, and H4R.

  4. Interstitial microwave hyperthermia treatment investigations

    International Nuclear Information System (INIS)

    Siauve, N; Lormel, C

    2012-01-01

    Microwave ablation also called interstitial hyperthermia is a medical procedure used in the treatment of many cancers, cardiac arrhythmias and other medical conditions. With this medical therapy, an electromagnetic source (antenna) is directly positioned in the target tissue and a sufficient power is injected to necrosis the tissue. The aim of this study is to propose a design procedure and develop the associated tools, for determining the optimal shape, dimensions, type and operating frequency of antenna according to the target volume. In this context, a 3D numerical predictive model of temperature elevation induced by the electric fields and two benches for thermal and electrical tissues properties characterization have been developed. To validate the procedure and the different tools, an experimental bench test which includes interstitial antenna, external microwave generator, phantom that represents the target tissue and measurement system of temperature and electric field has been elaborated.

  5. Origins of Protein Functions in Cells

    Science.gov (United States)

    Seelig, Burchard; Pohorille, Andrzej

    2011-01-01

    In modern organisms proteins perform a majority of cellular functions, such as chemical catalysis, energy transduction and transport of material across cell walls. Although great strides have been made towards understanding protein evolution, a meaningful extrapolation from contemporary proteins to their earliest ancestors is virtually impossible. In an alternative approach, the origin of water-soluble proteins was probed through the synthesis and in vitro evolution of very large libraries of random amino acid sequences. In combination with computer modeling and simulations, these experiments allow us to address a number of fundamental questions about the origins of proteins. Can functionality emerge from random sequences of proteins? How did the initial repertoire of functional proteins diversify to facilitate new functions? Did this diversification proceed primarily through drawing novel functionalities from random sequences or through evolution of already existing proto-enzymes? Did protein evolution start from a pool of proteins defined by a frozen accident and other collections of proteins could start a different evolutionary pathway? Although we do not have definitive answers to these questions yet, important clues have been uncovered. In one example (Keefe and Szostak, 2001), novel ATP binding proteins were identified that appear to be unrelated in both sequence and structure to any known ATP binding proteins. One of these proteins was subsequently redesigned computationally to bind GTP through introducing several mutations that introduce targeted structural changes to the protein, improve its binding to guanine and prevent water from accessing the active center. This study facilitates further investigations of individual evolutionary steps that lead to a change of function in primordial proteins. In a second study (Seelig and Szostak, 2007), novel enzymes were generated that can join two pieces of RNA in a reaction for which no natural enzymes are known

  6. Morfologia das células intersticiais de ovários policísticos de ratas: um estudo experimental Morphology of the interstitial cells of rat polycystic ovaries: an experimental study

    Directory of Open Access Journals (Sweden)

    Leonardo Augusto Lombardi

    2012-07-01

    Full Text Available OBJETIVOS: Avaliar a histomorfometria das células intersticiais dos ovários, bem como analisar a concentração sanguínea de esteroides sexuais de ratas portadoras de ovários policísticos induzidos pela luz contínua. MÉTODOS: Vinte ratas foram divididas em dois grupos: ratas na fase de estro (GCtrl e ratas portadoras de ovários policísticos induzidos pela iluminação contínua (GOP. Os animais do GCtrl permaneceram com período de luz das 7:00 s 19:00 horas, e os animais do GOP, com iluminação contínua (400 Lux, durante um período de 60 dias. Ao final desse período todos os animais foram anestesiados, foi coletado o sangue, para determinação dos níveis séricos de estradiol (E2, progesterona (P4 e testosterona (T, seguido da retirada dos ovários que foram fixados em formol a 10% e processados para inclusão em parafina. Cortes histológicos com 5 µm corados pela hematoxilina e eosina foram utilizados para análise histomorfométrica. As análises morfológicas, contagem de cistos, determinação da concentração e do volume nuclear das células intersticiais foram realizadas com o auxílio de microscópio de luz adaptado a uma câmera de alta resolução (AxioCam, cujas imagens foram transmitidas e analisadas em computador com software AxioVision Rel 4.8 (Carl Zeiss. Os dados obtidos foram submetidos ao teste t de Student (pGCtrl=73,2±6,5; pGCtrl=80,6±3,9; pGOP=4,2±1,5; pGCtrl=63,6±16,5; pGCtrl=6,9±3,2; pPURPOSES: To evaluate the histomorphometry of ovarian interstitial cells, as well as the blood sex steroid concentrations of female rats with polycystic ovaries induced by continuous light. METHODS: Twenty female rats were divided into two groups: Control Group - in the estrous phase (CtrlG, and a group of rats with polycystic ovaries induced by continuous illumination (POG. CtrlG animals were maintained on a light period from 07:00 a.m. to 07:00 p.m., and POG animals with continuous illumination (400 Lux for 60 days

  7. The multiple faces of leukocyte interstitial migration

    Science.gov (United States)

    Lämmermann, Tim; Germain, Ronald N.

    2014-01-01

    Spatiotemporal control of leukocyte dynamics within tissues is critical for successful innate and adaptive immune responses. Homeostatic trafficking and coordinated infiltration into and within sites of inflammation and infection rely on signaling in response to extracellular cues that in turn controls a variety of intracellular protein networks regulating leukocyte motility, migration, chemotaxis, positioning, and cell–cell interaction. In contrast to mesenchymal cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin polymerization and actomyosin contraction, and their migration in tissues is generally referred to as low adhesive and nonproteolytic. The interplay of actin network expansion, contraction, and adhesion shapes the exact mode of amoeboid migration, and in this review, we explore how leukocyte subsets potentially harness the same basic biomechanical mechanisms in a cell-type-specific manner. Most of our detailed understanding of these processes derives from in vitro migration studies in three-dimensional gels and confined spaces that mimic geometrical aspects of physiological tissues. We summarize these in vitro results and then critically compare them to data from intravital imaging of leukocyte interstitial migration in mouse tissues. We outline the technical challenges of obtaining conclusive mechanistic results from intravital studies, discuss leukocyte migration strategies in vivo, and present examples of mode switching during physiological interstitial migration. These findings are also placed in the context of leukocyte migration defects in primary immunodeficiencies. This overview of both in vitro and in vivo studies highlights recent progress in understanding the molecular and biophysical mechanisms that shape robust leukocyte migration responses in physiologically complex and heterogeneous environments. PMID:24573488

  8. Interstitial photonic radiosurgery for brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Osami; Muragaki, Yoshihiro; Iseki, Hiroshi; Hori, Tomokatsu; Takakura, Kintomo [Tokyo Women' s Medical Coll. (Japan). Neurological Inst.

    1999-12-01

    The photon radiosurgery system (PRS) is a developed of the Photo-electron Corp. of Walham, Mass. The heart of this system is a thin needle, 3 mm in diameter and 100 mm long, from whose tip low-energy X-ray photon are isotropically emitted. This apparatus is a compact radiosurgery system that irradiates soft X ray from the tip of its small probe (weight of the machine=1.9 Kg). The PRS can be used either with a stereotactic frame or during a craniotomy as interstitial radiotherapy. The PRS is able to irradiate 15 Gy at the portion of 1.5 cm from the center for about 20 minutes and avoid severe damage to surrounding normal brain because of steep dose distribution curve. Because this system emits low-energy photons, almost the x-rays are attenuated in the patient. For a treatment of this system, dose rates outside the patient are close to background radiation levels. No special shielding of the patient or health care personnel is required. Basic examination of this system was done. C 6 cell line of Glioma was irradiated by PRS in vitro. A majority of tumor cells were died after 24 hrs. This time we estimated the effect of the PRS for brain tumors. We underwent the PRS to 72 patients from June 1995 to May 1999. Sixty-eight patients underwent intraoperative irradiation after removal and 4 patients had interstitial irradiation after stereotactic biopsy. All 16 cases of primary anaplastic astrocytomas survived and demonstrated good Karnofski performance scale. Median survival tomes of 17 primary cases of glioblastoma is 14 month. Two cases of malignant lymphoma showed complete remission in CT scan 24 hours after intraoperative radiosurgery using PRS and 2 cases of germ cell tumor demonstrated dramatic decrease of tumor size in a short period. There was no definite newly neurological deficit. The intraoperative radiosurgery using PRS is useful adjuvant therapy for brain tumors. (author)

  9. Early history of subplate and interstitial neurons: from Theodor Meynert (1867) to the discovery of the subplate zone (1974)

    Science.gov (United States)

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil

    2010-01-01

    In this historical review, we trace the early history of research on the fetal subplate zone, subplate neurons and interstitial neurons in the white matter of the adult nervous system. We arrive at several general conclusions. First, a century of research clearly testifies that interstitial neurons, subplate neurons and the subplate zone were first observed and variously described in the human brain – or, in more general terms, in large brains of gyrencephalic mammals, characterized by an abundant white matter and slow and protracted prenatal and postnatal development. Secondly, the subplate zone cannot be meaningfully defined using a single criterion – be it a specific population of cells, fibres or a specific molecular or genetic marker. The subplate zone is a highly dynamic architectonic compartment and its size and cellular composition do not remain constant during development. Thirdly, it is important to make a clear distinction between the subplate zone and the subplate (and interstitial) neurons. The transient existence of the subplate zone (as a specific architectonic compartment of the fetal telencephalic wall) should not be equated with the putative transient existence of subplate neurons. It is clear that in rodents, and to an even greater extent in humans and monkeys, a significant number of subplate cells survive and remain functional throughout life. PMID:20979585

  10. Interstitial laser photocoagulation in the treatment of liver tumors. Personal technique, short term results and complications in patients with normal and impaired liver function; Fotocoagulazione laser-interstiziale ecoguidata dei tumori maligni del fegato: tecnica personale, risultati immediati e complicanze a breve termine nei pazienti con funzionalita' epatica normale e alterata

    Energy Technology Data Exchange (ETDEWEB)

    Giorgio, A.; Tarantino, L.; De Stefano, G.; Farella, N. [Azienda Ospedaliera D. Cotugno, Naples (Italy). Servizio di Ecografia ed Ecointerventistica; Catalano, O.; Cusati, B. [Ospedale S. Maria delle Grazie, Pozzuoli, NA (Italy). Servizio di Radiologia; Alalia, A. [Azienda Ospedaliera D. Cotugno, Naples (Italy). Servizio di Anestesia e Rianimazione; Del Vescovo, L. [Naples Univ. II, Naples (Italy). Ist. di Radiologia

    2000-04-01

    The work reports the personal experience with interstitial laser photocoagulation in patients with liver tumors (mostly cirrhotics with hepatocellular carcinoma). The aim was to evaluate the short term efficacy of percutaneous interstitial laser photocoagulation in inducing focal ablation of liver tumors and the possible complications in patients with normal and impaired liver function. [Italian] Il presente lavoro riporta l'esperienza personale con l'utilizzazione della fotocoagulazione laser-interstiziale per tumori maligni del fegato, rappresentati in gran parte da epatocarcinomi in cirrosi. Lo scopo e' quello di verificare l'efficacia terapeutica in termini di volume di necrosi e di valutare gli effetti collaterali e le complicanze a breve termine sulla riserva funzionale del fegato e di altri organi, soprattutto nei pazienti con alterata funzionalita' epatica.

  11. Uncovering Factors Related to Pancreatic Beta-Cell Function

    OpenAIRE

    Curran, Aoife M.; Ryan, Miriam F.; Drummond, Elaine; Gibney, Eileen R.; Gibney, Michael J.; Roche, Helen M.; Brennan, Lorraine

    2016-01-01

    Aim: The incidence of type 2 diabetes has increased rapidly on a global scale. Beta-cell dysfunction contributes to the overall pathogenesis of type 2 diabetes. However, factors contributing to beta-cell function are not clear. The aims of this study were (i) to identify factors related to pancreatic beta-cell function and (ii) to perform mechanistic studies in vitro. Methods: Three specific measures of beta-cell function were assessed for 110 participants who completed an oral glucose tolera...

  12. Expression and function of nicotinic acetylcholine receptors in stem cells

    Directory of Open Access Journals (Sweden)

    Herman S. Cheung

    2016-07-01

    Full Text Available Nicotinic acetylcholine receptors are prototypical ligand gated ion channels typically found in muscular and neuronal tissues. Functional nicotinic acetylcholine receptors, however, have also recently been identified on other cell types, including stem cells. Activation of these receptors by the binding of agonists like choline, acetylcholine, or nicotine has been implicated in many cellular changes. In regards to stem cell function, nicotinic acetylcholine receptor activation leads to changes in stem cell proliferation, migration and differentiation potential. In this review we summarize the expression and function of known nicotinic acetylcholine receptors in different classes of stem cells including: pluripotent stem cells, mesenchymal stem cells, periodontal ligament derived stem cells, and neural progenitor cells and discuss the potential downstream effects of receptor activation on stem cell function.

  13. Potential urine and serum biomarkers for patients with bladder pain syndrome/interstitial cystitis.

    Science.gov (United States)

    Kuo, Hann-Chorng

    2014-04-01

    There is a lack of consensus on the pathophysiology of bladder pain syndrome/interstitial cystitis. The chronic pain symptoms of bladder pain syndrome/interstitial cystitis refractory to local treatment could be a result of central nervous system sensitization and persisting abnormalities in the bladder wall, which activate the afferent sensory system. Evidence also shows that bladder pain syndrome/interstitial cystitis is a heterogeneous syndrome and that the two subtypes, the ulcerative (classic) and non-ulcerative types, represent different disease entities. There is a need for non-invasive markers for the differential diagnoses of the subtypes of bladder pain syndrome/interstitial cystitis, and between bladder pain syndrome/interstitial cystitis and bladder sensory disorders, such as hypersensitive bladder syndrome or overactive bladder. Bladder pain syndrome/interstitial cystitis, but not overactive bladder, involves an aberrant differentiation program in the bladder urothelium that leads to altered synthesis of several proteoglycans, cell adhesion and tight junction proteins, and bacterial defense molecules. These findings have led to the rationale for identifying urinary biomarkers to detect bladder pain syndrome/interstitial cystitis in patients with frequency urgency syndrome. Recently, the markers that have been the focus of the most research are antiproliferative factor, epidermal growth factor, heparin-binding epidermal growth factor, glycosaminoglycans and bladder nitric oxide. In addition, inflammatory proteins in the urine and serum play important roles in the pathogenesis of bladder pain syndrome/interstitial cystitis. The urinary proteome is an easily accessible source of biomarkers for differentiation between inflammatory bladder disorders. Analysis of multiple urinary proteins and serum cytokines could provide a diagnostic basis for bladder pain syndrome/interstitial cystitis, and could be a tool for the differential diagnosis of bladder pain

  14. Differential perturbation of the interstitial cystitis-associated genes of bladder and urethra in rat model.

    Science.gov (United States)

    Choi, Bo-Hwa; You, Sungyong; Park, Chang-Shin; Cho, Eun-Ho; Park, Taeeun D; Kim, Sungsoo; Kim, Young-Ju; Lee, Tack; Kim, Jayoung

    2017-04-18

    Interstitial cystitis (IC) is a chronic bladder dysfunction characterized as urinary frequency, urgency, nocturia, and pelvic pain. The changes in urethra may wind up with the bladder changes in structure and functions, however, the functions of the urethra in IC remains elusive. The aim of this study was to understand the perturbed gene expression in urethra, compared with urinary bladder, associated with the defected urodynamics. Using female IC mimic rats, a comprehensive RNA-sequencing combined with a bioinformatics analysis was performed and revealed that IC-specific genes in bladder or urethra. Gene ontology analysis suggested that the cell adhesion or extracellular matrix regulation, intracellular signaling cascade, cardiac muscle tissue development, and second messenger-mediated signaling might be the most enriched cellular processes in IC context. Further study of the effects of these bladder- or urethra-specific genes may suggest underlying mechanism of lower urinary tract function and novel therapeutic strategies against IC.

  15. Systems medicine advances in interstitial lung disease.

    Science.gov (United States)

    Greiffo, Flavia R; Eickelberg, Oliver; Fernandez, Isis E

    2017-09-30

    Fibrotic lung diseases involve subject-environment interactions, together with dysregulated homeostatic processes, impaired DNA repair and distorted immune functions. Systems medicine-based approaches are used to analyse diseases in a holistic manner, by integrating systems biology platforms along with clinical parameters, for the purpose of understanding disease origin, progression, exacerbation and remission.Interstitial lung diseases (ILDs) refer to a heterogeneous group of complex fibrotic diseases. The increase of systems medicine-based approaches in the understanding of ILDs provides exceptional advantages by improving diagnostics, unravelling phenotypical differences, and stratifying patient populations by predictable outcomes and personalised treatments. This review discusses the state-of-the-art contributions of systems medicine-based approaches in ILDs over the past 5 years. Copyright ©ERS 2017.

  16. Stability and mobility of self-interstitials and small interstitial clusters in α-iron: ab initio and empirical potential calculations

    International Nuclear Information System (INIS)

    Willaime, F.; Fu, C.C.; Marinica, M.C.; Dalla Torre, J.

    2005-01-01

    The stability and mobility of self-interstitials and small interstitial clusters, I n , in α-Fe is investigated by means of calculations performed in the framework of the density functional theory using the SIESTA code. The mono-, di- and tri-interstitials are shown to be made of (parallel) dumbbells and to migrate by nearest-neighbor translation-rotation jumps, according to Johnson's mechanism. The orientation of the dumbbells becomes energetically more favourable for I 5 and larger clusters. The performance of a semi-empirical potential recently developed for Fe, including ab initio self-interstitial data in the fitted properties, is evaluated over the present results. The superiority over previous semi-empirical potentials is confirmed. Finally the impact of the present results on the formation mechanism of loops, observed experimentally in α-Fe is discussed

  17. [Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

    Science.gov (United States)

    Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

    2014-09-15

    Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  18. Quantitative pulmonary gallium scanning in interstitial lung disease

    International Nuclear Information System (INIS)

    Ramsay, S.C.; Yeates, M.G.; Burke, W.M.J.; Morgan, G.W.; Breit, S.N.; Bryant, D.H.

    1992-01-01

    The mechanisms responsible for gallium uptake in chronic, non-infective, diffuse lung disease are not completely understood. This study attempted to clarify some of them. A lung/liver gallium index was calculated in 113 subjects, some normal and some with various interstitial lung diseases, predominantly those associated with connective tissue disease. The mean gallium index was significantly higher in the groups with active interstitial lung disease (5.7) and non-infective bronchiolitis (4.1) compared with non-smoking normals (3.0; P<0.05). To investigate the mechanisms responsible for gallium uptake, the gallium index was correlated with bronchoalveolar lavage findings, respiratory function tests and clinical features. Significant correlations (P<0.05) were found with age in non-smoking normals; lavage macrophages in smoking normals; age but no other parameter in bronchiolitis; lavage lymphocytes, lavage albumin and improvement in diffusion capacity for carbon monoxide in those with active interstitial lung disease. It is concluded that in normal smokers gallium uptake may be due to a macrophage-mediated process. Gallium uptake in active interstitial lung disease associated with connective tissue disease appears to be an immunological process in which transport and retention of gallium is associated with that of albumin. (orig.)

  19. Investigations of lymphatic drainage from the interstitial space

    Science.gov (United States)

    Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration

    2017-11-01

    The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.

  20. Motility patterns and distribution of interstitial cells of Cajal and nitrergic neurons in the proximal, mid- and distal-colon of the rat

    DEFF Research Database (Denmark)

    Albertí, E; Mikkelsen, Hanne Birte; Larsen, Jytte Overgaard

    2005-01-01

    . We described two types of spontaneous contractions: high frequency (HF) and low frequency (LF) contractions, which were recorded in the presence of tetrodotoxin, suggesting a non-neurogenic origin. Regional differences were found in the motility patterns depending on the muscle layer and on the part...... of the colon studied. Muscle strips without submuscular plexus (SMP) showed only LF contractions. The density of ICCs was of the same magnitude along the extent of the colon: about 90-120 cells mm(-2) at Auerbach's plexus (AP) and 50-60 cells mm(-2) at the SMP. nNOS positive cells were found at the level...... of the AP and the major density was found in the mid-colon. Electrical field stimulation abolished LF but did not affect HF contractions. Our results indicate that HF contractions are due to the ICC network found associated with the submuscular plexus (ICC-SMP). The origin of LF contractions is still...

  1. Inflammation characteristics in bladder pain syndrome ESSIC type 3C/classic interstitial cystitis.

    Science.gov (United States)

    Logadottir, Yr; Delbro, Dick; Lindholm, Catharina; Fall, Magnus; Peeker, Ralph

    2014-04-01

    Interstitial cystitis is regarded as a heterogenous syndrome with two distinguishable forms: the non-ulcer and the classic form of interstitial cystitis, the latter with Hunner's lesions; or bladder pain syndrome type 3C and non-Hunner bladder pain syndrome, respectively. A cohort of 379 patients diagnosed with interstitial cystitis was studied. Nitric oxide release from the bladder was measured using a chemiluminescence nitric oxide analyzer. Bladder biopsies from the patients and healthy controls were analyzed by routine histopathological examination. Biopsies from a subset of patients and controls were also analyzed by immunohistochemistry and cytokine gene expression by real-time polymerase chain reaction. Patients with bladder pain syndrome type 3C/classic interstitial cystitis had considerably higher levels of nitric oxide as compared with non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients and healthy individuals, and showed histologically a chronic inflammation in the bladder mucosa, with abundant mast cell infiltration in all layers of the bladder wall. No inflammation was noted in non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients. The isoenzymes inducible nitric oxide synthase, the catalyst in the nitric oxide production, was strongly expressed in the inflammatory cells in the bladder mucosa of bladder pain syndrome type 3C/classic interstitial cystitis patients. In addition, the expression of the pro-inflammatory cytokines interleukin-6 and interleukin-17A messenger ribonucleic acid, and of anti-inflammatory interleukin-10 messenger ribonucleic acid showed significantly increased levels in bladder pain syndrome type 3C/classic interstitial cystitis compared with healthy controls. Bladder pain syndrome type 3C/classic interstitial cystitis is a distinct inflammatory disease and in many aspects shares features of inflammatory autoimmune diseases. These findings could open up novel research avenues with

  2. The in vitro cytotoxicity of urine from patients with interstitial cystitis

    DEFF Research Database (Denmark)

    Beier-Holgersen, R; Hermann, G G; Mortensen, S O

    1994-01-01

    Urine from patients with interstitial cystitis has been reported to be more cytotoxic than urine from healthy subjects when tested in vitro against cells from a normal urothelial cell line. The purpose of the present study was to develop a method to measure urinary cytotoxicity and so make...... it possible to estimate the toxicity of urine from interstitial cystitis patients. The study included 10 women with interstitial cystitis and 10 healthy controls. Urine specimens were obtained from both groups and urine cytotoxicity was measured by a modified 51Cr-release assay: A range of urine dilutions...... in urine cytotoxicity between interstitial cystitis patients and healthy controls. Urine cytotoxicity was increased by dilution in both groups....

  3. Computer-Aided Tomographic Analysis of Interstitial Lung Disease (ILD in Patients with Systemic Sclerosis (SSc. Correlation with Pulmonary Physiologic Tests and Patient-Centred Measures of Perceived Dyspnea and Functional Disability.

    Directory of Open Access Journals (Sweden)

    Fausto Salaffi

    Full Text Available This study was designed (a to evaluate an improved quantitative lung fibrosis score based on a computer-aided diagnosis (CaM system in patients with systemic sclerosis (SSc,-related interstitial lung disease (SSc-ILD, (b to investigate the relationship between physiologic parameters (forced vital capacity [FVC] and single-breath diffusing capacity for carbon monoxide [DLCO], patient-centred measures of dyspnea and functional disability and CaM and visual reader-based (CoVR methods, and (c to identify potential surrogate measures from quantitative and visual HRCT measurement.126 patients with SSc underwent chest radiography, HRCT and PFTs. The following patient-centred measures were obtained: modified Borg Dyspnea Index (Borg score, VAS for breathing, and Health Assessment Questionnaire-Disability Index (HAQ-DI. HRCT abnormalities were scored according to the conventional visual reader-based score (CoVR and by a CaM. The relationships among the HRCT scores, physiologic parameters (FVC and DLCO, % predicted results and patient-centred measures, were calculated using linear regression analysis and Pearson's correlation. Multivariate regression models were performed to identify the predictor variables on severity of pulmonary fibrosis.Subjects with limited cutaneous SSc had lower HAQ-DI scores than subjects with diffuse cutaneous SSc (p <0.001. CaM and CoVR scores were similar in the 2 groups. In univariate analysis, a strong correlation between CaM and CoVR was observed (p <0.0001. In multivariate analysis the CaM and CoVR scores were predicted by DLco, FVC, Borg score and HAQ-DI. Age, sex, disease duration, anti-topoisomerase antibodies and mRSS were not significantly associated with severity of pulmonary fibrosis on CaM- and CoVR methods.Although a close correlation between CaM score results and CoVR total score was found, CaM analysis showed a more significant correlation with DLco (more so than the FVC, patient-centred measures of perceived

  4. 99mTc-IgG-Lung Scintigraphy in the Assessment of Pulmonary Involvement in Interstitial Lung Disease and Its Comparison With Pulmonary Function Tests and High-Resolution Computed Tomography: A Preliminary Study

    International Nuclear Information System (INIS)

    Bahtouee, Mehrzad; Saberifard, Jamshid; Javadi, Hamid; Nabipour, Iraj; Malakizadeh, Hasan; Monavvarsadegh, Gholamhossein; Ilkhani Pak, Hoda; Sadeghi, Azadeh; Assadi, Majid

    2015-01-01

    The discrimination of inactive inflammatory processes from the active form of the disease is of great importance in the management of interstitial lung disease (ILD). The aim of this study was to determine the efficacy of 99mTc-IgG scan for the detection of severity of disease compared to high-resolution computed tomography (HRCT) and pulmonary function test (PFT). Eight known cases of ILD including four cases of Mustard gas (MG) intoxication and four patients with ILD of unknown cause were included in this study. A population of six patients without lung disease was considered as the control group. The patients underwent PFT and high-resolution computed tomography, followed by 99mTc-IgG scan. They were followed up for one year. 99mTc-IgG scan assessment of IgG uptake was accomplished both qualitatively (subjectively) and semiquantitatively. All eight ILD patients demonstrated a strong increase in 99mTc-IgG uptake in the lungs, compared to the control patients. The 99mTc-IgG scan scores were higher in the patient group (0.64[95% confidence interval(CI)=0.61-0.69])) than the control group (0.35 (0.35[95% CI=0.28-0.40]), (P<0.05)). In patients, a statistically significant positive correlation was detected between 99mTc-IgG scan and HRCT scores (Spearman’s correlation coefficient = 0.92, P < 0.008). The 99mTc-Human Immunoglobulin (HIG) scores were not significantly correlated with PFT findings (including FVC, FEV1, FEV1/FVC), O 2 saturation and age (P values > 0.05). There were no significant correlations between 99mTc-IgG score and HRCT patterns including ground glass opacity, reticular fibrosis and honeycombing (P value > 0.05). The present results confirmed that 99mTc-IgG scan could be applied to detect the severity of pulmonary involvement, which was well correlated with HRCT findings. This data also showed that the 99mTc-IgG scan might be used as a complement to HRCT in the functional evaluation of the clinical status in ILD; however, further studies are

  5. Tumor necrosis factor-α accelerates the calcification of human aortic valve interstitial cells obtained from patients with calcific aortic valve stenosis via the BMP2-Dlx5 pathway.

    Science.gov (United States)

    Yu, Zaiqiang; Seya, Kazuhiko; Daitoku, Kazuyuki; Motomura, Shigeru; Fukuda, Ikuo; Furukawa, Ken-Ichi

    2011-04-01

    Calcific aortic valve stenosis (CAS) is the most frequent heart valve disease in the elderly, accompanied by valve calcification. Tumor necrosis factor-α (TNF-α), a pleiotropic cytokine secreted mainly from macrophages, has been detected in human calcified valves. However, the role of TNF-α in valve calcification remains unclear. To clarify whether TNF-α accelerates the calcification of aortic valves, we investigated the effect of TNF-α on human aortic valve interstitial cells (HAVICs) obtained from patients with CAS (CAS group) and with aortic regurgitation or aortic dissection having a noncalcified aortic valve (control group). HAVICs (2 × 10(4)) were cultured in a 12-well dish in Dulbecco's modified Eagle's medium with 10% fetal bovine serum. The medium containing TNF-α (30 ng/ml) was replenished every 3 days after the cells reached confluence. TNF-α significantly accelerated the calcification and alkaline phosphatase (ALP) activity of HAVICs from CAS but not the control group after 12 days of culture. Furthermore, gene expression of calcigenic markers, ALP, bone morphogenetic protein 2 (BMP2), and distal-less homeobox 5 (Dlx5) were significantly increased after 6 days of TNF-α treatment in the CAS group but not the control group. Dorsomorphin, an inhibitor of mothers against decapentaplegic homologs (Smads) 1/5/8 phosphorylation, significantly inhibited the enhancement of TNF-α-induced calcification, ALP activity, Smad phosphorylation, and Dlx5 gene expression of HAVICs from the CAS group. These results suggest that HAVICs from the CAS group have greater sensitivity to TNF-α, which accelerates the calcification of aortic valves via the BMP2-Dlx5 pathway.

  6. Free fatty acid palmitate impairs the vitality and function of cultured human bladder smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Andreas Oberbach

    Full Text Available BACKGROUND: Incidence of urinary tract infections is elevated in patients with diabetes mellitus. Those patients show increased levels of the saturated free fatty acid palmitate. As recently shown metabolic alterations induced by palmitate include production and secretion of the pro-inflammatory cytokine interleukine-6 (IL-6 in cultured human bladder smooth muscle cells (hBSMC. Here we studied the influence of palmitate on vital cell properties, for example, regulation of cell proliferation, mitochondrial enzyme activity and antioxidant capacity in hBSMC, and analyzed the involvement of major cytokine signaling pathways. METHODOLOGY/PRINCIPAL FINDINGS: HBSMC cultures were set up from bladder tissue of patients undergoing cystectomy and stimulated with palmitate. We analyzed cell proliferation, mitochondrial enzyme activity, and antioxidant capacity by ELISA and confocal immunofluorescence. In signal transduction inhibition experiments we evaluated the involvement of NF-κB, JAK/STAT, MEK1, PI3K, and JNK in major cytokine signaling pathway regulation. We found: (i palmitate decreased cell proliferation, increased mitochondrial enzyme activity and antioxidant capacity; (ii direct inhibition of cytokine receptor by AG490 even more strongly suppressed cell proliferation in palmitate-stimulated cells, while counteracting palmitate-induced increase of antioxidant capacity; (iii in contrast knockdown of the STAT3 inhibitor SOCS3 increased cell proliferation and antioxidant capacity; (iv further downstream JAK/STAT3 signaling cascade the inhibition of PI3K or JNK enhanced palmitate induced suppression of cell proliferation; (v increase of mitochondrial enzyme activity by palmitate was enhanced by inhibition of PI3K but counteracted by inhibition of MEK1. CONCLUSIONS/SIGNIFICANCE: Saturated free fatty acids (e.g., palmitate cause massive alterations in vital cell functions of cultured hBSMC involving distinct major cytokine signaling pathways. Thereby

  7. Interstitial lung disease pattern turned out to be a predominantly lepidic lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Irena Hammen, Dr. Med

    2017-01-01

    Full Text Available We report a case of a 46-year-old woman without any medical history who presented to our Respiratory Department with exertional dyspnoea for the last 6 weeks associated with non-productive cough. Chest radiography showed bilateral diffuse interstitial opacity. Bronchoalveolar lavage and transbronchial biopsies performed during flexible bronchoscopy as a step in the diagnostic workup of idiopathic interstitial pneumonia showed cells of pulmonary adenocarcinoma.

  8. Apoptotic effect as biomarker of disease, severity and follow-up in interstitial cystitis.

    Science.gov (United States)

    Di Capua-Sacoto, C; Sanchez-Llopis, A; Oconnor, J E; Martinez-Romero, A; Ruiz-Cerdá, J L

    2017-11-10

    To determine whether the apoptotic effect test could serve as a biomarker of severity in bladder pain syndrome/interstitial cystitis. A prospective study was conducted between January 2010 and January 2015, which included 57 patients diagnosed with interstitial cystitis and 49 diagnosed with chronic pelvic pain of gynaecological origin. The urine was exposed to cell cultures, and the urine's capacity for inducing apoptosis in the cultures was analysed. A statistical analysis was then conducted to assess whether the apoptotic effect was associated with the symptoms. After performing an analysis of the association between the degree of apoptotic effect and the symptoms of patients with interstitial cystitis, we observed a significant increase in the mean percentages of apoptosis as the degree of symptom severity increased. After analysing the association between the apoptotic effect and symptoms, we obtained a positive correlation in the patients with interstitial cystitis and a lack of correlation in the patients with chronic pelvic pain of gynaecological origin. The rates of apoptosis increased progressively in the patients with interstitial cystitis as the symptoms increased, while the patients with chronic pelvic pain of gynaecological origin remained stable. The apoptotic effect of the urine of patients with interstitial cystitis could be a marker of disease, thus differentiating patients with interstitial cystitis from patients with chronic pelvic pain. The effect could also provide an objective measure of symptom severity. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Ontogeny and function of murine epidermal Langerhans cells.

    Science.gov (United States)

    Kaplan, Daniel H

    2017-09-19

    Langerhans cells (LCs) are epidermis-resident antigen-presenting cells that share a common ontogeny with macrophages but function as dendritic cells (DCs). Their development, recruitment and retention in the epidermis is orchestrated by interactions with keratinocytes through multiple mechanisms. LC and dermal DC subsets often show functional redundancy, but LCs are required for specific types of adaptive immune responses when antigen is concentrated in the epidermis. This Review will focus on those developmental and functional properties that are unique to LCs.

  10. Defining the functional states of Th17 cells

    OpenAIRE

    Lee, Youjin; Kuchroo, Vijay

    2015-01-01

    The molecular mechanisms governing T helper (Th) cell differentiation and function have revealed a complex network of transcriptional and protein regulators. Cytokines not only initiate the differentiation of CD4 Th cells into subsets but also influence the identity, plasticity and effector function of a T cell. Of the subsets, Th17 cells, named for producing interleukin 17 (IL-17) as their signature cytokine, secrete a cohort of other cytokines, including IL-22, IL-21, IL-10, IL-9, IFNγ, and...

  11. Interstitial ectopic pregnancy: a case report.

    Science.gov (United States)

    Alagbe, Olayemi Atinuke; Adeniyi, Tinuola Omolade; Abayomi, Olawale Ayobami; Onifade, Emmanuel Olugbenga

    2017-01-01

    Interstitial ectopic pregnancy is a rare type of tubal pregnancy that poses diagnostic challenge. It is associated with the highest risk of massive, uncontrollable bleeding and can result in uterine rupture in the second trimester. This is a rare case of unruptured interstitial ectopic diagnosed in the first trimester by ultrasonography and managed medically with systemic methrotrexate and serial ultrasound monitoring.`.

  12. Pitfalls in diagnosis of interstitial pregnancy.

    Science.gov (United States)

    Chan, Louis Yik-Si; Fok, Wing Yee; Yuen, Pong Mo

    2003-09-01

    To determine the incidence and reasons for misdiagnosis in interstitial ectopic pregnancy. We conducted a retrospective study from 1990 to 2001. Women with interstitial pregnancy were identified and their case records retrieved and reviewed. Reasons for delay in diagnosis and associated morbidity were recorded. Thirty-six women were diagnosed as having interstitial pregnancy during the study period. Initial diagnosis was incorrect in 15 cases (41.7%). In 14 cases, the interstitial pregnancies were mistaken as intrauterine pregnancy. These misdiagnoses resulted in six inappropriate surgical procedures (evacuation of uterus) being performed and led to rupture of interstitial pregnancy in eight women. In two women, the interstitial pregnancy was mistaken as normal intrauterine pregnancy while the uterus itself was thought to be a cervical fibroid. In both cases, the interstitial pregnancies ruptured at 18-20 weeks of gestation. Despite advances in sonographic skills and equipment and the availability of beta-human chorionic gonadotropin (hCG) monitoring, misdiagnosis of interstitial pregnancy still occurs frequently. Clinicians should be aware of the limitations of various investigations and maintain a high index of suspicion.

  13. Telomere length in interstitial lung diseases

    NARCIS (Netherlands)

    Snetselaar, Reinier; Van Moorsel, Coline H M; Kazemier, Karin M.; Van Der Vis, Joanne J.; Zanen, Pieter; Van Oosterhout, Matthijs F M; Grutters, Jan C.

    2015-01-01

    Background: Interstitial lung disease (ILD) is a heterogeneous group of rare diseases that primarily affect the pulmonary interstitium. Studies have implicated a role for telomere length (TL) maintenance in ILD, particularly in idiopathic interstitial pneumonia (IIP). Here, we measure TL in a wide

  14. The interstitial pneumonitis induced by cytostatics

    International Nuclear Information System (INIS)

    Dubrava, M.; Markova, I.; Mistina, L.

    1998-01-01

    The author presents a cause of 9-year old boy with ALL-F2B in the stage of the prevention treatment where in the its course the induced interstitial pneumonitis by cytostatics was developed. The bacterial, virus, mycological and parasitic causes of the interstitial pneumonitis on the basis of the bronchoscopy, BAL, CT, scintigraphy, laboratory and by cultivation were excluded. (authors)

  15. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils

    DEFF Research Database (Denmark)

    Galli, Stephen J; Borregaard, Niels; Wynn, Thomas A

    2011-01-01

    Hematopoietic cells, including lymphoid and myeloid cells, can develop into phenotypically distinct 'subpopulations' with different functions. However, evidence indicates that some of these subpopulations can manifest substantial plasticity (that is, undergo changes in their phenotype and function...

  16. Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Rufener, Nora; Nielsen, Jens J

    2008-01-01

    were analyzed for mRNA content of VEGF, endothelial nitric oxide synthase (eNOS), and matrix metalloproteinase-2 (MMP-2). The passive leg movement caused an increase (P ... to cultured endothelial cells revealed that dialysate obtained during leg movement induced a 3.2-fold higher proliferation rate (P MMP-2 mRNA levels were......The present study used passive limb movement as an experimental model to study the effect of increased blood flow and passive stretch, without enhanced metabolic demand, in young healthy male subjects. The model used was 90 min of passive movement of the leg leading to a 2.8-fold increase (P

  17. The immunological response created by interstitial and non-invasive laser immunotherapy

    Science.gov (United States)

    Bahavar, Cody F.; Zhou, Feifan; Hasanjee, Aamr M.; West, Connor L.; Nordquist, Robert E.; Hode, Tomas; Liu, Hong; Chen, Wei R.

    2015-03-01

    Laser immunotherapy (LIT) is an innovative cancer modality that uses laser irradiation and immunological stimulation to treat late-stage, metastatic cancers. LIT can be performed through either interstitial or non-invasive laser irradiation. Although LIT is still in development, recent clinical trials have shown that it can be used to successfully treat patients with late-stage breast cancer and melanoma. The development of LIT has been focused on creating an optimal immune response created by irradiating the tumor. One important factor that could enhance the immune response is the duration of laser irradiation. Irradiating the tumor for a shorter or longer amount of time could weaken the immune response created by LIT. Another factor that could weaken this immune response is the proliferation of regulatory T cells (TRegs) in response to the laser irradiation. However, low dose cyclophosphamide (CY) can help suppress the proliferation of TRegs and help create a more optimal immune response. An additional factor that could weaken the effectiveness of LIT is the selectivity of the laser. If LIT is performed non-invasively, then deeply embedded tumors and highly pigmented skin could cause an uneven temperature distribution inside the tumor. To solve this problem, an immunologically modified carbon nanotube system was created by using an immunoadjuvant known as glycated chitosan (GC) as a surfactant for single-walled carbon nanotubes (SWNTs) to immunologically modify SWNTs. SWNT-GC retains the optical properties of SWNTs and the immunological functions of GC to help increase the selectivity of the laser and create a more optimal immune response. In this preliminary study, tumor-bearing rats were treated with LIT either interstitially by an 805-nm laser with GC and low-dose CY, or non-invasively by a 980-nm laser with SWNT-GC. The goal was to observe the effects of CY on the immune response induced by LIT and to also determine the effect of irradiation duration for

  18. Computed Tomography–Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non–Small Cell Lung Cancer: A Phase 1 Clinical Trial

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Li; Zhang, Jian-wen; Lin, Sheng; Luo, Hui-Qun; Wen, Qing-Lian; He, Li-Jia; Shang, Chang-Ling; Ren, Pei-Rong; Yang, Hong-Ru; Pang, Hao-Wen; Yang, Bo; He, Huai-Lin [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Chen, Yue, E-mail: chenyue5523@126.com [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Wu, Jing-Bo, E-mail: wjb6147@163.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China)

    2015-08-01

    Purpose: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non–small cell lung cancer (NSCLC). Methods and Materials: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planning target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. Results: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. Conclusion: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.

  19. Visualizing chemical functionality in plant cell walls

    OpenAIRE

    Zeng, Yining; Himmel, Michael E.; Ding, Shi-You

    2017-01-01

    Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell wa...

  20. Deficient natural killer cell function in preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Alanen, A.; Lassila, O.

    1982-11-01

    Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour /sup 51/Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder.

  1. Interstitial lung disease: Diagnostic approach

    Directory of Open Access Journals (Sweden)

    Kaushik Saha

    2014-01-01

    Full Text Available Interstitial lung disease (ILD is a final common pathway of a broad heterogeneous group of parenchymal lung disorders. It is characterized by progressive fibrosis of the lung leading to restriction and diminished oxygen transfer. Clinically, the presenting symptoms of ILD are non-specific (cough and progressive dyspnea on exertion and are often attributed to other diseases, thus delaying diagnosis and timely therapy. Clues from the medical history along with the clinical context and radiologic findings provide the initial basis for prioritizing diagnostic possibilities for a patient with ILD. An accurate prognosis and optimal treatment strategy for patients with ILDs can only be after an accurate diagnosis. This review will assist pulmonary physicians and medicine specialist in recognition of ILD. Extensive literature search has been made through PubMed and also Book References has been used for writing this review.

  2. Navigation system for interstitial brachytherapy

    International Nuclear Information System (INIS)

    Strassmann, G.; Kolotas, C.; Heyd, R.

    2000-01-01

    The purpose of the stud was to develop a computed tomography (CT) based electromagnetic navigation system for interstitial brachytherapy. This is especially designed for situations when needles have to be positioned adjacent to or within critical anatomical structures. In such instances interactive 3D visualisation of the needle positions is essential. The material consisted of a Polhemus electromagnetic 3D digitizer, a Pentium 200 MHz laptop and a voice recognition for continuous speech. In addition, we developed an external reference system constructed of Perspex which could be positioned above the tumour region and attached to the patient using a non-invasive fixation method. A specially designed needle holder and patient bed were also developed. Measurements were made on a series of phantoms in order to study the efficacy and accuracy of the navigation system. The mean navigation accuracy of positioning the 20.0 cm length metallic needles within the phantoms was in the range 2.0-4.1 mm with a maximum of 5.4 mm. This is an improvement on the accuracy of a CT-guided technique which was in the range 6.1-11.3 mm with a maximum of 19.4 mm. The mean reconstruction accuracy of the implant geometry was 3.2 mm within a non-ferromagnetic environment. We found that although the needles were metallic this did not have a significant influence. We also found for our experimental setups that the CT table and operation table non-ferromagnetic parts had no significant influence on the navigation accuracy. This navigation system will be a very useful clinical tool for interstitial brachytherapy applications, particularly when critical structures have to be avoided. It also should provide a significant improvement on our existing technique

  3. Dose, time and volume effects in interstitial radiation therapy

    International Nuclear Information System (INIS)

    Burgers, J.M.V.

    1982-01-01

    This study presents the main features and uncertainties of interstitial therapy and was undertaken to examine whether differences could be found in different clinical situations treated by interstitial implants with removable sources, that were not simply related to dose. In chapter 2, dating from 1978, continuous low dose rate irradiation is discussed from the radiobiological point of view together with some points related to variation in dose rate. A benefit of continuous low dose rate irradiation could be surmised in a few situations with special cell-kinetic properties. The problem of dose specification, the sharp dose gradient and other volume characteristics are discussed in chapter 3. Possible adjustments to variations in dose rate are discussed in chapter 4. The clinical material is reviewed in chapter 5, including aspects of dose specification, dose fall-off and variation in dose rate. The general discussion and conclusions are given in chapter 6. (Auth.)

  4. Increased bladder permeability in interstitial cystitis/painful bladder syndrome

    Science.gov (United States)

    Greenwood-Van Meerveld, Beverley; Wisniewski, Amy B.; VanGordon, Samuel; Lin, HsuehKung; Kropp, Bradley P.; Towner, Rheal A.

    2015-01-01

    The definition of interstitial cystitis (IC) has evolved over the years from being a well-defined entity characterized by diagnostic lesion (Hunner’s ulcer) in the urothelium to a clinical diagnosis by exclusion [painful bladder syndrome (PBS)]. Although the etiology is unknown, a central theme has been an association with increased permeability of the bladder. This article reviews the evidence for increased permeability being important to the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) and in treating the disorder. Recent work showing cross-communication among visceral organs is also reviewed to provide a basis for understanding IC/PBS as a systemic disorder of a complex, interconnected system consisting of the bladder, bowel and other organs, nerves, cytokine-responding cells and the nervous system. PMID:26751576

  5. Chylothorax in dermatomyositis complicated with interstitial pneumonia.

    Science.gov (United States)

    Isoda, Kentaro; Kiboshi, Takao; Shoda, Takeshi

    2017-04-01

    Chylothorax is a disease in which chyle leaks and accumulates in the thoracic cavity. Interstitial pneumonia and pneumomediastinum are common thoracic manifestations of dermatomyositis, but chylothorax complicated with dermatomyositis is not reported. We report a case of dermatomyositis with interstitial pneumonia complicated by chylothorax. A 77-year-old woman was diagnosed as dermatomyositis with Gottron's papules, skin ulcers, anti-MDA5 antibody and rapid progressive interstitial pneumonia. Treatment with betamethasone, tacrolimus and intravenous high-dose cyclophosphamide was initiated, and her skin symptoms and interstitial pneumonia improved once. However, right-sided chylothorax began to accumulate and gradually increase, and at the same time, her interstitial pneumonia began to exacerbate, and skin ulcers began to reappear on her fingers and auricles. Although her chylothorax improved by fasting and parenteral nutrition, she died due to further exacerbations of dermatomyositis and interstitial pneumonia in spite of steroid pulse therapy, increase in the betamethasone dosage, additional intravenous high-dose cyclophosphamide and plasma pheresis. An autopsy showed no lesions such as malignant tumors in the thoracic cavity. This is the first report of chylothorax complicated by dermatomyositis with interstitial pneumonia.

  6. Generation of functional organs from stem cells

    Directory of Open Access Journals (Sweden)

    Yunying Liu

    2013-01-01

    Full Text Available We are now well entering the exciting era of stem cells. Potential stem cell therapy holds great promise for the treatment of many diseases such as stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral-sclerosis, myocardial infarction, muscular dystrophy, diabetes, and etc. It is generally believed that transplantation of specific stem cells into the injured tissue to replace the lost cells is an effective way to repair the tissue. In fact, organ transplantation has been successfully practiced in clinics for liver or kidney failure. However, the severe shortage of donor organs has been a major obstacle for the expansion of organ transplantation programs. Toward that direction, generation of transplantable organs using stem cells is a desirable approach for organ replacement and would be of great interest for both basic and clinical scientists. Here we review recent progress in the field of organ generation using various methods including single adult tissue stem cells, a blastocyst complementation system, tissue decellularization/recellularization and a combination of stem cells and tissue engineering.

  7. Revisiting the Functional Impact of NK Cells.

    Science.gov (United States)

    Poli, Aurélie; Michel, Tatiana; Patil, Neha; Zimmer, Jacques

    2018-02-26

    Immune responses are critical for the maintenance of homeostasis but can also upset the equilibrium, depending on the context and magnitude of the response. Natural killer (NK) cells are well known for their important roles in antiviral and antitumor immune responses, and they are currently used, mostly under optimized forms, as immunotherapeutic agents against cancer. Nevertheless, with accumulating examples of deleterious effects of NK cells, it is paramount to consider their negative contributions. Here, we critically review and comment on the literature surrounding undesirable aspects of NK cell activity, focusing on situations where they play a harmful rather than a protective role. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Bone marrow transplantations to study gene function in hematopoietic cells

    NARCIS (Netherlands)

    de Winther, Menno P. J.; Heeringa, Peter

    2011-01-01

    Immune cells are derived from hematopoietic stem cells in the bone marrow. Experimental replacement of bone marrow offers the unique possibility to replace immune cells, to study gene function in mouse models of disease. Over the past decades, this technique has been used extensively to study, for

  9. Synthetic RNA Controllers for Programming Mammalian Cell Fate and Function

    Science.gov (United States)

    2015-11-04

    Final report for “Synthetic RNA controllers for programming mammalian cell fate and function” Principal Investigator: Christina D. Smolke...SUBTITLE Synthetic RNA controllers for programming mammalian cell fate and function 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18   2 Synthetic RNA controllers for programming mammalian cell fate and function Task 1

  10. Mechanical regulation of T-cell functions

    OpenAIRE

    Chen, Wei; Zhu, Cheng

    2013-01-01

    T cells are key players of the mammalian adaptive immune system. They experience different mechanical microenvironments during their life cycles, from the thymus, secondary lymph organs, and peripheral tissues that are free of externally applied force but display variable substrate rigidities, to the blood and lymphatic circulation systems where complicated hydrodynamic forces are present. Regardless of whether T cells are subject to external forces or generate their own internal forces, they...

  11. Interstitial ectopic pregnancy: conservative surgical management.

    Science.gov (United States)

    Warda, Hussein; Mamik, Mamta M; Ashraf, Mohammad; Abuzeid, Mostafa I

    2014-01-01

    Interstitial pregnancy is a rare and life-threatening condition. Diagnosis and appropriate management are critical in preventing morbidity and death. Four cases of interstitial pregnancy are presented. Diagnostic laparoscopy followed by laparotomy and cornuostomy with removal of products of conception was performed in 1 case. Laparoscopic cornuostomy and removal of products of conception were performed in the subsequent 3 cases with some modifications of the technique. Subsequent successful reproductive outcomes are also presented. Progressively conservative surgical measures are being used to treat interstitial pregnancy successfully, with no negative impact on subsequent pregnancies.

  12. Pleuroparenchymal fibroelastosis: a rare interstitial lung disease

    Science.gov (United States)

    English, John C; Mayo, John R; Levy, Robert; Yee, John; Leslie, Kevin O

    2015-01-01

    Pleuroparenchymal fibroelastosis (PPFE) is a newly described form of interstitial lung disease that originates in the upper lung zones and typically progresses to involve the entire lung. The disease may be idiopathic but is often associated with other pre- or coexisting conditions. Pneumothorax is a common complication and can occur at presentation or at other times during the course of the disease. Pathologically, interstitial fibrosis takes the form of a dense consolidation with some preservation of alveolar septal outlines and demonstrates a distinctly abrupt interface with residual normal lung. Unrecognized cases of PPFE may be incorrectly diagnosed as sarcoidosis, atypical idiopathic pulmonary fibrosis, or other unclassifiable interstitial pneumonias. PMID:26090119

  13. HRCT of diffuse interstitial pneumonia during treatment

    International Nuclear Information System (INIS)

    Takahashi, Masashi; Sano, Akira; Imanaka, Kazufumi

    1989-01-01

    HRCT was carried out in twenty patients with diffuse interstitial pneumonia: 13 cases of IIP, 3 of BOOP, 2 of drug-induced pneumonia, 1 of rheumatoid lung and acute interstitial pneumonia of unknown origin. With special attention to inflammatory activity, the patients underwent HRCT periodically during the treatment. Correlative investigation between HRCT image and grade of accumulation in 67 Ga scintigraphy was also performed. Response to steroid therapy was clearly reflected on HRCT image, that was shown as decreasing pulmonary density or thinning of honeycomb wall. HRCT is considered to be useful in assessing the activity of diffuse interstitial pneumonia. (author)

  14. Perturbative diffusion theory formalism for interpreting temporal light intensity changes during laser interstitial thermal therapy.

    Science.gov (United States)

    Chin, Lee C L; Whelan, William M; Vitkin, I Alex

    2007-03-21

    In an effort to understand dynamic optical changes during laser interstitial thermal therapy (LITT), we utilize the perturbative solution of the diffusion equation in heterogeneous media to formulate scattering weight functions for cylindrical line sources. The analysis explicitly shows how changes in detected interstitial light intensity are associated with the extent and location of the volume of thermal coagulation during treatment. Explanations for previously reported increases in optical intensity observed early during laser heating are clarified using the model and demonstrated with experimental measurements in ex vivo bovine liver tissue. This work provides an improved understanding of interstitial optical signal changes during LITT and indicates the sensitivity and potential of interstitial optical monitoring of thermal damage.

  15. Statin Use Is Associated with Reduced Mortality in Patients with Interstitial Lung Disease

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune F; Nordestgaard, Børge G

    2015-01-01

    INTRODUCTION: We hypothesized that statin use begun before the diagnosis of interstitial lung disease is associated with reduced mortality. METHODS: We studied all patients diagnosed with interstitial lung disease in the entire Danish population from 1995 through 2009, comparing statin use versus...... no statin use in a nested 1:2 matched study. RESULTS: The cumulative survival as a function of follow-up time from the date of diagnosis of interstitial lung disease (n = 1,786 + 3,572) and idiopathic lung fibrosis (n = 261 + 522) was higher for statin users versus never users (log-rank: P = 7 · 10......(-9) and P = 0.05). The median survival time in patients with interstitial lung disease was 3.3 years in statin users and 2.1 years in never users. Corresponding values in patients with idiopathic lung fibrosis were 3.4 versus 2.4 years. After multivariable adjustment, the hazard ratio for all...

  16. Interstitial brachytherapy in carcinoma of the penis

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhary, A.J.; Ghosh, S.; Bhalavat, R.L. [Tata Memorial Hospital, Mumbai (India). Dept. of Radiation Oncology; Kulkarni, J.N. [Tata Memorial Hospital, Mumbai (India). Dept. of Surgery; Sequeira, B.V.E. [Tata Memorial Hospital, Mumbai (India). Dept. of Medical Physics

    1999-01-01

    Aim: Keeping in line with the increasing emphasis on organ preservation, we at the Tata Memorial Hospital have evaluated the role of Ir-192 interstitial implant as regards local control, functional and cosmetic outcome in early as well as locally recurrent carcinoma of the distal penis. Patients and Methods: From October 1988 to December 1996, 23 patients with histopathologically proven cancer of the penis were treated with radical radiation therapy using Ir-192 temporary interstitial implant. Our patients were in the age group of 20 to 60 years. The primary lesions were T1 and 7, T2 in 7 and recurrent in 9 patients. Only 7 patients had palpable groin nodes at presentation, all of which were pathologically negative. The median dose of implant was 50 Gy (range 40 to 60 Gy), using the LDR afterloading system and the Paris system of implant rules for dosimetry. Follow-up ranged from 4 to 117 months (median 24 months). Results: At last follow-up 18 of the 23 patients remained locally controlled with implant alone. Three patients failed only locally, 2 locoregionally and 1 only at the groin. Of the 5 patients who failed locally, 4 were successfully salvaged with partial penectomy and remained controlled when last seen. Local control with implant alone at 8 years was 70% by life table analysis. The patients had excellent functional and cosmetic outcome. We did not record any case of skin or softtissue necrosis. Only 2 patients developed meatal stenosis, both of which were treated endoscopically. Conclusion: Our results lead us to interpret that interstitial brachytherapy with Ir-192 offers excellent local control rates with preservation of organ and function. Penectomy can be reserved as a means for effective salvage. (orig.) [Deutsch] Ziel: Das Prinzip des Organerhalts gewinnt in der Onkologie zunehmend an Bedeutung. Ziel dieser Untersuchung war es, die Rolle der interstitiellen Brachytherapie mit Ir-192 zur Behandlung des fruehen und rezidivierten Peniskarzinoms zu

  17. Correlations and functional connections in a population of grid cells

    OpenAIRE

    Dunn, Benjamin; Mørreaunet, Maria; Roudi, Yasser

    2014-01-01

    We study the statistics of spike trains of simultaneously recorded grid cells in freely behaving rats. We evaluate pairwise correlations between these cells and, using a maximum entropy kinetic pairwise model (kinetic Ising model), study their functional connectivity. Even when we account for the covariations in firing rates due to overlapping fields, both the pairwise correlations and functional connections decay as a function of the shortest distance between the vertices of the spatial firi...

  18. Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers.

    Science.gov (United States)

    Ash, Samuel Y; Harmouche, Rola; Putman, Rachel K; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Onieva Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R

    2017-10-01

    Smoking-related lung injury may manifest on CT scans as both emphysema and interstitial changes. We have developed an automated method to quantify interstitial changes and hypothesized that this measurement would be associated with lung function, quality of life, mortality, and a mucin 5B (MUC5B) polymorphism. Using CT scans from the Genetic Epidemiology of COPD Study, we objectively labeled lung parenchyma as a tissue subtype. We calculated the percentage of the lung occupied by interstitial subtypes. A total of 8,345 participants had clinical and CT scanning data available. A 5% absolute increase in interstitial changes was associated with an absolute decrease in FVC % predicted of 2.47% (P percentage of lung with interstitial changes. Objective interstitial changes on CT scans were associated with impaired lung function, worse quality of life, increased mortality, and more copies of a MUC5B promoter polymorphism, suggesting that these changes may be a marker of susceptibility to smoking-related lung injury, detectable even in those who are healthy by other measures. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Ex vivo cytosolic delivery of functional macromolecules to immune cells.

    Directory of Open Access Journals (Sweden)

    Armon Sharei

    Full Text Available Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.

  20. Double knockout of Bax and Bak from kidney proximal tubules reduces unilateral urethral obstruction associated apoptosis and renal interstitial fibrosis.

    Science.gov (United States)

    Mei, Shuqin; Li, Lin; Wei, Qingqing; Hao, Jielu; Su, Yunchao; Mei, Changlin; Dong, Zheng

    2017-03-20

    Interstitial fibrosis, a common pathological feature of chronic kidney diseases, is often associated with apoptosis in renal tissues. To determine the associated apoptotic pathway and its role in renal interstitial fibrosis, we established a mouse model in which Bax and Bak, two critical genes in the intrinsic pathway of apoptosis, were deleted specifically from kidney proximal tubules and used this model to examine renal apoptosis and interstitial fibrosis following unilateral urethral obstruction (UUO). It was shown that double knockout of Bax and Bak from proximal tubules attenuated renal tubular cell apoptosis and suppressed renal interstitial fibrosis in UUO. The results indicate that the intrinsic pathway of apoptosis contributes significantly to the tubular apoptosis and renal interstitial fibrosis in kidney diseases.

  1. The diffuse interstitial lung disease - with emphasis in the idiopathic interstitial pneumonias

    International Nuclear Information System (INIS)

    Bustillo P, Jose G; Pacheco, Pedro M; Matiz, Carlos; Ojeda, Paulina; Carrillo B, Jorge A.

    2003-01-01

    The term diffuse interstitial lung disease, it refers to those diseases that commit the interstice basically, the space between the membrane basal epithelial and endothelial, although the damage can also commit the outlying air spaces and the vessels; the supplement is centered in the diffuse interstitial lung illness of unknown cause; well-known as idiopathic interstitial pneumonias, making emphasis in the more frequents, the pulmonary fibrosis idiopathic or cryptogenic fibrosant alveolitis

  2. Interpreting heterogeneity in intestinal tuft cell structure and function.

    Science.gov (United States)

    Banerjee, Amrita; McKinley, Eliot T; von Moltke, Jakob; Coffey, Robert J; Lau, Ken S

    2018-05-01

    Intestinal tuft cells are a morphologically unique cell type, best characterized by striking microvilli that form an apical tuft. These cells represent approximately 0.5% of gut epithelial cells depending on location. While they are known to express chemosensory receptors, their function has remained unclear. Recently, numerous groups have revealed startling insights into intestinal tuft cell biology. Here, we review the latest developments in understanding this peculiar cell type's structure and function. Recent advances in volumetric microscopy have begun to elucidate tuft cell ultrastructure with respect to its cellular neighbors. Moreover, single-cell approaches have revealed greater diversity in the tuft cell population than previously appreciated and uncovered novel markers to characterize this heterogeneity. Finally, advanced model systems have revealed tuft cells' roles in mucosal healing and orchestrating type 2 immunity against eukaryotic infection. While much remains unknown about intestinal tuft cells, these critical advances have illuminated the physiological importance of these previously understudied cells and provided experimentally tractable tools to interrogate this rare cell population. Tuft cells act as luminal sensors, linking the luminal microbiome to the host immune system, which may make them a potent clinical target for modulating host response to a variety of acute or chronic immune-driven conditions.

  3. Membrane phosphorylation and nerve cell function

    International Nuclear Information System (INIS)

    Baer, P.R.

    1982-01-01

    This thesis deals with the phosphorylation of membrane components. In part I a series of experiments is described using the hippocampal slice as a model system. In part II a different model system - cultured hybrid cells - is used to study protein and lipid phosphorylation, influenced by incubation with neuropeptides. In part III in vivo and in vitro studies are combined to study protein phosphorylation after neuroanatomical lesions. In a section of part II (Page 81-90) labelling experiments of the membrane inositol-phospholipids are described. 32 P-ATP was used to label phospholipids in intact hybrid cells, and short incubations were found to be the most favourable. (C.F.)

  4. Interstitial Metabolic Monitoring During Hemorrhagic Shock

    National Research Council Canada - National Science Library

    Pamnani, Motilal

    2003-01-01

    .... We hypothesize that decompensation results from potassium-mediated vasodilation and/or loss of cardiac contractility, and thus a method of measuring interstitial potassium should be a crucial part...

  5. Interstitial Metabolic Monitoring During Hemorrhagic Shock

    National Research Council Canada - National Science Library

    Pamnani, Motilal

    2004-01-01

    .... We hypothesize that decompensation results from potassium-mediated vasodilation and/or loss of cardiac contractility, and thus a method of measuring interstitial potassium should be a crucial part...

  6. Blood and interstitial flow in the hierarchical pore space architecture of bone tissue.

    Science.gov (United States)

    Cowin, Stephen C; Cardoso, Luis

    2015-03-18

    There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Skeletal Stem Cells: Origins, Functions and Uncertainties.

    Science.gov (United States)

    Mohamed, Fatma F; Franceschi, Renny T

    2017-12-01

    The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

  8. INTERSTITIAL ECTOPIC PREGNANCY-A REVIEW

    OpenAIRE

    Fateme parooei1, Mahmood Anbari2, Morteza Salarzaei

    2017-01-01

    Introduction:. Interstitial ectopic pregnancy, in which rupture occurs much later than other forms of pregnancy, is a rare phenomenon that occurs in 2% of ectopic pregnancies; delayed rupture is due to the expandability of myometrium. Methods: In this review article, the databases Medline, Cochrane, Science Direct, and Google Scholar were thoroughly searched to identify the Interstitial ectopic pregnancy. In this review, the papers published until early January 2017 that were conducted ...

  9. Interstitial Cystitis: Chronic Pelvic Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Fatih Atuğ

    2005-01-01

    Full Text Available Interstitial cystitis, is a chronic inflammatory disease of the bladder of unknown etiology characterized by urinary frequency, urgency, nocturia and suprapubic pain. The syndrome presents differently in many patients, with the unifying factor being chronic pelvic pain and disruption of daily life activities.Although there are abundance of theories, the etiology of the condition remains unclear. This review focuses on recently published literature on the epidemiology, etiology, diagnosis and treatment of interstitial cystitis.

  10. Interstitial Metabolic Monitoring During Hemorrhagic Shock

    Science.gov (United States)

    2005-11-01

    Mass Spectometry (ICP- MS) ATACCC St. Pete Beach, FL 15 Apr 03 Microdialysis (µD) Measurement Of Interstitial Markers of Hemorrhagic Shock...Jackson Foundation Rockville, MD 20852-1428 REPORT DATE : November 2005 TYPE OF REPORT: Final PREPARED FOR... DATE (DD-MM-YYYY) 01-11-2005 2. REPORT TYPE Final 3. DATES COVERED (From - To) 15 MAR 2004 - 14 OCT 2006 4. TITLE AND SUBTITLE Interstitial Metabolic

  11. Uncovering Factors Related to Pancreatic Beta-Cell Function.

    Science.gov (United States)

    Curran, Aoife M; Ryan, Miriam F; Drummond, Elaine; Gibney, Eileen R; Gibney, Michael J; Roche, Helen M; Brennan, Lorraine

    2016-01-01

    The incidence of type 2 diabetes has increased rapidly on a global scale. Beta-cell dysfunction contributes to the overall pathogenesis of type 2 diabetes. However, factors contributing to beta-cell function are not clear. The aims of this study were (i) to identify factors related to pancreatic beta-cell function and (ii) to perform mechanistic studies in vitro. Three specific measures of beta-cell function were assessed for 110 participants who completed an oral glucose tolerance test as part of the Metabolic Challenge Study. Anthropometric and biochemical parameters were assessed as potential modulators of beta-cell function. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Validation of findings were performed in a second human cohort. Waist-to-hip ratio was the strongest anthropometric modulator of beta-cell function, with beta-coefficients of -0.33 (p = 0.001) and -0.30 (p = 0.002) for beta-cell function/homeostatic model assessment of insulin resistance (HOMA-IR), and disposition index respectively. Additionally, the resistin-to-adiponectin ratio (RA index) emerged as being strongly associated with beta-cell function, with beta-coefficients of -0.24 (p = 0.038) and -0.25 (p = 0.028) for beta-cell function/HOMA-IR, and disposition index respectively. Similar results were obtained using a third measure for beta-cell function. In vitro experiments revealed that the RA index was a potent regulator of acute insulin secretion where a high RA index (20ng ml-1 resistin, 5nmol l-1 g-adiponectin) significantly decreased insulin secretion whereas a low RA index (10ng ml-1 resistin, 10nmol l-1 g-adiponectin) significantly increased insulin secretion. The RA index was successfully validated in a second human cohort with beta-coefficients of -0.40 (p = 0.006) and -0.38 (p = 0.008) for beta-cell function/ HOMA-IR, and disposition index respectively. Waist-to-hip ratio and RA index were identified as significant modulators of

  12. Uncovering Factors Related to Pancreatic Beta-Cell Function.

    Directory of Open Access Journals (Sweden)

    Aoife M Curran

    Full Text Available The incidence of type 2 diabetes has increased rapidly on a global scale. Beta-cell dysfunction contributes to the overall pathogenesis of type 2 diabetes. However, factors contributing to beta-cell function are not clear. The aims of this study were (i to identify factors related to pancreatic beta-cell function and (ii to perform mechanistic studies in vitro.Three specific measures of beta-cell function were assessed for 110 participants who completed an oral glucose tolerance test as part of the Metabolic Challenge Study. Anthropometric and biochemical parameters were assessed as potential modulators of beta-cell function. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Validation of findings were performed in a second human cohort.Waist-to-hip ratio was the strongest anthropometric modulator of beta-cell function, with beta-coefficients of -0.33 (p = 0.001 and -0.30 (p = 0.002 for beta-cell function/homeostatic model assessment of insulin resistance (HOMA-IR, and disposition index respectively. Additionally, the resistin-to-adiponectin ratio (RA index emerged as being strongly associated with beta-cell function, with beta-coefficients of -0.24 (p = 0.038 and -0.25 (p = 0.028 for beta-cell function/HOMA-IR, and disposition index respectively. Similar results were obtained using a third measure for beta-cell function. In vitro experiments revealed that the RA index was a potent regulator of acute insulin secretion where a high RA index (20ng ml-1 resistin, 5nmol l-1 g-adiponectin significantly decreased insulin secretion whereas a low RA index (10ng ml-1 resistin, 10nmol l-1 g-adiponectin significantly increased insulin secretion. The RA index was successfully validated in a second human cohort with beta-coefficients of -0.40 (p = 0.006 and -0.38 (p = 0.008 for beta-cell function/ HOMA-IR, and disposition index respectively.Waist-to-hip ratio and RA index were identified as significant modulators

  13. Structure and function of stem cell pools in mammalian cell renewal systems

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Nothdurft, W.

    1979-01-01

    Stem cells play a key-role in the maintenance of the equilibrium between cell loss and cell production in cell renewal systems as well as in the understanding of the radiation pathophysiology of mammalian organisms. The integrity of mammalian organisms with the need to maintain a constant ''millieu interior'' is depending on the normal functioning of cell renewal systems, especially those of epithelial surfaces and blood cell forming organs. All cell renewal systems of bodies have a very similar functional structure consisting of functional, proliferative - amplifying and stem cell compartments. They differ in transit and cell cycle times and in the number of amplification division - aside from the difference in their functional and biochemical make-up. The stem cell pools are providing the cells capable of differentiation without depleting their own kind. This can be achieved by symmetrical or assymmetrical stem cell division. In normal steady state, 50% of the stem cell division remain in the stem cell pool, while the other 50% leave it to differentiate, proliferate and mature, hemopoietic system is distributed throughout bodies. This is an important factor in the radiation biology of mammalian organisms since the loss of function in one area can be compensated for by more production in other areas, and locally depleted sites can be reseeded with the stem cells migrating in from blood. (Yamashita, S.)

  14. Behavior and function of tissue-resident memory T cells.

    Science.gov (United States)

    Ariotti, Silvia; Haanen, John B; Schumacher, Ton N

    2012-01-01

    Our understanding of memory T cell function in mice and men is to date in large part restricted to the behavior of circulating memory T cells. Emerging evidence, however, suggests that in addition to such systemic memory T cell populations, a separate population of locally confined memory T cells is generated at former sites of antigen encounter. Here, we discuss the potential function of these long-term tissue-resident memory T cells (T(TRM)), how such local T cell memory can be maintained for prolonged periods of time, and how the induction of long-term tissue-resident memory T cells may potentially be exploited during vaccination. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Phenotype and functions of memory Tfh cells in human blood.

    Science.gov (United States)

    Schmitt, Nathalie; Bentebibel, Salah-Eddine; Ueno, Hideki

    2014-09-01

    Our understanding of the origin and functions of human blood CXCR5(+) CD4(+) T cells found in human blood has changed dramatically in the past years. These cells are currently considered to represent a circulating memory compartment of T follicular helper (Tfh) lineage cells. Recent studies have shown that blood memory Tfh cells are composed of phenotypically and functionally distinct subsets. Here, we review the current understanding of human blood memory Tfh cells and the subsets within this compartment. We present a strategy to define these subsets based on cell surface profiles. Finally, we discuss how increased understanding of the biology of blood memory Tfh cells may contribute insight into the pathogenesis of autoimmune diseases and the mode of action of vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. The function of BAFF on T helper cells in autoimmunity.

    Science.gov (United States)

    Chen, Maogen; Lin, Xiaohong; Liu, Ya; Li, Qiang; Deng, Yiling; Liu, Zhongmin; Brand, David; Guo, Zhiyong; He, Xiaoshun; Ryffel, Bernhard; Zheng, Song Guo

    2014-06-01

    B cell-activating factor belonging to the TNF family (BAFF) exerts its pathogenic role in supporting the survival and proliferation of B cells, regulating class switch recombination as well as the selection of autoreactive B cells. Overexpression of BAFF induces a dramatic expansion of activated B cells, particularly marginal zone B cells, as well as hypergammaglobulinemia, autoantibody production and immune complex deposition. However, in addition to its effect on B cells, recent work has also demonstrated that BAFF can promote T cell activation, proliferation and differentiation. In this review, we have discussed the recent progress on the function and role of BAFF on T cells and T cell-mediated diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. The function of BAFF on T helper cells in autoimmunity

    Science.gov (United States)

    Chen, Maogen; Lin, Xiaohong; Liu, Ya; Li, Qiang; Deng, Yiling; Liu, Zhongmin; Brand, David; Guo, Zhiyong; He, Xiaoshun; Ryffel, Bernhard; Zheng, Song Guo

    2014-01-01

    Summary B cell-activating factor belonging to the TNF family (BAFF) exerts its pathogenic role in supporting the survival and proliferation of B cells, regulating class switch recombination as well as the selection of autoreactive B cells. Overexpression of BAFF induces a dramatic expansion of activated B cells, particularly marginal zone B cells, as well as hypergammaglobulinemia, autoantibody production and immune complex deposition. However, in addition to its effect on B cells, recent work has also demonstrated that BAFF can promote T cell activation, proliferation and differentiation. In this review, we have discussed the recent progress on the function and role of BAFF on T cells and T cell-mediated diseases. PMID:24411564

  18. Low-dose corticosteroid and gallium-67 scintigraphy and acute interstitial nephritis

    Directory of Open Access Journals (Sweden)

    Tetsu Akimoto

    2014-01-01

    Full Text Available We describe a 19-year-old male who developed diclofenac-induced acute inters-titial nephritis (AIN. Diffuse mononuclear cell infiltration was confirmed by renal biopsy and a Gallium (Ga-67 scintigraphy revealed diffuse uptake of the isotope in both kidneys. His renal function had gradually and promptly recovered after initiation of low-dose prednisolone (0.5 mg/kg/day. There are no established criteria for the administration of corticosteroids in the treatment of drug-induced AIN. Moreover, no clear recommendations regarding the optimal dose and duration of steroid administration in the treatment for drug-induced AIN has been established. In addition, we discuss the clinical benefit of steroid treatment and the diagnostic impact of Ga scanning on the management of drug-induced AIN.

  19. Human embryonic stem cells form functional thyroid follicles.

    Science.gov (United States)

    Ma, Risheng; Latif, Rauf; Davies, Terry F

    2015-04-01

    The molecular events that lead to human thyroid cell speciation remain incompletely characterized. It has been shown that overexpression of the regulatory transcription factors Pax8 and Nkx2-1 (ttf-1) directs murine embryonic stem (mES) cells to differentiate into thyroid follicular cells by initiating a transcriptional regulatory network. Such cells subsequently organized into three-dimensional follicular structures in the presence of extracellular matrix. In the current study, human embryonic stem (hES) cells were studied with the aim of recapitulating this scenario and producing functional human thyroid cell lines. Reporter gene tagged pEZ-lentiviral vectors were used to express human PAX8-eGFP and NKX2-1-mCherry in the H9 hES cell line followed by differentiation into thyroid cells directed by Activin A and thyrotropin (TSH). Both transcription factors were expressed efficiently in hES cells expressing either PAX8, NKX2-1, or in combination in the hES cells, which had low endogenous expression of these transcription factors. Further differentiation of the double transfected cells showed the expression of thyroid-specific genes, including thyroglobulin (TG), thyroid peroxidase (TPO), the sodium/iodide symporter (NIS), and the TSH receptor (TSHR) as assessed by reverse transcription polymerase chain reaction and immunostaining. Most notably, the Activin/TSH-induced differentiation approach resulted in thyroid follicle formation and abundant TG protein expression within the follicular lumens. On stimulation with TSH, these hES-derived follicles were also capable of dose-dependent cAMP generation and radioiodine uptake, indicating functional thyroid epithelial cells. The induced expression of PAX8 and NKX2-1 in hES cells was followed by differentiation into thyroid epithelial cells and their commitment to form functional three-dimensional neo-follicular structures. The data provide proof of principal that hES cells can be committed to thyroid cell speciation under

  20. Interstitial Lung disease in Systemic Sclerosis

    International Nuclear Information System (INIS)

    Ooi, G.C.; Mok, M.Y.; Tsang, K.W.T.; Khong, P.L.; Fung, P.C.W.; Chan, S.; Tse, H.F.; Wong, R.W.S.; Lam, W.K.; Lau, C.S.; Wong, Y.

    2003-01-01

    Purpose: To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. Material and Methods: : 45 SSc patients (40 women, 48.5±13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. Results: ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. Conclusion: Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively

  1. Endocrine disruptors and Leydig cell function.

    Science.gov (United States)

    Svechnikov, K; Izzo, G; Landreh, L; Weisser, J; Söder, O

    2010-01-01

    During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs) on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

  2. Endocrine Disruptors and Leydig Cell Function

    Directory of Open Access Journals (Sweden)

    K. Svechnikov

    2010-01-01

    Full Text Available During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

  3. T-cell dysfunction in HIV infection: anergy due to defective antigen-presenting cell function?

    NARCIS (Netherlands)

    Meyaard, L.; Schuitemaker, H.; Miedema, F.

    1993-01-01

    Before CD4+ T cells are depleted, T cells in asymptomatic HIV-infected individuals are functionally abnormal. These T cells are programmed for death, are non-responsive and fail to produce interleukin-2 after antigenic stimulation. Our view is that these different T-cell abnormalities are explained

  4. Acute interstitial pneumonia in mink kits inoculated with defined isolates of Aleutian mink disease parvovirus

    DEFF Research Database (Denmark)

    Alexandersen, Søren; Larsen, S; Aasted, B

    1994-01-01

    The present study addressed the causal role of Aleutian mink disease parvovirus (ADV) in acute interstitial pneumonia in mink kits. All the examined isolates of ADV caused interstitial pneumonia in newborn kits, although the severity of disease and the mortality varied. These findings indicate...... that ADV is the direct causal agent of this disease in mink kits and that cofactors, which could have been present in the original ADV-K isolate, do not play a role. Acute interstitial pneumonia characterized by hypertrophy and hyperplasia of alveolar type II cells, intranuclear viral inclusions...... plasma cells in lung, liver, spleen, kidney, mesenteric lymph node, and intestine. Surviving kits also had hypertrophy of the bronchus-associated lymphoid tissue and focal subpleural, intraalveolar accumulations of large cells with foamy cytoplasm, so-called lipid pneumonia....

  5. Airway-centered interstitial fibrosis: etiology, clinical findings and prognosis.

    Science.gov (United States)

    Kuranishi, Lilian Tiemi; Leslie, Kevin O; Ferreira, Rimarcs Gomes; Coletta, Ester Aparecida Ney; Storrer, Karin Mueller; Soares, Maria Raquel; de Castro Pereira, Carlos Alberto

    2015-05-09

    Airway-centered Interstitial Fibrosis (ACIF) is a common pathologic pattern observed in our practice. The objectives of this study are to describe the causes associated with ACIF in a large sample of patients and its effect on survival. A retrospective study in three centers of interstitial lung disease in São Paulo, between January of 1995 and December of 2012. The surgical lung biopsy specimens were reviewed by three pathologists. The clinical, functional and tomographic findings were analyzed by a standardized protocol. There were 68 cases of ACIF, most of them women. The mean age was 57 ± 12 yr. Dyspnea, cough, restrictive pattern at spirometry and oxygen desaturation at exercise were common. A reticular pattern with peribronchovascular infiltrates was found in 79% of the cases. The etiologies of ACIF were hypersensitivity pneumonitis in 29 (42.6%), gastroesophageal reflux disease in 17 (25.0%), collagen vascular disease in 4 (5.9%), a combination of them in 15 cases and idiopathic in 3 (4.4%). The median survival was 116 months (95% CI = 58.5 - 173.5). Lower values of oxygen saturation at rest, presence of cough and some histological findings--organizing tissue in the airways, fibroblastic foci and microscopic honeycombing--were predictors of worse survival. ACIF is an interstitial lung disease with a better survival when compared with IPF. The main etiologies are HP and GERD. The oxygen saturation at rest, the presence of cough and some histological findings are predictors of survival.

  6. Gallium arsenide exposure impairs splenic B cell accessory function.

    Science.gov (United States)

    Gondre-Lewis, Timothy A; Hartmann, Constance B; Caffrey, Rebecca E; McCoy, Kathleen L

    2003-03-01

    Gallium arsenide (GaAs) is utilized in industries for its semiconductor and optical properties. Chemical exposure of animals systemically suppresses several immune functions. The ability of splenic B cells to activate antigen-specific helper CD4(+) T cell hybridomas was assessed, and various aspects of antigen-presenting cell function were examined. GaAs-exposed murine B cells were impaired in processing intact soluble protein antigens, and the defect was antigen dependent. In contrast, B cells after exposure competently presented peptides to the T cells, which do not require processing. Cell surface expression of major histocompatibility complex (MHC) class II molecules and several costimulatory molecules on splenic B cells, which are critical for helper T cell activation, was not affected by chemical exposure. GaAs exposure also did not influence the stability of MHC class II heterodimers, suggesting that the defect may precede peptide exchange. GaAs-exposed B cells contained a normal level of aspartyl cathepsin activity; however, proteolytic activities of thiol cathepsins B and L were approximately half the control levels. Furthermore, two cleavage fragments of invariant chain, a molecular chaperone of MHC class II molecules, were increased in GaAs-exposed B cells, indicative of defective degradation. Thus, diminished thiol proteolytic activity in B cells may be responsible for their impaired antigen processing and invariant chain degradation, which may contribute to systemic immunosuppression caused by GaAs exposure.

  7. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils

    DEFF Research Database (Denmark)

    Galli, Stephen J; Borregaard, Niels; Wynn, Thomas A

    2011-01-01

    ). Here we focus on the occurrence of phenotypically distinct subpopulations in three lineages of myeloid cells with important roles in innate and acquired immunity: macrophages, mast cells and neutrophils. Cytokine signals, epigenetic modifications and other microenvironmental factors can substantially...... and, in some cases, rapidly and reversibly alter the phenotype of these cells and influence their function. This suggests that regulation of the phenotype and function of differentiated hematopoietic cells by microenvironmental factors, including those generated during immune responses, represents...

  8. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Directory of Open Access Journals (Sweden)

    Wataru Sonoyama

    2006-12-01

    Full Text Available Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla. Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  9. Human CD8 T cells generated in vitro from hematopoietic stem cells are functionally mature

    Directory of Open Access Journals (Sweden)

    Zúñiga-Pflücker Juan

    2011-03-01

    Full Text Available Abstract Background T cell development occurs within the highly specialized thymus. Cytotoxic CD8 T cells are critical in adaptive immunity by targeting virally infected or tumor cells. In this study, we addressed whether functional CD8 T cells can be generated fully in vitro using human umbilical cord blood (UCB hematopoietic stem cells (HSCs in coculture with OP9-DL1 cells. Results HSC/OP9-DL1 cocultures supported the differentiation of CD8 T cells, which were TCR/CD3hi CD27hi CD1aneg and thus phenotypically resembled mature functional CD8 single positive thymocytes. These in vitro-generated T cells also appeared to be conventional CD8 cells, as they expressed high levels of Eomes and low levels of Plzf, albeit not identical to ex vivo UCB CD8 T cells. Consistent with the phenotypic and molecular characterization, upon TCR-stimulation, in vitro-generated CD8 T cells proliferated, expressed activation markers (MHC-II, CD25, CD38, secreted IFN-γ and expressed Granzyme B, a cytotoxic T-cell effector molecule. Conclusion Taken together, the ability to direct human hematopoietic stem cell or T-progenitor cells towards a mature functional phenotype raises the possibility of establishing cell-based treatments for T-immunodeficiencies by rapidly restoring CD8 effector function, thereby mitigating the risks associated with opportunistic infections.

  10. Investigating evolutionary conservation of dendritic cell subset identity and functions

    Directory of Open Access Journals (Sweden)

    Thien-Phong eVu Manh

    2015-06-01

    Full Text Available Dendritic cells (DC were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types

  11. Investigating Evolutionary Conservation of Dendritic Cell Subset Identity and Functions.

    Science.gov (United States)

    Vu Manh, Thien-Phong; Bertho, Nicolas; Hosmalin, Anne; Schwartz-Cornil, Isabelle; Dalod, Marc

    2015-01-01

    Dendritic cells (DCs) were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T-cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks, and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization, and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation, and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes, and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types, organs, and

  12. Microculture system for studying monolayers of functional beta-cells.

    Science.gov (United States)

    Dobersen, M J; Scharff, J E; Notkins, A L

    1980-04-01

    A method is described for growing monolayers of newborn rat beta-cells in microculture trays. After disruption of the pancreas with collagenase, islets were isolated by Ficoll density gradient centrifugation, trypsinized to obtain individual cells, and plated in 96-well tissue culture trays. The cells were incubated for the first 3 days in growth medium containing 0.1 mM 3-isobutyl-1-methylxanthine to promote monolayer formation. The cultures could be maintained in a functional state, as defined by their responsiveness to known modulators of insulin secretion, for at least 2 weeks. As few as 1 X 10(3) islet cells/well gave results that were reproducible within +/- 10%. It is suggested that the microculture system for islet cells might prove to be a rapid and reproducible screening technique for studying drugs, viruses, or other agents that affect beta-cell function.

  13. Diacylglycerol kinases in T cell tolerance and effector function

    Directory of Open Access Journals (Sweden)

    Shelley S Chen

    2016-11-01

    Full Text Available Diacylglycerol kinases (DGKs are a family of enzymes that regulate the relative levels of diacylglycerol (DAG and phosphatidic acid (PA in cells by phosphorylating DAG to produce PA. Both DAG and PA are important second messengers cascading T cell receptor (TCR signal by recruiting multiple effector molecules such as RasGRP1, PKC, and mTOR. Studies have revealed important physiological functions of DGKs in the regulation of receptor signaling and the development and activation of immune cells. In this review, we will focus on recent progresses in our understanding of two DGK isoforms,  and , in CD8 T effector and memory cell differentiation, regulatory T cell development and function, and invariant NKT cell development and effector lineage differentiation.

  14. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Science.gov (United States)

    Kosan, Christian; Godmann, Maren

    2016-01-01

    All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function. PMID:26798358

  15. Modulation of Conjunctival Goblet Cell Function by Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    L. Contreras-Ruiz

    2013-01-01

    Full Text Available Ocular surface inflammation associated with Sjögren’s syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sjögren’s syndrome (Thrombospondin-1 deficient mice. We found that apoptosis of goblet cells was primarily induced by TNF-α and IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.

  16. Programming cell fate on bio-functionalized silicon.

    Science.gov (United States)

    Premnath, Priyatha; Tan, Bo; Venkatakrishnan, Krishnan

    2015-04-01

    Controlling the growth of cells on the surface of silicon without an additive layer or topographical modification is unexplored. This research article delineates the discovery of unique properties of a bio-functionalized silicon substrate, programmed to repel or control cells, generated by ultrafast femtosecond pulse interaction with silicon. Remarkably, bio-functionalization in any shape or size without change in topology or morphology is observed indicating only sub-surface phase transformations. Material characterization reveals the presence of a unique mixture of phases of SiO2 and Si. Consequently, these variations in phase alter the physicochemical characteristics on the surface of silicon resulting in its bio-functionalization. The culture of mouse embryonic fibroblasts shows unique adhesion characteristics on these bio-functionalized silicon surfaces that include cell controlling, cell trapping, and cell shaping. Furthermore, the directionality of fibroblasts is restrained parallel to bio-functionalized zones as evidenced by changes in cytoskeleton. The controlling of proliferation, migration and adhesion of cells is attributed to unique phase bio-functionalization. This method presents considerable promise in a myriad of applications such as tissue engineering, MEMS, and lab-on-a-chip devices. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Potential of bursa-immigrated hematopoietic precursor cells to differentiate to functional B and T cells

    International Nuclear Information System (INIS)

    Weber, W.T.; Alexander, J.E.

    1978-01-01

    The potential of hematopoietic precursor cells, recently immigrated into the 13- and 14-day-old embryonic bursa, to migrate to the thymus and to differentiate to functional T cells was investigated. Chromosomally marked cell populations obtained from 13- and 14-day-old embryonic bursas were transferred i.v. to 780 R γ-irradiated chick embryos of equivalent age. When appropriate chimeras were examined at 4 to 12 weeks after cell transfer, donor cells were found to proliferate primarily in the bursa. Significant donor cell influx into the thymus was not detected. In correlation with these findings, Con A- and PHA-responsive T cells in thymus and spleen cell cultures of recipients remained of host origin whereas the number of anti-CIg responsive B cells of donor type increased gradually in the spleens of recipients. An initial lag period preceded the accumulation of functional donor B cells in the spleens of recipients, despite the predominant presence of dividing donor cells in the bursa. This suggests that the transferred bursal cell population required substantially longer to mature and emigrate from the bursa as functional B cells than the host cell population remaining in the irradiated bursas at time of cell transfer. The failure to detect significant influx of donor cells into the thymus and their failure to differentiate to functional T cells suggest that the recently bursa-immigrated hematopoietic stem cells of 13- and 14-day-old embryos may not be pluripotential cells, but rather cells already committed to the B cell line of differentiation

  18. Left ventricular systolic function in sickle cell anaemia: an ...

    African Journals Online (AJOL)

    Dennenberg BS, Criner G, Jones R, Spann JF. Car- diac function in sickle cell anaemia. Am J Cardiol 1983;. 51: 1674-1678. 5. Rees AH, Stefadouros MA, Strong WB, et al. Left ven- tricular performance in children with homozygous sickle cell anaemia. Br Heart J 1978; 40: 690-696 PubMed . 6. Balfour IC, Covitz W, Davis H, ...

  19. Expression of functional human C1 inhibitor in COS cells

    NARCIS (Netherlands)

    Eldering, E.; Nuijens, J. H.; Hack, C. E.

    1988-01-01

    Full length human C1 inhibitor cDNA was cloned into a vector suitable for transient expression in COS-1 cells. Transfected COS cells secreted an immunoreactive protein of Mr approximately 110,000 that appeared to be functionally equivalent to the plasma-derived protein as established by the

  20. Origin of inner ear hair cells: morphological and functional differentiation from ciliary cells into hair cells in zebrafish inner ear.

    Science.gov (United States)

    Tanimoto, Masashi; Ota, Yukiko; Inoue, Maya; Oda, Yoichi

    2011-03-09

    Auditory and vestibular functions in vertebrates depend on the transduction of sound vibration or head acceleration into electrical responses in inner ear hair cells. Mechanoelectrical transduction occurs at the tip of stereocilia, which are polarized to form an orientational arrangement that determines directional sensitivity. It remains to be clarified when and how premature hair cells acquire their specialized structure and function in living animals. The developmental origin of inner ear hair cells has been studied in vivo in zebrafish embryos. Tether cells, a small number of ciliated cells associated with an "ear stone" (or otolith) in the embryonic zebrafish inner ear, are believed to be precocious hair cells. However, whether or not tether cells acquire hair bundles and mechanosensitivity remains unknown. In the present study, we investigated the morphological and functional development of tether cells. Immunohistochemical examination revealed that stereocilia appeared on the tether cell apex in a polarized arrangement at 22 h postfertilization (hpf). Labeling with FM1-43, a marker of functional mechanotransduction channels, and the in vivo electrophysiological recording of mechanotransducer responses in the developing inner ear demonstrated that tether cells acquired direction-selective mechanosensitivity at 23 hpf. These results revealed that tether cells begin to function as hair cells within an hour after the appearance of a polarized array of stereociliary bundles. Thus, the ciliary cells morphologically and functionally differentiate into the first sensory hair cells in the inner ear of the zebrafish.

  1. How does interstitial cystitis begin?

    Science.gov (United States)

    Parsons, C Lowell

    2015-12-01

    Interstitial cystitis (IC) does not start as an endstage disease, it has a beginning when symptoms are milder, intermittent and the disease is misdiagnosed. To determine how IC develops patients were interviewed on when their symptoms began, what they were and are now as well as the various diagnoses that they received before they were determined to have IC. One hundred female IC patients were screened. They filled out a questionnaire asking about the age their disease presented, their initial and current symptoms, what their original diagnoses were, effect of the menstrual cycle and sexual activity on their symptoms and about any relatives with bladder symptoms or a current diagnosis of IC. By age 30, 81% of patients had bladder symptoms, 21% before age 10. The first symptom was frequency in 81%, pain present in 59% and the symptoms were intermittent in 64%. Most common early misdiagnosis was UTI in 74% with 93% reporting negative urine cultures. Sex was painful and causes symptom flares in 82%, symptoms flared the week before the menses in 75%. Most common gynecologic diagnosis was yeast vaginitis, 42%. Urge incontinence was present in 33%. There were 51% that reported bladder symptoms in a first degree female relative. IC begins primarily with frequency and is intermittent in most patients with symptom flares associated with sexual activity. Pain and urgency incontinence tend to be a later symptoms. When IC flares the most common misdiagnosis is UTI. Symptoms begin before age 30 in most but an IC diagnosis is often not made until age 40. Genetics appear to play a significant role. It is important to consider these facts when evaluating women with "early IC" because correct diagnosis will result in proper therapy and reduced health care costs.

  2. Human embryonic stem cells differentiate into functional renal proximal tubular-like cells.

    Science.gov (United States)

    Narayanan, Karthikeyan; Schumacher, Karl M; Tasnim, Farah; Kandasamy, Karthikeyan; Schumacher, Annegret; Ni, Ming; Gao, Shujun; Gopalan, Began; Zink, Daniele; Ying, Jackie Y

    2013-04-01

    Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels. Marker expression patterns of these differentiated stem cells and in vitro cultivated primary human renal proximal tubular cells were comparable. The differentiated stem cells showed morphological and functional characteristics of renal proximal tubular cells, and generated tubular structures in vitro and in vivo. In addition, the differentiated stem cells contributed in organ cultures for the formation of simple epithelia in the kidney cortex. Bioreactor experiments showed that these cells retained their functional characteristics under conditions as applied in bioartificial kidneys. Thus, our results show that human embryonic stem cells can differentiate into renal proximal tubular-like cells. Our approach would provide a source for human renal proximal tubular cells that are not affected by problems associated with immortalized cell lines or primary cells.

  3. Cellular Allometry of Mitochondrial Functionality Establishes the Optimal Cell Size.

    Science.gov (United States)

    Miettinen, Teemu P; Björklund, Mikael

    2016-11-07

    Eukaryotic cells attempt to maintain an optimal size, resulting in size homeostasis. While cellular content scales isometrically with cell size, allometric laws indicate that metabolism per mass unit should decline with increasing size. Here we use elutriation and single-cell flow cytometry to analyze mitochondrial scaling with cell size. While mitochondrial content increases linearly, mitochondrial membrane potential and oxidative phosphorylation are highest at intermediate cell sizes. Thus, mitochondrial content and functional scaling are uncoupled. The nonlinearity of mitochondrial functionality is cell size, not cell cycle, dependent, and it results in an optimal cell size whereby cellular fitness and proliferative capacity are maximized. While optimal cell size is controlled by growth factor signaling, its establishment and maintenance requires mitochondrial dynamics, which can be controlled by the mevalonate pathway. Thus, optimization of cellular fitness and functionality through mitochondria can explain the requirement for size control, as well as provide means for its maintenance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Salivary gland NK cells are phenotypically and functionally unique.

    Directory of Open Access Journals (Sweden)

    Marlowe S Tessmer

    2011-01-01

    Full Text Available Natural killer (NK cells and CD8(+ T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV. However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or T(reg cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells.

  5. Roquin Paralogs Differentially Regulate Functional NKT Cell Subsets.

    Science.gov (United States)

    Drees, Christoph; Vahl, J Christoph; Bortoluzzi, Sabrina; Heger, Klaus D; Fischer, Julius C; Wunderlich, F Thomas; Peschel, Christian; Schmidt-Supprian, Marc

    2017-04-01

    NKT cells represent a small subset of glycolipid-recognizing T cells that are heavily implicated in human allergic, autoimmune, and malignant diseases. In the thymus, precursor cells recognize self-glycolipids by virtue of their semi-invariant TCR, which triggers NKT cell lineage commitment and maturation. During their development, NKT cells are polarized into the NKT1, NKT2, and NKT17 subsets, defined through their cytokine-secretion patterns and the expression of key transcription factors. However, we have largely ignored how the differentiation into the NKT cell subsets is regulated. In this article, we describe the mRNA-binding Roquin-1 and -2 proteins as central regulators of murine NKT cell fate decisions. In the thymus, T cell-specific ablation of the Roquin paralogs leads to a dramatic expansion of NKT17 cells, whereas peripheral mature NKT cells are essentially absent. Roquin-1/2-deficient NKT17 cells show exaggerated lineage-specific expression of nearly all NKT17-defining proteins tested. We show through mixed bone marrow chimera experiments that NKT17 polarization is mediated through cell-intrinsic mechanisms early during NKT cell development. In contrast, the loss of peripheral NKT cells is due to cell-extrinsic factors. Surprisingly, Roquin paralog-deficient NKT cells are, in striking contrast to conventional T cells, compromised in their ability to secrete cytokines. Altogether, we show that Roquin paralogs regulate the development and function of NKT cell subsets in the thymus and periphery. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. Pancreatic islet-cell viability, functionality and oxidative status ...

    Indian Academy of Sciences (India)

    Unknown

    lar) in case of lean and obese mice (Dalpe-Scott et al. 1983). Antibiotics also show concentration dependant effect on the islet functionality. Injection of tetracycline hydrochloride at the dose of 25 mg/kg body weight in mice did not change the functional activity of the β-cells and the rate of insulin formation and secretion for ...

  7. Caveolae, caveolins, cavins and endothelial cell function: new insights

    Directory of Open Access Journals (Sweden)

    Grzegorz eSowa

    2012-01-01

    Full Text Available Caveolae are cholesterol and glycosphingolipid-rich flask-shaped invaginations of the plasma membrane which are particularly abundant in vascular endothelium and present in all other cell types of the cardiovascular system, including vascular smooth muscle cells, macrophages, cardiac myocytes, and fibroblasts. Caveolins and the more recently discovered cavins are the major protein components of caveolae. When caveolae were discovered, their functional role was believed to be limited to transport across the endothelial cell barrier. Since then, however, a large body of evidence has accumulated, suggesting that these microdomains are very important in regulating many other important endothelial cell functions, mostly due to their ability to concentrate and compartmentalize various signaling molecules. Over the course of several years, multiple studies involving knockout mouse and small interfering RNA approaches have considerably enhanced our understanding of the role of caveolae and caveolin-1 in regulating many cardiovascular functions. New findings have been reported implicating other caveolar protein components in endothelial cell signaling and function, such as the understudied caveolin-2 and newly discovered cavin proteins. The aim of this review is to focus primarily on molecular and cellular aspects of the role of caveolae, caveolins, and cavins in endothelial cell signaling and function. In addition, where appropriate, the possible implications for the cardiovascular and pulmonary physiology and pathophysiology will be discussed.

  8. Expression and function of the endocannabinoid system in glial cells.

    Science.gov (United States)

    Massi, Paola; Valenti, Marta; Bolognini, Daniele; Parolaro, Daniela

    2008-01-01

    In the last few years the role and significance of the glia in CNS function and pathology have been drastically reassessed. Glial cells physiology appears very different in healthy versus pathological brain and the recent identification of cannabinoid receptors and their endogenous ligands in glia has triggered a number of studies exploring the role of (endo)cannabinoid system in glia functionality and disease. (Endo)cannabinoids exert their effects in these cells directly affecting some important peculiar functions of the glia and actively promoting biochemical signals ending in a pro-survival fate for these cells. By contrast, (endo)cannabinoids induce a selective death in glia-derived tumor cells. Of special physiological and therapeutic relevance is the reported ability of glial cells during neuropathological conditions to release an increased amount of endocannabinoids and to overexpress cannabinoid receptors. This evidence has suggested that the endocannabinoids production by glial cells may constitute an endogenous defense mechanism preventing the propagation of neuroinflammation and cell damage. The present paper will review the evidence supporting the regulatory role of (endo)cannabinoids in glia function, holding in consideration their therapeutic potential as neuroprotective and/or anticancer agents.

  9. Analysis of Glial Cell Development and Function in Drosophila

    Science.gov (United States)

    Stork, Tobias; Bernardos, Rebecca; Freeman, Marc R.

    2016-01-01

    Glial cells are the most abundant cell type in our brains, yet we understand very little about their development and function. An accumulating body of work over the last decade has revealed that glia are critical regulators of nervous system development, function, and health. Based on morphological and molecular criteria, glia in Drosophila melanogaster are very similar to their mammalian counterparts, suggesting that a detailed investigation of fly glia has the potential to add greatly to our understanding of fundamental aspects of glial cell biology. In this article, we provide an overview of the subtypes of glial cells found in Drosophila and discuss our current understanding of their functions, the development of a subset of well-defined glial lineages, and the molecular-genetic tools available for manipulating glial subtypes in vivo. PMID:22194269

  10. Curcumin Modulates Pancreatic Adenocarcinoma Cell-Derived Exosomal Function

    Science.gov (United States)

    Osterman, Carlos J. Diaz; Lynch, James C.; Leaf, Patrick; Gonda, Amber; Ferguson Bennit, Heather R.; Griffiths, Duncan; Wall, Nathan R.

    2015-01-01

    Pancreatic cancer has the highest mortality rates of all cancer types. One potential explanation for the aggressiveness of this disease is that cancer cells have been found to communicate with one another using membrane-bound vesicles known as exosomes. These exosomes carry pro-survival molecules and increase the proliferation, survival, and metastatic potential of recipient cells, suggesting that tumor-derived exosomes are powerful drivers of tumor progression. Thus, to successfully address and eradicate pancreatic cancer, it is imperative to develop therapeutic strategies that neutralize cancer cells and exosomes simultaneously. Curcumin, a turmeric root derivative, has been shown to have potent anti-cancer and anti-inflammatory effects in vitro and in vivo. Recent studies have suggested that exosomal curcumin exerts anti-inflammatory properties on recipient cells. However, curcumin’s effects on exosomal pro-tumor function have yet to be determined. We hypothesize that curcumin will alter the pro-survival role of exosomes from pancreatic cancer cells toward a pro-death role, resulting in reduced cell viability of recipient pancreatic cancer cells. The main objective of this study was to determine the functional alterations of exosomes released by pancreatic cancer cells exposed to curcumin compared to exosomes from untreated pancreatic cancer cells. We demonstrate, using an in vitro cell culture model involving pancreatic adenocarcinoma cell lines PANC-1 and MIA PaCa-2, that curcumin is incorporated into exosomes isolated from curcumin-treated pancreatic cancer cells as observed by spectral studies and fluorescence microscopy. Furthermore, curcumin is delivered to recipient pancreatic cancer cells via exosomes, promoting cytotoxicity as demonstrated by Hoffman modulation contrast microscopy as well as AlamarBlue and Trypan blue exclusion assays. Collectively, these data suggest that the efficacy of curcumin may be enhanced in pancreatic cancer cells through

  11. Flock worker's lung: chronic interstitial lung disease in the nylon flocking industry.

    Science.gov (United States)

    Kern, D G; Crausman, R S; Durand, K T; Nayer, A; Kuhn, C

    1998-08-15

    Two young men working at a nylon flocking plant in Rhode Island developed interstitial lung disease of unknown cause. Similar clusters at the same company's Canadian plant were reported previously. To define the extent, clinicopathologic features, and potential causes of the apparent disease outbreak. Case-finding survey and retrospective cohort study. Academic occupational medicine program. All workers employed at the Rhode Island plant on or after 15 June 1990. Symptomatic employees had chest radiography, pulmonary function tests, high-resolution computed tomography, and serologic testing. Those with unexplained radiographic or pulmonary function abnormalities underwent bronchoalveolar lavage, lung biopsy, or both. The case definition of "flock worker's lung" required histologic evidence of interstitial lung disease (or lavage evidence of lung inflammation) not explained by another condition. Eight cases of flock worker's lung were identified at the Rhode Island plant. Three cases were characterized by a high proportion of eosinophils (25% to 40%) in lavage fluid. Six of the seven patients who had biopsy had histologic findings of nonspecific interstitial pneumonia, and the seventh had bronchiolitis obliterans organizing pneumonia. All seven of these patients had peribronchovascular interstitial lymphoid nodules, usually with germinal centers, and most had lymphocytic bronchiolitis and interstitial fibrosis. All improved after leaving work. Review of the Canadian tissue specimens showed many similar histologic findings. Among the 165-member study cohort, a 48-fold or greater increase was seen in the sex-adjusted incidence rate of all interstitial lung disease. Work in the nylon flocking industry poses substantial risk for a previously unrecognized occupational interstitial lung disease. Nylon fiber is the suspected cause of this condition.

  12. Function of bunching segment in multi-cell RF gun

    International Nuclear Information System (INIS)

    Yang Xingfan; Xu Zhou Liu Xisan

    2001-01-01

    With a bunching segment and a shortened first cell, the 4 + 1/2 cell RF gun produced in CAEP has been proved experimentally to be effective in reducing electron back bombardment. The analysis of the electric field distribution and electron motion in bunching segment of multi-cell RF gun is presented. The electron capture efficiency and electron trajectory with different initial phase are calculated using Runge-Kutta method. The function of the bunching segment is discussed. The calculated parameters of the 4 + 1/2 cell RF gun agree well with the experimental results

  13. Physiological and pathophysiological functions of intestinal mast cells.

    Science.gov (United States)

    Bischoff, Stephan C

    2009-07-01

    The normal gastrointestinal (GI) mucosa is equipped with mast cells that account for 2-3% of lamina propria cells under normal conditions. Mast cells are generally associated with allergic disease, and indeed, food allergy that manifests in the GI tract is usually mast cell dependent. On the other hand, mast cells have a number of physiological functions in the GI tract, namely regulatory functions such as control of blood flow and coagulation, smooth muscle contraction and peristalsis, and secretion of acid, electrolytes, and mucus by epithelial cells. One of the most intriguing functions of intestinal mast cells is their role in host defense against microbes like bacteria, viruses, or parasites. Mast cells recognize microbes by antibody-dependent mechanisms and through pattern-recognition receptors. They direct the subsequent immune response by attracting both granulocytes and lymphocytes to the site of challenge via paracrine cytokine release. Moreover, mast cells initiate, by releasing proinflammatory mediators, innate defense mechanisms such as enhanced epithelial secretion, peristalsis, and alarm programs of the enteric nervous This initiation can occur in response to a primary contact to the microbe or other danger signals, but becomes much more effective if the triggering antigen reappears and antibodies of the IgE or IgG type have been generated in the meantime by the specific immune system. Thus, mast cells operate at the interface between innate and adaptive immune responses to enhance the defense against pathogens and, most likely, the commensal flora. In this respect, it is important to note that mast cells are directly involved in controlling the function of the intestinal barrier that turned out to be a crucial site for the development of infectious and immune-mediated diseases. Hence, intestinal mast cells perform regulatory functions to maintain tissue homeostasis, they are involved in host defense mechanisms against pathogens, and they can induce

  14. Heterogeneity of functional properties of Clone 66 murine breast cancer cells expressing various stem cell phenotypes.

    Science.gov (United States)

    Mukhopadhyay, Partha; Farrell, Tracy; Sharma, Gayatri; McGuire, Timothy R; O'Kane, Barbara; Sharp, J Graham

    2013-01-01

    Breast cancer grows, metastasizes and relapses from rare, therapy resistant cells with a stem cell phenotype (cancer stem cells/CSCs). However, there is a lack of studies comparing the functions of CSCs isolated using different phenotypes in order to determine if CSCs are homogeneous or heterogeneous. Cells with various stem cell phenotypes were isolated by sorting from Clone 66 murine breast cancer cells that grow orthotopically in immune intact syngeneic mice. These populations were compared by in vitro functional assays for proliferation, growth, sphere and colony formation; and in vivo limiting dilution analysis of tumorigenesis. The proportion of cells expressing CD44(high)CD24(low/neg), side population (SP) cells, ALDH1(+), CD49f(high), CD133(high), and CD34(high) differed, suggesting heterogeneity. Differences in frequency and size of tumor spheres from these populations were observed. Higher rates of proliferation of non-SP, ALDH1(+), CD34(low), and CD49f(high) suggested properties of transit amplifying cells. Colony formation was higher from ALDH1(-) and non-SP cells than ALDH1(+) and SP cells suggesting a progenitor phenotype. The frequency of clonal colonies that grew in agar varied and was differentially altered by the presence of Matrigel™. In vivo, fewer cells with a stem cell phenotype were needed for tumor formation than "non-stem" cells. Fewer SP cells were needed to form tumors than ALDH1(+) cells suggesting further heterogeneities of cells with stem phenotypes. Different levels of cytokines/chemokines were produced by Clone 66 with RANTES being the highest. Whether the heterogeneity reflects soluble factor production remains to be determined. These data demonstrate that Clone 66 murine breast cancer cells that express stem cell phenotypes are heterogeneous and exhibit different functional properties, and this may also be the case for human breast cancer stem cells.

  15. Idiopathic interstitial pneumonias: radiologic-pathologic correlation

    International Nuclear Information System (INIS)

    Yoon, Young Cheol; Suh, Gee Young; Han, Joung Ho; Lee, Kyung Soo

    2002-01-01

    Idiopathic interstitial pneumonias are at present classified as one of four types: usual, nonspecific, acute, or desquamative. The acute form has the worst prognosis, followed by the usual and the nonspecific form; it is in desquamative cases that prognosis is best. At high-resolution CT, usual interstitial pneumonia, the most frequent type, manifests as patchy subpleural areas of ground-glass attenuation, irregular linear opacity, and honeycombing, which the nonspecific type, the second most frequent, appears as subpleural patchy areas of ground-glass attenuation with associated areas of irregular linear opacity. Acute interstitial pneumonia demonstrates extensive bilateral airspace consolidation and patchy or diffuse bilateral areas of ground-glass attenuation in middle and lower lung zones

  16. Altered effector function of peripheral cytotoxic cells in COPD

    Directory of Open Access Journals (Sweden)

    Corne Jonathan M

    2009-06-01

    Full Text Available Abstract Background There is mounting evidence that perforin and granzymes are important mediators in the lung destruction seen in COPD. We investigated the characteristics of the three main perforin and granzyme containing peripheral cells, namely CD8+ T lymphocytes, natural killer (NK; CD56+CD3- cells and NKT-like (CD56+CD3+ cells. Methods Peripheral blood mononuclear cells (PBMCs were isolated and cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry. Immunomagnetically selected CD8+ T lymphocytes, NK (CD56+CD3- and NKT-like (CD56+CD3+ cells were used in an LDH release assay to determine cytotoxicity and cytotoxic mechanisms were investigated by blocking perforin and granzyme B with relevant antibodies. Results The proportion of peripheral blood NKT-like (CD56+CD3+ cells in smokers with COPD (COPD subjects was significantly lower (0.6% than in healthy smokers (smokers (2.8%, p +CD3- cells from COPD subjects were significantly less cytotoxic than in smokers (16.8% vs 51.9% specific lysis, p +CD3+ cells (16.7% vs 52.4% specific lysis, p +CD3- and NKT-like (CD56+CD3+ cells from smokers and HNS. Conclusion In this study, we show that the relative numbers of peripheral blood NK (CD56+CD3- and NKT-like (CD56+CD3+ cells in COPD subjects are reduced and that their cytotoxic effector function is defective.

  17. Novel approaches in function-driven single-cell genomics.

    Science.gov (United States)

    Doud, Devin F R; Woyke, Tanja

    2017-07-01

    Deeper sequencing and improved bioinformatics in conjunction with single-cell and metagenomic approaches continue to illuminate undercharacterized environmental microbial communities. This has propelled the 'who is there, and what might they be doing' paradigm to the uncultivated and has already radically changed the topology of the tree of life and provided key insights into the microbial contribution to biogeochemistry. While characterization of 'who' based on marker genes can describe a large fraction of the community, answering 'what are they doing' remains the elusive pinnacle for microbiology. Function-driven single-cell genomics provides a solution by using a function-based screen to subsample complex microbial communities in a targeted manner for the isolation and genome sequencing of single cells. This enables single-cell sequencing to be focused on cells with specific phenotypic or metabolic characteristics of interest. Recovered genomes are conclusively implicated for both encoding and exhibiting the feature of interest, improving downstream annotation and revealing activity levels within that environment. This emerging approach has already improved our understanding of microbial community functioning and facilitated the experimental analysis of uncharacterized gene product space. Here we provide a comprehensive review of strategies that have been applied for function-driven single-cell genomics and the future directions we envision. © FEMS 2017.

  18. Correlations and functional connections in a population of grid cells.

    Science.gov (United States)

    Dunn, Benjamin; Mørreaunet, Maria; Roudi, Yasser

    2015-02-01

    We study the statistics of spike trains of simultaneously recorded grid cells in freely behaving rats. We evaluate pairwise correlations between these cells and, using a maximum entropy kinetic pairwise model (kinetic Ising model), study their functional connectivity. Even when we account for the covariations in firing rates due to overlapping fields, both the pairwise correlations and functional connections decay as a function of the shortest distance between the vertices of the spatial firing pattern of pairs of grid cells, i.e. their phase difference. They take positive values between cells with nearby phases and approach zero or negative values for larger phase differences. We find similar results also when, in addition to correlations due to overlapping fields, we account for correlations due to theta oscillations and head directional inputs. The inferred connections between neurons in the same module and those from different modules can be both negative and positive, with a mean close to zero, but with the strongest inferred connections found between cells of the same module. Taken together, our results suggest that grid cells in the same module do indeed form a local network of interconnected neurons with a functional connectivity that supports a role for attractor dynamics in the generation of grid pattern.

  19. Simulation of interstitial fluid flow in ligaments: comparison among Stokes, Brinkman and Darcy models.

    Science.gov (United States)

    Yao, Wei; Shen, Zhoufeng; Ding, Guanghong

    2013-01-01

    In this paper, we use Stokes, Brinkman and Darcy equations to approximate the porous continuum media of ligament tissues respectively, simulate the flow field with FLUENT software, and study the shear stress on the cell surface due to the interstitial fluid flow. Since the Brinkman equation approaches Stokes equation well in high hydraulic permeability (k p) condition (k p ≥1.0×10(-8) m(2) in our numerical simulation), and it is an approximation to Darcy model in low k p condition (k p ≤5.0×10(-12) m(2) in our numerical simulation), we used the Brinkman model to simulate the interstitial fluid flow in the ligament where k p is approximately 1.0×10(-16) m(2). It shows k p and anisotropic property have a little effect on the flow field, but have a great effect on the shear stress on the membrane of interstitial cellscell). There is a linear relationship between τ cell and , when k p =1.0×10(-16) m(2) and the maximum τ cellcell,max) is approximately 10 Pa. The anisotropic property will affect τ cell's distribution on the cell surface. When k x/k y>1, low τ cell dominates the cell, while when k x/k y<1, high τ cell dominants the cell.

  20. Cell viability and functionality of probiotic bacteria in dairy products

    Directory of Open Access Journals (Sweden)

    Gabriel eVinderola

    2011-05-01

    Full Text Available Probiotic bacteria, according to the definition adopted by the World Health Organization in 2002, are live microorganisms, which when administered in adequate amounts confer a health benefit to the host. Recent studies show that the same probiotic strain produced and/or preserved under different storage conditions, may present different responses regarding their susceptibility to the adverse conditions of the gastrointestinal tract, its capacity to adhere to the intestinal epithelium, or its immunomodulating capacity, being the functionality affected without changes in cell viability. This could imply that the control of cell viability is not always enough to guarantee the functionality (probiotic capacity of a strain. Therefore, a new challenge arises for food technologists and microbiologists when it comes to designing and monitoring probiotic food: to be able to monitor the cell functionality a probiotic microorganism along all the stages the strain goes through from the moment it is produced and included into the food vehicle until to the moment of consumption. Conventional methodological tools or others still to be developed must be used. The application of cell membrane functionality markers, the use of tests of resistence to intestinal barriers, the study of surface properties and the application of in vivo models comes together as complementary tools to assess the actual capacity of a probiotic into a specific food to exert functional effects regardless the number of viable cells present at the moment of consumption.

  1. Human lung mast cells modulate the functions of airway smooth muscle cells in asthma.

    Science.gov (United States)

    Alkhouri, H; Hollins, F; Moir, L M; Brightling, C E; Armour, C L; Hughes, J M

    2011-09-01

    Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction. To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays. Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation. Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma. © 2011 John Wiley & Sons A/S.

  2. Functional cell mediated lympholysis I. Description of the assay

    International Nuclear Information System (INIS)

    Goeken, N.E.; Thompson, J.S.

    1981-01-01

    The anamnestic response by human bi-directional (BD) mixed lymphocyte cultures (MLC) to restimulation by cells of the original stimulating type is generally strikingly reduced as compared to that of standard one-way cultures. This difference was shown not to be related to a change in kinetics nor was it due to exhaustion of the media or soluble factors since fresh media did not ameliorate the effect nor were supernatants from BD cultures found to be suppressive. The relative inhibition was also not reversed by removal of the allogeneic cells by phenotype specific antiserum. Cytotoxic tests with donor and responder specific antisera revealed that the cells bearing that phenotype were dramatically reduced in BD as compared to one-way cultures. Thus, the diminished secondary response appears to be due to cytotoxic elimination of the responder cells. This allogeneic cytotoxicity is dependent on non-T, phagocytic, adherent cells. The phenomenon is called Functional Cell Mediated Lympholysis (F-CML). (author)

  3. Isolation and functional aspects of free luteal cells

    International Nuclear Information System (INIS)

    Luborsky, J.L.; Berhrman, H.R.

    1985-01-01

    Methods of luteal cell isolation employ enzymatic treatment of luteal tissue with collagenase and deoxyribonuclease. Additional enzymes such as hyaluronidase or Pronase are also used in some instances. Isolated luteal cells retain the morphological characteristics of steroid secreting cells after isolation. They contain mitochondria, variable amounts of lipid droplets, and an extensive smooth endoplasmic reticulum. Isolated luteal cells have been used in numerous studies to examine the regulation of steriodogenesis by luteinizing hormone (LH). LH receptor binding studies were employed to quantitate specific properties of hormone-receptor interaction in relation to cellular function. Binding of [ 125 I]LH to bovine luteal cells and membranes was compared and it was concluded that the enzymatic treatment used to isolate cells did not change the LH receptor binding kinetics

  4. Overexpression of neurofilament H disrupts normal cell structure and function

    Science.gov (United States)

    Szebenyi, Gyorgyi; Smith, George M.; Li, Ping; Brady, Scott T.

    2002-01-01

    Studying exogenously expressed tagged proteins in live cells has become a standard technique for evaluating protein distribution and function. Typically, expression levels of experimentally introduced proteins are not regulated, and high levels are often preferred to facilitate detection. However, overexpression of many proteins leads to mislocalization and pathologies. Therefore, for normative studies, moderate levels of expression may be more suitable. To understand better the dynamics of intermediate filament formation, transport, and stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)-green fluorescent protein (GFP) fusion constructs in adenoviral vectors with tetracycline (tet)-regulated promoters. This system allows for turning on or off the synthesis of NFH-GFP at a selected time, for a defined period, in a dose-dependent manner. We used this inducible system for live cell imaging of changes in filament structure and cell shape, motility, and transport associated with increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP were structurally and functionally similar to neighboring, nonexpressing cells. In contrast, overexpression led to pathological alterations in both filament organization and cell function. Copyright 2002 Wiley-Liss, Inc.

  5. Childhood acromegaly successfully treated with interstitial irradiation using Yttrium-90

    International Nuclear Information System (INIS)

    Rosenstock, J.; Doyle, F.H.; Mashiter, K.; Joplin, G.F.

    1982-01-01

    A child with a growth hormone producing tumour presented at the age of 4 1/2 years. The onset of the disease was at 18 months of age. Treatment was given with three doses of interstitial irradiation using yttrium-90 implants. There were no local complications from the procedures. Now, 11 years after diagnosis, she is asymptomatic, of normal appearance, and her height and the size of the pituitary fossa are normal. Growth hormone levels are almost normal, thyroid function is intact, and she is maintained on prednisone and sex hormones. (Authors)

  6. Novel immunomodulatory effects of adiponectin on dendritic cell functions.

    Science.gov (United States)

    Tsang, Julia Yuen Shan; Li, Daxu; Ho, Derek; Peng, Jiao; Xu, Aimin; Lamb, Jonathan; Chen, Yan; Tam, Paul Kwong Hang

    2011-05-01

    Adiponectin (ADN) is an adipocytokine with anti-inflammatory properties. Although it has been reported that ADN can inhibit the immunostimulatory function of monocytes and macrophages, little is known of its effect on dendritic cells (DC). Recent data suggest that ADN can regulate immune responses. DCs are uniquely specialised antigen presenting cells that play a central role in the initiation of immunity and tolerance. In this study, we have investigated the immuno- modulatory effects of ADN on DC functions. We found that ADN has only moderate effect on the differentiation of murine bone marrow (BM) derived DCs but altered the phenotype of DCs. The expression of major histocompatibilty complex class II (MHCII), CD80 and CD86 on ADN conditioned DCs (ADN-DCs) was lower than that on untreated cells. The production of IL-12p40 was also suppressed in ADN-DCs. Interestingly, ADN treated DCs showed an increase in the expression of the inhibitory molecule, programmed death-1 ligand (PDL-1) compared to untreated cells. In vitro co-culture of ADN-DCs with allogeneic T cells led to a decrease in T cell proliferation and reduction of IL-2 production. Concomitant with that, a higher percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was detected in co-cultures of T cells and ADN-DCs. Blocking PD-1/PDL-1 pathway could partially restore T cell function. These findings suggest that the immunomodulatory effect of ADN on immune responses could be at least partially be mediated by its ability to alter DC function. The PD-1/PDL-1 pathway and the enhancement of Treg expansion are implicated in the immunomodulatory mechanisms. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Qian-Kun Yang

    2013-01-01

    Full Text Available NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

  8. On the existence of two-interstitial species in platinum after thermal-neutron irradiation

    International Nuclear Information System (INIS)

    Piani, C.S.B.; Aspeling, J.

    1979-01-01

    The prediction of the conversion-two-interstitial model that the crowdion in platinum converts at some temperature (approximately 150 K) in stage II to the dumbbell, and that this conversion will be seen as a change in the initial slopes of the production curves, is investigated. A change in the initial slopes of the production curves as a function of temperature is observed in stage II between 150 and 170 K. However, both the one-interstitial model and two-interstitial model can explain the behaviour of the initial slopes as a function of temperature from the lowest temperature to the minimum in the production curve. Both models cannot satisfactorily explain the behaviour of the initial slopes after the minimum. (author)

  9. Components, structure, biogenesis and function of the Hydra extracellular matrix in regeneration, pattern formation and cell differentiation.

    Science.gov (United States)

    Sarras, Michael P

    2012-01-01

    The body wall of Hydra is organized as an epithelial bilayer (ectoderm and endoderm) with an intervening extracellular matrix (ECM), termed mesoglea by early biologists. Morphological studies have determined that Hydra ECM is composed of two basal lamina layers positioned at the base of each epithelial layer with an intervening interstitial matrix. Molecular and biochemical analyses of Hydra ECM have established that it contains components similar to those seen in more complicated vertebrate species. These components include such macromolecules as laminin, type IV collagen, and various fibrillar collagens. These components are synthesized in a complicated manner involving cross-talk between the epithelial bilayer. Any perturbation to ECM biogenesis leads to a blockage in Hydra morphogenesis. Blockage in ECM/cell interactions in the adult polyp also leads to problems in epithelial transdifferentiation processes. In terms of biophysical parameters, Hydra ECM is highly flexible; a property that facilitates continuous movements along the organism's longitudinal and radial axis. This is in contrast to the more rigid matrices often found in vertebrates. The flexible nature of Hydra ECM can in part now be explained by the unique structure of the organism's type IV collagen and fibrillar collagens. This review will focus on Hydra ECM in regard to: 1) its general structure, 2) its molecular composition, 3) the biophysical basis for the flexible nature of Hydra's ECM, 4) the relationship of the biogenesis of Hydra ECM to regeneration of body form, and 5) the functional role of Hydra ECM during pattern formation and cell differentiation.

  10. [Diagnosis and treatment of interstitial cystitis].

    Science.gov (United States)

    Meyer, D; Gregorin, J; Schmid, H-P

    2011-02-16

    Interstitial Cystitis, first described in 1887 as an inflammatory disease of the bladder wall, is now regarded as a very common disease with an estimated number of unreported cases. Reasons for underdiagnosis is the widespread use of strict exclusion criteria. The disease can already be suspected by a careful medical history and physical examination in an early stage and then be treated with promising multimodal therapeutic approaches. In addition to a symptomatic oral therapy, local instillations with constituents of the protective glycosaminoglycan-layer are the most common therapeutic approach, because its defective integrity plays a key role in the pathogenesis of interstitial cystitis.

  11. Radionuclide diagnosis of interstitial lung edema

    International Nuclear Information System (INIS)

    Khodzhibekov, M.Kh.

    1991-01-01

    Perfusion scintigraphy of the lungs has shown that a reverse direction of postural reactions of the pulmonary blood flow is observed in patients with mitral valvular disease. It is accounted for by the action of gravitation on capillary hydrostatic pressure resulting in the localization of interstitial edema in pulmonary venous hypertension mainly in the lower lung, its microcirculatory bed being compressed and the blood flow redistributed to the opposite upper lung. Therefore successive perfusion scintigraphy of the lungs in the vertical position and in the lateral position with a RP administered twice, can serve as a sensitive test for diagnosis of interstitial lung edema

  12. Functional Proteomics to Identify Moderators of CD8+ T Cell Function in Melanoma

    Science.gov (United States)

    2015-05-01

    reads. Highly represented phage have been subcloned and are being tested for in vitro function. We have identified one phage that augments T...other cell populations, and subclone differentially expressed sequences the phage backbone for functional assessment (or have peptides synthesized

  13. Effect of subsurface Ti-interstitials on the bonding of small gold clusters on rutile TiO2(110)

    DEFF Research Database (Denmark)

    Madsen, Georg; Hammer, Bjørk

    2009-01-01

    The density functional theory is used to examine the electronic structure of small Au clusters, supported on rutile TiO2(110) surfaces having subsurface Ti-interstitials. The interstitials reduce the surface and we find that negatively charged gold clusters are stabilized with respect to the stoi...

  14. Co-morbidities of Interstitial Cystitis

    Directory of Open Access Journals (Sweden)

    Gisela eChelimsky

    2012-08-01

    Full Text Available Introduction: This study aimed to estimate the proportion of patients with Interstitial Cystitis/Painful Bladder Syndrome (IC/BPS with systemic dysfunction associated co-morbidities such as irritable bowel syndrome (IBS and fibromyalgia (FM. Material and Methods: Two groups of subjects with IC/BPS were included: 1 Physician diagnosed patients with IC/BPS and 2 Subjects meeting NIDDK IC/PBS criteria based on a questionnaire (ODYSA. These groups were compared to healthy controls matched for age and socio-economic status. NIDDK criteria required: pain with bladder filling that improves with emptying, urinary urgency due to discomfort or pain, polyuria > 11 times/24 hrs, and nocturia > 2 times/night. The ODYSA instrument evaluates symptoms pertaining to a range of disorders including chronic fatigue, orthostatic intolerance, syncope, IBS, dyspepsia, cyclic vomiting syndrome, headaches and migraines, sleep, Raynaud’s syndrome and chronic aches and pains. Results: IC/BPS was diagnosed in 26 subjects (mean age 47 +/- 16 yrs, 92% females, 58 had symptoms of IC/BPS by NIDDK criteria, (mean age 40 +/- 17 yrs, 79% females and 48 were healthy controls (mean age 31+/- 14 yrs, mean age 77%. Co-morbid complaints in the IC/BPS groups included gastrointestinal symptoms suggestive of IBS and dyspepsia, sleep abnormalities with delayed onset of sleep, feeling poorly refreshed in the morning, waking up before needed, snoring, severe chronic fatigue and chronic generalized pain, migraines and syncope. Discussion: Patients with IC/BPS had co-morbid central and autonomic nervous system disorders. Our findings mirror those of others in regard to IBS, symptoms suggestive of FM, chronic pain and migraine. High rates of syncope and functional dyspepsia found in the IC/BPS groups merit further study to determine if IC/BPS is part of a diffuse disorder of central, autonomic and sensory processing affecting multiple organs outside the bladder.

  15. Function of survivin in trophoblastic cells of the placenta.

    Directory of Open Access Journals (Sweden)

    Cornelia Muschol-Steinmetz

    Full Text Available BACKGROUND: Preeclampsia is one of the leading causes of maternal and perinatal mortality and morbidity worldwide and its pathogenesis is not totally understood. As a member of the chromosomal passenger complex and an inhibitor of apoptosis, survivin is a well-characterized oncoprotein. Its roles in trophoblastic cells remain to be defined. METHODS: The placental samples from 16 preeclampsia patients and 16 well-matched controls were included in this study. Real-time PCR, immunohistochemistry and Western blot analysis were carried out with placental tissues. Primary trophoblastic cells from term placentas were isolated for Western blot analysis. Cell proliferation, cell cycle analysis and immunofluorescence staining were performed in trophoblastic cell lines BeWo, JAR and HTR-8/SVneo. RESULTS: The survivin gene is reduced but the protein amount is hardly changed in preeclamptic placentas, compared to control placentas. Upon stress, survivin in trophoblastic cells is phosphorylated on its residue serine 20 by protein kinase A and becomes stabilized, accompanied by increased heat shock protein 90. Depletion of survivin induces chromosome misalignment, abnormal centrosome integrity, and reduced localization and activity of Aurora B at the centromeres/kinetochores in trophoblastic metaphase cells. CONCLUSIONS: Our data indicate that survivin plays pivotal roles in cell survival and proliferation of trophoblastic cells. Further investigations are required to define the function of survivin in each cell type of the placenta in the context of proliferation, differentiation, apoptosis, angiogenesis, migration and invasion.

  16. XIAP reverses various functional activities of FRNK in endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Sunyoung; Kim, Hyun Jeong [Department of Molecular Biology and Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook Univiersity, 126, Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701 (Korea, Republic of); Chi, Sung-Gil [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Park, Heonyong, E-mail: heonyong@dankook.ac.kr [Department of Molecular Biology and Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook Univiersity, 126, Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701 (Korea, Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer FRNK domain is recruited into focal adhesion (FA), controlling endothelial cell adhesion. Black-Right-Pointing-Pointer XIAP binds the FRNK domain of FAK. Black-Right-Pointing-Pointer XIAP inhibits recruitment of FRNK into Fas and FRNK-promoted cell adhesion. Black-Right-Pointing-Pointer XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK. -- Abstract: In endothelial cells, focal adhesion kinase (FAK) regulates cell proliferation, migration, adhesion, and shear-stimulated activation of MAPK. We recently found that FAK is recruited into focal adhesion (FA) sites through interactions with XIAP (X-chromosome linked inhibitor of apoptosis protein) and activated by Src kinase in response to shear stress. In this study, we examined which domain(s) of FAK is(are) important for various vascular functions such as FA recruiting, XIAP-binding and shear stress-stimulated ERK activation. Through a series of experiments, we determined that the FRNK domain is recruited into FA sites and promotes endothelial cell adhesion. Interestingly, XIAP knockdown was shown to reduce FA recruitment of FRNK and the cell adhesive effect of FRNK. In addition, we found that XIAP interacts with FRNK, suggesting cross-talk between XIAP and FRNK. We also demonstrated that FRNK inhibits endothelial cell migration and shear-stimulated ERK activation. These inhibitory effects of FRNK were reversed by XIAP knockdown. Taken together, we can conclude that XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK.

  17. Activated NKT cells imprint NK-cell differentiation, functionality and education.

    Science.gov (United States)

    Riese, Peggy; Trittel, Stephanie; May, Tobias; Cicin-Sain, Luka; Chambers, Benedict J; Guzmán, Carlos A

    2015-06-01

    NK cells represent a vital component of the innate immune system. The recent discoveries demonstrating that the functionality of NK cells depends on their differentiation and education status underscore their potential as targets for immune intervention. However, to exploit their full potential, a detailed understanding of the cellular interactions involved in these processes is required. In this regard, the cross-talk between NKT cells and NK cells needs to be better understood. Our results provide strong evidence for NKT cell-induced effects on key biological features of NK cells. NKT-cell activation results in the generation of highly active CD27(high) NK cells with improved functionality. In this context, degranulation activity and IFNγ production were mainly detected in the educated subset. In a mCMV infection model, we also demonstrated that NKT-cell stimulation induced the generation of highly functional educated and uneducated NK cells, crucial players in viral control. Thus, our findings reveal new fundamental aspects of the NKT-NK cell axis that provide important hints for the manipulation of NK cells in clinical settings. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. [Correlations among disease perceptions, attitudes and self-care behaviors in patients with interstitial cystitis].

    Science.gov (United States)

    Yeh, Hui-Ling; Kuo, Hann-Chorng; Lin, Zu-Chun; Lee, Ru-Ping

    2012-02-01

    Interstitial cystitis (IC) is an enigmatic disease that currently remains incurable. Failure to adopt positive self-care behaviors can exacerbate recurrent clinical symptoms and significantly affect a patient's capacity to function normally in work, family and social setting. Proper disease perception can improve patient attitudes toward disease management and positively influence behavior. This study investigated correlations between disease perceptions, attitudes and self-care behaviors in patients with interstitial cystitis. This study used a cross-sectional method and enrolled 82 outpatients currently receiving treatment for interstitial cystitis at a medical center in East Taiwan. A structured questionnaires filled out individually and submitted by mail was used for date collection. (1) The mean perception scale score was 7.6, with 63.3% providing correct responses. (2) The mean attitude score of 3.5 indicated respondents held positive attitudes. (3) The mean self-care behavior score of 3.4 indicated a leaning toward "occasional" self-care behavior. (4) Correlations among disease perception, attitude and self-care behavior in participants exhibited a significant, mild and positive correlation. (5) Higher education level correlated positively with insight and attitude toward interstitial cystitis. Participants with lower "current voiding problems" had a more positive attitude toward their disease. Participants with higher "numbers of painful sites" had better disease perception and better self care behaviors. Patients reporting "symptoms aggravated by other conditions" also had better interstitial cystitis perception. We found positive correlations among disease perceptions, attitudes and self-care behaviors in patients with interstitial cystitis. We strongly recommend that all healthcare providers evaluate patient disease perception extent. Nurses should provide patients with correct disease concepts, and encourage positive attitudes and self-caring behaviors

  19. An analytical model to predict interstitial lubrication of cartilage in migrating contact areas.

    Science.gov (United States)

    Moore, A C; Burris, D L

    2014-01-03

    For nearly a century, articular cartilage has been known for its exceptional tribological properties. For nearly as long, there have been research efforts to elucidate the responsible mechanisms for application toward biomimetic bearing applications. It is now widely accepted that interstitial fluid pressurization is the primary mechanism responsible for the unusual lubrication and load bearing properties of cartilage. Although the biomechanics community has developed elegant mathematical theories describing the coupling of solid and fluid (biphasic) mechanics and its role in interstitial lubrication, quantitative gaps in our understanding of cartilage tribology have inhibited our ability to predict how tribological conditions and material properties impact tissue function. This paper presents an analytical model of the interstitial lubrication of biphasic materials under migrating contact conditions. Although finite element and other numerical models of cartilage mechanics exist, they typically neglect the important role of the collagen network and are limited to a specific set of input conditions, which limits general applicability. The simplified approach taken in this work aims to capture the broader underlying physics as a starting point for further model development. In agreement with existing literature, the model indicates that a large Peclet number, Pe, is necessary for effective interstitial lubrication. It also predicts that the tensile modulus must be large relative to the compressive modulus. This explains why hydrogels and other biphasic materials do not provide significant interstitial pressure under high Pe conditions. The model quantitatively agrees with in-situ measurements of interstitial load support and the results have interesting implications for tissue engineering and osteoarthritis problems. This paper suggests that a low tensile modulus (from chondromalacia or local collagen rupture after impact, for example) may disrupt interstitial

  20. A DFT study on modification mechanism of (N,S) interstitial co-doped rutile TiO2

    Science.gov (United States)

    Chen, Hao; Li, Xuechao; Wan, Rundong; Kao-Walter, Sharon; Lei, Ying; Leng, Chongyan

    2018-03-01

    To obtain a more efficient (N,S) co-doping scheme, we systematically analyze the geometrical parameters, density of states, charge densities, relative dielectric functions and UV-Vis absorption spectra for pure, N/S substitution/interstitial doped and (N,S) substitution/interstitial co-doped TiO2 by using density functional calculations. Compared with (N,S) substitution co-doping, (N,S) interstitial co-doping TiO2 exhibits a more obvious red-shift of absorption edge, because of the band gap is further reduced. Furthermore, there are shallow impurity levels coupling with the top of valence band. The calculated UV-Vis absorption spectra illustrate that (N,S) interstitial co-doping TiO2 has much higher photocatalytic activity in the visible light region.

  1. Effects of Radiation on Proteasome Function in Prostate Cancer Cells

    Science.gov (United States)

    2012-02-01

    radiation treatment may ultimately improve curability and may allow for de -escalation of the total radiation doses currently given to breast cancer ...Radiation-induced cancer stem cells 15 Figure 3. Radiation induces de novo generation of functional CSCs. ZsGreen-cODC-negative cells...advanced cancer of the uterine cervix . Cancer Res 1996;56(19):4509–4515. 98 Brizel DM, Scully SP, Harrelson JM et al. Tumor oxygenation pre- dicts for

  2. Alternative mitochondrial functions in cell physiopathology: beyond ATP production

    Directory of Open Access Journals (Sweden)

    Kowaltowski A.J.

    2000-01-01

    Full Text Available It is well known that mitochondria are the main site for ATP generation within most tissues. However, mitochondria also participate in a surprising number of alternative activities, including intracellular Ca2+ regulation, thermogenesis and the control of apoptosis. In addition, mitochondria are the main cellular generators of reactive oxygen species, and may trigger necrotic cell death under conditions of oxidative stress. This review concentrates on these alternative mitochondrial functions, and their role in cell physiopathology.

  3. Invariant NKT cells: regulation and function during viral infection.

    Directory of Open Access Journals (Sweden)

    Jennifer A Juno

    Full Text Available Natural killer T cells (NKT cells represent a subset of T lymphocytes that express natural killer (NK cell surface markers. A subset of NKT cells, termed invariant NKT cells (iNKT, express a highly restricted T cell receptor (TCR and respond to CD1d-restricted lipid ligands. iNKT cells are now appreciated to play an important role in linking innate and adaptive immune responses and have been implicated in infectious disease, allergy, asthma, autoimmunity, and tumor surveillance. Advances in iNKT identification and purification have allowed for the detailed study of iNKT activity in both humans and mice during a variety of chronic and acute infections. Comparison of iNKT function between non-pathogenic simian immunodeficiency virus (SIV infection models and chronic HIV-infected patients implies a role for iNKT activity in controlling immune activation. In vitro studies of influenza infection have revealed novel effector functions of iNKT cells including IL-22 production and modulation of myeloid-derived suppressor cells, but ex vivo characterization of human iNKT cells during influenza infection are lacking. Similarly, as recent evidence suggests iNKT involvement in dengue virus pathogenesis, iNKT cells may modulate responses to a number of emerging pathogens. This Review will summarize current knowledge of iNKT involvement in responses to viral infections in both human and mouse models and will identify critical gaps in knowledge and opportunities for future study. We will also highlight recent efforts to harness iNKT ligands as vaccine adjuvants capable of improving vaccination-induced cellular immune responses.

  4. Glucose metabolism regulates T cell activation, differentiation and functions

    Directory of Open Access Journals (Sweden)

    Clovis Steve Palmer

    2015-01-01

    Full Text Available The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The Warburg effect originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

  5. Mortality following unilateral twin interstitial ectopic pregnancy. A case report.

    Science.gov (United States)

    Jackson, G M; Rubin, S M; Sondheimer, S J

    1992-10-01

    Twin ectopic pregnancy is an uncommon event, usually occurring as simultaneous intrauterine and tubal gestations. Interstitial implantation of an ectopic pregnancy is also a rare event, associated with a high mortality rate. Twin interstitial pregnancy has been previously reported only three times in the English literature. We report a recent case of unilateral twin interstitial ectopic pregnancy that resulted in maternal death and review the literature with regard to both ectopic pregnancy and factors associated with mortality from interstitial implantation.

  6. Plant and algal cell walls: diversity and functionality.

    Science.gov (United States)

    Popper, Zoë A; Ralet, Marie-Christine; Domozych, David S

    2014-10-01

    Although plants and many algae (e.g. the Phaeophyceae, brown, and Rhodophyceae, red) are only very distantly related they are united in their possession of carbohydrate-rich cell walls, which are of integral importance being involved in many physiological processes. Furthermore,wall components have applications within food, fuel, pharmaceuticals, fibres (e.g. for textiles and paper) and building materials and have long been an active topic of research. As shown in the 27 papers in this Special Issue, as the major deposit of photosynthetically fixed carbon, and therefore energy investment, cell walls are of undisputed importance to the organisms that possess them, the photosynthetic eukaryotes ( plants and algae). The complexities of cell wall components along with their interactions with the biotic and abiotic environment are becoming increasingly revealed. The importance of plant and algal cell walls and their individual components to the function and survival of the organism, and for a number of industrial applications, are illustrated by the breadth of topics covered in this issue, which includes papers concentrating on various plants and algae, developmental stages, organs, cell wall components, and techniques. Although we acknowledge that there are many alternative ways in which the papers could be categorized (and many would fit within several topics), we have organized them as follows: (1) cell wall biosynthesis and remodelling, (2) cell wall diversity, and (3) application of new technologies to cell walls. Finally, we will consider future directions within plant cell wall research. Expansion of the industrial uses of cell walls and potentially novel uses of cell wall components are both avenues likely to direct future research activities. Fundamentally, it is the continued progression from characterization (structure, metabolism, properties and localization) of individual cell wall components through to defining their roles in almost every aspect of plant

  7. Defective immunoregulatory T-cell function in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Han, T.; Ozer, H.; Henderson, E.S.; Dadey, B.; Nussbaum-Blumenson, A.; Barcos, M.

    1981-01-01

    Chronic lymphocytic leukemia (CLL) of B-cell origin results in the malignant proliferation of small immunoglobulin-bearing lymphocytes. There is currently a controversy in the literature regarding both the ability of this leukemic population to differentiate into mature plasma cells, as well as the ability of apparently normal T cells from these patients to regulate allogeneic B-cell differentiation. In the present study we have examined the lymphocytes of CLL patients in various clinical stages of their disease and with different surface phenotypes of their leukemic B-cell population. Our results show that leukemic CLL B cells from all 20 patients (including one patient with a monoclonal IgM paraprotein and another with a monoclonal IgG paraprotein) are incapable of further differentiation even in the absence of suppressor T cells and the presence of helper T lymphocytes. This lack of capacity to differentiate is unaffected by clinical stage, by therapy, or by the phenotype of the malignant population. Since the leukemic B population did not suppress normal allogeneic B-cell differentiation, the maturation deficit is evidently intrinsic to the leukemic clone rather than a result of activity of non-T suppressor cells. T helper function was also variably depressed in the blood of some patients with CLL, and this depression did not correlate with clinical stage, with therapy, or with the degree of lymphocytosis. Dysfunction of radiosensitive T suppressor cells was found to be the most consistent regulatory deficit of CLL T cells. Each of 11 patients whose leukemic cell population was of the μdelta, μα, or μ phenotype had both helper and suppressor cell defects

  8. Novel methods of automated quantification of gap junction distribution and interstitial collagen quantity from animal and human atrial tissue sections.

    Directory of Open Access Journals (Sweden)

    Jiajie Yan

    Full Text Available Gap junctions (GJs are the principal membrane structures that conduct electrical impulses between cardiac myocytes while interstitial collagen (IC can physically separate adjacent myocytes and limit cell-cell communication. Emerging evidence suggests that both GJ and interstitial structural remodeling are linked to cardiac arrhythmia development. However, automated quantitative identification of GJ distribution and IC deposition from microscopic histological images has proven to be challenging. Such quantification is required to improve the understanding of functional consequences of GJ and structural remodeling in cardiac electrophysiology studies.Separate approaches were employed for GJ and IC identification in images from histologically stained tissue sections obtained from rabbit and human atria. For GJ identification, we recognized N-Cadherin (N-Cad as part of the gap junction connexin 43 (Cx43 molecular complex. Because N-Cad anchors Cx43 on intercalated discs (ID to form functional GJ channels on cell membranes, we computationally dilated N-Cad pixels to create N-Cad units that covered all ID-associated Cx43 pixels on Cx43/N-Cad double immunostained confocal images. This approach allowed segmentation between ID-associated and non-ID-associated Cx43. Additionally, use of N-Cad as a unique internal reference with Z-stack layer-by-layer confocal images potentially limits sample processing related artifacts in Cx43 quantification. For IC quantification, color map thresholding of Masson's Trichrome blue stained sections allowed straightforward and automated segmentation of collagen from non-collagen pixels. Our results strongly demonstrate that the two novel image-processing approaches can minimize potential overestimation or underestimation of gap junction and structural remodeling in healthy and pathological hearts. The results of using the two novel methods will significantly improve our understanding of the molecular and structural

  9. Form and function in cell motility: from fibroblasts to keratocytes.

    Science.gov (United States)

    Herant, Marc; Dembo, Micah

    2010-04-21

    It is plain enough that a horse is made for running, but similar statements about motile cells are not so obvious. Here the basis for structure-function relations in cell motility is explored by application of a new computational technique that allows realistic three-dimensional simulations of cells migrating on flat substrata. With this approach, some cyber cells spontaneously display the classic irregular protrusion cycles and handmirror morphology of a crawling fibroblast, and others the steady gliding motility and crescent morphology of a fish keratocyte. The keratocyte motif is caused by optimal recycling of the cytoskeleton from the back to the front so that more of the periphery can be devoted to protrusion. These calculations are a step toward bridging the gap between the integrated mechanics and biophysics of whole cells and the microscopic molecular biology of cytoskeletal components. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  10. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

  11. Functionalized scaffolds to control dental pulp stem cell fate

    Science.gov (United States)

    Piva, Evandro; Silva, Adriana F.; Nör, Jacques E.

    2014-01-01

    Emerging understanding about interactions between stem cells, scaffolds and morphogenic factors has accelerated translational research in the field of dental pulp tissue engineering. Dental pulp stem cells constitute a sub-population of cells endowed with self-renewal and multipotency. Dental pulp stem cells seeded in biodegradable scaffolds and exposed to dentin-derived morphogenic signals give rise to a pulp-like tissue capable of generating new dentin. Notably, dentin-derived proteins are sufficient to induce dental pulp stem cell differentiation into odontoblasts. Ongoing work is focused on developing ways of mobilizing dentin-derived proteins and disinfecting the root canal of necrotic teeth without compromising the morphogenic potential of these signaling molecules. On the other hand, dentin by itself does not appear to be capable of inducing endothelial differentiation of dental pulp stem cells, despite the well known presence of angiogenic factors in dentin. This is particularly relevant in the context of dental pulp tissue engineering in full root canals, where access to blood supply is limited to the apical foramina. To address this challenge, scientists are looking at ways to use the scaffold as a controlled release device for angiogenic factors. The aim of this manuscript is to present and discuss current strategies to functionalize injectable scaffolds and customize them for dental pulp tissue engineering. The long-term goal of this work is to develop stem cell-based therapies that enable the engineering of functional dental pulps capable of generating new tubular dentin in humans. PMID:24698691

  12. Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.

    Science.gov (United States)

    Moguche, Albanus O; Musvosvi, Munyaradzi; Penn-Nicholson, Adam; Plumlee, Courtney R; Mearns, Helen; Geldenhuys, Hennie; Smit, Erica; Abrahams, Deborah; Rozot, Virginie; Dintwe, One; Hoff, Søren T; Kromann, Ingrid; Ruhwald, Morten; Bang, Peter; Larson, Ryan P; Shafiani, Shahin; Ma, Shuyi; Sherman, David R; Sette, Alessandro; Lindestam Arlehamn, Cecilia S; McKinney, Denise M; Maecker, Holden; Hanekom, Willem A; Hatherill, Mark; Andersen, Peter; Scriba, Thomas J; Urdahl, Kevin B

    2017-06-14

    CD4 T cells are critical for protective immunity against Mycobacterium tuberculosis (Mtb), the cause of tuberculosis (TB). Yet to date, TB vaccine candidates that boost antigen-specific CD4 T cells have conferred little or no protection. Here we examined CD4 T cell responses to two leading TB vaccine antigens, ESAT-6 and Ag85B, in Mtb-infected mice and in vaccinated humans with and without underlying Mtb infection. In both species, Mtb infection drove ESAT-6-specific T cells to be more differentiated than Ag85B-specific T cells. The ability of each T cell population to control Mtb in the lungs of mice was restricted for opposite reasons: Ag85B-specific T cells were limited by reduced antigen expression during persistent infection, whereas ESAT-6-specific T cells became functionally exhausted due to chronic antigenic stimulation. Our findings suggest that different vaccination strategies will be required to optimize protection mediated by T cells recognizing antigens expressed at distinct stages of Mtb infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Oct4 targets regulatory nodes to modulate stem cell function.

    Directory of Open Access Journals (Sweden)

    Pearl A Campbell

    2007-06-01

    Full Text Available Stem cells are characterized by two defining features, the ability to self-renew and to differentiate into highly specialized cell types. The POU homeodomain transcription factor Oct4 (Pou5f1 is an essential mediator of the embryonic stem cell state and has been implicated in lineage specific differentiation, adult stem cell identity, and cancer. Recent description of the regulatory networks which maintain 'ES' have highlighted a dual role for Oct4 in the transcriptional activation of genes required to maintain self-renewal and pluripotency while concomitantly repressing genes which facilitate lineage specific differentiation. However, the molecular mechanism by which Oct4 mediates differential activation or repression at these loci to either maintain stem cell identity or facilitate the emergence of alternate transcriptional programs required for the realization of lineage remains to be elucidated. To further investigate Oct4 function, we employed gene expression profiling together with a robust statistical analysis to identify genes highly correlated to Oct4. Gene Ontology analysis to categorize overrepresented genes has led to the identification of themes which may prove essential to stem cell identity, including chromatin structure, nuclear architecture, cell cycle control, DNA repair, and apoptosis. Our experiments have identified previously unappreciated roles for Oct4 for firstly, regulating chromatin structure in a state consistent with self-renewal and pluripotency, and secondly, facilitating the expression of genes that keeps the cell poised to respond to cues that lead to differentiation. Together, these data define the mechanism by which Oct4 orchestrates cellular regulatory pathways to enforce the stem cell state and provides important insight into stem cell function and cancer.

  14. Interstitial Ectopic Pregnancy Report of Four Cases

    Directory of Open Access Journals (Sweden)

    Bülent Kars

    2009-12-01

    Interstitial pregnancy is a rare form of ectopic pregnancy which carries a higher risk of morbidity and mortality due to catastrophic hemorrhage. Early diagnosis is mandatory for management of this potentially fatal condition and a high index of suspicion is essential for early diagnosis.

  15. Rituximab-induced interstitial lung disease

    DEFF Research Database (Denmark)

    Naqibullah, Matiuallah; Shaker, Saher B; Bach, Karen S

    2015-01-01

    , rheumatoid arthritis, and autoimmune hemolytic anemia. Recently, RTX has also been suggested for the treatment of certain connective tissue disease-related interstitial lung diseases (ILD) and hypersensitivity pneumonitis. Rare but serious pulmonary adverse reactions are reported. To raise awareness about...

  16. Interstitial cystitis/painful bladder syndrome.

    Science.gov (United States)

    French, Linda M; Bhambore, Neelam

    2011-05-15

    Interstitial cystitis/painful bladder syndrome affects more than 1 million persons in the United States, but the cause remains unknown. Most patients with interstitial cystitis/painful bladder syndrome are women with symptoms of suprapubic pelvic and/or genital area pain, dyspareunia, urinary urgency and frequency, and nocturia. It is important to exclude other conditions such as infections. Tests and tools commonly used to diagnose interstitial cystitis/painful bladder syndrome include specific questionnaires developed to assess the condition, the potassium sensitivity test, the anesthetic bladder challenge, and cystoscopy with hydrodistension. Treatment options include oral medications, intravesical instillations, and dietary changes and supplements. Oral medications include pentosan polysulfate sodium, antihistamines, tricyclic antidepressants, and immune modulators. Intravesical medications include dimethyl sulfoxide, pentosan polysulfate sodium, and heparin. Pentosan polysulfate sodium is the only oral therapy and dimethyl sulfoxide is the only intravesical therapy with U.S. Food and Drug Administration approval for the treatment of interstitial cystitis/painful bladder syndrome. To date, clinical trials of individual therapies have been limited in size, quality, and duration of follow-up. Studies of combination or multimodal therapies are lacking.

  17. Interstitial laser thermotherapy in neurosurgery: a review

    NARCIS (Netherlands)

    Menovsky, T.; Beek, J. F.; van Gemert, M. J.; Roux, F. X.; Bown, S. G.

    1996-01-01

    One of the most recent laser treatment modalities in neurosurgery is interstitial laser thermotherapy (ILTT). In this review, experimental and clinical studies concerning intracranial ILTT are discussed. Two methods for intra-operative control of the laser induced lesions are described; i.e.,

  18. Linking stem cell function and growth pattern of intestinal organoids.

    Science.gov (United States)

    Thalheim, Torsten; Quaas, Marianne; Herberg, Maria; Braumann, Ulf-Dietrich; Kerner, Christiane; Loeffler, Markus; Aust, Gabriela; Galle, Joerg

    2018-01-15

    Intestinal stem cells (ISCs) require well-defined signals from their environment in order to carry out their specific functions. Most of these signals are provided by neighboring cells that form a stem cell niche, whose shape and cellular composition self-organize. Major features of this self-organization can be studied in ISC-derived organoid culture. In this system, manipulation of essential pathways of stem cell maintenance and differentiation results in well-described growth phenotypes. We here provide an individual cell-based model of intestinal organoids that enables a mechanistic explanation of the observed growth phenotypes. In simulation studies of the 3D structure of expanding organoids, we investigate interdependences between Wnt- and Notch-signaling which control the shape of the stem cell niche and, thus, the growth pattern of the organoids. Similar to in vitro experiments, changes of pathway activities alter the cellular composition of the organoids and, thereby, affect their shape. Exogenous Wnt enforces transitions from branched into a cyst-like growth pattern; known to occur spontaneously during long term organoid expansion. Based on our simulation results, we predict that the cyst-like pattern is associated with biomechanical changes of the cells which assign them a growth advantage. The results suggest ongoing stem cell adaptation to in vitro conditions during long term expansion by stabilizing Wnt-activity. Our study exemplifies the potential of individual cell-based modeling in unraveling links between molecular stem cell regulation and 3D growth of tissues. This kind of modeling combines experimental results in the fields of stem cell biology and cell biomechanics constituting a prerequisite for a better understanding of tissue regeneration as well as developmental processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. High-dose-rate interstitial brachytherapy for the treatment of penile carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Petera, J.; Odrazka, K.; Zouhar, M.; Bedrosova, J.; Dolezel, M. [Dept. of Oncology and Radiotherapy, Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic)

    2004-02-01

    Background: interstitial low-dose-rate (LDR) brachytherapy allows conservative treatment of T1-T2 penile carcinoma. High-dose-rate (HDR) is often considered to be dangerous for interstitial implants because of a higher risk of complications, but numerous reports suggest that results may be comparable to LDR. Nevertheless, there are no data in the literature available regarding HDR interstitial brachytherapy for carcinoma of the penis. Case report: a 64-year-old man with T1 NO MO epidermoid carcinoma of the glans is reported. Interstitial HDR brachytherapy was performed using the stainless hollow needle technique and a breast template for fixation and good geometry. The dose delivered was 18 x 3 Gy twice daily. Results: after 232 days from brachytherapy, the patient was without any evidence of the tumor, experienced no serious radiation-induced complications, and had a fully functional organ. Conclusion: HDR interstitial brachytherapy is feasible in selected case of penis carcinoma, when careful planning and small single fractions are used. (orig.)

  20. Near Infrared Photoimmunotherapy with Combined Exposure of External and Interstitial Light Sources.

    Science.gov (United States)

    Maruoka, Yasuhiro; Nagaya, Tadanobu; Sato, Kazuhide; Ogata, Fusa; Okuyama, Shuhei; Choyke, Peter L; Kobayashi, Hisataka

    2018-02-21

    Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell-specific cancer treatment that induces highly selective necrotic/immunogenic cell death after systemic administration of a photoabsorber antibody conjugate and subsequent NIR light exposure. However, the depth of NIR light penetration in tissue (approximately 2 cm) with external light sources limits the therapeutic effects of NIR-PIT. Interstitial light exposure using cylindrical diffusing optical fibers can overcome this limitation. The purpose in this study was to compare three NIR light delivery methods for treating tumors with NIR-PIT using a NIR laser system at an identical light energy; external exposure alone, interstitial exposure alone, and the combination. Panitumumab conjugated with the photoabsorber IRDye-700DX (pan-IR700) was intravenously administered to mice with A431-luc xenografts which are epithelial growth factor receptor (EGFR) positive. One and 2 days later, NIR light was administered to the tumors using one of three methods. Interstitial exposure alone and in combination with external sources showed the greatest decrease in bioluminescence signal intensity. Additionally, the combination of external and interstitial NIR light exposure showed significantly greater tumor size reduction and prolonged survival after NIR-PIT compared to external exposure alone. This result suggested that the combination of external and interstitial NIR light exposure was more effective than externally applied light alone. Although external exposure is the least invasive means of delivering light, the combination of external and interstitial exposures produces superior therapeutic efficacy in tumors greater than 2 cm in depth from the tissue surface.

  1. [Interstitial pregnancy: experience at Rouen's hospital].

    Science.gov (United States)

    Douysset, X; Verspyck, E; Diguet, A; Marpeau, L; Chanavaz-Lacheray, I; Rondeau, S; Resch, B; Sergent, F

    2014-04-01

    Presenting our experience concerning interstitial pregnancies (IP) surgical management and to evaluate our patients' subsequent long-term fertility. Twenty patients underwent surgical treatment of IP in our department over 15 years. In this retrospective study, we present symptoms that led to diagnosis, treatments, fertility and obstetrical outcome. Mean gestational age at diagnosis was 8SA, with a median BHCG rate of 7411 IU/L, and a patient mean age of 30 years. Ninety percent of patients had at least one risk factor for ectopic pregnancy. Pain or bleeding were the most common symptoms at admission, 4 patients were admitted in an hypovolemic shock status. Location of the interstitial ectopic pregnancy was discovered during surgery in 45 % of cases. Six patients had a large hemoperitoneum bigger than 1L, 5 patients had an IP of uterine stump after salpingectomy for a previous ectopic pregnancy. The most used surgical technique was in 60 % of cases the excision by Endo GIA stapling(®) with salpingectomy. Regarding fertility, 12 patients wished pregnancy in the aftermath of the intervention, 10 had at least one pregnancy, among them there is an ectopic contralateral ampullary pregnancy, and a contralateral recurrence of interstitial pregnancy. Four patients were delivered by cesarean section and 4 patients were delivered vaginally, some several times. No uterine rupture occured. Interstitial pregnancy is a rare ectopic pregnancy. Its diagnosis is difficult and may involve maternal life-threatening and fertility. In subsequent pregnancies, the clinician has to be careful concerning the risks of interstitial pregnancy recurrence and uterine rupture. Copyright © 2013. Published by Elsevier SAS.

  2. Left ventricular systolic function in sickle cell anaemia: an ...

    African Journals Online (AJOL)

    Keywords: Left ventricular systolic function, sickle cell anaemia, echocardiographic evaluation, adult Nigerian patients. ..... Quadratic .505. -0.390. 12.231. 8.587 .001*. Cubic .510. -0.180. 8.264. 8.619 .001*. This relationship was further evaluated by means of scat- ter plots and subsequently by regression analysis. The.

  3. Liver Function In Patients With Homozygous Sickle Cell Disease ...

    African Journals Online (AJOL)

    Using the sensitive ELISA technique, 213 patients with sickle cell anemia (112 males and 101 females) aged 6 months to 18 years were screened for Hepatitis B infection using Hepatitis B surface antigen (HBsAg) and antibody to Hepatitis B core antigen. A biochemical evaluation of liver function was carried out on all ...

  4. Lifelong dietary intervention does not affect hematopoietic stem cell function

    NARCIS (Netherlands)

    Lazare, Seka; Ausema, Albertina; Reijne, Aaffien C; van Dijk, Gertjan; van Os, Ronald; de Haan, Gerald

    Hematopoietic stem cells (HSCs) undergo a profound functional decline during normal aging. Because caloric or dietary restriction has been shown to delay multiple aspects of the aging process in many species, we explored the consequences of lifelong caloric restriction, or conversely, lifelong

  5. Reduced fetal androgen exposure compromises Leydig cell function in adulthood

    NARCIS (Netherlands)

    Teerds, K.J.; Keijer, J.

    2015-01-01

    Disruption of normal fetal development can influence functioning of organs and cells in adulthood. Circumstantial evidence suggests that subtle reductions in fetal androgen production may be the cause of adult male reproductive disorders due to reduced testosterone production. The mechanisms through

  6. Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

    Science.gov (United States)

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-10-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

  7. Functions of Prdm16 in thermogenic fat cells.

    Science.gov (United States)

    Ishibashi, Jeff; Seale, Patrick

    2015-01-01

    The PR-domain containing 16 (Prdm16) protein is a powerful inducer of the thermogenic phenotype in fat cells. In both developmental (brown) and induced (beige) thermogenic adipose tissue, Prdm16 has a critical role in maintaining proper tissue structure and function. It has roles throughout the course of differentiation, beginning with lineage determination activity in precursor cells, and continuing with coactivator functions that enable and maintain thermogenic gene expression. These abilities are primarily mediated by interactions with other adipogenic factors, suggesting that Prdm16 acts to coordinate the overall brown adipose phenotype. Mouse models have confirmed that thermogenic adipose depends upon Prdm16, and that this type of fat tissue provides substantial metabolic protection against the harmful effects of a high fat/high energy diet. Activation of Prdm16, therefore, holds promise for stimulating thermogenesis in fat cells to reduce human obesity and its complications.

  8. Persistence of ventilatory defect after resolution of pulmonary interstitial emphysema in a preterm baby.

    Science.gov (United States)

    Filho, Luiz Vicente Ferreira da Silva; Rossi, Felipe De Souza; Deutsch, Alice d'Agostini; Yagui, Ana Cristina Zanon; Timenetsky, Karina; Rebello, Celso de Moura

    2010-07-01

    Pulmonary interstitial emphysema is a common complication of mechanical ventilation in preterm babies. We report a case of severe unilateral pulmonary interstitial emphysema in a premature newborn, treated with high-frequency oscillatory ventilation, lateral decubitus positioning and selective intubation. After complete radiological resolution of the pulmonary emphysema in the left lung, the patient was studied by electrical impedance tomography and a marked reduction of ventilation was identified in the left lung despite radiological resolution of the cysts. This finding indicates that functional abnormalities may persist for longer periods after radiologic resolution of such lesions.

  9. Self-interstitials structure in the hcp metals: A further perspective from first-principles calculations

    Energy Technology Data Exchange (ETDEWEB)

    Pasianot, Roberto C., E-mail: pasianot@cnea.gov.ar [Gerencia Materiales, CAC-CNEA, Avda. Gral. Paz 1499, 1650 San Martín (Argentina); CONICET, Godoy Cruz 2290, 1425 Buenos Aires (Argentina); Instituto Sabato, UNSAM/CNEA, Avda. Gral. Paz 1499, 1650 San Martín (Argentina)

    2016-12-01

    We study the structure of several standard and non-standard self-interstitial configurations in a series of hcp metals, by using Density Functional Theory as embodied in the computer codes SIESTA and WIEN2k. The considered metals include Be, Mg, Ti, Zr, Co, Zn, and Cd, thus spanning the whole range of experimental c/a ratios, different kinds of bonding, and even magnetism (Co). The results show the importance of low symmetry configurations, closely related to the non-basal crowdion, in order to rationalize the experimental data on self-interstitial structure and migration.

  10. Evolutionary cell biology: functional insight from "endless forms most beautiful".

    Science.gov (United States)

    Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G; Dacks, Joel B

    2015-12-15

    In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. © 2015 Richardson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  11. Generation of functional podocytes from human induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Osele Ciampi

    2016-07-01

    Full Text Available Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro.

  12. Regulation of T cell differentiation and function by EZH2

    Directory of Open Access Journals (Sweden)

    THEODOROS KARANTANOS

    2016-05-01

    Full Text Available The enhancer of zeste homologue 2 (EZH2, one of the polycomb group (PcG proteins, is the catalytic subunit of Polycomb-repressive complex 2 (PRC2 and induces the trimethylation of the histone H3 lysine 27 (H3K27me3 promoting epigenetic gene silencing. EZH2 contains a SET domain promoting the methyltransferase activity while the three other protein components of PRC2, namely EED, SUZ12 and RpAp46/48 induce compaction of the chromatin permitting EZH2 enzymatic activity. Numerous studies highlight the role of this evolutionary conserved protein as a master regulator of differentiation in humans involved in the repression of the homeotic (Hox gene and the inactivation of X-chromosome. Through its effects in the epigenetic regulation of critical genes, EZH2 has been strongly linked to cell cycle progression, stem cell pluripotency and cancer biology. Most recently, EZH2 has been associated with hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis. Several studies have evaluated the role of EZH2 in the regulation of T cell differentiation and plasticity as well as its implications in the development of autoimmune diseases and graft versus host disease (GvHD. In this review we will briefly summarize the current knowledge regarding the role of EZH2 in the regulation of T cell differentiation, effector function and homing in the tumor microenvironment and we will discuss possible therapeutic targeting of EZH2 in order to alter T cell immune functions.

  13. Generation of functional podocytes from human induced pluripotent stem cells.

    Science.gov (United States)

    Ciampi, Osele; Iacone, Roberto; Longaretti, Lorena; Benedetti, Valentina; Graf, Martin; Magnone, Maria Chiara; Patsch, Christoph; Xinaris, Christodoulos; Remuzzi, Giuseppe; Benigni, Ariela; Tomasoni, Susanna

    2016-07-01

    Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro. Copyright © 2016. Published by Elsevier B.V.

  14. Functional Compartmentalization within Starburst Amacrine Cell Dendrites in the Retina

    Directory of Open Access Journals (Sweden)

    Alon Poleg-Polsky

    2018-03-01

    Full Text Available Summary: Dendrites in many neurons actively compute information. In retinal starburst amacrine cells, transformations from synaptic input to output occur within individual dendrites and mediate direction selectivity, but directional signal fidelity at individual synaptic outputs and correlated activity among neighboring outputs on starburst dendrites have not been examined systematically. Here, we record visually evoked calcium signals simultaneously at many individual synaptic outputs within single starburst amacrine cells in mouse retina. We measure visual receptive fields of individual output synapses and show that small groups of outputs are functionally compartmentalized within starburst dendrites, creating distinct computational units. Inhibition enhances compartmentalization and directional tuning of individual outputs but also decreases the signal-to-noise ratio. Simulations suggest, however, that the noise underlying output signal variability is well tolerated by postsynaptic direction-selective ganglion cells, which integrate convergent inputs to acquire reliable directional information. : Poleg-Polsky et al. examine the directional signaling fidelity of individual synapses on starburst amacrine cell dendrites. They identify functionally and morphologically distinct signaling compartments within SAC dendrites and show that inhibition enhances reliable decoding by postsynaptic direction-selective ganglion cells. Keywords: retina, synaptic transmission, amacrine cell, correlation, visual processing, inhibition, direction selectivity

  15. Functional somatostatin receptors on a rat pancreatic acinar cell line

    International Nuclear Information System (INIS)

    Viguerie, N.; Tahiri-Jouti, N.; Esteve, J.P.; Clerc, P.; Logsdon, C.; Svoboda, M.; Susini, C.; Vaysse, N.; Ribet, A.

    1988-01-01

    Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of 125 I-[Tyr 11 ]Somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites with a maximal binding capacity of 258 ± 20 fmol/10 6 cells. Somatostatin receptor structure was analyzed by covalently cross-linking 125 I-[Tyr 11 ]somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. The authors conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein N i to inhibit adenylate cyclase

  16. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions.

    Science.gov (United States)

    Zhou, Jinghua; Zhang, Jianyun; Li, Feixue; Liu, Jing

    2016-05-05

    Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Directory of Open Access Journals (Sweden)

    Christian Kosan

    2016-01-01

    Full Text Available All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

  18. Magnetic Properties Controlled by Interstitial or Interlayer Cations in Iron Chalcogenides

    Science.gov (United States)

    Tang, Shan-Chang; Ding, Ming-Cui; Zhang, Yu-Zhong

    2016-01-01

    By applying density functional theory calculations to iron chalcogenides, we find that magnetic order in Fe1+yTe and magnetic instability at (π, π) in KyFe2Se2 are controlled by interstitial and interlayer cations, respectively. While in Fe1+yTe, magnetic phase transitions occur among collinear, exotic bicollinear and plaquette-ordered antiferronmagnetic states when the height of interstitial irons measured from iron plane or the concentration of interstitial irons is varied, the magnetic instability at (π, π) which is believed to be responsible for the Cooper pairing in iron pnictides is significantly enhanced when y is much smaller than 1 in KyFe2Se2. Our results indicate that, similar to iron pnictides, itinerant electrons play important roles in iron chalcogenides, even though the fluctuating local moments become larger.

  19. Effects of applied strain on nanoscale self-interstitial cluster formation in BCC iron

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Ning; Setyawan, Wahyu; Kurtz, Richard J.; Wang, Zhiguang

    2017-09-01

    The effect of applied strains on the configurational evolution of self-interstitial clusters in BCC iron (Fe) is explored with atomistic simulations. A novel cluster configuration is discovered at low temperatures (<600 K), which consists of <110> dumbbells and <111> crowdions in a specific configuration, resulting in an immobile defect. The stabili