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Sample records for peritubular myoid cells

  1. Peritubular myoid cells in the testis: their structure and function.

    PubMed

    Maekawa, M; Kamimura, K; Nagano, T

    1996-03-01

    Peritubular myoid cells, surrounding the seminiferous tubules in the testis, have been found in all mammalian species, but their organization in the peritubular interstitial tissue varies by species. In laboratory rodents, including rats, hamsters and mice, only one layer of myoid cells is seen in the testis. The cells in these animals are joined by junctional complexes as are epithelial cells. On the other hand, several cellular layers exist in the lamina propria of the seminiferous tubule in the human and some other animals. Myoid cells contain abundant actin filaments which are distributed in the cells in a species-specific manner. In the rat, the filaments within one myoid cell run both longitudinally and circularly to the long axis of the seminiferous tubule, exhibiting a lattice-work pattern. The arrangement of the actin filaments in the cells changes during postnatal development, and the disruption of spermatogenesis, such as cryptorchidism, seems to affect further the arrangement of the filaments. Other cytoskeletal proteins, including myosin, desmin/vimentin and alpha-actinin, are also found in the cells. Myoid cells have been shown to be contractile, involved in the transport of spermatozoa and testicular fluid in the tubule. Several substances (prostaglandins, oxytocin, TGF beta, NO/cGMP) have been suggested to affect the contraction of the cell, though the mechanisms of the contraction are still unknown. Recent in vitro studies have demonstrated that the cells secrete a number of substances including extracellular matrix components (fibronectin, type I and IV collagens, proteoglycans) and growth factors (PModS, TGF beta, IGF-I, activin-A). Some of these substances are known to affect the Sertoli cell function. Furthermore, it has been reported that myoid cells contain androgen receptors and are involved in retinol processing. Considering all this, it is evident that peritubular myoid cells not only provide structural integrity to the tubule but also

  2. Sertoli Cells Maintain Leydig Cell Number and Peritubular Myoid Cell Activity in the Adult Mouse Testis

    PubMed Central

    Monteiro, Ana; Milne, Laura; Cruickshanks, Lyndsey; Jeffrey, Nathan; Guillou, Florian; Freeman, Tom C.; Mitchell, Rod T.; Smith, Lee B.

    2014-01-01

    The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR) specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health. PMID:25144714

  3. Identification and characterization of Xenopus tropicalis common progenitors of Sertoli and peritubular myoid cell lineages

    PubMed Central

    Tlapakova, Tereza; Nguyen, Thi Minh Xuan; Vegrichtova, Marketa; Sidova, Monika; Strnadova, Karolina; Blahova, Monika

    2016-01-01

    ABSTRACT The origin of somatic cell lineages during testicular development is controversial in mammals. Employing basal amphibian tetrapod Xenopus tropicalis we established a cell culture derived from testes of juvenile male. Expression analysis showed transcription of some pluripotency genes and Sertoli cell, peritubular myoid cell and mesenchymal cell markers. Transcription of germline-specific genes was downregulated. Immunocytochemistry revealed that a majority of cells express vimentin and co-express Sox9 and smooth muscle α-actin (Sma), indicating the existence of a common progenitor of Sertoli and peritubular myoid cell lineages. Microinjection of transgenic, red fluorescent protein (RFP)-positive somatic testicular cells into the peritoneal cavity of X. tropicalis tadpoles resulted in cell deposits in heart, pronephros and intestine, and later in a strong proliferation and formation of cell-to-cell net growing through the tadpole body. Immunohistochemistry analysis of transplanted tadpoles showed a strong expression of vimentin in RFP-positive cells. No co-localization of Sox9 and Sma signals was observed during the first three weeks indicating their dedifferentiation to migratory-active mesenchymal cells recently described in human testicular biopsies. PMID:27464670

  4. Changes of myoid and endothelial cells in the peritubular wall during contraction of the seminiferous tubule.

    PubMed

    Losinno, Antonella D; Sorrivas, Viviana; Ezquer, Marcelo; Ezquer, Fernando; López, Luis A; Morales, Alfonsina

    2016-08-01

    The wall of the seminiferous tubule in rodents consists of an inner layer of myoid cells covered by an outer layer of endothelial cells. Myoid cells are a type of smooth muscle cell containing α-actin filaments arranged in two independent layers that contract when stimulated by endothelin-1. The irregular surface relief of the tubular wall is often considered a hallmark of contraction induced by a variety of stimuli. We examine morphological changes of the rat seminiferous tubule wall during contraction by a combination of light, confocal, transmission and scanning electron microscopy. During ET-1-induced contraction, myoid cells changed from a flat to a conical shape, but their actin filaments remained in independent layers. As a consequence of myoid cell contraction, the basement membrane became wavy, orientation of collagen fibers in the extracellular matrix was altered and the endothelial cell layer became folded. To observe the basement of the myoid cell cone, the endothelial cell monolayer was removed by collagenase digestion prior to SEM study. In contracted tubules, it is possible to distinguish cell relief: myoid cells have large folds on the external surface oriented parallel to the tubular axis, whereas endothelial cells have numerous cytoplasmic projections facing the interstitium. The myoid cell cytoskeleton is unusual in that the actin filaments are arranged in two orthogonal layers, which adopt differing shapes during contraction with myoid cells becoming cone-shaped. This arrangement impacts on other components of the seminiferous tubule wall and affects the propulsion of the tubular contents to the rete testis.

  5. Identification and characterization of Myosin from rat testicular peritubular myoid cells.

    PubMed

    Fernández, Dario; Bertoldi, Maria V; Gómez, Laura; Morales, Alfonsina; Callegari, Eduardo; Lopez, Luis A

    2008-12-01

    In the mammalian testis, peritubular myoid cells (PMCs) surround seminiferous tubules. These cells are contractile, express the cytoskeletal markers of true smooth muscle-alpha-isoactin and F-actin-and participate in the contraction of seminiferous tubules during the transport of spermatozoa and testicular fluid to the rete testis. Myosin from PMCs (PMC-myosin) was isolated from adult rat testis and purified by cycles of assembly-disassembly and sucrose gradient centrifugation. PMC-myosin was recognized by a monoclonal anti-smooth muscle myosin antibody, and the peptide sequence shared partial homology with rat smooth muscle myosin-II, MYH11 (also known as SMM-II). Most PMC-myosin (95%) was soluble in the PMC cytosol, and purified PMC-myosin did not assemble into filaments in the in vitro salt dialysis assay at 4 degrees C, but did at 20 degrees C. PMC-myosin filaments are stable to ionic strength to the same degree as gizzard MYH11 filaments, but PMC-myosin filaments were more unstable in the presence of ATP. When PMCs were induced to contract by endothelin 1, a fraction of the PMC-myosin was found to be involved in the contraction. From these results we infer that PMCs express an isoform of smooth muscle myosin-II that is characterized by solubility at physiological ionic strength, a requirement for high temperature to assemble into filaments in vitro, and instability at low ATP concentrations. PMC-myosin is part of the PMC contraction apparatus when PMCs are stimulated with endothelin 1.

  6. Identification and Characterization of Myosin from Rat Testicular Peritubular Myoid Cells1

    PubMed Central

    Fernández, Dario; Bertoldi, Maria V.; Gómez, Laura; Morales, Alfonsina; Callegari, Eduardo; Lopez, Luis A.

    2008-01-01

    In the mammalian testis, peritubular myoid cells (PMCs) surround seminiferous tubules. These cells are contractile, express the cytoskeletal markers of true smooth muscle—alpha-isoactin and F-actin—and participate in the contraction of seminiferous tubules during the transport of spermatozoa and testicular fluid to the rete testis. Myosin from PMCs (PMC-myosin) was isolated from adult rat testis and purified by cycles of assembly-disassembly and sucrose gradient centrifugation. PMC-myosin was recognized by a monoclonal anti-smooth muscle myosin antibody, and the peptide sequence shared partial homology with rat smooth muscle myosin-II, MYH11 (also known as SMM-II). Most PMC-myosin (95%) was soluble in the PMC cytosol, and purified PMC-myosin did not assemble into filaments in the in vitro salt dialysis assay at 4°C, but did at 20°C. PMC-myosin filaments are stable to ionic strength to the same degree as gizzard MYH11 filaments, but PMC-myosin filaments were more unstable in the presence of ATP. When PMCs were induced to contract by endothelin 1, a fraction of the PMC-myosin was found to be involved in the contraction. From these results we infer that PMCs express an isoform of smooth muscle myosin-II that is characterized by solubility at physiological ionic strength, a requirement for high temperature to assemble into filaments in vitro, and instability at low ATP concentrations. PMC-myosin is part of the PMC contraction apparatus when PMCs are stimulated with endothelin 1. PMID:18716291

  7. Sertoli Cell Wt1 Regulates Peritubular Myoid Cell and Fetal Leydig Cell Differentiation during Fetal Testis Development

    PubMed Central

    Wen, Qing; Wang, Yuqian; Tang, Jixin; Cheng, C. Yan; Liu, Yi-Xun

    2016-01-01

    Sertoli cells play a significant role in regulating fetal testis compartmentalization to generate testis cords and interstitium during development. The Sertoli cell Wilms’ tumor 1 (Wt1) gene, which encodes ~24 zinc finger-containing transcription factors, is known to play a crucial role in fetal testis cord assembly and maintenance. However, whether Wt1 regulates fetal testis compartmentalization by modulating the development of peritubular myoid cells (PMCs) and/or fetal Leydig cells (FLCs) remains unknown. Using a Wt1-/flox; Amh-Cre mouse model by deleting Wt1 in Sertoli cells (Wt1SC-cKO) at embryonic day 14.5 (E14.5), Wt1 was found to regulate PMC and FLC development. Wt1 deletion in fetal testis Sertoli cells caused aberrant differentiation and proliferation of PMCs, FLCs and interstitial progenitor cells from embryo to newborn, leading to abnormal fetal testis interstitial development. Specifically, the expression of PMC marker genes α-Sma, Myh11 and Des, and interstitial progenitor cell marker gene Vcam1 were down-regulated, whereas FLC marker genes StAR, Cyp11a1, Cyp17a1 and Hsd3b1 were up-regulated, in neonatal Wt1SC-cKO testes. The ratio of PMC:FLC were also reduced in Wt1SC-cKO testes, concomitant with a down-regulation of Notch signaling molecules Jag 1, Notch 2, Notch 3, and Hes1 in neonatal Wt1SC-cKO testes, illustrating changes in the differentiation status of FLC from their interstitial progenitor cells during fetal testis development. In summary, Wt1 regulates the development of FLC and interstitial progenitor cell lineages through Notch signaling, and it also plays a role in PMC development. Collectively, these effects confer fetal testis compartmentalization. PMID:28036337

  8. Sertoli Cell Wt1 Regulates Peritubular Myoid Cell and Fetal Leydig Cell Differentiation during Fetal Testis Development.

    PubMed

    Wen, Qing; Wang, Yuqian; Tang, Jixin; Cheng, C Yan; Liu, Yi-Xun

    2016-01-01

    Sertoli cells play a significant role in regulating fetal testis compartmentalization to generate testis cords and interstitium during development. The Sertoli cell Wilms' tumor 1 (Wt1) gene, which encodes ~24 zinc finger-containing transcription factors, is known to play a crucial role in fetal testis cord assembly and maintenance. However, whether Wt1 regulates fetal testis compartmentalization by modulating the development of peritubular myoid cells (PMCs) and/or fetal Leydig cells (FLCs) remains unknown. Using a Wt1-/flox; Amh-Cre mouse model by deleting Wt1 in Sertoli cells (Wt1SC-cKO) at embryonic day 14.5 (E14.5), Wt1 was found to regulate PMC and FLC development. Wt1 deletion in fetal testis Sertoli cells caused aberrant differentiation and proliferation of PMCs, FLCs and interstitial progenitor cells from embryo to newborn, leading to abnormal fetal testis interstitial development. Specifically, the expression of PMC marker genes α-Sma, Myh11 and Des, and interstitial progenitor cell marker gene Vcam1 were down-regulated, whereas FLC marker genes StAR, Cyp11a1, Cyp17a1 and Hsd3b1 were up-regulated, in neonatal Wt1SC-cKO testes. The ratio of PMC:FLC were also reduced in Wt1SC-cKO testes, concomitant with a down-regulation of Notch signaling molecules Jag 1, Notch 2, Notch 3, and Hes1 in neonatal Wt1SC-cKO testes, illustrating changes in the differentiation status of FLC from their interstitial progenitor cells during fetal testis development. In summary, Wt1 regulates the development of FLC and interstitial progenitor cell lineages through Notch signaling, and it also plays a role in PMC development. Collectively, these effects confer fetal testis compartmentalization.

  9. Peritubular myoid cells from rat seminiferous tubules contain actin and myosin filaments distributed in two independent layers.

    PubMed

    Losinno, Antonella D; Morales, Alfonsina; Fernández, Dario; Lopez, Luis A

    2012-05-01

    In the mammalian testis, peritubular myoid cells (PM cells) surround the seminiferous tubules (STs), express cytoskeletal markers of true smooth muscle cells, and participate in the contraction of the ST. It has been claimed that PM cells contain bundles of actin filaments distributed orthogonally in an intermingled mesh. Our hypothesis is that these actin filaments are not forming a random intermingled mesh, but are actually arranged in contractile filaments in independent layers. The aim of this study is to describe the organization of the actin cytoskeleton in PM cells from adult rat testes and its changes during endothelin-1-induced ST contraction. For this purpose, we isolated segments of ST corresponding to the stages IX-X of the spermatogenic cycle (ST segments), and analyzed the actin and myosin filament distribution by confocal and transmission electron microscopy. We found that PM cells have actin and myosin filaments interconnected in thick bundles (AF-MyF bundles). These AF-MyF bundles are distributed in two independent layers: an inner layer toward the seminiferous epithelium, and an outer layer toward the interstitium, with the bundles oriented perpendicularly and in parallel to the main ST axis, respectively. In endothelin-1 contracted ST segments, PM cells increased their thickness and reduced their length in both directions, parallel and perpendicular to the main ST axis. The AF-MyF bundles maintained the same organization in two layers, although both layers appeared significantly thicker. We believe that this is the first time this arrangement of AF-MyF bundles in two independent layers has been shown in smooth muscle cells, and that this organization would allow the cell to generate contractile force in two directions.

  10. Sertoli cells in culture secrete paracrine factor(s) that inhibit peritubular myoid cell proliferation: identification of heparinoids as likely candidates

    SciTech Connect

    Tung, P.S.; Fritz, I.B. )

    1991-06-01

    Conditioned medium from Sertoli cells, prepared from testes of 20-day-old rats, contains component(s) that inhibit the incorporation of (3H)-thymidine into DNA of peritubular myoid cells (PMC) and inhibit the proliferation of PMC. These components are trypsin-resistant, heat-stable compounds having a molecular weight less than 30,000. The active inhibitory components in Sertoli cell conditioned medium are inactivated by treatment with heparinase, but not by treatment with hyaluronidase or chondroitin sulfate lyases. Addition of heparin or heparan sulfate results in inhibition of DNA synthesis by PMC in a dose-dependent manner, whereas other glycosaminoglycans (GAGs) examined (hyaluronic acid, keratan sulfate, and chondroitin sulfate) have no detectable effects. Heparin and heparan sulfate are unique among GAGs tested in inhibiting the characteristic multilayer growth pattern of PMC following the attainment of confluence in serum-rich medium. On the basis of these and other data presented, it is concluded that heparin and other heparin-like GAGs synthesized by Sertoli cells are implicated in the modulation of growth of PMC in vitro during co-culture. It is postulated that heparin may play a similar role in maintaining the quiescent peritubular myoid cell phenotype in vivo.

  11. Establishment of a Human Thymic Myoid Cell Line

    PubMed Central

    Wakkach, Abdel; Poea, Sandrine; Chastre, Eric; Gespach, Christian; Lecerf, Florence; De la Porte, Sabine; Tzartos, Socrates; Coulombe, Alain; Berrih-Aknin, Sonia

    1999-01-01

    The subset of myoid cells is a normal component of the thymic stroma. To characterize these cells, we immortalized stromal cells from human thymus by using a plasmid vector encoding the SV40 T oncogene. Among the eight cell lines obtained, one had myoid characteristics including desmin and troponin antigens. This new line was designated MITC (myoid immortalized thymic cells). These cells expressed both the fetal and adult forms of muscle acetylcholine receptor (AChR) at the mRNA level, as well as the myogenic transcription factor MyoD1. α-Subunit AChR protein expression was detected by flow cytometry and the AChR was functional in patch-clamp studies. In addition, AChR expression was down-modulated by myasthenia gravis sera or by monoclonal antibody anti-AChR on MITC line similarly to TE671 rhabdomyosarcoma cells, making the MITC line an interesting tool for AChR antigenic modulation experiments. Finally, the MITC line expressed LFA-3, produced several cytokines able to act on T cells, and protected total thymocytes from spontaneous apoptosis in vitro. These results are compatible with a role of thymic myoid cells in some steps of thymocyte development. Therefore MITC line appears to be a useful tool to investigate the physiological role of thymic myoid cells. PMID:10514405

  12. Myoid cells and neuroendocrine markers in myasthenic thymuses.

    PubMed

    Zółtowska, A; Pawełczyk, T; Stopa, M; Skokowski, J; Stepiński, J; Roszkiewicz, A; Nyka, W

    1998-01-01

    We have studied myoid cells in normal and myasthenic thymuses as well as in thymomas. For the presence of neuroendocrine markers-producing cells and identification of synaptophysin (Syn) the immunohistochemical method and immunoblot analysis were used. Myoid cells can be demonstrated in the thymus of myasthenic patients in high number. These cells occur in the vicinity of Hassall's bodies but also within them. Some regenerated Hassall's bodies displayed majority of myoid cells with their concentric arrangement around the centrally situated lacunar-like cell with nuclei of monocytogenic origin. Such phenomenon may suggest cooperation of myoid cells and their epithelial transitional forms with monocytogenic cells in various thymic hormone production. It is likely that myoid cells are the source of some thymic epithelial cells. According to some authors, thymomatous epithelial cells and skeletal muscle share a common epitope defined by a monoclonal antibody (mAb), whereas thymic epithelial cells possess acetylocholine receptor (AChR) on their surface. The epithelial cells of some thymomas express also desmin. In normal thymuses of children, Syn and chromogranin A (Chg A) were demonstrated in some cells of Hassall's bodies by immunohistochemical method. In addition, antibodies to Syn stained nerve structures surrounding the thymic blood vessels. In myasthenic thymuses, Syn expression was in cortical and medullary epithelial cells, in myoid cells and only scanty and focal in keratinized epithelial cells of Hassall's bodies. The epithelial cells of some thymomas also express Syn. In some thymuses of all groups investigated in this study Chg A was seen in single cells of Hassall's bodies and focally in cortical epithelial cells. Our results show that in normal thymuses of cardiac surgery patients and in the adult myasthenic thymuses antibody raised against Syn recognized protein with molecular weight of 48,000 but not normal (38,000) Syn. It remains to be elucidated if

  13. Insights into the nature of human testicular peritubular cells.

    PubMed

    Albrecht, Martin

    2009-12-01

    Human testicular peritubular cells are myofibroblast-like cells that surround the seminiferous tubules and are responsible for tubular contractility and sperm transport. In the last few years, several reports have augmented this simplified view, showing that peritubular cells are not only structural cells but also actively secrete paracrine mediators, thereby influencing the homeostasis of the testicular environment. This review is focussed on general aspects and functions of testicular peritubular cells, their potential role in male infertility and also on the recently described in vitro culture systems of human testicular peritubular cells, which will enable us to gain deeper insight into the regulation and functions of this peculiar cell type in health and disease.

  14. Implications of caveolae in testicular and epididymal myoid cells to sperm motility.

    PubMed

    Oliveira, Regiana L; Parent, Adam; Cyr, Daniel G; Gregory, Mary; Mandato, Craig A; Smith, Charles E; Hermo, Louis

    2016-06-01

    Seminiferous tubules of the testis and epididymal tubules in adult rodents are enveloped by contractile myoid cells, which move sperm and fluids along the male reproductive tract. Myoid cells in the testis influence Sertoli cells by paracrine signaling, but their role in the epididymis is unknown. Electron microscopy revealed that elongated myoid cells formed several concentric layers arranged in a loose configuration. The edges of some myoid cells in a given layer closely approximated one another, and extended small foot-like processes to cells of overlying layers. Gap junction proteins, connexins 32 and 43, were detected within the myoid cell layers by immunohistochemistry. These myoid cells also had caveolae that contained caveolin-1 and cavin-1 (also known as PTRF). The number of caveolae per unit area of plasma membrane was significantly reduced in caveolin-1-deficient mice (Cav1(-/-) ). Morphometric analyses of Cav1-null testes revealed an enlargement in whole-tubule and epithelial profile areas, whereas these parameters were slightly reduced in the epididymis. Although sperm are non-motile as they pass through the proximal epididymis, statistical analyses of cauda epididymidis sperm concentrations revealed no significant differences between wild-type and Cav1(-/-) mice. Motility analyses, however, indicated that sperm velocity parameters were reduced while beat cross frequency was higher in gametes of Cav1(-/-) mice. Thus while caveolae and their associated proteins are not necessary for myoid cell contractility, they appear to be crucial for signaling with the epididymal epithelium to regulate the proper acquisition of sperm motility. Mol. Reprod. Dev. 83: 526-540, 2016. © 2016 Wiley Periodicals, Inc.

  15. Morphological evidences indicate that the interference of cimetidine on the peritubular components is responsible for detachment and apoptosis of Sertoli cells.

    PubMed

    Sasso-Cerri, Estela; Cerri, Paulo S

    2008-05-09

    Cimetidine, referred as antiandrogenic agent, has caused alterations in the seminiferous tubules, including alterations in the peritubular tissue and death of myoid cells by apoptosis. Regarding the structural and functional importance of the peritubular tissue for the maintenance of Sertoli cells (SC), we purpose to investigate the SC-basement membrane interface, focusing the morphological features of SC and their interaction with the basement membrane in the affected tubules by cimetidine. Ten animals were distributed into two groups, control (CG) and cimetidine (CmG) which received saline solution and 50 mg of cimetidine per kg of body weight, respectively, for 52 days. The testes were fixed, dehydrated and embedded for analyses under light and transmission electron microscopy. Paraffin sections were submitted to the TUNEL method; sections of testes embedded in glycol methacrylate were submitted to PAS method and stained by H&E for morphological and quantitative analyses of Sertoli Cells. In the CmG, the SC nuclei were positive to the TUNEL method and showed typical morphological alterations of cell death by apoptosis (from early to advanced stages). A significant reduction in the number of Sertoli Cells was probably due to death of these cells by apoptosis. A close relationship between SC nuclear alterations (including a high frequency of dislocated nuclei from the basal portion) and damage in the peritubular tissue was observed. The ultrastructural analysis showed a parallelism between the gradual advancement of apoptotic process in SC and detachment of the anchoring sites (hemidesmosomes) of SC plasma membrane from the lamina densa. The presence of portions of lamina densa underlying the detached hemidesmosomes indicates a continuous deposition of lamina densa, resulting in the thickening of the basal lamina. The results indicate a possible disarrangement of the SC cytoskeleton, including the focal adhesion structure. These alterations are related to SC

  16. Protein secretory patterns of rat Sertoli and peritubular cells are influenced by culture conditions

    SciTech Connect

    Kierszenbaum, A.L.; Crowell, J.A.; Shabanowitz, R.B.; DePhilip, R.M.; Tres, L.L.

    1986-08-01

    An approach combining two-dimensional gel electrophoresis and autoradiography was used to correlate patterns of secretory proteins in cultures of Sertoli and peritubular cells with those observed in the incubation medium from segments of seminiferous tubules. Sertoli cells in culture and in seminiferous tubules secreted three proteins designated S70 (Mr 72,000-70,000), S45 (Mr 45,000), and S35 (Mr 35,000). Cultured Sertoli and peritubular cells and incubated seminiferous tubules secreted two proteins designated SP1 (Mr 42,000) and SP2 (Mr 50,000). SP1 and S45 have similar Mr but differ from each other in isoelectric point (pI). Cultured peritubular cells secreted a protein designated P40 (Mr 40,000) that was also seen in intact seminiferous tubules but not in seminiferous tubules lacking the peritubular cell wall. However, a large number of high-Mr proteins were observed only in the medium of cultured peritubular cells but not in the incubation medium of intact seminiferous tubules. Culture conditions influence the morphology and patterns of protein secretion of cultured peritubular cells. Peritubular cells that display a flat-stellate shape transition when placed in culture medium free of serum (with or without hormones and growth factors), accumulate various proteins in the medium that are less apparent when these cells are maintained in medium supplemented with serum. Two secretory proteins stimulated by follicle-stimulating hormone (FSH) (designated SCm1 and SCm2) previously found in the medium of cultured Sertoli cells, were also observed in the incubation medium of seminiferous tubular segments stimulated by FSH. Results of this study show that, although cultured Sertoli and peritubular cells synthesize and secrete proteins also observed in segments of incubated seminiferous tubules anther group of proteins lacks seminiferous tubular correlates.

  17. Partial loss of contractile marker proteins in human testicular peritubular cells in infertility patients.

    PubMed

    Welter, H; Kampfer, C; Lauf, S; Feil, R; Schwarzer, J U; Köhn, F-M; Mayerhofer, A

    2013-03-01

    Fibrotic remodelling of the testicular tubular wall is common in human male infertility caused by impaired spermatogenesis. We hypothesized that this morphological change bears witness of an underlying fundamentally altered state of the cells building this wall, that is, peritubular smooth muscle-like cells. This could include a loss of the contractile abilities of these cells and thus be a factor in male infertility. Immune cells are increased in the tubular wall in these cases, hence local immune cell-related factors, including a prostaglandin (PG) metabolite may be involved. To explore these points in the human, we used testicular biopsies, in which tubules with normal spermatogenesis and impaired spermatogenesis are next to each other [mixed atrophy (MA)], normal biopsies and cultured human testicular peritubular cells. Proteins essential for contraction, myosin heavy chain (MYH11), calponin (Cal) and relaxation, cGMP-dependent protein kinase 1 (cGKI), were readily detected by immunohistochemistry and were equally distributed in all peritubular cells of biopsies with normal spermatogenesis. In all biopsies, vascular smooth muscle cells also stained and served as important intrinsic controls, which showed that in MA samples when spermatogenesis was impaired, staining was restricted to only few peritubular cells or was absent. When spermatogenesis was normal, regular peritubular staining became obvious. This pattern suggests complex regulatory influences, which in face of the identical systemic hormonal situation in MA patients, are likely caused by the local testicular micromilieu. The PG metabolite 15dPGJ2 may represent such a factor and it reduced Cal protein levels in peritubular cells from patients with/without impaired spermatogenesis. The documented phenotypic switch of peritubular, smooth muscle-like cells in MA patients may impair the abilities of the afflicted seminiferous tubules to contract and relax and must now be considered as a part of the complex

  18. Low micromolar concentrations of cadmium and mercury ions activate peritubular membrane K+ conductance in proximal tubular cells of frog kidney.

    PubMed

    Nesovic-Ostojic, Jelena; Cemerikic, Dusan; Dragovic, Simon; Milovanovic, Aleksandar; Milovanovic, Jovica

    2008-03-01

    The present study was designed to investigate the acute effects of extracellular low micromolar concentrations of cadmium and mercury ions on the peritubular cell membrane potential and its potassium selectivity in proximal tubular cells of the frog kidney. Peritubular exposure to 3 micromol/L Cd(2+) or 1 micromol/L Hg(2+) led to a rapid, sustained and reversible hyperpolarization of the peritubular cell membrane, paralleled by an increase in fractional K(+) conductance. Peritubular barium abolished hyperpolarization of the peritubular cell membrane to peritubular 3 micromol/L Cd(2+) or 1 micromol/L Hg(2+). Perfusing the lumen with 10 mmol/L l-alanine plus/minus 3 micromol/L Cd(2+) or Hg(2+) did not modify rapid depolarization and rate of slow repolarization of the peritubular cell membrane potential. In conclusion, low micromolar concentrations of Cd(2+) and Hg(2+) increase K(+) conductive pathway in the peritubular cell membrane and in this way can enhance ability of proximal renal tubular cells to maintain the driving force for electrogenic Na(+) and substrate reabsorption.

  19. Structural characterization of proteoglycans produced by testicular peritubular cells and Sertoli cells

    SciTech Connect

    Skinner, M.K.; Fritz, I.B.

    1985-09-25

    The structural characteristics of proteoglycans produced by seminiferous peritubular cells and by Sertoli cells are defined. Peritubular cells secrete two proteoglycans designated PC I and PC II. PC I is a high molecular mass protein containing chondroitin glycosaminoglycan (GAG) chains (maximum 70 kDa). PC II has a protein core of 45 kDa and also contains chondroitin GAG chains (maximum 70 kDa). Preliminary results imply that PC II may be a degraded or processed form of PC I. Sertoli cells secrete two different proteoglycans, designated SC I and SC II. SC I is a large protein containing both chondroitin (maximum 62 kDa) and heparin (maximum 15 kDa) GAG chains. Results obtained suggest that this novel proteoglycan contains both chondroitin and heparin GAG chains bound to the same core protein. SC II has a 50-kDa protein core and contains chondroitin (maximum 25 kDa) GAG chains. A proteoglycan obtained from extracts of Sertoli cells is described which contains heparin (maximum 48 kDa) GAG chains. In addition, Sertoli cells secrete a sulfoprotein, SC III, which is not a proteoglycan. The stimulation by follicle-stimulating hormone of the incorporation of (TVS)SO2) U) into moieties secreted by Sertoli cells is shown to represent an increased production or sulfation of SC III, and not an increased production or sulfation of proteoglycans. Results are discussed in relation to the possible functions of proteoglycans in the seminiferous tubule.

  20. A stromal myoid cell line provokes thymic erythropoiesis between 16th to 20th weeks of intrauterine life.

    PubMed

    Tamiolakis, D; Venizelos, J; Kotini, A; Karamanidis, D; Boglou, P; Papadopoulos, N

    2004-02-01

    The thymus provides an optimal cellular and humoral microenvironment for cell line committed differentiation of haematopoietic stem cells. The immigration process requires the secretion of at least one peptide called thymotaxine by cells of the reticulo-epithelial (RE) network of the thymic stromal cellular microenvironment. The thymic RE cells are functionally specialised based on their intrathymic location and this differentiation is modulated by various interaction signals of differentiating thymocytes and other non lymphatic haematopoietic stem cells. To study the role of another cell line in fetal thymic haematopoietic proliferation and differentiation in different stages of development: the stromal myoid cells. Fifteen cases of fetal thymic specimens (4th to 8th weeks: five cases 16th to 20th weeks: five cases and 28th to 32nd weeks: five cases respectively) were studied. Tissue paraffin samples were stained immunohistochemically using (i) a monoclonal antibody recognising alpha-smooth muscle actin, a contractile microfilament expressed exclusively by smooth muscle cells, myofibroblasts and related cells, (ii) a monoclonal antibody glycophorin C recognising the erythropoietic cells. Histology-Embryology Department of Democritus University of Thrace (Alexandroupolis) over ten year period (1991-2001). The number of alpha-smooth muscle actin-positive cells significantly increased during the late second and third trimester of gestation. In the above period a relevant increase in the number of glycophorin C positive cells were observed. Our data suggest that a myoid cell line is involved in the formation of an appropriate microenvironment for homing and proliferation of erythropoietic cells.

  1. Tubular cell dedifferentiation and peritubular inflammation are coupled by the transcription regulator Id1 in renal fibrogenesis

    PubMed Central

    Li, Yingjian; Wen, Xiaoyan; Liu, Youhua

    2011-01-01

    During renal fibrogenesis, tubular epithelial-mesenchymal transition is closely associated with peritubular inflammation; however, it is not clear whether these two processes are connected. We previously identified the inhibitor of differentiation-1 (Id1), a dominant negative antagonist of basic helix-loop-helix transcription factors, as a major trigger of tubular cell dedifferentiation after injury. Id1 was induced selectively in degenerated proximal tubule and collecting duct epithelia after injury and was present in both the cytoplasm and nucleus, suggesting shuttling between these two compartments. Interestingly, the upregulation of Id1 was associated with peritubular inflammation in mouse and human nephropathies. In vitro, Id1 potentiated NF-κB signaling and augmented RANTES expression in kidney epithelial cells, which led to an enhanced recruitment of inflammatory cells. Id1 also induced Snail1 expression and triggered tubular epithelial dedifferentiation. In vivo, genetic ablation of Id1 in mice reduced peritubular inflammation and decreased tubular expression of RANTES following ureteral obstruction. Mice lacking Id1 were also protected against myofibroblast activation and matrix expression, leading to a reduced total collagen deposition in obstructive nephropathy. Thus, these results indicate that Id1 shuttles between nucleus and cytoplasm and promotes peritubular inflammation and tubular epithelial dedifferentiation, suggesting that these two events are intrinsically coupled during renal fibrogenesis. PMID:22278018

  2. Discriminative analysis of rat Sertoli and peritubular cells and their proliferation in vitro: evidence for follicle-stimulating hormone-mediated contact inhibition of Sertoli cell mitosis.

    PubMed

    Schlatt, S; de Kretser, D M; Loveland, K L

    1996-08-01

    A new methodological approach using immunohistochemical markers for Sertoli cells (alpha inhibin), peritubular cells (alpha smooth muscle actin), and S-phase cells (bromodeoxyuridine; BrdU) is presented that allows an accurate and simultaneous analysis of morphogenetic and mitogenic changes occurring in vitro. Sertoli cells and peritubular cells were isolated by sequential enzymatic digestion from 7-day-old rats. Laminin, as a major component of the extracellular matrix of the seminiferous tubule, and FSH, as a hormone stimulating Sertoli cell proliferation, were tested for their ability to influence the morphology or mitotic activity of the cultured cells. After fixation, the coverslips were stained for these antigens with use of specific primary antibodies and horseradish peroxidase- or alkaline phosphatase-labeled secondary antibodies for visualization of the respective antigens with different-colored precipitates. This approach allowed us to distinguish the two cell populations, which could not be done unequivocally without the antibody staining. We scored striking changes in cell densities and cell ratios during the culture period. Peritubular cells showed a consistently higher BrdU-labeling index than Sertoli cells. While Sertoli cells were not labeled until Day 7, peritubular cells proliferated as soon as on Day 3, and their density doubled from Day 3 to Day 7. A linear negative correlation was established for Sertoli cell proliferation in response to their local density on the coverslip, indicating contact inhibition as a signal for cessation of mitosis. At high cell densities, this inhibition was partially overcome in the presence of FSH. The presence of laminin had striking effects on the morphogenetic response but only a minor influence on mitogenesis.

  3. 15-Deoxy-delta 12-14-prostaglandin-J2 induces hypertrophy and loss of contractility in human testicular peritubular cells: implications for human male fertility.

    PubMed

    Schell, C; Albrecht, M; Spillner, S; Mayer, C; Kunz, L; Köhn, F M; Schwarzer, U; Mayerhofer, A

    2010-03-01

    The wall of the seminiferous tubules contains contractile smooth-muscle-like peritubular cells, thought to be important for sperm transport. Impaired spermatogenesis in men typically involves remodeling of this wall, and we now found that smooth muscle cell (SMC) markers, namely myosin heavy chain (MYH11) and smooth muscle actin (SMA) are often lost or diminished in peritubular cells of testes of men with impaired spermatogenesis. This suggests reduced contractility of the peritubular wall, which may contribute to sub- or infertility. In these cases, testicular expression of cyclooxygenase-2 (COX-2) implies formation of prostaglandins (PGs). When screening different PGs for their ability to target human testicular peritubular cells (HTPCs), only a PG metabolite, 15-deoxy-Delta(12-14)-prostaglandin-J2 (15dPGJ2), was effective. In primary cultures of HTPCs, 15dPGJ2 increased cell size in a reversible manner. Importantly, 15dPGJ2 treatment resulted in a loss of typical differentiation markers for SMCs, namely MYH11, calponin, and SMA, whereas fibroblast markers were unchanged. Collagen gel contraction assays revealed that this loss correlates with a reduced ability to contract. Experiments with an antagonist (bisphenol A diglycidyl ether) and agonist (troglitazone) for a cognate 15dPGJ2 receptor (i.e. peroxisome proliferator-activated receptor-gamma) indicated that peroxisome proliferator-activated receptor-gamma is not directly involved. Rather, the mode of action of 15dPGJ2 involves reactive oxygen species. The antioxidant N-acetylcysteine not only blocked ROS formation but also prevented the increase in cell size and the loss of contractility in HTPCs challenged with 15dPGJ2. We conclude that 15dPGJ2, via reactive oxygen species, influences SMC phenotype and contractility of human peritubular cells and possibly is involved in the development of human male sub-/infertility.

  4. The testicular capsule and peritubular tissue of birds: morphometry, histology, ultrastructure and immunohistochemistry

    PubMed Central

    Aire, T A; Ozegbe, P C

    2007-01-01

    The testicular capsule was studied histologically, morphometrically, ultrastructurally and immunohistochemically in the Japanese quail, domestic fowl, turkey and duck (all members of the Galloanserae). The testicular capsule was, relative to mammals, thin, being 81.5 ± 13.7 µm in the quail, 91.7 ± 6.2 µm in the domestic fowl, 104.5 ± 29.8 µm in the turkey and 91.8 ± 18.9 µm in the duck. The orchido-epididymal border (hilus) of the capsule was much thicker than elsewhere in all birds (from 233.7 ± 50.7 µm in the duck to 550.0 ± 147.3 µm thick in the turkey). The testicular capsule, other than the tunica serosa and tunica vasculosa, comprised, in the main, smooth muscle-like or myoid cells running mainly in one direction, and disposed in one main mass. Peritubular tissue was similarly composed of smooth muscle-like cells disposed in several layers. Actin and desmin intermediate filaments were immunolocalized in the inner cellular layers of the capsule in the quail, domestic fowl and duck, but uniformly in the turkey. Vimentin intermediate filament immunoreaction in the capsule was moderately and uniformly positive in the testicular capsule of only the quail. Actin and desmin, but not vimentin (except very faintly in the turkey) or cytokeratin, were immunolocalized in the peritubular tissue of all birds. The results therefore establish, or complement, some previous observations that these birds have contractile cells in their testicular capsule and peritubular tissue, whose function probably includes the transport of testicular fluid into the excurrent duct system. PMID:17451470

  5. The testicular capsule and peritubular tissue of birds: morphometry, histology, ultrastructure and immunohistochemistry.

    PubMed

    Aire, T A; Ozegbe, P C

    2007-06-01

    The testicular capsule was studied histologically, morphometrically, ultrastructurally and immunohistochemically in the Japanese quail, domestic fowl, turkey and duck (all members of the Galloanserae). The testicular capsule was, relative to mammals, thin, being 81.5 +/- 13.7 microm in the quail, 91.7 +/- 6.2 microm in the domestic fowl, 104.5 +/- 29.8 microm in the turkey and 91.8 +/- 18.9 microm in the duck. The orchido-epididymal border (hilus) of the capsule was much thicker than elsewhere in all birds (from 233.7 +/- 50.7 microm in the duck to 550.0 +/- 147.3 microm thick in the turkey). The testicular capsule, other than the tunica serosa and tunica vasculosa, comprised, in the main, smooth muscle-like or myoid cells running mainly in one direction, and disposed in one main mass. Peritubular tissue was similarly composed of smooth muscle-like cells disposed in several layers. Actin and desmin intermediate filaments were immunolocalized in the inner cellular layers of the capsule in the quail, domestic fowl and duck, but uniformly in the turkey. Vimentin intermediate filament immunoreaction in the capsule was moderately and uniformly positive in the testicular capsule of only the quail. Actin and desmin, but not vimentin (except very faintly in the turkey) or cytokeratin, were immunolocalized in the peritubular tissue of all birds. The results therefore establish, or complement, some previous observations that these birds have contractile cells in their testicular capsule and peritubular tissue, whose function probably includes the transport of testicular fluid into the excurrent duct system.

  6. Trypanosoma cruzi and myoid cells from seminiferous tubules: interaction and relation with fibrous components of extracellular matrix in experimental Chagas' disease

    PubMed Central

    Carvalho, Luiz Otávio Pereira; Abreu-Silva, Ana Lucia; Hardoim, Daiana de Jesús; Tedesco, Roberto Carlos; Mendes, Verônica Gonçalves; da Costa, Sylvio Celso Gonçalves; Calabrese, Kátia da Silva

    2009-01-01

    The main transmission route of Trypanosoma cruzi is by triatomine bugs. However, T. cruzi is also transmitted through blood transfusion, organ transplantation, ingestion of contaminated food or fluids, or is congenital. Sexual transmission, although suggested since the discovery of Chagas’ disease, has remained unproven. Sexual transmission would require T. cruzi to be located at the testes and ovaries. Here we investigated whether T. cruzi is present in the gonads of mice infected with 104 T. cruzi trypomastigotes from the CL strain. Fourteen days after experimental infection, histopathological examination showed alterations in the extracellular matrix of the lamina propria of the seminiferous tubules. Furthermore, amastigotes were present in seminiferous tubules, within myoid cells, and in the adjacencies of the basal compartment. These results indicate that T. cruzi is able to reach seminiferous tubule lumen, thus suggesting that Chagas’ disease could potentially be transmitted through sexual intercourse. Complementary studies are required to demonstrate that Chagas’ disease can be transmitted by coitus. PMID:19200251

  7. Synovial Sarcoma With Myoid Differentiation.

    PubMed

    Qassid, Omar; Ali, Ahmed; Thway, Khin

    2016-09-01

    Synovial sarcoma is a malignant mesenchymal tumor with variable epithelial differentiation, which is defined by the presence of a specific t(X;18)(p11.2;q11.2) chromosomal translocation that generates SS18-SSX fusion oncogenes. Synovial sarcoma typically arises within extremity deep soft tissue (particularly around large joints) of young adults, but has been shown to occur at almost any location. When it arises in more unusual sites, such as the abdomen, it can present a significant diagnostic challenge. We describe a case of intraabdominal monophasic synovial sarcoma that immunohistochemically showed strong expression of smooth muscle actin and calponin but only very scanty cytokeratin, and which showed morphologic and immunohistochemical overlap with other spindle cell neoplasms that can arise at this site, such as gastrointestinal stromal tumor and myofibrosarcoma. As correct diagnosis is of clinical and prognostic importance, surgical pathologists should be aware of the potential for synovial sarcoma to occur at a variety of anatomic sites and of its spectrum of immunoreactivity. Synovial sarcoma should be in the differential diagnosis of spindle cell neoplasms with myoid differentiation that do not fall into any definite tumor category, for which there should be a relatively low threshold for performing fluorescence in situ hybridization or reverse transcription-polymerase chain reaction to assess for the specific SS18 gene rearrangement or SS18-SSX fusion transcripts, which remain the diagnostic gold standard. © The Author(s) 2016.

  8. Co-localization of erythropoietin mRNA and ecto-5'-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin.

    PubMed

    Bachmann, S; Le Hir, M; Eckardt, K U

    1993-03-01

    In adults, the kidneys are the major site of production of the glycoprotein hormone erythropoietin (EPO), but the type of renal cell producing EPO has not yet been identified. In the present study we used non-radioactive in situ hybridization with a digoxigenin-labeled cRNA probe to localize cells that produce erythropoietin (EPO) in kidneys of anemic rats. Cryostat sections from both native and perfusion-fixed tissue were used. Cells containing EPO mRNA were found exclusively in the peritubular space of the renal cortex. Using high-resolution interference contrast optics, we found that cells expressing EPO mRNA were not associated with the lumina of peritubular capillaries but rather were located in the angles between adjacent tubules or between tubules and vessels. These spaces are predominantly occupied by resident interstitial fibroblasts and by their cytoplasmic processes. To further identify the type of cell containing EPO mRNA, a double-labeling protocol was established that permitted on the same tissue section both in situ hybridization for EPO mRNA and parallel immunolabeling of ecto-5'-nucleotidase (5'-Nu), a surface marker of peritubular interstitial fibroblasts. The combined labeling technique revealed that a clear majority of cells expressing EPO mRNA also displayed staining for anti-5'-Nu. Staining for EPO mRNA was localized in central perinuclear parts of the interstitial cells, whereas 5'-Nu label was present on the cell surface, including the cytoplasmic processes. These data indicate that peritubular fibroblasts are cellular sites for production of erythropoietin.

  9. Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells

    PubMed Central

    Mayer, C.; Adam, M.; Glashauser, L.; Dietrich, K.; Schwarzer, J.U.; Köhn, F.-M.; Strauss, L.; Welter, H.; Poutanen, M.; Mayerhofer, A.

    2016-01-01

    Changes in the wall of seminiferous tubules in men with impaired spermatogenesis imply sterile inflammation of the testis. We tested the hypothesis that the cells forming the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), orchestrate inflammatory events and that Toll like receptors (TLRs) and danger signals from the extracellular matrix (ECM) of this wall are involved. In cultured HTPCs we detected TLRs, including TLR2. A TLR-2 ligand (PAM) augmented interleukin 6 (IL-6), monocyte chemo-attractant protein-1 (MCP-1) and pentraxin 3 (PTX3) in HTPCs. The ECM-derived proteoglycan biglycan (BGN) is secreted by HTPCs and may be a TLR2-ligand at HTPCs. In support, recombinant human BGN increased PTX3, MCP-1 and IL-6 in HTPCs. Variable endogenous BGN levels in HTPCs derived from different men and differences in BGN levels in the tubular wall in infertile men were observed. In testes of a systemic mouse model for male infertility, testicular sterile inflammation and elevated estradiol (E2) levels, BGN was also elevated. Hence we studied the role of E2 in HTPCs and observed that E2 elevated the levels of BGN. The anti-estrogen ICI 182,780 blocked this action. We conclude that TLR2 and BGN contribute to sterile inflammation and infertility in man. PMID:27849015

  10. [Development and differentiation of the rat epididymis. I: ultrastructural aspects of the peritubular zone].

    PubMed

    Francavilla, S; Santiemma, V; Francavilla, F; Moscardelli, S; Forcella, G; Fabbrini, A

    1979-07-15

    We investigated the ultrastructural aspects of the peritubular cells of epididymis and their development from birth to adult age. At birth the peritubular zone consisted of polygonal cells which did not differ from other interstitial cells. Cytoplasmic filaments were visible in the cells of the inner layer at day 6. From day 22 the peritubular cells reached the adult aspect. The peritubular cells in the rat epididymis had aspects similar to those of peritubular smooth muscle cells of rat testis, with a more precocious appearance of cytoplasmic filaments. This finding concurs with the observed precocious contractility of epididymis.

  11. Myf5 and Myogenin in the development of thymic myoid cells - Implications for a murine in vivo model of myasthenia gravis.

    PubMed

    Hu, Bo; Simon-Keller, Katja; Küffer, Stefan; Ströbel, Philipp; Braun, Thomas; Marx, Alexander; Porubsky, Stefan

    2016-03-01

    Myasthenia gravis (MG) is caused by autoantibodies against the neuromuscular junction of striated muscle. Most MG patients have autoreactive T- and B-cells directed to the acetylcholine receptor (AChR). To achieve immunologic tolerance, developing thymocytes are normally eliminated after recognition of self-antigen-derived peptides. Presentation of muscle-specific antigens is likely achieved through two pathways: on medullary thymic epithelial cells and on medullary dendritic cells cross-presenting peptides derived from a unique population of thymic myoid cells (TMC). Decades ago, it has been hypothesized that TMC play a key role in the induction of immunological tolerance towards skeletal muscle antigens. However, an experimental model to address this postulate has not been available. To generate such a model, we tested the hypothesis that the development of TMC depends on myogenic regulatory factors. To this end, we utilized Myf5-deficient mice, which lack the first wave of muscle cells but form normal skeletal muscles later during development, and Myogenin-deficient mice, which fail to form differentiated myofibers. We demonstrate for the first time that Myf5- and Myogenin-deficient mice showed a partial or complete, respectively, loss of TMC in an otherwise regularly structured thymus. To overcome early postnatal lethality of muscle-deficient, Myogenin-knockout mice we transplanted Myogenin-deficient fetal thymuses into Foxn1(nu/nu) mice that lack their own thymus anlage. We found that the transplants are functional but lack TMC. In combination with established immunization strategies (utilizing AChR or Titin), this model should enable us in the future testing the hypothesis that TMC play an indispensable role in the development of central tolerance towards striated muscle antigens. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Human testicular peritubular cells secrete pigment epithelium-derived factor (PEDF), which may be responsible for the avascularity of the seminiferous tubules.

    PubMed

    Windschüttl, S; Kampfer, C; Mayer, C; Flenkenthaler, F; Fröhlich, T; Schwarzer, J U; Köhn, F M; Urbanski, H; Arnold, G J; Mayerhofer, A

    2015-09-03

    Male fertility depends on spermatogenesis, which takes place in the seminiferous tubules of the testis. This compartment is devoid of blood vessels, which are however found in the wall of the seminiferous tubules. Our proteomic study using cultured human testicular peritubular cells (HTPCs) i.e. the cells, which form this wall, revealed that they constitutively secrete pigment epithelium-derived factor, PEDF, which is known to exert anti-angiogenic actions. Immunohistochemistry supports its presence in vivo, in the human tubular wall. Co-culture studies and analysis of cell migration patterns showed that human endothelial cells (HUVECs) are repulsed by HTPCs. The factor involved is likely PEDF, as a PEDF-antiserum blocked the repulsing action. Thus testicular peritubular cells, via PEDF, may prevent vascularization of human seminiferous tubules. Dihydrotestosterone (DHT) increased PEDF (qPCR) in HTPCs, however PEDF expression in the testis of a non-human primate occurs before puberty. Thus PEDF could be involved in the establishment of the avascular nature of seminiferous tubules and after puberty androgens may further reinforce this feature. Testicular microvessels and blood flow are known to contribute to the spermatogonial stem cell niche. Hence HTPCs via control of testicular microvessels may contribute to the regulation of spermatogonial stem cells, as well.

  13. [Development and differentiation of the rat epididymis. II: histochemical aspects of the peritubular zone].

    PubMed

    Francavilla, F; Santiemma, V; Francavilla, S; Forcella, G; Moscardelli, S; Properzi, G

    1979-07-15

    Development of the contractile peritubular structures of rat testis, from birth to full maturation, was investigated by histochemical evaluation of alkaline phosphatase activity (A.P.A.) at 0, 16, 22 e 35 days of age. A.P.A. appeared at 6 days, age of appearance also of the cytoplasmic microfilaments of peritubular cells. The correlation between cytoplasmic microfilaments and A.P.A. was confirmed by the pattern of A.P.A. positivity at 6 degree day, when the inner peritubular cells layer, in which the microfilaments are present, are more positive than the outer layer in which the microfilaments are not yet present. These findings give further support to the belief that the cytoplasmic microfilaments of peritubular cells are contractile structures.

  14. Myoid Angioendothelioma of the Spleen: A Rare Case Report and Literature Review

    PubMed Central

    Geramizadeh, Bita; Anbardar, Mohammadhossein; Malekhosseini, Seyed-Ali

    2017-01-01

    Most common tumors of the spleen are hematologic and lymphoid malignancies. Non-lymphoid and non-hematologic tumors of the spleen are very rare, the most common of which are vascular tumors. This group of tumors in the spleen is composed of heterogeneous tumors such as hemangioma, angioendothelioma (AE), littoral cell angioma, and angiosarcoma. There are several histologic forms of AE such as epithelioid AE, Kaposiform AE, and myoid AE. Among these splenic vascular tumors, myoid angioendothelioma (MAE) seems to be the least common type. It is a distinct tumor; composed of endothelium-derived tumor cells and a special type of stromal tumor cells that seems to have borderline low-grade malignant potential. Herein, we report our experience with a young woman presented with chronic abdominal pain and splenic mass that turned out to be myoid AE of spleen with an uneventful surgery and excellent recovery period. To the best of our knowledge, such an occurrence is very rare in the spleen. PMID:28293056

  15. Peritubular capillaries: an important piece of the puzzle.

    PubMed

    Hohenstein, Bernd; Hugo, Christian

    2017-01-01

    The thorough investigation of peritubular capillary changes during renal fibrosis presented in this issue provides novel insights, not only into the value of elaborate methodological approaches, but also the necessity to carefully dissect pathophysiology using current techniques. This study strengthens the existing view of a uniform progression of renal fibrosis and is consistent with other recent studies pointing toward the relevance of early alterations of peritubular capillaries as initiators of renal fibrosis.

  16. Interrelationship among testicular cells in wall lizard Hemidactylus flaviviridis (Rüppell): an ultrastructural seasonal and experimental study.

    PubMed

    Khan, U W; Rai, Umesh

    2004-04-01

    The present study was aimed at investigating ultrastructure of different testicular cells and their interactions through various junctional specializations during different phases of reproductive cycle in wall lizard H. flaviviridis to develop an integrated approach of cell-cell interaction in control of testicular functions. Specialized steroid synthesizing cell organelles such as smooth endoplasmic reticulum (SER) and long slender mitochondria with tubulo-vesicular cristae were predominantly seen in Leydig as well as Sertoli cells during spermatogenically active phase, suggesting their active involvement in steroid biosynthesis. Peritubular cells also exhibited marked seasonal variations. Multi-layered fibroblast-like peritubular cells during regressed phase became single layered myoid-like during spermatogenically active phase. The presence of various types of junctions, including gap and tight junctions (occluding junctions) and adhering junctions such as desmosomes, septate-like junction, ectoplasmic specializations and tubulo-bulbar complexes, were demonstrated among testicular cells in wall lizard H. flaviviridis. However, the nature and degree of junctional (environmental) interaction varied with the reproductive state of the wall lizard. Further, administration of dihydrotestosterone in wall lizards during regressed phase resulted in increase of lipid droplets in Leydig cells and accumulation of germ cell debris in seminiferous tubules. Some of the Sertoli cells were seen darker in response to testosterone treatment probably due to its inhibitory effect on lipid metabolism. These results suggest that testosterone either directly or via inhibiting pituitary basal gonadotropin secretion has suppressive effect on testicular cells.

  17. Bovine and equine peritubular and intertubular dentin.

    PubMed

    Stock, S R; Deymier-Black, A C; Veis, A; Telser, A; Lux, E; Cai, Z

    2014-09-01

    Dentin contains 1-2μm diameter tubules extending from the pulp cavity to near the junction with enamel. Peritubular dentin (PTD) borders the tubule lumens and is surrounded by intertubular dentin (ITD). Differences in PTD and ITD composition and microstructure remain poorly understood. Here, a (∼200nm)(2), 10.1keV synchrotron X-ray beam maps X-ray fluorescence and X-ray diffraction simultaneously around tubules in 15-30μm thick bovine and equine specimens. Increased Ca fluorescence surrounding tubule lumens confirms that PTD is present, and the relative intensities in PTD and ITD correspond to carbonated apatite (cAp) volume fraction of ∼0.8 in PTD vs. 0.65 assumed for ITD. In the PTD near the lumen edges, Zn intensity is strongly peaked, corresponding to a Zn content of ∼0.9mgg(-1) for an assumed concentration of ∼0.4mgg(-1) for ITD. In the equine specimen, the Zn K-edge position indicates that Zn(2+) is present, similar to bovine dentin (Deymier-Black et al., 2013), and the above edge structure is consistent with spectra from macromolecules related to biomineralization. Transmission X-ray diffraction shows only cAp, and the 00.2 diffraction peak (Miller-Bravais indices) width is constant from ITD to the lumen edge. The cAp 00.2 average preferred orientation is axisymmetric (about the tubule axis) in both bovine and equine dentin, and the axisymmetric preferred orientation continues from ITD through the PTD to the tubule lumen. These data indicate that cAp structure does not vary from PTD to ITD.

  18. The peritubular reinforcement effect of porous dentine microstructure.

    PubMed

    Wang, Rong; Niu, Lin; Li, Qun; Liu, Qida; Zuo, Hong

    2017-01-01

    In the current study, we evaluate the equivalent stiffness of peritubular reinforcement effect (PRE) of porous dentine optimized by the thickness of peritubular dentine (PTD). Few studies to date have evaluated or quantitated the effect of PRE on composite dentine. The miscrostructure of porous dentine is captured by scanning electron microscope images, and then finite element modeling is used to quantitate the deformation and stiffness of the porous dentine structure. By optimizing the radius of PTD and dentine tubule (DT), the proposed FE model is able to demonstrate the effect of peritubular reinforcement on porous dentine stiffness. It is concluded that the dentinal equivalent stiffness is reduced and degraded with the increase of the radius of DT (i.e., porosity) in the certain ratio value of Ep/Ei and certain radius of PTD, where Ep is the PTD modulus and Ei is the intertubular dentine modulus. So in order to ensure the whole dentinal equivalent stiffness is not loss, the porosity should get some value while the Ep/Ei is certain. Thus, PTD prevents the stress concentration around DTs and reduces the risk of DTs failure. Mechanically, the overall role of PTD appears to enhance the stiffness of the dentine composite structure. These results provide some new and significant insights into the biological evolution of the optimal design for the porous dentine microstructure. These findings on the biological microstructure design of dentine materials are applicable to other engineering structural designs aimed at increasing the overall structural strength.

  19. The peritubular reinforcement effect of porous dentine microstructure

    PubMed Central

    Niu, Lin; Li, Qun; Liu, Qida; Zuo, Hong

    2017-01-01

    In the current study, we evaluate the equivalent stiffness of peritubular reinforcement effect (PRE) of porous dentine optimized by the thickness of peritubular dentine (PTD). Few studies to date have evaluated or quantitated the effect of PRE on composite dentine. The miscrostructure of porous dentine is captured by scanning electron microscope images, and then finite element modeling is used to quantitate the deformation and stiffness of the porous dentine structure. By optimizing the radius of PTD and dentine tubule (DT), the proposed FE model is able to demonstrate the effect of peritubular reinforcement on porous dentine stiffness. It is concluded that the dentinal equivalent stiffness is reduced and degraded with the increase of the radius of DT (i.e., porosity) in the certain ratio value of Ep/Ei and certain radius of PTD, where Ep is the PTD modulus and Ei is the intertubular dentine modulus. So in order to ensure the whole dentinal equivalent stiffness is not loss, the porosity should get some value while the Ep/Ei is certain. Thus, PTD prevents the stress concentration around DTs and reduces the risk of DTs failure. Mechanically, the overall role of PTD appears to enhance the stiffness of the dentine composite structure. These results provide some new and significant insights into the biological evolution of the optimal design for the porous dentine microstructure. These findings on the biological microstructure design of dentine materials are applicable to other engineering structural designs aimed at increasing the overall structural strength. PMID:28859165

  20. Peritubular capillary rarefaction: a new therapeutic target in chronic kidney disease

    PubMed Central

    Kida, Yujiro; Tchao, Bie Nga; Yamaguchi, Ikuyo

    2013-01-01

    Chronic kidney disease (CKD) is epidemic around the world and desparately needs new therapies. Peritubular capillary (PTC) rarefaction, along with interstitial fibrosis and tubular atorophy, is one of the major hallmarks of CKD and predicts renal outcome in patients with CKD. PTC endothelial cells (ECs) undergo apoptosis during CKD, leading to capillary loss, tissue hypoxia, and oxidant stress. Although the mechanisms of PTC rarefaction are not well understood, the process of PTC rarefaction depends on multiple events that happen during CKD. These events, which lead to an antiangiogenic environment, include deprivation of EC survival factors, increased production of vascular growth inhibitors, malfunction of ECs, dysfunction of endothelial progenitor cells, and loss of EC integrity via pericyte detachment from vasculature. In this review, we focus on major factors regulating angiogenesis and EC survival and describe roles of these factors in PTC rarefaction during CKD and possible therapeutic applications. PMID:23475077

  1. Hepatocyte growth factor-modulated rat Leydig cell functions.

    PubMed

    Del Bravo, Jessica; Catizone, Angela; Ricci, Giulia; Galdieri, Michela

    2007-01-01

    Hepatocyte growth factor (HGF) regulates many cellular functions acting through c-Met, its specific tyrosine kinase receptor. We previously reported that in prepuberal rats HGF is secreted by the peritubular myoid cells during the entire postnatal testicular development and by the Sertoli cells only at puberty. We have also demonstrated that germ cells at different stages of development express c-Met and that HGF modulates germ cell proliferation and apoptosis. In the present article, we extend our study to the interstitial compartment of the testis and demonstrate that the c-Met protein is present on Leydig cells. The receptor is functionally active as demonstrated by the detected effects of HGF. We report in this article that HGF significantly increases the amount of testosterone secreted by the Leydig cells and decreases the number of Leydig cells undergoing apoptosis. The antiapoptotic effect of HGF is mediated by caspase-3 activity because the amount of the active fragment of the enzyme is decreased in Leydig cells cultured in the presence of HGF. However, treatment with the growth factor does not modify the expression levels of caspase-3 mRNA. These data indicate that HGF regulates the functional activities of Leydig cells. Interestingly, the steroidogenetic activity of the cells is increased by HGF in cultured explants of testicular tissues as well as the antiapoptotic effect of HGF. Therefore, our data indicate that HGF has a crucial role in the regulation of male fertility.

  2. Role of distal reabsorption and peritubular environment in glomerulotubular balance.

    NASA Technical Reports Server (NTRS)

    Schrier, R. W.; Humphreys, M. H.

    1972-01-01

    Total kidney glomerulotubular balance was examined during aortic constriction and release in saline-loaded dogs and in dogs undergoing water diuresis. Aortic constriction lowered the glomerular filtration rate by 45% in both groups, and glomerulotubular balance, as judged by changes in absolute sodium reabsorption, was also comparable. During water diuresis, a linear relationship was observed between free water clearance and urine flow during all maneuvers, suggesting that distal sodium reabsorption is related primarily to distal delivery. The results suggest that if alterations in the peritubular environment are responsible for the changes in tubular sodium reabsorption during aortic constriction in the saline- or water-loaded dog, then a change in renal plasma flow, and presumably delivery rate of oncotic force, may be the most likely mediator.

  3. Relationship between tubular net sodium reabsorption and peritubular potassium uptake in the perfused Necturus kidney

    PubMed Central

    Giebisch, G.; Sullivan, L. P.; Whittembury, G.

    1973-01-01

    1. K influx from peritubular space into renal tubular cells, ϕiK, was measured in doubly perfused Necturus kidneys by studying tissue uptake of 42K added exclusively to the portal circulation. Concomitantly, net tubular Na reabsorption, ϕnNa, was measured by clearance techniques. ϕnNa and ϕiK were varied widely by replacing solutions of physiological composition (controls) with solutions containing high K, low K, low Na, cyclamate instead of Cl, ouabain (10-7-10-4 M) or ethacrynic acid (10-5-10-4 M). 2. The ratio of ϕnNa to ϕiK was found to vary with the experimental conditions, the control value of about 2 was maintained over a threefold variation in absolute Na reabsorption. This ratio increased with low K or ouabain to values near 4. With high K, ethacrynic acid, low Na or cyclamate the relationship was one or lower. Thus, net Na reabsorption can be uncoupled from peritubular K influx. 3. These results can be best explained if there are two Na pumps working in parallel: pump A transporting Na (with Cl) and pump B, a Na-for-K-exchange pump. The ratio of Na efflux to K influx could approach ∞ if only pump A works (if B is inhibited) and could approach one if only B works. It should vary between these limits in controls when both pumps are active, or when neither of the two pumps is completely inhibited. 4. Alternatively, the experimental findings could be explained by a Na pump with a coupling ratio that varies within two extreme values, from high Na-K ratios (with Na reabsorption at, or near, control values but with very low K influx values) to low ratios (with normal K influx values but with low Na reabsorption values). PMID:4702444

  4. Immunocytochemical localization of taurine in different muscle cell types of the dog and rat.

    PubMed

    Lobo, M V; Alonso, F J; Martin del Rio, R

    2000-01-01

    The presence and distribution of the amino acid taurine in different muscle cell types of the dog and rat was examined by immunocytochemical methods. The light microscope study revealed that smooth muscle cells were similarly immunoreactive for taurine, whereas skeletal muscle fibres showed wide differences in taurine immunoreactivity among individual cells. Some skeletal fibres were strongly immunoreactive whereas others did not display immunolabelling. Mononucleated satellite cells, found adjacent to skeletal fibres in a quiescent stage, were also immunostained. Other myoid cells, such as testicular peritubular cells showed a cytoplasmic and a nuclear pool of taurine. By means of electron microscope immunolabelling, the subcellular localization of taurine was studied in vascular and visceral smooth muscle cells. Taurine was present in most subcellular compartments and frequently appeared randomly distributed. Taurine was localized on myofilaments, dense bodies, mitochondria, the plasma membrane and the cell nucleus. Moreover, the labelling density within individual smooth muscle cells was variable and depended on the state of contraction of each single fibre. Contracted cells showed a higher density of gold particles than relaxed cells. Unmyelinated nerve fibres, found adjacent to smooth muscle cells from the muscularis mucosae and the lamina propria of the stomach, were unstained or poorly stained.

  5. Changes in levels of plasminogen activator activity in normal and germ-cell-depleted testes during development.

    PubMed

    Lacroix, M; Smith, F E; Fritz, I B

    1982-05-01

    Levels of plasminogen activator activity were determined in testes obtained from normal and irradiated rats in various ages. During normal development, plasminogen activator activity per g testis increased rapidly between 40 and 60 days of age, but a comparable rise did not occur in germ-cell depleted testes of irradiated rats. Levels of enzyme in various populations of testicular cells were highest in Sertoli (varying between 1800 and 6300 units/mg protein in cell maintained under different culture conditions), and lowest in peritubular myoid cells (about 1 unit/mg protein), with intermediate levels in germinal cells (ranging between 147 and 560 units/Mg protein in residual bodies, spermatocytes and spermatids). No protease inhibitor could be detected in germ-cell extracts. The addition to the medium in which Sertoli cells were in culture of particles which can be phagocytosed (autoclaved E. coli) resulted in an increased formation of plasminogen activator activity by Sertoli cells. A synergistic enhancement of enzyme production resulted following the addition of submaximal quantities of dibutyryl cyclic AMP and autoclaved bacteria to sertoli cells in culture. On the basis of these data, we suggest that the presence of advanced germinal cells during gonadal development may stimulate the synthesis of plasminogen activator by Sertoli cells, mediated in part by the phagocytosis of residual bodies by sertoli cells which occurs prior to spermiation.

  6. A 24,500 Da protein derived from rat germ cells is associated with sertoli cell secretory function.

    PubMed

    Onoda, M; Djakiew, D

    1993-12-15

    A function and identify of a 24,500 Da protein derived from round spermatids of the rat testis was investigated with a specific polyclonal antiserum raised against RSP-24.5. The proteins released from cultured round spermatids significantly stimulated the secretion of de novo synthesized protein from cultured immature rat Sertoli cells 2.4-fold above control levels. Immunoprecipitation of RSP-24.5 from round spermatid protein further enhanced the stimulation of Sertoli cell protein secretion up to 3.1-fold above control levels, indicating that RSP-24.5 plays a role in the down regulation of Sertoli cell secretion. The antiserum recognized the 24,500 Da protein in Western blots of round spermatid protein, pachytene spermatoctye protein, Sertoli cell lysate and peritubular myoid cell lysate. A 40 amino acid sequence of a cyanogen bromide cleaved internal fragment of RSP-24.5 showed 80.5% homology to a phosphatidylethanolamine binding protein. These results suggest that phosphatidylethanolamine binding protein participates in the negative regulation of Sertoli cell secretory function during spermatogenesis.

  7. Tubulointerstitial immune complex nephritis in a patient with systemic lupus erythematosus: role of peritubular capillaritis with immune complex deposits in the pathogenesis of the tubulointerstitial nephritis.

    PubMed

    Hayakawa, Satoshi; Nakabayashi, Kimimasa; Karube, Miho; Arimura, Yoshihiro; Arimura, Yoshiro; Soejima, Akinori; Yamada, Akira; Fujioka, Yasunori

    2006-06-01

    Class IV-G (A/C) diffuse lupus nephritis and tubulointerstitial (TI) nephritis in a 31-year old woman was studied by light, immunofluorescence (IF), and electron microscopy (EM), to determine the pathogenesis of the TI lesions. The light microscopic findings showed peritubular capillaritis in the interstitium, with ruptures in the capillary structure, lysis of the surrounding tubular basement membrane (TBM), extravasated red blood cells (RBCs), the infiltration of neutrophils and mononuclear cells, and edema. The IF study revealed IgG, IgA, IgM, C1q, C3, and C4 depositions along the TBM, on the capillary walls, and in the interstitium proper. The EM study disclosed the deposition of immune complexes in the TBM, the capillary wall, and the interstitium proper. Based on these findings, the TI nephritis in this patient was considered to be due to peritubular capillaritis secondary to the immune complex depositions in the capillary wall of the interstitium.

  8. Cimetidine-induced vascular cell apoptosis impairs testicular microvasculature in adult rats.

    PubMed

    Beltrame, Flávia L; Yamauti, Caroline T; Caneguim, Breno H; Cerri, Paulo S; Miraglia, Sandra M; Sasso-Cerri, Estela

    2012-10-01

    Cimetidine, an H₂ receptor antagonist used for treatment of gastric ulcers, exerts antiandrogenic and antiangiogenic effects. In the testes cimetidine impairs spermatogenesis, Sertoli cells and peritubular tissue, inducing apoptosis in the myoid cells. Regarding the importance of histamine and androgens for vascular maintenance, the effect of cimetidine on the structural integrity of the testicular vasculature was evaluated. Adult male rats received cimetidine (CMTG) and saline (CG) for 50 days. The testes were fixed in buffered 4% formaldehyde and embedded in historesin and paraffin. In the PAS-stained sections, the microvascular density (MVD) and the vascular luminal area (VLA) were obtained. TUNEL method was performed for detection of cell death. Testicular fragments embedded in Araldite were analyzed under transmission electron microscopy. A significant decrease in the MVD and VLA and a high number of collapsed blood vessel profiles were observed in CMTG. Endothelial cells and vascular muscle cells were TUNEL-positive and showed ultrastructural features of apoptosis. These results indicate that cimetidine induces apoptosis in vascular cells, leading to testicular vascular atrophy. A possible antagonist effect of cimetidine on the H₂ receptors and/or androgen receptors in the vascular cells may be responsible for the impairment of the testicular microvasculature.

  9. Pharmacological targets in the renal peritubular microenvironment: implications for therapy for sepsis-induced acute kidney injury

    PubMed Central

    Mayeux, Philip R.; MacMillan-Crow, Lee Ann

    2012-01-01

    One of the most frequent and serious complications to develop in septic patients is acute kidney injury (AKI), a disorder characterized by a rapid failure of the kidneys to adequately filter the blood, regulate ion and water balance, and generate urine. AKI greatly worsens the already poor prognosis of sepsis and increases cost of care. To date, therapies have been mostly supportive; consequently there has been little change in the mortality rates over the last decade. This is due, at least in part, to the delay in establishing clinical evidence of an infection and the associated presence of the systemic inflammatory response syndrome and thus, a delay in initiating therapy. A second reason is a lack of understanding regarding the mechanisms leading to renal injury, which has hindered the development of more targeted therapies. In this review, we summarize recent studies, which have examined the development of renal injury during sepsis and propose how changes in the peritubular capillary microenvironment lead to and then perpetuate microcirculatory failure and tubular epithelial cell injury. We also discuss a number of potential therapeutic targets in the renal peritubular microenvironment, which may prevent or lessen injury and/or promote recovery. PMID:22274552

  10. Characterization and functionality of proliferative human Sertoli cells.

    PubMed

    Chui, Kitty; Trivedi, Alpa; Cheng, C Yan; Cherbavaz, Diana B; Dazin, Paul F; Huynh, Ai Lam Thu; Mitchell, James B; Rabinovich, Gabriel A; Noble-Haeusslein, Linda J; John, Constance M

    2011-01-01

    It has long been thought that mammalian Sertoli cells are terminally differentiated and nondividing postpuberty. For most previous in vitro studies immature rodent testes have been the source of Sertoli cells and these have shown little proliferative ability when cultured. We have isolated and characterized Sertoli cells from human cadaveric testes from seven donors ranging from 12 to 36 years of age. The cells proliferated readily in vitro under the optimized conditions used with a doubling time of approximately 4 days. Nuclear 5-ethynyl-2'-deoxyuridine (EdU) incorporation confirmed that dividing cells represented the majority of the population. Classical Sertoli cell ultrastructural features, lipid droplet accumulation, and immunoexpression of GATA-4, Sox9, and the FSH receptor (FSHr) were observed by electron and fluorescence microscopy, respectively. Flow cytometry revealed the expression of GATA-4 and Sox9 by more than 99% of the cells, and abundant expression of a number of markers indicative of multipotent mesenchymal cells. Low detection of endogenous alkaline phosphatase activity after passaging showed that few peritubular myoid cells were present. GATA-4 and SOX9 expression were confirmed by reverse transcription polymerase chain reaction (RT-PCR), along with expression of stem cell factor (SCF), glial cell line-derived neurotrophic factor (GDNF), and bone morphogenic protein 4 (BMP4). Tight junctions were formed by Sertoli cells plated on transwell inserts coated with fibronectin as revealed by increased transepithelial electrical resistance (TER) and polarized secretion of the immunoregulatory protein, galectin-1. These primary Sertoli cell populations could be expanded dramatically in vitro and could be cryopreserved. The results show that functional human Sertoli cells can be propagated in vitro from testicular cells isolated from adult testis. The proliferative human Sertoli cells should have important applications in studying infertility

  11. Starvation is more efficient than the washing technique for purification of rat Sertoli cells.

    PubMed

    Ghasemzadeh-Hasankolaei, Mohammad; Eslaminejad, Mohamadreza Baghaban; Sedighi-Gilani, Mohammadali; Mokarizadeh, Aram

    2014-09-01

    Sertoli cells (SCs), one of the most important components of seminiferous tubules, are vital for normal spermatogenesis and male fertility. In recent years, numerous in vitro studies have shown the potential and actual activities of SCs. However, pure SCs are necessary for various in vitro studies. In this study, we have evaluated the efficiency of the starvation method for SC purification as compared with the washing method. Seminiferous tubule-derived cells (STDCs) of rats' testes underwent two different techniques for SC purification. In the first group (washing group), the medium was changed every 3-4 d, and cells were washed twice with phosphate-buffered saline that lacked CaC12 and MgSO4 (PBS(-)) before the addition of fresh medium. In the second group (starvation), the medium was changed every 7-8 d. Primary culture (P0), passage 1 (P1), and passage 2 (P2) cells were analyzed for the expression of SC-specific genes, vimentin, Wilm's tumor 1 (WT1), germ cell gene (vasa), Leydig cell marker, 17beta-hydroxysteroid dehydrogenase type 3 (Hsd17b3), and a marker of peritubular myoid cells, alpha smooth muscle actin (αSma), by reverse transcriptase polymerase chain reaction (RT-PCR) and real-time RT-PCR. Gene expression analysis showed that P0 cells expressed all tested genes except Hsd17b3. The starvation method caused significant downregulation of vasa and αSma expression in P0, P1, and P2 cells, whereas vimentin and WT1 were upregulated. In contrast, the washing method was less effective than the starvation method for the removal of germ and pretubular myoid cells (p < 0.001). Totally, the results have revealed that although washing is the only common technique for elimination of contaminant cells in SC cultures, starvation has a stronger effect and is a suitable, affordable technique for SC purification. We propose that starvation is an efficient, inexpensive method that can be used for purification of SCs in animal species.

  12. Decreased dentin tubules density and reduced thickness of peritubular dentin in hyperbilirubinemia-related green teeth

    PubMed Central

    Neves-Silva, Rodrigo; Alves, Fabio-Abreu; Antunes, Alberto; Goes, Mario-Fernando; Giannini, Marcelo; Tenório, Maria-Dânia; Machado, José-Lécio; Paes-Leme, Adriana-Franco; Lopes, Marcio-Ajudarte

    2017-01-01

    Background It is stated anecdotally that patients with liver diseases in childhood who develop green teeth have increased risk for rampant caries, which may be secondary to changes in dental structure. The aim of this study was to test the hypothesis that hyperbilirubinemia affects the dentin morphology of green teeth. Material and Methods Sixteen primary teeth were prepared and divided into two groups (green teeth, n = 8 and control, n = 8), which were transversely fractured across the cervical third of the dental crowns; dentin was prepared and sputter-coated with gold, and examined under a scanning electron microscope. The mean density and mean diameter of dentin tubules, as well as the thickness of peritubular dentin, were compared. Results Hyperbilirubinemia was associated with a decrease in the density of the dentin tubules (p< .01) and the thickness of peritubular dentin of green teeth (p< .01). Conclusions There was a correlation between childhood hyperbilirubinemia and changes in the dentin morphology, including a decrease in the density of the dentin tubules and a reduction in the thickness of peritubular dentin in green teeth. Key words:Hyperbilirubinemia, liver disease, childhood, dentin tubules, human teeth, scanning electron microscopy. PMID:28512537

  13. Importance of age on the dynamic mechanical behavior of intertubular and peritubular dentin.

    PubMed

    Ryou, Heonjune; Romberg, Elaine; Pashley, David H; Tay, Franklin R; Arola, Dwayne

    2015-02-01

    An experimental evaluation of human coronal dentin was performed using nanoscopic dynamic mechanical analysis (nanoDMA). The primary objectives were to quantify any unique changes in mechanical behavior of intertubular and peritubular dentin with age, and to evaluate the microstructure and mechanical behavior of the mineral deposited within the lumens. Specimens of coronal dentin were evaluated by nanoDMA using single indents and in scanning mode via scanning probe microscopy. Results showed that there were no significant differences in the storage modulus or complex modulus between the two age groups (18-25 versus 54-83 yrs) for either the intertubular or peritubular tissue. However, there were significant differences in the dampening behavior between the young and old dentin, as represented in the loss modulus and tanδ responses. For both the intertubular and peritubular components, the capacity for dampening was significantly lower in the old group. Scanning based nanoDMA showed that the tubules of old dentin exhibit a gradient in elastic behavior, with decrease in elastic modulus from the cuff to the center of tubules filled with newly deposited mineral. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Importance of Age on the Dynamic Mechanical Behavior of Intertubular and Peritubular Dentin

    PubMed Central

    Ryou, Heonjune; Romberg, Elaine; Pashley, David H.; Tay, Franklin R.; Arola, Dwayne

    2014-01-01

    An experimental evaluation of human coronal dentin was performed using nanoscopic Dynamic Mechanical Analysis (nanoDMA). The primary objectives were to quantify any unique changes in mechanical behavior of intertubular and peritubular dentin with age, and to evaluate the microstructure and mechanical behavior of the mineral deposited within the lumens. Specimens of coronal dentin were evaluated by nanoDMA using single indents and in scanning mode via scanning probe microscopy. Results showed that there were no significant differences in the storage modulus or complex modulus between the two age groups (18–25 versus 54–83 yrs) for either the intertubular or peritubular tissue. However, there were significant differences in the dampening behavior between the young and old dentin, as represented in the loss modulus and tanδ responses. For both the intertubular and peritubular components, the capacity for dampening was significantly lower in the old group. Scanning based nanoDMA showed that the tubules of old dentin exhibit a gradient in elastic behavior, with decrease in elastic modulus from the cuff to the center of tubules filled with newly deposited mineral. PMID:25498296

  15. Hormonal control of germ cell development and spermatogenesis.

    PubMed

    O'Shaughnessy, Peter J

    2014-05-01

    Spermatogenesis is completely dependent on the pituitary hormone follicle-stimulating hormone (FSH) and androgens locally produced in response to luteinising hormone (LH). This dual control has been known since the 1930s and 1940s but more recent work, particularly using transgenic mice, has allowed us to determine which parts of the spermatogenic pathway are regulated by each hormone. During the first spermatogenic cycle after puberty both FSH and androgen act to limit the massive wave of germ cell apoptosis which occurs at this time. The established role of FSH in all cycles is to increase spermatogonial and subsequent spermatocyte numbers with a likely effect also on spermiation. Mice lacking FSH or its receptor are fertile, albeit with reduced germ cell numbers, and so this hormone is not an essential regulator of spermatogenesis but acts to optimise germ cell production Androgens also appear to regulate spermatogonial proliferation but, crucially, they are also required to allow spermatocytes to complete meiosis and form spermatids. Animals lacking androgen receptors fail to generate post-meiotic germ cells, therefore, and are infertile. There is also strong evidence that androgens act to ensure appropriate spermiation of mature spermatids. Androgen regulation of spermatogenesis is dependent upon action on the Sertoli cell but recent studies have shown that androgenic stimulation of the peritubular myoid cells is also essential for normal germ cells development. While FSH or androgen alone will both stimulate germ cell development, together they act synergistically to maximise germ cell number. The other hormones/local factors which can regulate spermatogenesis include activins and estrogens although their role in normal physiological regulation of this process needs to be more clearly established. Regulation of spermatogenesis in primates appears to be similar to that in rodents although the role of FSH may be greater. While our knowledge of hormone function

  16. Identification and regulation of receptor tyrosine kinases Rse and Mer and their ligand Gas6 in testicular somatic cells.

    PubMed

    Chan, M C; Mather, J P; McCray, G; Lee, W M

    2000-01-01

    Receptor tyrosine kinases act to convey extracellular signals to intracellular signaling pathways and ultimately control cell proliferation and differentiation. Rse, Axl, and Mer belong to a newly identified family of cell adhesion molecule-related receptor tyrosine kinase. They bind the vitamin K-dependent protein growth arrest-specific gene 6 (Gas6), which is also structurally related to the anticoagulation factor Protein S. The aim of this study is to investigate the possible role of Rse/Axl/Mer tyrosine kinase receptors and their ligand in regulating testicular functions. Gene expression of Rse, Axl, Mer, and Gas6 in the testis was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot analysis. The results indicated that receptors Rse and Mer and the ligand Gas6 were expressed in the rat endothelial cell line (TR1), mouse Leydig cell line (TM3), rat peritubular myoid cell line (TRM), mouse Sertoli cell line (TM4), and primary rat Sertoli cells. Axl was not expressed in the testicular somatic cells by RT-PCR or Northern blot analysis. The highest level of expression of Gas6 messenger RNA (mRNA) was observed in the Sertoli cells, and its expression was responsive to the addition of forskolin in vitro. The effects of serum, insulin, and transferrin on Gas6 expression by TM4 cells were examined. It was shown that they all exhibited an up-regulating effect on Gas6 expression. The forskolin-stimulated Gas6 expression was accompanied by an increase in tyrosine phosphorylation of the Rse receptor in vitro, suggesting that Gas6 may exhibit an autocrine effect in the Sertoli cells through multiple tyrosine kinase receptors. Our studies so far have demonstrated that tyrosine kinase receptors Rse and Mer and their ligand Gas6 are widely expressed in the testicular somatic cell lines and may play a marked role in promoting testicular cell survival.

  17. A 29,000 M(r) protein derived from round spermatids regulates Sertoli cell secretion.

    PubMed

    Onoda, M; Djakiew, D

    1993-05-01

    Within the last decade it has become accepted that germ cells can modulate Sertoli cell function in a paracrine interactive manner during the regulation of spermatogenesis. In this context, we undertook to identify a specific factor in round spermatid conditioned media that could stimulate Sertoli cell secretory function. Rat round spermatids isolated by centrifugal elutriation were cultured and the concentrated conditioned media were fractionated by Sephacryl S-200 gel filtration column chromatography. The biological activity of the fractionated round spermatid protein was assessed as stimulation of total protein and transferrin secretion from Sertoli cells that had been isolated from 18-day-old immature rat testes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the gel-filtration fractions showed two predominant proteins of 29,000 and 24,500 molecular weight which coexisted in the fractions containing the greatest biological activity. These two proteins were transferred to a nitrocellulose membrane and excised to raise polyclonal antibodies. Western blot analysis of the 29,000 M(r) protein demonstrated that it specifically occurred in round spermatid conditioned media, whereas no immunoreactive band was observed in either the conditioned media or cell lysates of other testicular cell types such as primary spermatocytes, Sertoli cells and peritubular myoid cells. Following subcellular fractionation of round spermatids by differential centrifugation, the 29,000 M(r) protein was detected by Western blots specifically in the cytosolic fraction of round spermatids, and was absent from the nuclear, mitochondrial, lysosomal and microsomal fractions. The antibody did recognize a few higher molecular bands in the cytosolic fraction which may represent precursor forms of the 29,000 M(r) protein.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. The spermatogonial stem cell niche in the collared peccary (Tayassu tajacu).

    PubMed

    Campos-Junior, Paulo Henrique A; Costa, Guilherme M J; Lacerda, Samyra M S N; Rezende-Neto, José V; de Paula, Ana M; Hofmann, Marie-Claude; de França, Luiz R

    2012-05-01

    In the seminiferous epithelium, spermatogonial stem cells (SSCs) are located in a particular environment called the "niche" that is controlled by the basement membrane, key testis somatic cells, and factors originating from the vascular network. However, the role of Leydig cells (LCs) as a niche component is not yet clearly elucidated. Recent studies showed that peccaries (Tayassu tajacu) present a peculiar LC cytoarchitecture in which these cells are located around the seminiferous tubule lobes, making the peccary a unique model for investigating the SSC niche. This peculiarity allowed us to subdivide the seminiferous tubule cross-sections in three different testis parenchyma regions (tubule-tubule, tubule-interstitium, and tubule-LC contact). Our aims were to characterize the different spermatogonial cell types and to determine the location and/or distribution of the SSCs along the seminiferous tubules. Compared to differentiating spermatogonia, undifferentiated spermatogonia (A(und)) presented a noticeably higher nuclear volume (P < 0.05), allowing an accurate evaluation of their distribution. Immunostaining analysis demonstrated that approximately 93% of A(und) were GDNF receptor alpha 1 positive (GFRA1(+)), and these cells were preferentially located adjacent to the interstitial compartment without LCs (P < 0.05). The expression of colony-stimulating factor 1 was observed in LCs and peritubular myoid cells (PMCs), whereas its receptor was present in LCs and in GFRA1(+) A(und). Taken together, our findings strongly suggest that LCs, different from PMCs, might play a minor role in the SSC niche and physiology and that these steroidogenic cells are probably involved in the differentiation of A(und) toward type A(1) spermatogonia.

  19. Insights into the structure and composition of the peritubular dentin organic matrix and the lamina limitans.

    PubMed

    Bertassoni, Luiz Eduardo; Stankoska, Katerina; Swain, Michael Vincent

    2012-02-01

    Dentin is a mineralized dental tissue underlying the outer enamel that has a peculiar micro morphology. It is composed of micrometer sized tubules that are surrounded by a highly mineralized structure, called peritubular dentin (PTD), and embedded in a collagen-rich matrix, named intertubular dentin. The PTD has been thought to be composed of a highly mineralized collagen-free organic matrix with unknown composition. Here we tested the hypothesis that proteoglycans and glycosaminoglycans, two important organic structural features found in dentin, are key participants in the microstructure and composition of the PTD. To test this hypothesis dentin blocks were demineralized with 10 vol% citric acid for 2 min and either digested with 1mg/ml TPCK-treated trypsin with 0.2 ammonium bicarbonate at pH 7.9 (TRY) or 0.1 U/mL C-ABC with 50mM Tris, 60mM sodium acetate and 0.02% bovine serum albumin at pH 8.0 (C-ABC). TRY is known to cleave the protein core of dentin proteoglycans, whereas C-ABC is expected to selectively remove glycosaminoglycans. All specimens were digested for 48 h in 37°C, dehydrated in ascending grades of acetone, immersed in HMDS, platinum coated and imaged using an FE-SEM. Images of demineralized dentin revealed a meshwork of noncollagenous fibrils protruding towards the tubule lumen following removal of the peritubular mineral and confirmed the lack of collagen in the peritubular matrix. Further, images revealed that the peritubular organic network originates from a sheet-like membrane covering the entire visible length of tubule, called lamina limitans. Confirming our initial hypothesis, after the digestion with C-ABC the organic network appeared to vanish, while the lamina limitans was preserved. This suggests that glycosaminoglycans are the main component of the PTD organic network. Following digestion with TRY, both the organic network and the lamina limitans disappeared, thus suggesting that the lamina limitans may be primarily composed of

  20. Young's modulus of peritubular and intertubular human dentin by nano-indentation tests.

    PubMed

    Ziskind, Daniel; Hasday, Moran; Cohen, Sidney R; Wagner, H Daniel

    2011-04-01

    The local Young modulus of dry dentin viewed as a hierarchical composite was measured by nano-indentation using two types of experiments, both in a continuous stiffness measurement mode. First, tests were performed radially along straight lines running across highly mineralized peritubular dentin sections and through less mineralized intertubular dentin areas. These tests revealed a gradual decrease in Young's modulus from the bulk of the peritubular dentin region where modulus values of up to ∼40-42GPa were observed, down to approximately constant values of ∼17GPa in the intertubular dentin region. A second set of nano-indentation experiments was performed on the facets of an irregular polyhedron specimen cut from the intertubular dentin region, so as to probe the modulus of intertubular dentin specimens at different orientations relative to the tubular direction. The results demonstrated that the intertubular dentin region may be considered to be quasi-isotropic, with a slightly higher modulus value (∼22GPa) when the indenting tip axis is parallel to the tubular direction, compared to the values (∼18GPa) obtained when the indenting tip axis is perpendicular to the tubule direction.

  1. A Model of Peritubular Capillary Control of Isotonic Fluid Reabsorption by the Renal Proximal Tubule

    PubMed Central

    Deen, W. M.; Robertson, C. R.; Brenner, B. M.

    1973-01-01

    A mathematical model of peritubular transcapillary fluid exchange has been developed to investigate the role of the peritubular environment in the regulation of net isotonic fluid transport across the mammalian renal proximal tubule. The model, derived from conservation of mass and the Starling transcapillary driving forces, has been used to examine the quantitative effects on proximal reabsorption of changes in efferent arteriolar protein concentration and plasma flow rate. Under normal physiological conditions, relatively small perturbations in protein concentration are predicted to influence reabsorption more than even large variations in plasma flow, a prediction in close accord with recent experimental observations in the rat and dog. Changes either in protein concentration or plasma flow have their most pronounced effects when the opposing transcapillary hydrostatic and osmotic pressure differences are closest to equilibrium. Comparison of these theoretical results with variations in reabsorption observed in micropuncture studies makes it possible to place upper and lower bounds on the difference between interstitial oncotic and hydrostatic pressures in the renal cortex of the rat. PMID:4696761

  2. Antibodies directed against antigens on the endothelium of peritubular capillaries in patients with rejecting renal allografts.

    PubMed

    Paul, L C; van Es, L A; van Rood, J J; van Leeuwen, A; de la Rivière, G B; de Graeff, J

    1979-03-01

    This study was undertaken to examine the humoral immune response against endothelial antigens of the donor kidney in human renal allograft recipients. Sera from 61 transplant recipients who received 62 grafts were studied for the presence of circulating endothelial antibodies (CEAb) using an indirect immunofluorescence technique with a pretransplant biopsy of the graft as a substrate. IgG antibodies directed against the endothelium of peritubular capillaries were found in the sera of 6 of the 10 patients with graft rejection within 7 weeks after transplantation, whereas these antibodies were not found in the absence of rejection (P less than 0.001). Immunofluorescence studies of post-transplant biopsies showed IgG along the endothelium of peritubular capillaries only in the grafts of patients with CEAb. Eluates from these grafts contained IgG antibodies that bound to the endothelium of the donor as shown by the indirect immunofluorescence technique. Absorption of endothelial antibody (EAb)-positive sera with human platelets or Wistar strain rat erythrocytes showed that the EAb were not directed against serologically defined HLA antigens or against heterophile antigens on rat erythrocytes. We conclude from this study that the presence of antibodies directed against endothelial antigens is associated with poor graft prognosis and that these antibodies may be responsible for the rejection process.

  3. Reconstruction of a seminiferous tubule-like structure in a 3 dimensional culture system of re-aggregated mouse neonatal testicular cells within a collagen matrix.

    PubMed

    Zhang, Jidong; Hatakeyama, Jun; Eto, Ko; Abe, Shin-Ichi

    2014-09-01

    Male gonad development is initiated by the aggregation of pre-Sertoli cells (SCs), which surround germ cells to form cords. Several attempts to reconstruct testes from dissociated testicular cells have been made; however, only very limited morphogenesis beyond seminiferous cord formation has been achieved. Therefore, we aimed to reconstruct seminiferous tubules using a 3-dimensional (D) re-aggregate culture of testicular cells, which were dissociated from 6-dpp neonatal mice, inside a collagen matrix. We performed a short-term culture (for 3 days) and a long-term culture (up to 3 wks). The addition of KnockOut Serum Replacement (KSR) promoted (1) the enlargement of SC re-aggregates; (2) the attachment of peritubular myoid (PTM) cells around the SC re-aggregates; (3) the sorting of germ cells inside, and Leydig cells outside, seminiferous cord-like structures; (4) the alignment of SC polarity inside a seminiferous cord-like structure relative to the basement membrane; (5) the differentiation of SCs (the expression of the androgen receptor); (6) the formation of a blood-testis-barrier between the SCs; (7) SC elongation and lumen formation; and (8) the proliferation of SCs and spermatogonia, as well as the differentiation of spermatogonia into primary spermatocytes. Eventually, KSR promoted the formation of seminiferous tubule-like structures, which accompanied germ cell differentiation. However, these morphogenetic events did not occur in the absence of KSR. This in vitro system presents an excellent model with which to identify the possible factors that induce these events and to analyze the mechanisms that underlie cellular interactions during testicular morphogenesis and germ cell differentiation. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. The nuclear receptor NR2F2 activates star expression and steroidogenesis in mouse MA-10 and MLTC-1 Leydig cells.

    PubMed

    Mendoza-Villarroel, Raifish E; Robert, Nicholas M; Martin, Luc J; Brousseau, Catherine; Tremblay, Jacques J

    2014-07-01

    Testosterone production is dependent on cholesterol transport within the mitochondrial matrix, an essential step mediated by a protein complex containing the steroidogenic acute regulatory (STAR) protein. In steroidogenic Leydig cells, Star expression is hormonally regulated and involves several transcription factors. NR2F2 (COUP-TFII) is an orphan nuclear receptor that plays critical roles in cell differentiation and lineage determination. Conditional NR2F2 knockout prior to puberty leads to male infertility due to insufficient testosterone production, suggesting that NR2F2 could positively regulate steroidogenesis and Star expression. In this study we found that NR2F2 is expressed in the nucleus of some peritubular myoid cells and in interstitial cells, mainly in steroidogenically active adult Leydig cells. In MA-10 and MLTC-1 Leydig cells, small interfering RNA (siRNA)-mediated NR2F2 knockdown reduces basal steroid production without affecting hormone responsiveness. Consistent with this, we found that STAR mRNA and protein levels were reduced in NR2F2-depleted MA-10 and MLTC-1 cells. Transient transfections of Leydig cells revealed that a -986 bp mouse Star promoter construct was activated 3-fold by NR2F2. Using 5' progressive deletion constructs, we mapped the NR2F2-responsive element between -131 and -95 bp. This proximal promoter region contains a previously uncharacterized direct repeat 1 (DR1)-like element to which NR2F2 is recruited and directly binds. Mutations in the DR1-like element that prevent NR2F2 binding severely blunted NR2F2-mediated Star promoter activation. These data identify an essential role for the nuclear receptor NR2F2 as a direct activator of Star gene expression in Leydig cells, and thus in the control of steroid hormone biosynthesis.

  5. Peritubular capillary changes in alport syndrome, diabetic glomerulopathy, Balkan endemic nephropathy and hemorrhagic fever with renal syndrome.

    PubMed

    Hvala, Anastazija; Ferluga, Dusan; Rott, Tomaz; Kobenter, Tatjana; Koselj-Kajtna, Mira; Trnacević, Seneid

    2005-01-01

    The morphology of peritubular capillary has been mostly studied in relation to chronic transplant rejection, where an association has been found between transplant glomerulopathy and reduplication of peritubular capillary basement membranes (PCBM). This electron microscopy study of peritubular capillaries was done on kidney biopsies performed on patients with conditions involving primarily glomeruli (diabetic glomerulopathy (23), Alport syndrome (37)) or causing more or less isolated changes of nephron structures outside the glomeruli (Balkan endemic nephropathy (15) and hemorrhagic fever with renal syndrome (19)). The aim was to explore the ultrastructural features of the PCBM. In patients with diabetic glomerulopathy, the PCBM was homogeneous, with a width ranging from normal to evidently increased (55-355 nm). In patients with Alport syndrome, the PCBM was homogeneous, with no substantial splitting or prominent thickening. Mean thickness varied between 80 (85-100) nm in children and 120 (46-250) nm in adults. Mean PCBM thickness in patients with Balkan endemic nephropathy was 209 (90-1270) nm. The thickened PCBM was also often split. In patients with hemorrhagic fever with renal syndrome, peritubular capillaries and medular vasa recta were generally extremely congested and focally ruptured, and their basal lamina showed prevailing thinning and focal discontinuities.

  6. Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes.

    PubMed

    Li, Shuyi; Shu, Feng-Jue; Li, Zhentian; Jaafar, Lahcen; Zhao, Shourong; Dynan, William S

    2017-03-01

    The tandem RNA recognition motif protein, NONO, was previously identified as a candidate DNA double-strand break (DSB) repair factor in a biochemical screen for proteins with end-joining stimulatory activity. Subsequent work showed that NONO and its binding partner, SFPQ, have many of the properties expected for bona fide repair factors in cell-based assays. Their contribution to the DNA damage response in intact tissue in vivo has not, however, been demonstrated. Here we compare DNA damage sensitivity in the testes of wild-type mice versus mice bearing a null allele of the NONO homologue (Nono (gt)). In wild-type mice, NONO protein was present in Sertoli, peritubular myoid, and interstitial cells, with an increase in expression following induction of DNA damage. As expected for the product of an X-linked gene, NONO was not detected in germ cells. The Nono (gt/0) mice had at most a mild testis developmental phenotype in the absence of genotoxic stress. However, following irradiation at sublethal, 2-4 Gy doses, Nono (gt/0) mice displayed a number of indicators of radiosensitivity as compared to their wild-type counterparts. These included higher levels of persistent DSB repair foci, increased numbers of apoptotic cells in the seminiferous tubules, and partial degeneration of the blood-testis barrier. There was also an almost complete loss of germ cells at later times following irradiation, evidently arising as an indirect effect reflecting loss of stromal support. Results demonstrate a role for NONO protein in protection against direct and indirect biological effects of ionizing radiation in the whole animal.

  7. The Composition of Bovine Peritubular Dentin: Matching TOF-SIMS, Scanning Electron Microscopy and Biochemical Component Distributions

    PubMed Central

    Gotliv, Bat Ami; Veis, Arthur

    2008-01-01

    Peritubular dentin (PTD) is a hypermineralized phase within the dentinal tubules in some vertebrate teeth as an interface between the intertubular dentin (ITD) and the cell processes. Our aim has been to understand the composition, structure and role of PTD as a mineralized tissue. We have utilized the technique of time of flight secondary ion mass spectrometry (TOF-SIMS) to map the distribution of positive and negative inorganic ions as well as organic components in the fully mineralized, intact PTD structure in bovine tooth cross-sections, and correlated these with scanning electron microscopy (SEM) in standard and backscatter modes. In recent work, we developed a procedure to freeze fracture the teeth and separate PTD from the less dense ITD by the use of aqueous sodium phosphotungstate step density gradients, after degrading the ITD collagen with NaOCl. Here, PTD-containing fragments were characterized by SEM and TOF-SIMS surface structure analysis. The TOF-SIMS data show that the isolated PTD does not contain collagen, but its surface is rich in glutamic acid-containing protein(s). The TOF-SIMS spectra also indicated that the intact PTD fragments contain phospholipids, and chemical analyses showed phosphatidylserine, phosphatidylinositol and phosphatidylcholine as the principal lipid components. In SEM sections, untreated PTD shows as a smooth collar around the tubule, but after digestion with ethylenediamine to remove all organic components, the porous nature of the mineral phase of small, thin platy apatite crystals becomes evident. Thus, the organic matrix of PTD appears to be a proteolipid-phospholipid complex. PMID:18728348

  8. Chondroitin sulfate is involved in the hypercalcification of the organic matrix of bovine peritubular dentin.

    PubMed

    Dorvee, Jason R; Gerkowicz, Lauren; Bahmanyar, Sara; Deymier-Black, Alix; Veis, Arthur

    2016-02-01

    Apatitic mineral of dentin forms within the collagenous matrix (intertubular dentin, ITD) secreted from the odontoblastic processes (OP). Highly calcified mineral (peritubular dentin, PTD) is deposited at the interface between the ITD and each process membrane, creating a tubular system penetrating the dentin that extends from the dentino-enamel junction to the predentin-dentin junction. We focus on determining the composition of the PTD both with regard to its organic matrix and the inorganic phase. A laser capture technique has been adapted for the isolation of the mineralized PTD free from the ITD, and for the analysis of the PTD by SEM, TEM, and energy dispersive spectrometry (EDS), these data were subsequently compared with similar analyses of intact dentin slices containing ITD bounded-PTD annuli. Elemental line scans reveal clearly marked boundaries between ITD, PTD, and OP components, and illustrate the differences in composition, and topographical surface roughness. The organic matrix of the PTD was shown to be sulfur rich, and further antibody labeling showed the sulfated organic component to be chondroitin sulfate B. In this PTD organic matrix the S/Ca and Ca/P ratios were distinctly higher than in the ITD, indicating that polysaccharide bound S supplies the anionic counterion facilitating the formation of the apatitic PTD mineral.

  9. Chondroitin sulfate is involved in the hypercalcification of the organic matrix of bovine peritubular dentin

    PubMed Central

    Dorvee, Jason R.; Gerkowicz, Lauren; Bahmanyar, Sara; Deymier-Black, Alix; Veis, Arthur

    2015-01-01

    Apatitic mineral of dentin forms within the collagenous matrix (intertubular dentin, ITD) secreted from the odontoblastic processes (OP). Highly calcified mineral (peritubular dentin, PTD) is deposited at the interface between the ITD and each process membrane, creating a tubular system penetrating the dentin that extends from the dentino-enamel junction to the predentin-dentin junction. We focus on determining the composition of the PTD both with regard to its organic matrix and the inorganic phase. A laser capture technique has been adapted for isolation of the mineralized PTD free of the ITD, and for the analysis of the PTD by SEM, TEM, and energy dispersive spectrometry (EDS), and comparison with similar analyses of intact dentin slices containing ITD bounded-PTD annuli. Elemental line scans clearly marked the boundaries between ITD, PTD, and OP components, and revealed differences in composition, and topographical surface roughness. The organic matrix of the PTD was shown to be sulfur rich, and further antibody labeling showed the sulfated organic component to be chondroitin sulfate B. In this organic matrix the Ca/P ratio was distinctly higher than in the ITD and intact PTD, indicating that polysaccharide bound S supplies the anionic counterion facilitating the formation of the apatitic PTD mineral. PMID:26656507

  10. Renal handling of technetium-99m DMSA: Evidence for glomerular filtration and peritubular uptake

    SciTech Connect

    de Lange, M.J.; Piers, D.A.; Kosterink, J.G.; van Luijk, W.H.; Meijer, S.; de Zeeuw, D.; van der Hem, G.K.

    1989-07-01

    The finding of an enhanced excretion of (/sup 99m/Tc)dimercaptosuccinic acid (DMSA) in patients with tubular reabsorption disorders prompted us to investigate the role of filtration in the renal handling of (/sup 99m/Tc)DMSA. Our studies in human serum indicated that binding to serum proteins was approximately 90%. Chromatography of human urine and studies in rats showed that the complex was excreted unaltered into the urine. Renal extraction of (/sup 99m/Tc)DMSA in a human volunteer was 5.8%. Continuous infusion of (/sup 99m/Tc)DMSA in 13 individuals with normal renal function gave the following results (mean +/- s.d.): plasma clearance of (/sup 99m/Tc)DMSA 34 +/- 4 ml/min, urinary clearance of (/sup 99m/Tc)DMSA 12 +/- 3 ml/min. The calculated filtered load of (/sup 99m/Tc)DMSA closely resembled the urinary clearance, whereas the plasma clearance was about three times faster. This indicates that peritubular uptake accounts for approximately 65% and filtration for approximately 35% of the renal handling of (/sup 99m/Tc)DMSA.

  11. Modulation of proximal tubular hydraulic conductivity by peritubular capillary oncotic pressure.

    PubMed

    Agerup, B; Persson, A E

    1982-07-01

    Fluid absorption from the proximal tubular lumen is probably a multifactorial process. Earlier studies from our laboratory have indicated that a transepithelial hydrostatic and oncotic pressure difference may be the driving force for as much as 30% of the reabsorbed fluid. During saline volume expansion proximal tubular reabsorption declines and the present experiments were undertaken to investigate whether this reduction could be caused by changes in the passively driven flux component. The hydraulic conductivity was therefore determined from the reabsorptive rate in split oil droplets with normal and high hydrostatic pressure gradients across the wall, at the same time as the peritubular capillary net-work was perfused with solutions containing a colloid of high or low concentration. In the reabsorption experiments the split oil droplet radius was measured and in a separate series of experiments the relationship between droplet radius and pressure was determined; this was found to be 7.3 mmHg pressure increase per 1 micrometer increase in radius. The increase in the rate of reabsorption from the droplets due to increased intraluminal hydrostatic pressure was 1.02 +/- 0.13 nl/min/mm tubular length when a solution with a high colloid concentration was perfused through the capillary net-work, compared with 0.41=0.11 nl/min/mm tubular length when a low colloid containing solution was used for perfusion. The hydraulic conductance in the proximal tubular wall at high colloid perfusion was calculated to be 0.54 nl/min.mm.mmHg while at a low capillary colloid oncotic pressure it was significantly lower 0.025 nl/min.mm.mmHg. This drop in hydraulic conductance might be one factor responsible for the decline in fluid absorption in animals exposed to saline volume expansion.

  12. Thrombotic Microangiopathy and Peritubular Capillary C4d Expression in Renal Allograft Biopsies

    PubMed Central

    Kremer, Joseph; Ali, Farah N.; Curley, Jessica; Marino, Susana; Chang, Anthony; Kadambi, Pradeep V.

    2011-01-01

    Summary Background and objectives This study characterizes the pathologic and clinical relationships of thrombotic microangiopathy (TMA) to antibody-mediated rejection (AMR) in renal allograft biopsies. Design, setting, participants, & measurements Consecutive renal allograft biopsies, routinely stained for C4d over a period of 51 months (n = 1101), were reviewed. For comparative analysis of histology and clinical features, additional patients with TMA and peritubular capillary (PTC) C4d (n = 5) were combined with those identified in the 51-month period of review (n = 6). Results One hundred eighty-two of 1073 adequate biopsies from 563 allografts had PTC C4d in the study period. Six of 37 biopsies with TMA had PTC C4d (five at ≤90 days and one at 213 days). Early (≤90 days) C4d+ biopsies (n = 5) had more frequent TMA (11.9% C4d+ versus 3.4% C4d−; odds ratio, 3.84; P = 0.03). Graft loss was significantly greater in an early C4d+TMA+ group (n = 5 study + 2 archival patients) than in C4d+ controls without TMA (n = 21) (57% versus 9.5%; P = 0.02). Early TMA+C4d+ biopsies had more severe glomerulopathy and less severe arteriolopathy than TMA+C4d− and had more frequent neutrophilic capillaritis than TMA−C4d+ biopsies. Conclusions TMA was infrequent in this series of unselected, consecutive, renal allograft biopsies (3.4%). PTC C4d may be a significant risk factor for early TMA, and TMA is associated with glomerular thrombi and neutrophilic capillaritis. TMA in allografts with suspected AMR may portend a higher risk of graft loss. PMID:20966124

  13. Peritubular capillary changes and C4d deposits are associated with transplant glomerulopathy but not IgA nephropathy.

    PubMed

    Vongwiwatana, Attapong; Gourishankar, Sita; Campbell, Patricia M; Solez, Kim; Halloran, Philip F

    2004-01-01

    We examined our renal transplant population for glomerular diseases demonstrated on biopsy between January 1993 and April 2002, focusing on transplant glomerulopathy (TGP). Of 1156 patients followed in our clinics during this period, glomerular disease was diagnosed in 132 cases (11.4%). Glomerulonephritis was diagnosed in 86 transplants (7.4%), with IgA nephropathy (IgAN) being the commonest diagnosis [32 cases (2.8%)]. Thirty-one cases (2.7%) of biopsy-proven TGP were analyzed for associated factors compared with 27 cases (2.3%) of recurrent IgAN. Transplant glomerulopathy was less frequent with mycophenolate mofetil (MMF) and/or tacrolimus, whereas recurrent IgAN showed no such tendency (P= 0.02). Peritubular capillary (PTC) C4d deposition was observed in six of 24 cases (25%) with TGP but none with recurrent IgAN (P= 0.02). Peritubular capillary basement membrane (BM) multilayering was significantly greater in TGP (4.92 +/- 2.94) than in recurrent IgAN (1.86 +/- 1.04) (P < 0.001). The graft survival of TGP was worse than recurrent IgAN (P= 0.05). The association of TGP with BM multilayering and C4d deposits in PTC suggests a generalized disorder of the graft microcirculation and its BM, owing to antibody-mediated rejection in at least some cases. Transplant glomerulopathy has a serious prognosis but is less frequent in patients on newer immunosuppression, unlike recurrent IgAN.

  14. Peritubular Capillary Basement Membrane Multilayering in Renal Allograft Biopsies of Patients With De Novo Donor-Specific Antibodies.

    PubMed

    de Kort, Hanneke; Willicombe, Michelle; Brookes, Paul; Moran, Linda B; Santos-Nunez, Eva; Galliford, Jack W; Taube, David; McLean, Adam G; Moss, Jill; Cook, H Terence; Roufosse, Candice

    2016-04-01

    Severe peritubular capillary basement membrane multilayering (PTCBML) is part of the Banff definition of chronic antibody-mediated rejection. We retrospectively investigated whether assessment of the mean number of layers of basement membrane (BM) around peritubular capillaries (PTC) can be used in a cohort of patients with de novo donor-specific antibodies (dnDSA) as an early marker to predict long-term antibody-mediated injury. This is a retrospective cohort study with 151 electron microscopy samples from 54 patients with dnDSA, assessed at around 1 year after transplantation, for a mean number of BM layers around PTC and in serial biopsies. Graft survival and time to transplant glomerulopathy (TG) development were estimated in survival analyses. We found that a mean PTCBML count greater than 2.5 layers assessed in a sample of 25 PTCs around 1 year after transplantation is indicative of the development of TG in patients with dnDSA (P = 0.001). In addition, in patients with serial biopsies available for electron microscopy analysis, we could distinguish 2 groups: patients with a mean PTCBML count of 2.5 or less on all biopsies, and patients who developed greater than 2.5 layers at any time after transplantation. The latter group reflected dnDSA patients at risk for TG development (P < 0.001). In patients with dnDSA, PTCBML score added significantly to the sensitivity and specificity of prediction of TG compared with microcirculation injury score alone. Our results highlight the potential value of assessing the mean number of BM in PTC for early prediction of progression to chronic antibody-mediated injury.

  15. Seasonal Changes in the Immunolocalization of Cytoskeletal Proteins and Laminin in the Testis of the Black-Backed Jackal (Canis mesomelas).

    PubMed

    Madekurozwa, M-C; Booyse, D

    2017-02-01

    Manipulation of the reproductive activity of jackals is dependent on a thorough understanding of the reproductive biology of this species. This study describes seasonal morphological changes in the adult testis of the black-backed jackal in relation to the immunoexpression of the basement membrane marker, laminin and the cytoskeletal proteins, cytokeratin, smooth muscle actin and vimentin. Laminin was immunolocalized in basement membranes surrounding seminiferous tubules, as well as in basement membranes associated with Leydig, peritubular myoid and vascular smooth muscle cells. Scalloped basement membranes enclosed seminiferous tubules in regressing testes. The seminiferous epithelium and interstitial tissue in all animals studied were cytokeratin immunonegative. Smooth muscle actin was demonstrated in vascular smooth muscle cells, as well as in peritubular myoid cells encircling seminiferous tubules. Vimentin immunoreactivity was exhibited in the cytoplasm of Sertoli cells, Leydig cells, vascular endothelial cells, vascular smooth muscle cells and fibrocytes. Vimentin immunostaining in Sertoli, Leydig and peritubular myoid cells varied depending on the functional state of the testis. The results of the study have shown that dramatic seasonal histological changes occur in the testes of the jackal. In addition, the use of immunohistochemistry accentuates these morphological changes.

  16. Effects of cumene hydroperoxide on cellular cation composition in frog kidney proximal tubular cells.

    PubMed

    Petrovic, S; Cemerikic, D

    2000-06-01

    Effects of cumene hydroperoxide were studied on the peritubular membrane potential and cellular cation composition in frog kidney proximal tubular cells. After perfusion of isolated frog kidneys for 30 min with 1.3x10(-4) mol l(-1) cumene hydroperoxide Ringer solution, the peritubular membrane potential gradually declined. The ouabain-like effects were demonstrated on cell Na and K activities after 1 h of perfusion with cumene hydroperoxide. The peritubular apparent transference number for potassium was decreased. Intracellular pH was not altered in the presence of cumene hydroperoxide. Intracellular free Ca(2+) concentration increased slowly and moderately. The concentration of the malondialdehyde in the kidney homogenates, measured as an index of lipid peroxidation, was increased. A previously observable effect of cumene hydroperoxide on the peritubular membrane potential was prevented by oxygen radical scavengers.

  17. Refinement of the criteria for ultrastructural peritubular capillary basement membrane multilayering in the diagnosis of chronic active/acute antibody-mediated rejection.

    PubMed

    Go, Heounjeong; Shin, Sung; Kim, Young Hoon; Han, Duck Jong; Cho, Yong Mee

    2017-04-01

    Chronic active/acute antibody-mediated rejection (cABMR) is the main cause of late renal allograft loss. Severe peritubular capillary basement membrane multilayering (PTCML) assessed on electron microscopy is one diagnostic feature of cABMR according to the Banff 2013 classification. We aimed to refine the PTCML criteria for an earlier diagnosis of cABMR. We retrospectively investigated ultrastructural features of 159 consecutive renal allografts and 44 nonallografts. The presence of serum donor-specific antibodies at the time of biopsy of allografts was also examined. Forty-three patients (27.0%) fulfilled the criteria of cABMR, regardless of PTCML, and comprised the cABMR group. Forty-one patients (25.8%) did not exhibit cABMR features and comprised the non-cABMR allograft control group. In addition, 15 zero-day wedge resections and 29 native kidney biopsies comprised the nonallograft control group. When the diagnostic accuracies of various PTCML features were assessed using the cABMR and non-cABMR allograft control groups, ≥4 PTCML, either circumferential or partial, in ≥2 peritubular capillaries of the three most affected capillaries exhibited the highest AUC value (0.885), greater than the Banff 2013 classification (0.640). None of the nonallograft control groups exhibited PTCML features. We suggest that ≥4 PTCML in ≥2 peritubular capillaries of the three most affected cortical capillaries represents the proper cutoff for cABMR. © 2017 Steunstichting ESOT.

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

    PubMed

    Rumessen, J J; Vanderwinden, J-M; Horn, T

    2010-10-01

    Interstitial cells of Cajal (ICC) are key regulatory cells in the gut. In the colon of patients with severe ulcerative colitis (UC), myenteric ICC had myoid ultrastructural features and were in close contact with nerve terminals. In all patients as opposed to controls, some ICC profiles showed 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 and cytological changes may be of pathophysiological significance in patients with UC.

  19. Postmortem examination of the kidney in allogeneic hematopoietic stem cell transplantation recipients: possible involvement of graft-versus-host disease.

    PubMed

    Kusumi, Eiji; Kami, Masahiro; Hara, Shigeo; Hoshino, Junichi; Yamaguchi, Yutaka; Murashige, Naoko; Kishi, Yukiko; Shibagaki, Yugo; Shibata, Taro; Matsumura, Tomoko; Yuji, Koichiro; Masuoka, Kazuhiro; Wake, Atsushi; Miyakoshi, Shigesaburo; Taniguchi, Shuichi

    2008-03-01

    To investigate the association between graft-versus-host disease (GVHD) and renal injury after allogeneic stem cell transplantation (allo-SCT), we compared autopsy findings of 26 consecutive allo-SCT recipients with two control groups: patients with hematologic malignancies who received cytotoxic chemotherapy alone (Control 1, n = 21) and those with non-hematologic diseases (Control 2, n = 12). We evaluated the following renal pathology; renal tubulitis, allograft glomerulitis, intimal arteritis, allograft nephropathy, and peritubular capillaritis. These changes were found in 11 allo-SCT recipients and 10 patients in Control 1, but none in Control 2. While overall frequency of renal impairments was similar between allo-SCT recipients and Control 1 (3/26 vs. 1/21), allo-SCT recipients were more likely to have renal tubulitis and peritubular capillaritis compared to Control 1 (5/26 vs. 1/21), but less likely to present with glomerulitis (1/26 vs. 6/21). Grade III-IV acute or extensive-type chronic GVHD were seen in all of the three patients with renal tubulitis and four of the five patients with peritubular capillaritis. Allo-SCT recipients with severe GVHD tended to have tubulitis and peritubular capillaritis. These findings have implications of some renal impairment attributable to GVHD.

  20. Morphological and histochemical characteristics of the lamina propria in scrotal and abdominal testes from postpubertal boars: correlation with the appearance of the seminiferous epithelium

    PubMed Central

    PINART, E.; BONET, S.; BRIZ, M.; PASTOR, L. M.; SANCHO, S.; GARCÍA, N.; BADIA, E.; BASSOLS, J.

    2001-01-01

    This study was undertaken to investigate the morphological characteristics and lectin affinity of the testicular lamina propria in healthy boars and in unilateral and bilateral abdominal cryptorchid boars. The lamina propria of scrotal testes from healthy boars and unilateral cryptorchid boars was constituted by an innermost noncellular layer, the basal lamina, and by 2 layers of peritubular cells, each separated by a fibrous layer. The noncellular layers contained collagen fibres and glycoconjugates with abundant N-acetylgalactosamine, galactose, fucose, N-acetylglucosamine and neuraminic acid residues. The inner peritubular cell layer was composed of myoid cells, the outer layer of fibroblasts. In the abdominal testes of unilateral and bilateral cryptorchid boars, the lamina propria of nondegenerating and degenerating seminiferous tubules appeared thickened due to an increased content of collagen fibres and glycoconjugates. Glycoconjugates showed decreased amounts of fucose, neuraminic acid and galactose, and increased amounts of N-acetylglucosamine residues. The basal lamina formed infoldings toward the seminiferous epithelium and contained small cells. Both inner and outer peritubular cells were fibroblasts of immature appearance. In degenerated seminiferous tubules of bilateral cryptorchid boars, the lamina propria was composed of a thickened and collagenised basal lamina, without peritubular cells and with a low content of glycoconjugates. In scrotal testes, therefore, the lamina propria was implicated in tubular contractility and in mediating the communication and the substrate diffusion between seminiferous tubules and interstitial tissue. Cryptorchidism induced morphological and histochemical alterations in the lamina propria of abdominal testes, which may be linked to evidence from other studies of lack of tubular contractility and defective cell–cell communication and substrate diffusion. The severity of these anomalies correlated with the severity of

  1. Thirsty business: cell, region, and membrane specificity of aquaporins in the testis, efferent ducts, and epididymis and factors regulating their expression.

    PubMed

    Hermo, Louis; Smith, Charles E

    2011-01-01

    Water content within the male reproductive tract is stringently regulated in order to promote sperm differentiation and maturation. Aquaporins (AQP) are a family of integral membrane proteins allowing the transcellular transport of water, gases, urea, glycerol, and ions. Past studies from our lab have revealed the following. In the testis, Sertoli cells express AQP 8, whereas germ cells express AQP 7. In the efferent ducts (ED), AQP 1, 9, and 10 localize to microvilli of nonciliated cells, in addition to a basolateral staining for AQP 1, whereas AQP 1 and 10 localize to ciliated cells. AQP 7 and 11 are expressed in the ED epithelium of young but not adult rats, suggesting suppression of translation as rats age. In the adult epididymis, AQP 1 appears in endothelial cells of vascular channels and myoid cells, whereas AQP 3 delineates basal cells. In principal cells, AQP 9 and 11 appear on microvilli, whereas AQP 7 localizes to lateral then to basal plasma membranes in a region-specific manner; AQP 7 also associates with myoid cells. AQP 5 is expressed in corpus and cauda regions. Additionally, several AQPs are expressed by some but not all basal (AQP 7, 11), clear (AQP 7, 9), and halo (AQP 7, 11) cells. Regulation studies reveal a role for estrogen, androgens, and lumicrine factors. These findings indicate unique associations of AQPs with specific membrane domains in a cell type- and region-specific manner within the EDs and epididymis, as well as complex regulation patterns of expression.

  2. Androgen receptor roles in spermatogenesis and infertility.

    PubMed

    O'Hara, Laura; Smith, Lee B

    2015-08-01

    Androgens such as testosterone are steroid hormones essential for normal male reproductive development and function. Mutations of androgen receptors (AR) are often found in patients with disorders of male reproductive development, and milder mutations may be responsible for some cases of male infertility. Androgens exert their action through AR and its signalling in the testis is essential for spermatogenesis. AR is not expressed in the developing germ cell lineage so is thought to exert its effects through testicular Sertoli and peri-tubular myoid (PTM) cells. AR signalling in spermatogenesis has been investigated in rodent models where testosterone levels are chemically supressed or models with transgenic disruption of AR. These models have pinpointed the steps of spermatogenesis that require AR signalling, specifically maintenance of spermatogonial numbers, blood-testis barrier integrity, completion of meiosis, adhesion of spermatids and spermiation, together these studies detail the essential nature of androgens in the promotion of male fertility.

  3. Effects of nanostructures and mouse embryonic stem cells on in vitro morphogenesis of rat testicular cords.

    PubMed

    Pan, Fei; Chi, Lifeng; Schlatt, Stefan

    2013-01-01

    Morphogenesis of tubular structures is a common event during embryonic development. The signals providing cells with topographical cues to define a cord axis and to form new compartments surrounded by a basement membrane are poorly understood. Male gonadal differentiation is a late event during organogenesis and continues into postnatal life. The cellular changes resemble the mechanisms during embryonic life leading to tubular structures in other organs. Testicular cord formation is dependent on and first recognized by SRY-dependent aggregation of Sertoli cells leading to the appearance of testis-specific cord-like structures. Here we explored whether testicular cells use topographical cues in the form of nanostructures to direct or stimulate cord formation and whether embryonic stem cells (ES) or soluble factors released from those cells have an impact on this process. Using primary cell cultures of immature rats we first revealed that variable nanogratings exerted effects on peritubular cells and on Sertoli cells (at less than <1000 cells/mm(2)) by aligning the cell bodies towards the direction of the nanogratings. After two weeks of culture testicular cells assembled into a network of cord-like structures. We revealed that Sertoli cells actively migrate towards existing clusters. Contractions of peritubular cells lead to the transformation of isolated clusters into cord-like structures. The addition of mouse ES cells or conditioned medium from ES cells accelerated this process. Our studies show that epithelial (Sertoli cell) and mesenchymal (peritubular cells) cells crosstalk and orchestrate the formation of cords in response to physical features of the underlying matrix as well as secretory factors from ES cells. We consider these data on testicular morphogenesis relevant for the better understanding of mechanisms in cord formation also in other organs which may help to create optimized in vitro tools for artificial organogenesis.

  4. Cell Volume Regulation in the Proximal Tubule of Rat Kidney : Proximal Tubule Cell Volume Regulation.

    PubMed

    Edwards, Aurélie; Layton, Anita T

    2017-09-12

    We developed a dynamic model of a rat proximal convoluted tubule cell in order to investigate cell volume regulation mechanisms in this nephron segment. We examined whether regulatory volume decrease (RVD), which follows exposure to a hyposmotic peritubular solution, can be achieved solely via stimulation of basolateral K[Formula: see text] and [Formula: see text] channels and [Formula: see text]-[Formula: see text] cotransporters. We also determined whether regulatory volume increase (RVI), which follows exposure to a hyperosmotic peritubular solution under certain conditions, may be accomplished by activating basolateral [Formula: see text]/H[Formula: see text] exchangers. Model predictions were in good agreement with experimental observations in mouse proximal tubule cells assuming that a 10% increase in cell volume induces a fourfold increase in the expression of basolateral K[Formula: see text] and [Formula: see text] channels and [Formula: see text]-[Formula: see text] cotransporters. Our results also suggest that in response to a hyposmotic challenge and subsequent cell swelling, [Formula: see text]-[Formula: see text] cotransporters are more efficient than basolateral K[Formula: see text] and [Formula: see text] channels at lowering intracellular osmolality and reducing cell volume. Moreover, both RVD and RVI are predicted to stabilize net transcellular [Formula: see text] reabsorption, that is, to limit the net [Formula: see text] flux decrease during a hyposmotic challenge or the net [Formula: see text] flux increase during a hyperosmotic challenge.

  5. Interdigitating reticulum cells in human renal grafts.

    PubMed

    Wakabayashi, T; Onoda, H

    1991-01-01

    Seventeen human renal graft biopsies taken 1 h to 50 days after transplantation and 3 human renal non-graft biopsies (2 minimal change and 1 non-tumour portion of angiomyolipoma) were investigated with immunoelectron microscopy in order to identify interdigitating reticulum cells (IDC) or dendritic cells (DC) in renal tissues. The antibodies used consisted of a rabbit polyclonal antibody of antihuman S100 beta protein, mouse monoclonal antibodies of antihuman HLA-DR, anti-CD3, and anti-CD1a. IDC or DC were identified in 11 renal grafts. They were found both in the glomerular and interstitial (peritubular) capillary lumens but not in the interstitium of 1 case: both were present in the interstitial capillary lumens and interstitium of another case, and in the interstitium only of 9 cases. In the remaining 6 grafts and 3 non-grafts they were not detected. These 6 grafts and 3 non-grafts did not show any pathological change except for foot process fusion of the glomerular epithelia in 2 cases of minimal change. These findings suggest that IDC or DC are not normally present in human renal tissues. The presence of the cell in the glomerular and peritubular capillary lumens of a biopsy taken after 1 h and their presence in the interstitial capillary lumens of another graft biopsy, suggest that the IDC or DC in human renal grafts are derived from recipients, not donors, and that they migrate from the circulating blood toward the interstitium.

  6. Injured kidney endothelium is only marginally repopulated by cells of extrarenal origin.

    PubMed

    Schirutschke, Holger; Vogelbacher, Regina; Stief, Andrea; Parmentier, Simon; Daniel, Christoph; Hugo, Christian

    2013-10-01

    The role of bone marrow marrow-derived cells after kidney endothelial injury is controversial. In this study, we investigated if and to what extent extrarenal cells incorporate into kidney endothelium after acute as well as during chronic endothelial injury. Fischer F-344wt (wild type) rat kidney grafts were transplanted into R26-hPAP (human placental alkaline phosphatase) transgenic Fischer F-344 recipient rats to allow identification of extrarenal cells by specific antibody staining. A severe model of renal thrombotic microangiopathy was induced via graft perfusion with antiglomerular endothelial cell (GEN) antibody and resulted in eradication of 85% of the glomerular and 69% of the peritubular endothelium (GEN group). At week 4 after injury, renal endothelial healing as well as recovery of the kidney function was seen. Endothelial chimerism was evaluated by double staining for hPAP and endothelial markers RECA-1 or JG-12. Just 0.25% of the glomerular and 0.1% of the peritubular endothelium was recipient derived. In a second experiment, chronic endothelial injury was induced by combination of kidney transplantation with 5/6 nephrectomy (5/6 Nx group). After 14 wk, only 0.86% of the peritubular and 0.05% of the glomerular endothelium was of recipient origin. In summary, despite demonstration of extensive damage and loss as well as excellent regeneration, just a minority of extrarenal cells were incorporated into kidney endothelium in rat models of acute and chronic renal endothelial cell injury. Our results highlight that kidney endothelial regeneration after specific and severe injury is almost exclusively of renal origin.

  7. Cell volume regulation in the proximal convoluted tubule.

    PubMed

    Gagnon, J; Ouimet, D; Nguyen, H; Laprade, R; Le Grimellec, C; Carrière, S; Cardinal, J

    1982-10-01

    To evaluate the effect of hyper- and hypotonicity on proximal convoluted tubule (PCT) cell volume, nonperfused PCT were studied in vitro with hypertonic solutions containing sodium chloride, urea, or mannitol (450 mosmol/kg H2O) and with hypotonic low sodium chloride solutions (160 mosmol/kg H2O). When the tubules were subjected to hypertonic peritubular solutions containing NaCl, cell volume immediately decreased by 15.5% and remained constant throughout the experimental period (60 min). With mannitol, the initial decrease was identical to that with NaCl (17.7%), but the PCT volume increased slightly during the experimental period. With urea, the decrease in cell volume was smaller (7%) and transient. In hypotonicity, the PCT swelled rapidly, but this swelling was followed by a rapid regulatory phase in which PCT volume nearly returned to control values after less than 10 min. With a potassium-free peritubular medium or 10(-3) M ouabain, the regulatory phase of hypotonicity completely disappeared, whereas the cells did not maintain their reduced volume in NaCl-induced hypertonicity. These results suggest that Na-K-ATPase plays an important role in the maintenance of a reduced cellular volume in hypertonicity and in the regulatory phase of hypotonicity, probably by an active extrusion of sodium and water from the cell.

  8. Endothelial marker-expressing stromal cells are critical for kidney formation.

    PubMed

    Mukherjee, Elina; Maringer, Katherine; Papke, Emily; Bushnell, Daniel; Schaefer, Caitlin; Kramann, Rafael; Ho, Jacqueline; Humphreys, Benjamin D; Bates, Carlton; Sims-Lucas, Sunder

    2017-09-01

    Kidneys are highly vascularized and contain many distinct vascular beds. However, the origins of renal endothelial cells and roles of the developing endothelia in the formation of the kidney are unclear. We have shown that the Foxd1-positive renal stroma gives rise to endothelial marker-expressing progenitors that are incorporated within a subset of peritubular capillaries; however, the significance of these cells is unclear. The purpose of this study was to determine whether deletion of Flk1 in the Foxd1 stroma was important for renal development. To that end, we conditionally deleted Flk1 (critical for endothelial cell development) in the renal stroma by breeding-floxed Flk1 mice (Flk1(fl/fl) ) with Foxd1cre mice to generate Foxd1cre; Flk1(fl/fl) (Flk1(ST-/-) ) mice. We then performed FACsorting, histological, morphometric, and metabolic analyses of Flk1(ST-/-) vs. control mice. We confirmed decreased expression of endothelial markers in the renal stroma of Flk1(ST-/-) kidneys via flow sorting and immunostaining, and upon interrogation of embryonic and postnatal Flk1(ST-/-) mice, we found they had dilated peritubular capillaries. Three-dimensional reconstructions showed reduced ureteric branching and fewer nephrons in developing Flk1(ST-/-) kidneys vs. Juvenile Flk1(ST-/-) kidneys displayed renal papillary hypoplasia and a paucity of collecting ducts. Twenty-four-hour urine collections revealed that postnatal Flk1(ST-/-) mice had urinary-concentrating defects. Thus, while lineage-tracing revealed that the renal cortical stroma gave rise to a small subset of endothelial progenitors, these Flk1-expressing stromal cells are critical for patterning the peritubular capillaries. Also, loss of Flk1 in the renal stroma leads to nonautonomous-patterning defects in ureteric lineages. Copyright © 2017 the American Physiological Society.

  9. Spleen histology in children with sickle cell disease and hereditary spherocytosis: hints on the disease pathophysiology.

    PubMed

    Pizzi, Marco; Fuligni, Fabio; Santoro, Luisa; Sabattini, Elena; Ichino, Martina; De Vito, Rita; Zucchetta, Pietro; Colombatti, Raffaella; Sainati, Laura; Gamba, Piergiorgio; Alaggio, Rita

    2017-02-01

    Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histologic and morphometric features of HS and SCD spleens, to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS, and control patients, the following parameters were considered: (i) macroscopic features, (ii) lymphoid follicle (LF) density, (iii) presence of perifollicular marginal zones, (iv) presence of Gamna-Gandy bodies, (v) density of CD8-positive sinusoids, (vi) density of CD34-positive microvessels, (vii) presence/distribution of fibrosis and smooth muscle actin (SMA)-positive myoid cells, and (viii) density of CD68-positive macrophages. SCD and HS spleens had similar macroscopic features. SCD spleens had lower LF density and fewer marginal zones than did HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than did controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, most HS spleens clustered with controls, whereas SCD grouped separately. A multiparametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS, and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Microparticles from Kidney-Derived Mesenchymal Stem Cells Act as Carriers of Proangiogenic Signals and Contribute to Recovery from Acute Kidney Injury

    PubMed Central

    Choi, Hoon Young; Moon, Sung Jin; Ratliff, Brian B.; Ahn, Sun Hee; Jung, Ara; Lee, Mirae; Lee, Seol; Lim, Beom Jin; Kim, Beom Seok; Plotkin, Matthew D.; Ha, Sung Kyu; Park, Hyeong Cheon

    2014-01-01

    We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC) protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs) from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188), bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC) via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys. PMID:24504266

  11. Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.

    PubMed

    Nagao, Ryan J; Xu, Jin; Luo, Ping; Xue, Jun; Wang, Yi; Kotha, Surya; Zeng, Wen; Fu, Xiaoyun; Himmelfarb, Jonathan; Zheng, Ying

    2016-10-01

    The kidney peritubular microvasculature is highly susceptible to injury from drugs and toxins, often resulting in acute kidney injury and progressive chronic kidney disease. Little is known about the process of injury and regeneration of human kidney microvasculature, resulting from the lack of appropriate kidney microvascular models that can incorporate the proper cells, extracellular matrices (ECMs), and architectures needed to understand the response and contribution of individual vascular components in these processes. In this study, we present methods to recreate the human kidney ECM (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex. The majority of native matrix proteins, such as collagen-IV, laminin, and heparan sulfate proteoglycan, and their isoforms were preserved in similar proportions as found in normal kidneys. Human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel compared with culture on collagen-I-assessed using phenotypic, genotypic, and functional assays; whereas human umbilical vein endothelial cells became stimulated on kECM gels. We demonstrate for the first time that human kidney cortex can form a hydrogel suitable for use in flow-directed microphysiological systems. Our findings strongly suggest that selecting the proper ECM is a critical consideration in the development of vascularized organs on a chip and carries important implications for tissue engineering of all vascularized organs.

  12. Modulation of transferrin secretion by epidermal growth factor in immature rat Sertoli cells in vitro.

    PubMed

    Onoda, M; Suarez-Quian, C A

    1994-03-01

    The modulation of transferrin secretion by FSH and epidermal growth factor (EGF) was studied in highly pure, primary cultures of immature rat Sertoli cells grown on a reconstituted basement membrane (Matrigel) in bicameral chambers. Sertoli cell purity was assessed by (1) morphometry, (2) alkaline phosphatase cytochemistry (a specific marker enzyme for peritubular cells) and (3) immunocytochemistry for the alpha-isoform of smooth muscle actin in contaminating peritubular cells. Results revealed a less than 0.5% peritubular cell contamination. During initial periods of culture with EGF or FSH alone or in combination, both EGF and FSH alone maintained transferrin secretion over basal values and their effects were additive. At subsequent times, EGF alone maintained transferrin secretion, but to less extent than did FSH alone, and inhibited significantly the ability of FSH to maintain transferrin secretion. The ratio of polarized transferrin secretion in response to FSH, EGF, or in combination was also examined. FSH significantly reversed the polarity of transferrin secretion, whereas EGF, although significantly reducing the ratio of apical to basal transferrin secretion, did not lead to a preferential basal secretion of transferrin. The change in the apical:basal transferrin secretion ratio, however, was not due to a reversal of the apically secreted transferrin towards a basal direction, but rather to an increase in the total basally secreted transferrin. The effects of cell density effects on transferrin secretion were then examined. At low cell density, the relative ability of EGF and FSH together to maintain transferrin secretion was greater than at high cell density, but overall transferrin secretion was greater as cell density increased. The inhibition of FSH by EGF on transferrin secretion was also density dependent: EGF significantly inhibited FSH effects at low cell density, but failed to do so at high cell density. These results suggest that regulation of

  13. Comparison of Different Electroporation Parameters on Transfection Efficiency of Sheep Testicular Cells

    PubMed Central

    Niakan, Sarah; Heidari, Banafsheh; Akbari, Ghasem; Nikousefat, Zahra

    2016-01-01

    Objective Electroporation can be a highly efficient method for introducing the foreign genetic materials into the targeted cells for transient and/or permanent genetic modification. Considering the application of this technique as a very efficient method for drug, oligonucleotide, antibody and plasmid delivery for clinical applications and production of transgenic animals, the present study aimed to optimize the transfection efficiency of sheep testicular cells including spermatogonial stem cells (SSCs) via electroporation. Materials and Methods This study is an experimental research conducted in Biotechnology Research Center (Avicenna Research Institute, Tehran, Iran) from September 2013 to March 2014. Following isolation and propagation of one-month lamb testicular cells (SSCs and somatic testicular cells including; Sertoli, Leydig, and myoid cells), the effect of different electroporation parameters including total voltages (280, 320, and 350 V), burst durations (10, 8, and 5 milliseconds), burst modes (single or double) and addition of dimethyl sulfoxide (DMSO) were evaluated on transfection efficiency, viability rate and mean fluorescent intensity (MFI) of sheep testicular cells. Results The most transfection efficiency was obtained in 320 V/8 milliseconds/single burst group in transduction medium with and without DMSO. There was a significantly inverse correlation between transfection efficiency with application of both following parameters: addition of DMSO and double burst. After transfection, the highest and lowest viability rates of testicular cells were demonstrated in 320 V/8 milliseconds with transduction medium without DMSO and 350 V/5 milliseconds in medium containing DMSO. Ad- dition of DMSO to transduction medium in all groups significantly decreased the viability rate. The comparison of gene expression indicated that Sertoli and SSCs had the most fluorescence intensity in 320 V/double burst/DMSO positive. However, myoid and Leydig cells showed the

  14. Testicular development involves the spatiotemporal control of PDGFs and PDGF receptors gene expression and action

    PubMed Central

    1995-01-01

    Platelet-derived growth factors (PDGFs) are growth-regulatory molecules that stimulate chemotaxis, proliferation and metabolism primarily of cells of mesenchymal origin. In this study, we found high levels of PDGFs and PDGFs receptors (PDGFRs) mRNAs, and specific immunostaining for the corresponding proteins in the rat testis. PDGFs and PDGFRs expression was shown to be developmentally regulated and tissue specific. Expression of PDGFs and PDGFRs genes was observed in whole testis RNA 2 d before birth, increased through postnatal day 5 and fell to low levels in adult. The predominant cell population expressing transcripts of the PDGFs and PDGFRs genes during prenatal and early postnatal periods were Sertoli cells and peritubular myoid cells (PMC) or their precursors, respectively, while in adult animals PDGFs and PDGFRs were confined in Leydig cells. We also found that early postnatal Sertoli cells produce PDGF-like substances and that this production is inhibited dose dependently by follicle-stimulating hormone (FSH). The expression of PDGFRs by PMC and of PDGFs by Sertoli cells corresponds in temporal sequence to the developmental period of PMC proliferation and migration from the interstitium to the peritubulum. Moreover, we observed that all the PDGF isoforms and the medium conditioned by early postnatal Sertoli cells show a strong chemotactic activity for PMC which is inhibited by anti-PDGF antibodies. These data indicate that, through the spatiotemporal pattern of PDGF ligands and receptors expression, PDGF may play a role in testicular development and homeostasis. PMID:7490286

  15. Steroidogenic Factor 1 Differentially Regulates Fetal and Adult Leydig Cell Development in Male Mice1

    PubMed Central

    Karpova, Tatiana; Ravichandiran, Kumarasamy; Insisienmay, Lovella; Rice, Daren; Agbor, Valentine; Heckert, Leslie L.

    2015-01-01

    The nuclear receptor steroidogenic factor 1 (SF-1, AD4BP, NR5A1) is a key regulator of the endocrine axes and is essential for adrenal and gonad development. Partial rescue of Nr5a1−/− mice with an SF-1-expressing transgene caused a hypomorphic phenotype that revealed its roles in Leydig cell development. In contrast to controls, all male rescue mice (Nr5a1−/−;tg+/0) showed varying signs of androgen deficiency, including spermatogenic arrest, cryptorchidism, and poor virilization. Expression of various Leydig cell markers measured by immunohistochemistry, Western blot analysis, and RT-PCR indicated fetal and adult Leydig cell development were differentially impaired. Whereas fetal Leydig cell development was delayed in Nr5a1−/−;tg+/0 embryos, it recovered to control levels by birth. In contrast, Sult1e1, Vcam1, and Hsd3b6 transcript levels in adult rescue testes indicated complete blockage in adult Leydig cell development. In addition, between Postnatal Days 8 and 12, peritubular cells expressing PTCH1, SF-1, and CYP11A1 were observed in control testes but not in rescue testes, indicating SF-1 is needed for either survival or differentiation of adult Leydig cell progenitors. Cultured prepubertal rat peritubular cells also expressed SF-1 and PTCH1, but Cyp11a1 was expressed only after treatment with cAMP and retinoic acid. Together, data show SF-1 is needed for proper development of fetal and adult Leydig cells but with distinct primary functions; in fetal Leydig cells, it regulates differentiation, whereas in adult Leydig cells it regulates progenitor cell formation and/or survival. PMID:26269506

  16. Subclinical antibody-mediated rejection due to anti-human-leukocyte-antigen-DR53 antibody accompanied by plasma cell-rich acute rejection in a patient with cadaveric kidney transplantation.

    PubMed

    Katsuma, Ai; Yamamoto, Izumi; Komatsuzaki, Yo; Niikura, Takahito; Kawabe, Mayuko; Okabayashi, Yusuke; Yamakawa, Takafumi; Katsumata, Haruki; Nakada, Yasuyuki; Kobayashi, Akimitsu; Tanno, Yudo; Miki, Jun; Yamada, Hiroki; Ohkido, Ichiro; Tsuboi, Nobuo; Yamamoto, Hiroyasu; Yokoo, Takashi

    2016-07-01

    A 56-year-old man who had undergone cadaveric kidney transplantation 21 months earlier was admitted to our hospital for a protocol biopsy; he had a serum creatinine level of 1.2 mg/dL and no proteinuria. Histological features showed two distinct entities: (i) inflammatory cell infiltration, in the glomerular and peritubular capillaries and (ii) focal, aggressive tubulointerstitial inflammatory cell infiltration, predominantly plasma cells, with mild tubulitis (Banff 13 classification: i2, t1, g2, ptc2, v0, ci1, ct1, cg0, cv0). Immunohistological studies showed mildly positive C4d immunoreactivity in the peritubular capillaries. The patient had donor specific antibody to human-leucocyte-antigen-DR53. We diagnosed him with subclinical antibody-mediated rejection accompanied by plasma cell-rich acute rejection. Both antibody-mediated rejection due to anti- human-leucocyte-antigen -DR53 antibodies and plasma cell-rich acute rejection are known to be refractory and have a poor prognosis. Thus, we started plasma exchange with intravenous immunoglobulin and rituximab for the former and 3 days of consecutive steroid pulse therapy for the latter. Three months after treatment, a follow-up allograft biopsy showed excellent responses to treatment for both histological features. This case report considers the importance of an early diagnosis and appropriate intervention for subclinical antibody-mediated rejection due to donor specific antibody to human-leucocyte-antigen-DR53 and plasma cell-rich acute rejection.

  17. Expression of DMRT1 in the mammalian ovary and testis--from marsupials to mice.

    PubMed

    Pask, A J; Behringer, R R; Renfree, M B

    2003-01-01

    Doublesex and mab3 related transcript (DMRT1) was identified as a candidate gene for human 9p24.3 associated sex reversal. DMRT1 orthologues have highly conserved roles in sexual differentiation from flies and worms to humans. A DMRT1 orthologue was isolated from a marsupial, the tammar wallaby Macropus eugenii. The wallaby gene is highly conserved with other vertebrate DMRT1 genes, especially within the P/S and DM domains. It is expressed in the differentiating testis from the late fetus, during pouch life and in the adult. As in eutherian mammals, DMRT1 protein was localized in the germ cells and the Sertoli cells of the testis, but in addition it was detected in the Leydig cells, peri-tubular myoid cells and within the acrosome of the sperm heads. DMRT1 protein was also detected in the fetal and adult ovary pre-granulosa, granulosa and germ cells. Similarly, we also detected DMRT1 in the granulosa cells of all developing follicles in the adult mouse ovary. This is the first report of DMRT1 expression in the adult mammalian ovary, and suggests a wider role for this gene in mammals, in both the testis and ovarian function.

  18. Postnatal expression of nerve growth factor receptors in the rat testis.

    PubMed

    Djakiew, D; Pflug, B; Dionne, C; Onoda, M

    1994-08-01

    Because nerve growth factor beta (NGF beta) and its corresponding receptors have been implicated in the paracrine regulation of spermatogenesis, we examined the postnatal developmental expression of the low- and high-affinity NGF receptors in the rat testis, and localized their expression to specific testicular cell types. The neurotropin receptors consist of a low-affinity p75 nerve growth factor receptor (LNGFR) and a family of high-affinity tyrosine receptor kinases (trk). Both the p75 LNGFR gene product and the trk receptor gene product were detected in immature rat testes, with maximal expression in 10- and 20-day-old rats. Expression of the testicular p75 LNGFR and the trk receptor progressively declined in older animals so that they were barely detectable in 90-day-old adult rats. The 75-kDa LNGFR was detected in membrane fractions of Sertoli cells, whereas the p75 LNGFR was not detected by Western blot in membrane fractions of round spermatids and primary spermatocytes. Interestingly, microsomal fractions of peritubular myoid cells were immunoreactive for a 65-kDa band on Western blots with the p75 LNGFR monoclonal antibody. Immunoblot analysis of the trk receptor in cell lysates of isolated cell types was inconclusive. Excess NGF beta and round spermatid protein, which is known to contain a NGF-like protein, were both capable of displacing the binding of 125I-NGF beta from the surface of Sertoli cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Seminiferous cord formation is regulated by hedgehog signaling in the marsupial.

    PubMed

    Chung, Jin Wei; Pask, Andrew J; Renfree, Marilyn B

    2012-03-01

    The signaling molecule DHH, secreted by Sertoli cells, has essential regulatory functions in testicular differentiation. DHH is required for the differentiation of peritubular myoid cells that line the seminiferous cords and steroidogenic Leydig cells. The testicular cords in Dhh-null male mice lack a basal lamina and develop abnormally. To date, the DHH-signaling pathway has never been examined outside of any eutherian mammals. This study examined the effects of inhibition of DHH signaling in a marsupial mammal, the tammar wallaby, by culturing gonads in vitro in the presence of the hedgehog-signaling inhibitors cyclopamine and forskolin. Disruption of hedgehog signaling in the tammar testes caused highly disorganized cord formation. SOX9 protein remained strongly expressed in Sertoli cells, laminin distribution was highly fragmented, and germ cells were distributed around the cortical regions of treated testes in an ovarianlike morphology. This suggests that hedgehog signaling regulates cord formation in the tammar wallaby testis as it does in eutherian mammals. These data demonstrate that the hedgehog pathway has been highly conserved in mammals for at least 160 million years.

  20. Immature Dental Pulp Stem Cells Showed Renotropic and Pericyte-Like Properties in Acute Renal Failure in Rats

    PubMed Central

    Barros, Michele A.; Martins, João Flávio Panattoni; Maria, Durvanei Augusto; Wenceslau, Crisitiane Valverde; De Souza, Dener Madeiro; Kerkis, Alexandre; Câmara, Niels Olsen S.; Balieiro, Julio Cesar C.; Kerkis, Irina

    2015-01-01

    Acute renal failure (ARF) is a common renal disease that can lead to high mortality. Recovery from ARF occurs with the replacement of necrotic tubular cells by functional tubular epithelial cells and the normalization of microvascular endothelial cell function in the peritubular capillaries. Conventional therapeutic techniques are often ineffective against ARF. Hence, stem cell therapies, which act through multiple trophic and regenerative mechanisms, are encouraging. We investigated the homing of human immature dental pulp stem cells (IDPSCs) after endovenous (EV) or intraperitoneal (IP) injection, in immunocompetent Wistar rats with ARF induced by intramuscular injection of glycerol, without the use of immunosuppression. The cells, which had been cryopreserved for 6 years, were CD105+, CD73+, CD44+, and partly, STRO-1+ and CD146+, and presented unaltered mesoderm differentiation potential. The presence of these cells in the tubular region of the kidney and in the peritubular capillaries was demonstrated. These cells accelerate tubular epithelial cell regeneration through significant increase of Ki-67-immunoreactive cells in damaged kidney. Flow cytometry analysis confirmed that IDPSCs home to the kidneys (EV 34.10% and IP 33.25%); a lower percentage of cells was found in the liver (EV 19.05% and IP 9.10%), in the muscles (EV 6.30% and IP 1.35%), and in the lungs (EV 2.0% and IP 1.85%). After infusion into rat, these cells express pericyte markers, such as CD146+, STRO-1+, and vascular endothelial growth factor (VEGF+). We found that IDPSCs demonstrate renotropic and pericyte-like properties and contributed to restore renal tubule structure in an experimental rat ARF model. PMID:26858898

  1. Prenatal exposure to pesticides disrupts testicular histoarchitecture and alters testosterone levels in male Caiman latirostris.

    PubMed

    Rey, Florencia; González, Marianela; Zayas, Marcelo A; Stoker, Cora; Durando, Milena; Luque, Enrique H; Muñoz-de-Toro, Mónica

    2009-07-01

    The increased use of agrochemical pesticides, such as atrazine (ATZ) and endosulfan (END), may have a significant impact on ecosystem health and biodiversity. The aim of this study was to investigate the consequences of in ovum exposure to ATZ and END on Caiman latirostris gonadal histo-functional features. Caiman eggs were collected from environmentally pristine areas and incubated in controlled conditions at male producing temperature (33 degrees C). At stage 20 of embryonic development, the sensitive stage for gonadal sex determination, eggs were exposed to one dose of either END or ATZ. Gonadal histo-morphology was examined in caiman hatchlings and serum levels of testosterone were measured. Regardless of treatment condition, all eggs incubated at 33 degrees C resulted in male hatchlings. Tortuous seminiferous tubules with increased perimeter, disrupted distribution of peritubular myoid cells (desmin positive), and emptied tubular lumens characterized the testes of pesticide-exposed caiman. An imbalance between proliferative activity and cell death was observed in the testes of caiman exposed to the higher doses of END, mainly due to a high frequency of apoptosis in intratubular cells. This altered cell turnover was associated with decreased testosterone levels. Prenatal exposure to only one dose of END and ATZ disrupted neonatal male gonadal histo-functional features. Alterations described here could have detrimental effects on the sexual maturation of the caiman and, ultimately, on the success of male caiman reproduction.

  2. Expression of CD34 and bcl-2 in phyllodes tumours, fibroadenomas and spindle cell lesions of the breast.

    PubMed

    Moore, T; Lee, A H

    2001-01-01

    Strong expression of CD34 and bcl-2 has been described in solitary fibrous tumours. It has been proposed that these lesions arise from long-lived mesenchymal cells. We tested the hypothesis that spindle cell lesions of the breast arise from similar mesenchymal cells in the mammary stroma. Sections of phyllodes tumours (26), fibroadenomas (15), myofibroblastomas (two), pseudoangiomatous hyperplasia (five) and myoid hamartoma (one) were stained immunohistochemically for CD34 and bcl-2. Conventional mammary carcinoma is known to be CD34-negative: we therefore stained 11 spindle cell carcinomas and one adenosquamous carcinoma. The mammary stroma, particularly around lobules, stained for CD34. All the lesions (except the carcinomas) showed spindle cell staining for CD34. There was more staining in fibroadenomas than in phyllodes tumours (especially malignant tumours). The staining in phyllodes tumours was typically patchy. In some there was increased or decreased staining adjacent to the epithelium. There were occasional spindle cells positive for bcl-2 in the normal perilobular stroma. bcl-2 was frequently expressed in spindle cells in fibroadenomas, phyllodes tumours and pseudoangiomatous hyperplasia, and rarely in the other lesions. The combined expression of CD34 and bcl-2 suggests that fibroadenomas, phyllodes tumours and pseudoangiomatous hyperplasia may arise from long-lived bcl-2-positive mesenchymal cells in the breast in a manner similar to that proposed for solitary fibrous tumours. The absence of CD34 staining in spindle cell carcinomas is of potential diagnostic value in the distinction from malignant phyllodes tumours in difficult cases.

  3. Vesicle-mediated phosphatidylcholine reapposition to the plasma membrane following hormone-induced phospholipase D activation.

    PubMed

    Coletti, D; Silvestroni, L; Naro, F; Molinaro, M; Adamo, S; Palleschi, S

    2000-04-10

    Phospholipase D (PLD) activation involved in signal transduction may lead to the hydrolysis of conspicuous amounts of phosphatidylcholine (PC). This study shows that PLD activation significantly alters the plasma membrane (PM) environment and the membrane exchange dynamics. PC-PLD activation in vasopressin (AVP)-stimulated L6 myogenic cells was accompanied by increased exocytosis and decreased membrane fluidity, as shown by transmission EM and fluorescence spectroscopy of trimethylammonium-diphenyl-hexatriene. AVP-induced exocytosis appeared to be brefeldin A-insensitive. PLD inhibition by Zn(2+) and PC de novo synthesis inhibition by hexadecylphosphocholine abolished AVP-induced vesicle traffic. Upon AVP stimulation, metabolically labeled PC decreased in PM, then transiently increased in microsomes, and returned to the prestimulus level in the PM within 5 min, a phenomenon requiring PC neosynthesis and microtubule functionality. Vesicle traffic with similar features was also observed after endothelin-1-induced PC-PLD activation in rat peritubular myoid cells. These results indicate that, in nonsecretory cells, exocytosis coupled to PC de novo synthesis restores PM-PC, conspicuously consumed during PLD-mediated signal transduction. Copyright 2000 Academic Press.

  4. Gravity Vector Changes Induce Alterations in Nervous and Testicular Cells in Cultures and in Testis Slices

    NASA Astrophysics Data System (ADS)

    Uva, B.; Strollo, F.; Ricci, F.; Masini, M. A.

    Cultured astrocytes, neurons and testicular cells (myoid, germ, Sertoli, Leydig cells) as well as rat testes and testes'slices, were subjected to modeled microgravity using a three dimensional Random Positioning Machine (10-6G) for 5min, 30min, 1h, 24h and 32h. Parallel cell cultures and tissues were submitted to hypergravity using an hyperfuge (2.5G) for the same period of time. At the end of the rotations the cultures and tissues were fixed, the tissue was sectioned (5 micron). All the specimens were processed for immunohistochemical identification of microtubules, mitochondria, 3 hydroxysteroid dehydrogenase, 17 hydroxysteroid dehydrogenase, caspase 7, heat shock proteins and identification of DNA fragmentation. At 5min at modeled microgravity and hypergravity, the histology of the cells in culture and the tissues was altered, microtubules and mitochondria were disorganized. Numerous cells underwent apoptosis. Immunostaining for enzymes involved in ion transmembrane transport, as Na+/K+ATPase and cotransporter proteins, and in steroidogenesis diminished or was abolished. At 1h in modeled microgravity or hypergravity, HSPs were expressed and ion transport enzymes as well as steroidogenic enzymes were again immunostainable. These data show that microgravity and hypergravity cause only transient alterations, and tissues and cells in cultures are able to adapt to different gravity conditions.

  5. Spontaneous myogenic differentiation of Flk-1-positive cells from adult pancreas and other nonmuscle tissues.

    PubMed

    Di Rocco, Giuliana; Tritarelli, Alessandra; Toietta, Gabriele; Gatto, Ilaria; Iachininoto, Maria Grazia; Pagani, Francesca; Mangoni, Antonella; Straino, Stefania; Capogrossi, Maurizio C

    2008-02-01

    At the embryonic or fetal stages, autonomously myogenic cells (AMCs), i.e., cells able to spontaneously differentiate into skeletal myotubes, have been identified from several different sites other than skeletal muscle, including the vascular compartment. However, in the adult animal, AMCs from skeletal muscle-devoid tissues have been described in only two cases. One is represented by thymic myoid cells, a restricted population of committed myogenic progenitors of unknown derivation present in the thymic medulla; the other is represented by a small subset of adipose tissue-associated cells, which we recently identified. In the present study we report, for the first time, the presence of spontaneously differentiating myogenic precursors in the pancreas and in other skeletal muscle-devoid organs such as spleen and stomach, as well as in the periaortic tissue of adult mice. Immunomagnetic selection procedures indicate that AMCs derive from Flk-1(+) progenitors. Individual clones of myogenic cells from nonmuscle organs are morphologically and functionally indistinguishable from skeletal muscle-derived primary myoblasts. Moreover, they can be induced to proliferate in vitro and are able to participate in muscle regeneration in vivo. Thus, we provide evidence that fully competent myogenic progenitors can be derived from the Flk-1(+) compartment of several adult tissues that are embryologically unrelated to skeletal muscle.

  6. Cytokines derived from activated human mononuclear cells markedly stimulate transferrin secretion by cultured Sertoli cells.

    PubMed

    Hoeben, E; Van Damme, J; Put, W; Swinnen, J V; Verhoeven, G

    1996-02-01

    There is considerable evidence that Sertoli cell function is controlled not only by hormones, but also by locally produced growth factors and cytokines. To gain more insight into the nature and effects of cytokines potentially involved in the control of Sertoli cell function, we incubated rat Sertoli cells with media conditioned by activated human peripheral blood mononuclear cells. Such media (PBMC-CM) are known to be an extremely rich source of a variety of cytokines. It was demonstrated that PMBC-CM and protein fractions derived from them stimulate Sertoli cell transferrin secretion and messenger RNA production more potently then peritubular cell-conditioned medium or FIRT (a combination of FSH, insulin, retinol, and testosterone). Transferrin secretion expressed per mg cell DNA was stimulated approximately 5-fold by peritubular cell-conditioned medium or FIRT and nearly 20-fold by PBMC-CM. The effects of PBMC-CM were accompanied by a limited increase in cAMP and a noticeable rise in cGMP. Affinity chromatography on a column coated with an antiserum directed against interleukin-1 beta (IL-1 beta) showed that part of the activity in the PBMC-CM was related to IL-1 beta. The remainder of the activity was largely retained by an affinity column coated with an antiserum that recognizes IL-6 and a number of other known and unknown cytokines. Purified IL-1 beta provoked a 2- to 3-fold stimulation of Sertoli cell transferrin secretion. More limited stimulatory effects were observed with IL-6. Neither of these cytokines or their combination approached the degree of stimulation observed with crude PBMC-CM, suggesting that other cytokines are involved. It is concluded that the mixture of cytokines present in PBMC-CM is a more powerful stimulator of Sertoli cell transferrin secretion than any other agonist known at the present time. IL-1 and IL-6 may be responsible for part of the observed effects, but one or more other cytokines are probably involved.

  7. Postischemic microvasculopathy and endothelial progenitor cell-based therapy in ischemic AKI: update and perspectives.

    PubMed

    Patschan, D; Kribben, A; Müller, G A

    2016-08-01

    Acute kidney injury (AKI) dramatically increases mortality of hospitalized patients. Incidences have been increased in recent years. The most frequent cause is transient renal hypoperfusion or ischemia which induces significant tubular cell dysfunction/damage. In addition, two further events take place: interstitial inflammation and microvasculopathy (MV). The latter evolves within minutes to hours postischemia and may result in permanent deterioration of the peritubular capillary network, ultimately increasing the risk for chronic kidney disease (CKD) in the long term. In recent years, our understanding of the molecular/cellular processes responsible for acute and sustained microvasculopathy has increasingly been expanded. The methodical approaches for visualizing impaired peritubular blood flow and increased vascular permeability have been optimized, even allowing the depiction of tissue abnormalities in a three-dimensional manner. In addition, endothelial dysfunction, a hallmark of MV, has increasingly been recognized as an inductor of both vascular malfunction and interstitial inflammation. In this regard, so-called regulated necrosis of the endothelium could potentially play a role in postischemic inflammation. Endothelial progenitor cells (EPCs), represented by at least two major subpopulations, have been shown to promote vascular repair in experimental AKI, not only in the short but also in the long term. The discussion about the true biology of the cells continues. It has been proposed that early EPCs are most likely myelomonocytic in nature, and thus they may simply be termed proangiogenic cells (PACs). Nevertheless, they reliably protect certain types of tissues/organs from ischemia-induced damage, mostly by modulating the perivascular microenvironment in an indirect manner. The aim of the present review is to summarize the current knowledge on postischemic MV and EPC-mediated renal repair. Copyright © 2016 the American Physiological Society.

  8. Stem cells derived from human amniotic fluid contribute to acute kidney injury recovery.

    PubMed

    Hauser, Peter V; De Fazio, Roberta; Bruno, Stefania; Sdei, Simona; Grange, Cristina; Bussolati, Benedetta; Benedetto, Chiara; Camussi, Giovanni

    2010-10-01

    Stem cells isolated from human amniotic fluid are gaining attention with regard to their therapeutic potential. In this work, we investigated whether these cells contribute to tubular regeneration after experimental acute kidney injury. Cells expressing stem cell markers with multidifferentiative potential were isolated from human amniotic fluid. The regenerative potential of human amniotic fluid stem cells was compared with that of bone marrow-derived human mesenchymal stem cells. We found that the intravenous injection of 3.5 × 10(5) human amniotic fluid stem cells into nonimmune-competent mice with glycerol-induced acute kidney injury was followed by rapid normalization of renal function compared with injection of mesenchymal stem cells. Both stem cell types showed enhanced tubular cell proliferation and reduced apoptosis. Mesenchymal stem cells were more efficient in inducing proliferation than amniotic fluid-derived stem cells, which, in contrast, were more antiapoptotic. Both cell types were found to accumulate within the peritubular capillaries and the interstitium, but amniotic fluid stem cells were more persistent than mesenchymal stem cells. In vitro experiments demonstrated that the two cell types produced different cytokines and growth factors, suggesting that a combination of different mediators is involved in their biological actions. These results suggest that the amniotic fluid-derived stem cells may improve renal regeneration in acute kidney injury, but they are not more effective than mesenchymal stem cells.

  9. Radiosensitivity of testicular cells in the fetal mouse

    SciTech Connect

    Vergouwen, R.P.F.A.; Roepers-Gajadien, H.L.; Rooij, D.G. de; Huiskamp, R.; Bas, R.J.; Davids, J.A.G.

    1995-01-01

    The effects of prenatal X irradiation on postnatal development of the CBA/P mouse testis was studied. At days 14, 15 and 18 post coitus pregnant female mice were exposed to single doses of X rays ranging from 0.25-1.5 Gy. Higher doses resulted in extensive loss of fetal mice. In the male offspring, at days 3 and 31 post partum, the numbers of gonocytes, type A spermatogonia and Sertoli cells per testis were determined using the disector method. Furthermore, after irradiation at day 15 post coitus, the numbers of Leydig cells, mesenchymal cells, macrophages, myoid cells, lymphatic endothelial cells, endothelial cells and perivascular cells per testis were also determined at days 3 and 31 post partum. At day 3 post partum, the number of germ cells was decreased after irradiation at days 14 and 15 post coitus. A D{sub o} value of 0.7 Gy was determined for the radiosensitivity of the gonocytes at day 14 post coitus. A D{sub o} value of 0.8 Gy was determined for the gonocytes at day 15 post coitus which, however, seems to be less accurate. No accurate D{sub o} value could be determined for the gonocytes at day 18 post coitus. At day 31 post partum, the repopulation of the seminiferous epithelium as well as testis weights and tubular diameters were more affected by irradiation with increasing age of the mice at the time of irradiation. The percentage of tubular cross sections showing spermatids decreased with increasing dose after irradiation at days 15 and 18 post coitus, but not after irradiation at day 14 post coitus. Furthermore, in tubular cross sections showing spermatids, exposure of testes to 1.25 and 1.5 Gy at day 18 post coitus resulted in significantly lower numbers of spermatids per cross section when compared to those testes exposed to the same doses at day 15 post coitus. 30 refs., 7 figs., 1 tab.

  10. Viability of rat spermatogenic cells in vitro is facilitated by their coculture with Sertoli cells in serum-free hormone-supplemented medium.

    PubMed Central

    Tres, L L; Kierszenbaum, A L

    1983-01-01

    Spermatogenic cells from 20- to 35-day-old rats were grown in vitro in the presence of Sertoli cells maintained in serum-free hormone/growth factor-supplemented medium and alternating high/low concentrations of follicle-stimulating hormone in the medium. In cell reaggregation experiments, spermatogenic cells reassociate with Sertoli cells but not with peritubular cells or cell-free substrate. Autoradiographic experiments using [3H]thymidine as a labeled precursor for DNA synthesis show that spermatogonia and preleptotene spermatocytes, connected by cytoplasmic bridges, have a synchronous S phase. [3H]Thymidine-labeled preleptotene spermatocytes progress until later stages of meiotic prophase. Time-lapse cinematographic studies of Sertoli/spermatogenic cell cocultures show three major movement patterns. While Sertoli cell cytoplasmic processes between adjacent cells display tensional forces, spermatogonia are engaged in oscillatory cell movements different from the nuclear rotation observed in meiotic prophase spermatocytes. Results of this study show that the proliferation of premeiotic cells and the differentiation of meiotic prophase cells do occur in vitro in association with Sertoli cells maintained in a medium that allows differentiated cell functions. Images PMID:6407012

  11. T-bet-positive mononuclear cell infiltration is associated with transplant glomerulopathy and interstitial fibrosis and tubular atrophy in renal allograft recipients.

    PubMed

    Yadav, Brijesh; Prasad, Narayan; Agrawal, Vinita; Jain, Manoj; Agarwal, Vikas; Jaiswal, Akhilesh; Bhadauria, Dharmendra; Sharma, R K; Gupta, Amit

    2015-04-01

    We aimed to study the role of T-bet-positive mononuclear cell infiltration in different compartments of kidney graft tissues in patients with chronic transplant glomerulopathy, interstitial fibrosis and tubular atrophy, and stable graft function. There were 80 living-related renal transplant recipients included (chronic transplant glomerulopathy, n = 28; interstitial fibrosis and tubular atrophy, n = 28; stable graft function, n = 24). Histologic characteristics and scoring for peritubular capillaritis, glomerulitis, interstitial fibrosis and tubular atrophy, and intimal arteritis were performed according to Banff 2007 classification and compared between the groups. Immunohistologic staining was performed for transcription factor T-bet, T-bet mononuclear cells were counted, and T-bet infiltration score was compared between groups. Patients in different groups had similar clinical profiles and human leukocyte antigen mismatches, except the groups differed in serum creatinine and proteinuria. The prevalence and scoring of peritubular capillaritis and glomerulitis were significantly higher in chronic transplant glomerulopathy than interstitial fibrosis and tubular atrophy (P = .001) and stable graft function (P < .001). Tubulitis was observed in 6 patients (21.4%) with chronic transplant glomerulopathy but no patients with interstitial fibrosis and tubular atrophy. The C4d/donor-specific antibody was positive in 100% patients with chronic transplant glomerulopathy, 0% patients with interstitial fibrosis and tubular atrophy, and 4.1 % patients with stable graft function. Interstitial fibrosis and tubular atrophy was seen in 100% patients who had interstitial fibrosis and tubular atrophy; in patients who had chronic transplant glomerulopathy, 24 patients (85.7%) had interstitial fibrosis and 78.5% patients had tubular atrophy. The degree and severity of T-bet-positive cell infiltration were significantly higher in chronic transplant glomerulopathy than interstitial

  12. Hematopoietic Stem Cell Transplantation Nephropathy Associated with Chronic Graft-versus-Host Disease without Extrarenal Involvement

    PubMed Central

    Ishida, Ryo; Shimizu, Akira; Kitani, Takashi; Nakata, Mayumi; Ota, Noriyoshi; Kado, Hiroshi; Shiotsu, Yayoi; Ishida, Mami; Tamagaki, Keiichi

    2016-01-01

    A 30-year-old woman with myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplantation (HSCT) derived from her HLA-matched sister six years previously. She received preconditioning total body irradiation with renal shielding and was subsequently administered cyclosporin A (CyA) as prophylaxis against graft-versus-host disease (GVHD). Four months after HSCT, asymptomatic proteinuria and glomerular hematuria developed during CyA tapering without obvious extrarenal involvements of GVHD, and persisted for six years. A renal biopsy revealed endothelial injury in the glomeruli, and the deposition of C4d was detected diffusely on glomerular capillaries and focally on peritubular capillaries, suggesting that nephropathy involved antibody- or complement-associated immune reactions. PMID:27725545

  13. Expression of cubilin in mouse testes and Leydig cells.

    PubMed

    Oh, Y S; Seo, J T; Ahn, H S; Gye, M C

    2016-04-01

    Cubilin (cubn) is a receptor for vitamins and various protein ligands. Cubn lacks a transmembrane domain but anchors to apical membranes by forming complexes with Amnionless or Megalin. In an effort to better understand the uptake of nutrients in testis, we analysed cubn expression in the developing mice testes. In testes, cubn mRNA increased from birth to adulthood. In the inter-stitium and isolated seminiferous tubules, neonatal increase in cubn mRNA until 14 days post-partum (pp) was followed by a marked increase at puberty (28 days pp). Cubn was found in the gonocytes, spermatogonia, spermatocytes and spermatids in the developing testes. In adult testes, strong Cubn immunoreactivity was found in the elongating spermatids, suggesting the role of Cubn in endocytosis during early spermiogenesis. In Sertoli cells and peritubular cells, Cubn immunoreactivity was weak throughout the testis development. In the inter-stitium, Cubn immunoreactivity was found in foetal Leydig cells, was weak to negligible in the stem cells and progenitor Leydig cells and was strong in immature and adult Leydig cells, demonstrating a positive association between Cubn and steroidogenic activity of Leydig cells. Collectively, these results suggest that Cubn may participate in the endocytotic uptake of nutrients in germ cells and somatic cells, supporting the spermatogenesis and steroidogenesis in mouse testes.

  14. Seasonal expression of androgen receptor, aromatase, and estrogen receptor alpha and beta in the testis of the wild ground squirrel (Citellus dauricus Brandt).

    PubMed

    Li, Q; Zhang, F; Zhang, S; Sheng, X; Han, X; Weng, Q; Yuan, Z

    2015-02-17

    The aim of this study was to investigate the seasonal expression of androgen receptor (AR), estrogen receptors α and β (ERα and ERβ) and aromatase cytochrome P450 (P450arom) mRNA and protein by real-time PCR and immunohistochemistry in the wild ground squirrel (WGS) testes. Histologically, all types of spermatogenic cells including mature spermatozoa were identified in the breeding season (April), while spermatogonia and primary spermatocytes were observed in the nonbreeding season (June), and spermatogonia, primary spermatocytes and secondary spermatocytes were found in pre-hibernation (September). AR was present in Leydig cells, peritubular myoid cells and Sertoli cells in the breeding season and pre-hibernation with more intense staining in the breeding season, whereas AR was only found in Leydig cells in the nonbreeding season; P450arom was expressed in Leydig cells, Sertoli cells and germ cells during the breeding season, whereas P450arom was found in Leydig cells and Sertoli cells during pre-hibernation, but P450arom was not present in the nonbreeding season; stronger immunohistochemical signal for ERα was present in Sertoli cells and Leydig cells during the breeding season; ERβ was only expressed in Leydig cells of the breeding season. Consistent with the immunohistochemical results, the mean mRNA level of AR, P450arom, ERα and ERβ were higher in the testes of the breeding season when compared to pre-hibernation and the nonbreeding season. These results suggested that the seasonal changes in spermatogenesis and testicular recrudescence and regression process in WGSs might be correlated with expression levels of AR, P450arom and ERs, and that estrogen and androgen may play an important autocrine/paracrine role to regulate seasonal testicular function.

  15. Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice

    SciTech Connect

    Semenza, G.L.; Nejfelt, M.K.; Gearhart, J.D.; Antonarakis, S.E. ); Koury, S.T. )

    1991-10-01

    Synthesis of erythropoietin, the primary humoral regulator or erythropoiesis, in liver and kidney is inducible by anemia or hypoxia. Analysis of human erythropoietin gene expression in transgenic mice revealed that sequences located 6-14 kilobases 5{prime} to the gene direct expression to the kidney, whereas sequences within the immediate 3{prime}-flanking region control hepatocyte-specific expression. Human erythropoietin transcription initiation sites were differentially utilized in liver and kidney. Inducible transgene expression was precisely targeted to peritubular interstitial cells in the renal cortex that synthesize endogenous mouse erythropoietin. These studies demonstrate that multiple erythropoietin gene regulatory elements control cello-type-specific expression and inducibility by a fundamental physiologic stimulus, hypoxia.

  16. Expanding the Spectrum of Colonic Manifestations in Tuberous Sclerosis: L-Cell Neuroendocrine Tumor Arising in the Background of Rectal PEComa.

    PubMed

    Kolin, David L; Duan, Kai; Ngan, Bo; Gerstle, J Ted; Krzyzanowska, Monika K; Somers, Gino R; Mete, Ozgur

    2017-07-21

    Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous condition that predisposes to numerous proliferative lesions, including perivascular epithelioid cell tumors (PEComas), such as lymphangioleiomyomatosis (LAM) and angiomyolipomas, and rare neuroendocrine neoplasms. We describe herein a TSC2-harboring tuberous sclerosis patient manifesting with a synchronous well-differentiated L-cell rectal neuroendocrine tumor and leiomyomatosis-like LAM of the rectum. The background large bowel wall was thickened by confluent nodular areas comprising vessels and spindle-to-epithelioid cells, which are immunoreactive for myoid (smooth muscle actin, muscle specific actin, and desmin) and melanocytic markers (HMB45, Melan-A, microphthalmia transcription factor, and CD117). With the exception of TSC-related pancreatic neuroendocrine tumors, the association between tuberous sclerosis and neuroendocrine neoplasms remains largely unknown in the gastrointestinal tract. Neuroendocrine tumorigenesis in tuberous sclerosis is often linked to inactivating mutations of TSC2 leading to aberrant activation of mammalian target of rapamycin (mTOR) pathway. In this report, we document, for the first time, two foci of L-cell rectal neuroendocrine tumor arising in the setting of tuberous sclerosis, thus broadening the spectrum of TSC-associated endocrine disorders. Moreover, to our knowledge, this is only the second documented case of gastrointestinal leiomyomatosis-like LAM in a patient with tuberous sclerosis. The current case provides further evidence that, similar to pancreatic neuroendocrine tumors, neuroendocrine tumors of the luminal gastrointestinal tract may also be a feature of tuberous sclerosis and can be seen in association with PEComas.

  17. Human amniotic fluid stem cell preconditioning improves their regenerative potential.

    PubMed

    Rota, Cinzia; Imberti, Barbara; Pozzobon, Michela; Piccoli, Martina; De Coppi, Paolo; Atala, Anthony; Gagliardini, Elena; Xinaris, Christodoulos; Benedetti, Valentina; Fabricio, Aline S C; Squarcina, Elisa; Abbate, Mauro; Benigni, Ariela; Remuzzi, Giuseppe; Morigi, Marina

    2012-07-20

    Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell-derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line-derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning.

  18. A Novel Mechanism of Bacterial Toxin Transfer within Host Blood Cell-Derived Microvesicles

    PubMed Central

    Ståhl, Anne-lie; Arvidsson, Ida; Johansson, Karl E.; Chromek, Milan; Rebetz, Johan; Loos, Sebastian; Kristoffersson, Ann-Charlotte; Békássy, Zivile D.; Mörgelin, Matthias; Karpman, Diana

    2015-01-01

    Shiga toxin (Stx) is the main virulence factor of enterohemorrhagic Escherichia coli, which are non-invasive strains that can lead to hemolytic uremic syndrome (HUS), associated with renal failure and death. Although bacteremia does not occur, bacterial virulence factors gain access to the circulation and are thereafter presumed to cause target organ damage. Stx was previously shown to circulate bound to blood cells but the mechanism by which it would potentially transfer to target organ cells has not been elucidated. Here we show that blood cell-derived microvesicles, shed during HUS, contain Stx and are found within patient renal cortical cells. The finding was reproduced in mice infected with Stx-producing Escherichia coli exhibiting Stx-containing blood cell-derived microvesicles in the circulation that reached the kidney where they were transferred into glomerular and peritubular capillary endothelial cells and further through their basement membranes followed by podocytes and tubular epithelial cells, respectively. In vitro studies demonstrated that blood cell-derived microvesicles containing Stx undergo endocytosis in glomerular endothelial cells leading to cell death secondary to inhibited protein synthesis. This study demonstrates a novel virulence mechanism whereby bacterial toxin is transferred within host blood cell-derived microvesicles in which it may evade the host immune system. PMID:25719452

  19. A novel mechanism of bacterial toxin transfer within host blood cell-derived microvesicles.

    PubMed

    Ståhl, Anne-lie; Arvidsson, Ida; Johansson, Karl E; Chromek, Milan; Rebetz, Johan; Loos, Sebastian; Kristoffersson, Ann-Charlotte; Békássy, Zivile D; Mörgelin, Matthias; Karpman, Diana

    2015-02-01

    Shiga toxin (Stx) is the main virulence factor of enterohemorrhagic Escherichia coli, which are non-invasive strains that can lead to hemolytic uremic syndrome (HUS), associated with renal failure and death. Although bacteremia does not occur, bacterial virulence factors gain access to the circulation and are thereafter presumed to cause target organ damage. Stx was previously shown to circulate bound to blood cells but the mechanism by which it would potentially transfer to target organ cells has not been elucidated. Here we show that blood cell-derived microvesicles, shed during HUS, contain Stx and are found within patient renal cortical cells. The finding was reproduced in mice infected with Stx-producing Escherichia coli exhibiting Stx-containing blood cell-derived microvesicles in the circulation that reached the kidney where they were transferred into glomerular and peritubular capillary endothelial cells and further through their basement membranes followed by podocytes and tubular epithelial cells, respectively. In vitro studies demonstrated that blood cell-derived microvesicles containing Stx undergo endocytosis in glomerular endothelial cells leading to cell death secondary to inhibited protein synthesis. This study demonstrates a novel virulence mechanism whereby bacterial toxin is transferred within host blood cell-derived microvesicles in which it may evade the host immune system.

  20. Human Amniotic Fluid Stem Cell Preconditioning Improves Their Regenerative Potential

    PubMed Central

    Rota, Cinzia; Imberti, Barbara; Pozzobon, Michela; Piccoli, Martina; De Coppi, Paolo; Atala, Anthony; Gagliardini, Elena; Xinaris, Christodoulos; Benedetti, Valentina; Fabricio, Aline S.C.; Squarcina, Elisa; Abbate, Mauro; Benigni, Ariela; Remuzzi, Giuseppe

    2012-01-01

    Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell–derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line–derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning. PMID:22066606

  1. Germ cell differentiation and proliferation in the developing testis of the South American plains viscacha, Lagostomus maximus (Mammalia, Rodentia).

    PubMed

    Gonzalez, C R; Muscarsel Isla, M L; Fraunhoffer, N A; Leopardo, N P; Vitullo, A D

    2012-08-01

    Cell proliferation and cell death are essential processes in the physiology of the developing testis that strongly influence the normal adult spermatogenesis. We analysed in this study the morphometry, the expression of the proliferation cell nuclear antigen (PCNA), cell pluripotency marker OCT-4, germ cell marker VASA and apoptosis in the developing testes of Lagostomus maximus, a rodent in which female germ line develops through abolished apoptosis and unrestricted proliferation. Morphometry revealed an increment in the size of the seminiferous cords with increasing developmental age, arising from a significant increase of PCNA-positive germ cells and a stable proportion of PCNA-positive Sertoli cells. VASA showed a widespread cytoplasmic distribution in a great proportion of proliferating gonocytes that increased significantly at late development. In the somatic compartment, Leydig cells increased at mid-development, whereas peritubular cells showed a stable rate of proliferation. In contrast to other mammals, OCT-4 positive gonocytes increased throughout development reaching 90% of germ cells in late-developing testis, associated with a conspicuous increase in circulating FSH from mid- to late-gestation. TUNEL analysis was remarkable negative, and only a few positive cells were detected in the somatic compartment. These results show that the South American plains viscacha displays a distinctive pattern of testis development characterized by a sustained proliferation of germ cells throughout development, with no signs of apoptosis cell demise, in a peculiar endocrine in utero ambiance that seems to promote the increase of spermatogonial number as a primary direct effect of FSH.

  2. Interaction of Oligomeric Breast Cancer Resistant Protein (BCRP) with Adjudin: A Male Contraceptive with Anti-Cancer Activity

    PubMed Central

    Cheng, Yan Ho; Jenardhanan, Pranitha; Mathur, Premendu P.; Qian, Xiaojing; Xia, Weiliang; Silvestrini, Bruno; Cheng, Chuen Yan

    2016-01-01

    Breast cancer resistant protein (BCRP, ABCG2) is an ATP-binding cassette (ABC) transporter, which together with two other ABC efflux drug pumps, namely P-glycoprotein (P-gp, ABCB1) and multidrug resistance-related protein 1 (MRP1, ABCC1) is the most important multidrug resistance protein found in eukaryotic cells including cells in the testis. However, unlike P-gp and MRP1, which are components of the Sertoli cell blood-testis barrier (BTB), BCRP is not expressed at the BTB in rodents and human testes. Instead, BCRP is expressed by peritubular myoid cells and endothelial cells of the lymphatic vessel in the tunica propria, residing outside the BTB. As such, the testis is equipped with two levels of defense against xenobiotics or drugs, preventing these harmful substances from entering the adluminal compartment to perturb meiosis and post-meiotic spermatid development: one at the level of the BTB conferred by P-gp and MRP1 and one at the tunica propria conferred by BCRP. The presence of drug transporters at the tunica propria as well as at the Sertoli cell BTB thus poses significant obstacles in developing non-hormonal contraceptives if these drugs (e.g., adjudin) exert their effects in germ cells behind the BTB, such as in the adluminal (apical) compartment of the seminiferous epithelium. Herein, we summarize recent findings pertinent to adjudin, a non-hormonal male contraceptive, and molecular interactions of adjudin with BCRP so that this information can be helpful to devise delivery strategies to evade BCRP in the tunica propria to improve its bioavailability in the testis. PMID:25620224

  3. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells.

    PubMed

    Cantaluppi, Vincenzo; Gatti, Stefano; Medica, Davide; Figliolini, Federico; Bruno, Stefania; Deregibus, Maria C; Sordi, Andrea; Biancone, Luigi; Tetta, Ciro; Camussi, Giovanni

    2012-08-01

    Endothelial progenitor cells are known to reverse acute kidney injury by paracrine mechanisms. We previously found that microvesicles released from these progenitor cells activate an angiogenic program in endothelial cells by horizontal mRNA transfer. Here, we tested whether these microvesicles prevent acute kidney injury in a rat model of ischemia-reperfusion injury. The RNA content of microvesicles was enriched in microRNAs (miRNAs) that modulate proliferation, angiogenesis, and apoptosis. After intravenous injection following ischemia-reperfusion, the microvesicles were localized within peritubular capillaries and tubular cells. This conferred functional and morphologic protection from acute kidney injury by enhanced tubular cell proliferation, reduced apoptosis, and leukocyte infiltration. Microvesicles also protected against progression of chronic kidney damage by inhibiting capillary rarefaction, glomerulosclerosis, and tubulointerstitial fibrosis. The renoprotective effect of microvesicles was lost after treatment with RNase, nonspecific miRNA depletion of microvesicles by Dicer knock-down in the progenitor cells, or depletion of pro-angiogenic miR-126 and miR-296 by transfection with specific miR-antagomirs. Thus, microvesicles derived from endothelial progenitor cells protect the kidney from ischemic acute injury by delivering their RNA content, the miRNA cargo of which contributes to reprogramming hypoxic resident renal cells to a regenerative program.

  4. The expression of epidermal growth factor (EGF) and its receptor (EGFR) during post-natal testes development in the yak.

    PubMed

    Pan, Y; Cui, Y; Yu, S; Zhang, Q; Fan, J; Abdul Rasheed, B; Yang, K

    2014-12-01

    Growth factors play critical role in cell proliferation, regulate tissue differentiation and modulate organogenesis. Several growth factors have been identified in the testes of various mammalian species in last few years. In present investigation, the objective was to determine the expression of epidermal growth factor (EGF) and the epidermal growth factor receptor (EGFR) in yak testicular tissue by relative quantitative real time polymerase chain reaction (RT-PCR), Western blot (WB) and immunohistochemistry (IHC) from mRNA and protein levels. The testicular tissues were collected from male yak at 6 and 24 months old. Results of RT-PCR and WB showed that the expression quantity of EGF and EGFR at 24 months of age was higher than at 6 months, and the increase rate of EGFR on mRNA and protein levels was higher than the increase rate EGF during post-natal testes development. Positive staining for EGF and EGFR was very low and mainly localized to Leydig cells testes at 6 months of age with immunohistochemistry, and seminiferous tubules were not observed. At 24 month of age, both the EGF and EGFR could be detected in Leydig cells, peritubular myoid cells, sertoli cells and germ cells of the yak testes. However, EGF and EGFR were localized to preferential adluminal compartment and basal compartment in the seminiferous tubules, respectively. In conclusion, the findings in present studies suggest that EGF and EGFR as important paracrine and/or autocrine regulators in yak testes development and spermatogenesis. © 2014 Blackwell Verlag GmbH.

  5. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin.

    PubMed

    Kobayashi, Hanako; Liu, Qingdu; Binns, Thomas C; Urrutia, Andres A; Davidoff, Olena; Kapitsinou, Pinelopi P; Pfaff, Andrew S; Olauson, Hannes; Wernerson, Annika; Fogo, Agnes B; Fong, Guo-Hua; Gross, Kenneth W; Haase, Volker H

    2016-05-02

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2-/- renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2-/- mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation.

  6. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin

    PubMed Central

    Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.

    2016-01-01

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

  7. Breast cancer resistance protein regulates apical ectoplasmic specialization dynamics stage specifically in the rat testis.

    PubMed

    Qian, Xiaojing; Mruk, Dolores D; Wong, Elissa W P; Cheng, C Yan

    2013-04-01

    Drug transporters determine the bioavailability of drugs in the testis behind the blood-testis barrier (BTB). Thus, they are crucial for male contraceptive development if these drugs (e.g., adjudin) exert their effects behind the BTB. Herein breast cancer resistance protein (Bcrp), an efflux drug transporter, was found to be expressed by both Sertoli and germ cells. Interestingly, Bcrp was not a component of the Sertoli cell BTB. Instead, it was highly expressed by peritubular myoid cells at the tunica propria and also endothelial cells of the microvessels in the interstitium at all stages of the epithelial cycle. Unexpectedly, Bcrp was found to be expressed at the Sertoli-step 18-19 spermatid interface but limited to stage VI-early VIII tubules, and an integrated component of the apical ectoplasmic specialization (apical ES). Apparently, Bcrp is being used by late-stage spermatids to safeguard their completion of spermiogenesis by preventing harmful drugs to enter these cells while they transform to spermatozoa. Also, the association of Bcrp with actin, Eps8 (epidermal growth factor receptor pathway substrate 8, an actin barbed end capping and bundling protein), and Arp3 (actin-related protein 3, a component of the Arp2/3 complex known to induce branched actin polymerization) at the apical ES suggest that Bcrp may be involved in regulating the organization of actin filament bundles at the site. Indeed, a knockdown of Bcrp by RNAi in the testis perturbed the apical ES function, disrupting spermatid polarity and adhesion. In summary, Bcrp is a regulator of the F-actin-rich apical ES in the testis.

  8. Platelet-Derived Growth Factor Receptor-Positive Pericytic Cells of White Adipose Tissue from Critical Limb Ischemia Patients Display Mesenchymal Stem Cell-Like Properties.

    PubMed

    Kim, Eo Jin; Seo, Sang Gyo; Shin, Hyuk Soo; Lee, Doo Jae; Kim, Ji Hye; Lee, Dong Yeon

    2017-06-01

    The pericytes in the blood vessel wall have recently been identified to be important in regulating vascular formation, stabilization, remodeling, and function. We isolated and identified pericyte-like platelet-derived growth factor receptor beta-positive (PDGFRβ+) cells from the stromal vascular fraction (SVF) of adipose tissue from critical limb ischemia (CLI) patients and investigated their potential as a reliable source of stem cells for cell-based therapy. De-identified subcutaneous fat tissues were harvested after amputation in CLI patients. Freshly isolated SVF cells and culture-expanded adipose-derived stem cells (ADSCs) were quantified using flow cytometry. A matrigel tube formation assay and multi-lineage differentiation were performed to assess pericytic and mesenchymal stem cell (MSC)-like characteristics of PDGFRβ+ ADSCs. PDGFRβ+ cells were located in the pericytic area of various sizes of blood vessels and coexpressed mesenchymal stem cell markers. PDGFRβ+ cells in freshly isolated SVF cells expressed a higher level of stem cell markers (CD34 and CXCR4) and mesenchymal markers (CD13, CD44, CD54, and CD90) than PDGFRβ- cells. In vitro expansion of PDGFRβ+ cells resulted in enrichment of the perivascular mesenchymal stem-like (PDGFRβ+/CD90+/CD45-/CD31-) cell fractions. The Matrigel tube formation assay revealed that PDGFRβ+ cells were located in the peritubular area. PDGFRβ+ ADSCs cells demonstrated a good multilineage differentiation potential. Pericyte-like PDGFRβ+ cells from the SVF of adipose tissue from CLI patients had MSC-like characteristics and could be amplified by in vitro culture with preservation of their cell characteristics. We believe PDGFRβ+ cells in the SVF of adipose tissue can be used as a reliable source of stem cells even in CLI patients.

  9. The structure and concentration of solids in photoreceptor cells studied by refractometry and interference microscopy.

    PubMed

    SIDMAN, R L

    1957-01-25

    Fragments of freshly obtained retinas of several vertebrate species were studied by refractometry, with reference to the structure of the rods and cones. The findings allowed a reassessment of previous descriptions based mainly on fixed material. The refractometric method was used also to measure the refractice indices and to calculate the concentrations of solids and water in the various cell segments. The main quantitative data were confirmed by interference microscopy. When examined by the method of refractometry the outer segments of freshly prepared retinal rods appear homogeneous. Within a few minutes a single eccentric longitudinal fiber appears, and transverse striations may develop. These changes are attributed to imbibition of water and swelling in structures normally too small for detection by light microscopy. The central "core" of outer segments and the chromophobic disc between outer and inner segments appear to be artifacts resulting from shrinkage during dehydration. The fresh outer segments of cones, and the inner segments of rods and cones also are described and illustrated. The volumes, refractive indices, concentrations of solids, and wet and dry weights of various segments of the photoreceptor cells were tabulated. Rod outer segments of the different species vary more than 100-fold in volume and mass but all have concentrations of solids of 40 to 43 per cent. Cone outer segments contain only about 30 per cent solids. The myoids, paraboloids, and ellipsoids of the inner segments likewise have characteristic refractive indices and concentrations of solids. Some of the limitations and particular virtues of refractometry as a method for quantitative analysis of living cells are discussed in comparison with more conventional biochemical techniques. Also the shapes and refractive indices of the various segments of photoreceptor cells are considered in relation to the absorption and transmission of light. The Stiles-Crawford effect can be accounted

  10. THE STRUCTURE AND CONCENTRATION OF SOLIDS IN PHOTORECEPTOR CELLS STUDIED BY REFRACTOMETRY AND INTERFERENCE MICROSCOPY

    PubMed Central

    Sidman, Richard L.

    1957-01-01

    Fragments of freshly obtained retinas of several vertebrate species were studied by refractometry, with reference to the structure of the rods and cones. The findings allowed a reassessment of previous descriptions based mainly on fixed material. The refractometric method was used also to measure the refractice indices and to calculate the concentrations of solids and water in the various cell segments. The main quantitative data were confirmed by interference microscopy. When examined by the method of refractometry the outer segments of freshly prepared retinal rods appear homogeneous. Within a few minutes a single eccentric longitudinal fiber appears, and transverse striations may develop. These changes are attributed to imbibition of water and swelling in structures normally too small for detection by light microscopy. The central "core" of outer segments and the chromophobic disc between outer and inner segments appear to be artifacts resulting from shrinkage during dehydration. The fresh outer segments of cones, and the inner segments of rods and cones also are described and illustrated. The volumes, refractive indices, concentrations of solids, and wet and dry weights of various segments of the photoreceptor cells were tabulated. Rod outer segments of the different species vary more than 100-fold in volume and mass but all have concentrations of solids of 40 to 43 per cent. Cone outer segments contain only about 30 per cent solids. The myoids, paraboloids, and ellipsoids of the inner segments likewise have characteristic refractive indices and concentrations of solids. Some of the limitations and particular virtues of refractometry as a method for quantitative analysis of living cells are discussed in comparison with more conventional biochemical techniques. Also the shapes and refractive indices of the various segments of photoreceptor cells are considered in relation to the absorption and transmission of light. The Stiles-Crawford effect can be accounted

  11. Acute T cell-mediated rejection accompanied by C4d-negative acute antibody-mediated rejection and cell debris in tubulus: A case report.

    PubMed

    Takamura, Tsuyoshi; Yamamoto, Izumi; Nakada, Yasuyuki; Katsumata, Haruki; Yamakawa, Takafumi; Furuya, Maiko; Mafune, Aki; Kobayashi, Akimitsu; Tanno, Yudo; Miki, Jun; Ohkido, Ichiro; Tsuboi, Nobuo; Yamamoto, Hiroyasu; Yokoo, Takashi

    2015-07-01

    Herein, we report a complicated case of acute T-cell-mediated rejection (ACR) accompanied by C4d-negative acute antibody-mediated rejection (AMR) and cell debris in tubulus. A 32 year-old male was admitted for an episode biopsy with a serum creatinine (S-Cr) level of 1.83 mg/dL and pyuria (20-29 white blood cells per high power field) 49 days following kidney transplantation. Histological features included three distinct entities, mainly, in one of the three specimens: 1) focal aggressive tubulointerstitial inflammatory cell infiltration with moderate tubulitis, 2) inflammatory cell infiltration in peritubular capillaries (including neutrophils) and glomerular capillaries, and 3) cell debris consisting mainly of neutrophils in tubulus. Laboratory examination revealed evidence of non-human leukocyte antigen donor-specific antibodies. However, urinary culture and gram staining were negative. Considering both the histological and laboratory findings, the patient was diagnosed with ACR accompanied by C4d-negative AMR and suspicion of a urinary tract infection (UTI). The patient was treated for three consecutive days with steroid pulse therapy. The patient's S-Cr level decreased to ~1.5 mg/dL following treatment and did not increase thereafter. A second biopsy 133 days following kidney transplantation showed an excellent response to treatment and revealed no evidence of rejection. This case report demonstrates the difficulty in the diagnosis of, and therapy for, the complicated pathological findings of ACR, AMR and suspicion of a UTI.

  12. CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.

    PubMed

    Kang, Yu; Zheng, Bo; Shen, Bin; Chen, Yongchang; Wang, Lei; Wang, Jianying; Niu, Yuyu; Cui, Yiqiang; Zhou, Jiankui; Wang, Hong; Guo, Xuejiang; Hu, Bian; Zhou, Qi; Sha, Jiahao; Ji, Weizhi; Huang, Xingxu

    2015-12-20

    Mutations in the DAX1 locus cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH), which manifest with primary adrenal insufficiency and incomplete or absent sexual maturation, respectively. The associated defects in spermatogenesis can range from spermatogenic arrest to Sertoli cell only syndrome. Conclusions from Dax1 knockout mouse models provide only limited insight into AHC/HH disease mechanisms, because mouse models exhibit more extensive abnormalities in testicular development, including disorganized and incompletely formed testis cords with decreased number of peritubular myoid cells and male-to-female sex reversal. We previously reported successful clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome targeting in cynomolgus monkeys. Here, we describe a male fetal monkey in which targeted genome editing using CRISPR/Cas9 produced Dax1-null mutations in most somatic tissues and in the gonads. This DAX1-deficient monkey displayed defects in adrenal gland development and abnormal testis architecture with small cords, expanded blood vessels and extensive fibrosis. Sertoli cell formation was not affected. This phenotype strongly resembles findings in human patients with AHC-HH caused by mutations in DAX1. We further detected upregulation of Wnt/β-catenin-VEGF signaling in the fetal Dax1-deficient testis, suggesting abnormal activation of signaling pathways in the absence of DAX1 as one mechanism of AHC-HH. Our study reveals novel insight into the role of DAX1 in HH and provides proof-of-principle for the generation of monkey models of human disease via CRISPR/Cas9-mediated gene targeting. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: background to spermatogenesis, spermatogonia, and spermatocytes.

    PubMed

    Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

    2010-04-01

    Spermatogenesis, a study of germ cell development, is a long, orderly, and well-defined process occurring in seminiferous tubules of the testis. It is a temporal event whereby undifferentiated spermatogonial germ cells evolve into maturing spermatozoa over a period of several weeks. Spermatogenesis is characterized by three specific functional phases: proliferation, meiosis, and differentiation, and it involves spermatogonia, spermatocytes, and spermatids. Germ cells at steps of development form various cellular associations or stages, with 6, 12, and 14 specific stages being identified in human, mouse, and rat, respectively. The stages evolve over time in a given area of the seminiferous tubule forming a cycle of the seminiferous epithelium that has a well-defined duration for a given species. In this part, we discuss the proliferation and meiotic phase whereby spermatogonia undergo several mitotic divisions to form spermatocytes that undergo two meiotic divisions to form haploid spermatids. In the rat, spermatogonia can be subdivided into several classes: stem cells (A(s)), proliferating cells (A(pr), A(al)), and differentiating cells (A(1)-A(4), In, B). They are dependent on a specific microenvironment (niche) contributed by Sertoli, myoid, and Leydig cells for proper development. Spermatogonia possess several surface markers whereby they can be identified from each other. During meiosis, spermatocytes undergo chromosomal pairing, synapsis, and genetic exchange as well as transforming into haploid cells following meiosis. The meiotic cells form specific structural entities such as the synaptonemal complex and sex body. Many genes involved in spermatogonial renewal and the meiotic process have been identified and shown to be essential for this event.

  14. Ramification of microglia, monocytes and macrophages in vitro: influences of various epithelial and mesenchymal cells and their conditioned media.

    PubMed

    Wilms, H; Hartmann, D; Sievers, J

    1997-02-01

    Microglial cells are able to switch between an "active" amoeboid and a ramified "resting" morphology during development and after experiencing lesions. We have previously shown that in vitro microglial morphology is controlled by their cellular environment, i. e. cells become ramified in astrocyte coculture but amoeboid on monolayers of fibroblasts. In the present study we have extended the analysis of the control of macrophage morphology by maintaining macrophages of different origins in coculture with different epithelial or mesenchymal cells and their conditioned media. Microglia, monocytes and spleen macrophages seeded onto monolayers of astrocytes, kidney epithelia or hepatoma cells developed the ramified morphology but remained amoeboid in fibroblast coculture. Ramification was also induced by media conditioned by these cells as well as by phorbolic esters, i.e. activators of protein kinase C. In double coculture assays, even small numbers of fibroblasts were able to override the "epithelial" influence. Likewise, microglia remained amoeboid, when incubated on several constituents of the extracellular matrix. These results indicate that macrophage ramification is an active process initiated by diffusible factors secreted by various epithelial cells, possibly acting upon a protein-kinase-C-related receptor. We interprete the modification of macrophage morphology as a functional adaptation to the surrounding type of tissue that is enforced by its constituent cells. Thus, the specific morphologies of microglia, hepatic von Kupffer's cells or peritubular kidney macrophages could be explained by similar epithelium-macrophage interaction.

  15. Sulforaphane Prevents Angiotensin II-Induced Testicular Cell Death via Activation of NRF2

    PubMed Central

    Wang, Yonggang; Xin, Ying; Tan, Yi

    2017-01-01

    Although angiotensin II (Ang II) was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN) via activating nuclear factor (erythroid-derived 2)-like 2 (NRF2), the governor of antioxidant-redox signalling. Eight-week-old male C57BL/6J wild type (WT) and Nrf2 gene knockout mice were treated with Ang II, in the presence or absence of SFN. In WT mice, SFN activated testicular NRF2 expression and function, along with a marked attenuation in Ang II-induced testicular oxidative stress, inflammation, endoplasmic reticulum stress, and apoptotic cell death. Deletion of the Nrf2 gene led to a complete abolishment of these efficacies of SFN. The present study indicated that Ang II may result in testicular apoptotic cell death, which can be prevented by SFN via the activation of NRF2. PMID:28191275

  16. The World Health Organization 2016 classification of testicular non-germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel.

    PubMed

    Idrees, Muhammad T; Ulbright, Thomas M; Oliva, Esther; Young, Robert H; Montironi, Rodolfo; Egevad, Lars; Berney, Daniel; Srigley, John R; Epstein, Jonathan I; Tickoo, Satish K

    2017-03-01

    The World Health Organization (WHO) released a new tumour classification for the genitourinary system in early 2016 after consensus by pathologists with expertise in these organs. It utilized the framework of the 2004 classification, and incorporated the most up-to-date information concerning these tumours. In testicular tumours, the majority of the changes occurred in the nomenclature and classification of germ cell tumours; however, several modifications were also made for non-germ cell tumours. Among sex cord-stromal tumours, sclerosing Sertoli cell tumour (SCT) is no longer recognized as a separate entity but as a morphological variant of SCT not otherwise specified (NOS), as CTNNB1 gene mutations have been noted in both neoplasms but not in the other forms of SCT. Similarly, the lipid cell variant is not separately classified, but is considered to be a morphological variant of SCT NOS. Large-cell calcifying SCT is recognized as a distinct entity that occurs either sporadically or in association with Carney complex, with the latter patients having a distinct germline PRKAR1A gene mutation. Intratubular large-cell hyalinizing Sertoli cell neoplasia is also accepted as a separate entity linked with Peutz-Jeghers syndrome. The subcategories of 'mixed' and 'incompletely differentiated' forms of sex cord/gonadal stromal tumours have been replaced by 'mixed and unclassified sex cord-stromal tumours'. New entities introduced in the latest WHO revision include: myoid gonadal stromal tumour and 'undifferentiated gonadal tissue', a putative precursor lesion of gonadoblastoma, whereas juvenile xanthogranuloma and haemangioma are included in the miscellaneous category of tumours.

  17. Influence of germ cells upon Sertoli cells during continuous low-dose rate gamma-irradiation of adult rats.

    PubMed

    Pinon-Lataillade, G; Vélez de la Calle, J F; Viguier-Martinez, M C; Garnier, D H; Folliot, R; Maas, J; Jégou, B

    1988-07-01

    The effects of continuous gamma-irradiation of adult rats at two low-dose rates (7 cGy and 12 cGy/day; up to a total dose of 9.1 Gy and 10.69 Gy 60Co gamma-ray, respectively) were investigated. Over a period of 3-131 days of irradiation, groups of experimental and control animals were killed. Body weight, testis, epididymis, prostate and seminal vesicle weights, the number of germ cells and Sertoli cells, tubular ultrastructure, epididymal and testicular levels of biologically active androgen-binding protein (ABP), and the plasma concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were monitored. Irradiation had no effect on body weight, whereas testicular and epididymal weight began to decrease following 35 and 50 days of irradiation at 7 and 12 cGy, respectively. At 7 cGy the target cells of the gamma-rays were essentially A spermatogonia, whereas at 12 cGy A spermatogonia and preleptotene spermatocytes were primarily affected. This resulted in a progressive and sequential dose-related reduction in the number of pachytene spermatocytes, round spermatids and late spermatids (LS). Under both irradiation procedures the Sertoli cell number remained unchanged whereas partial (7 cGy) or no change (12 cGy) was seen at the Leydig cell level. Whatever the irradiation protocol, from the time LS numbers decreased, vacuolisation of the Sertoli cell cytoplasm progressively occurred, followed by thickening and folding of the peritubular tissue. Moreover, in parallel to the drop in the number of these germ cell types, ABP production fell whereas FSH levels rose. A highly significant positive correlation was found between LS numbers and these Sertoli cell parameters. This study supports our previous concept of a control of certain important aspects of Sertoli cell function by late spermatids in the adult rat.

  18. Early-outgrowth bone marrow cells attenuate renal injury and dysfunction via an antioxidant effect in a mouse model of type 2 diabetes.

    PubMed

    Zhang, Yanling; Yuen, Darren A; Advani, Andrew; Thai, Kerri; Advani, Suzanne L; Kepecs, David; Kabir, M Golam; Connelly, Kim A; Gilbert, Richard E

    2012-08-01

    Cell therapy has been extensively investigated in heart disease but less so in the kidney. We considered whether cell therapy also might be useful in diabetic kidney disease. Cognizant of the likely need for autologous cell therapy in humans, we sought to assess the efficacy of donor cells derived from both healthy and diabetic animals. Eight-week-old db/db mice were randomized to receive a single intravenous injection of PBS or 0.5 × 10(6) early-outgrowth cells (EOCs) from db/m or db/db mice. Effects were assessed 4 weeks after cell infusion. Untreated db/db mice developed mesangial matrix expansion and tubular epithelial cell apoptosis in association with increased reactive oxygen species (ROS) and overexpression of thioredoxin interacting protein (TxnIP). Without affecting blood glucose or blood pressure, EOCs not only attenuated mesangial and peritubular matrix expansion, as well as tubular apoptosis, but also diminished ROS and TxnIP overexpression in the kidney of db/db mice. EOCs derived from both diabetic db/db and nondiabetic db/m mice were equally effective in ameliorating kidney injury and oxidative stress. The similarly beneficial effects of cells from healthy and diabetic donors highlight the potential of autologous cell therapy in the related clinical setting.

  19. Epithelial basal cells are distinct from dendritic cells and macrophages in the mouse epididymis.

    PubMed

    Shum, Winnie W; Smith, Tegan B; Cortez-Retamozo, Virna; Grigoryeva, Lubov S; Roy, Jeremy W; Hill, Eric; Pittet, Mikael J; Breton, Sylvie; Da Silva, Nicolas

    2014-05-01

    The epithelium that lines the epididymal duct establishes the optimal milieu in which spermatozoa mature, acquire motility, and are stored. This finely tuned environment also protects antigenic sperm against pathogens and autoimmunity, which are potential causes of transient or permanent infertility. The epididymal epithelium is pseudostratified and contains basal cells (BCs) that are located beneath other epithelial cells. Previous studies showed that in the mouse epididymis, BCs possess macrophage-like characteristics. However, we previously identified a dense population of cells belonging to the mononuclear phagocyte (MP) system (comprised of macrophages and dendritic cells) in the basal compartment of the mouse epididymis and showed that a subset of MPs express the macrophage marker F4/80. In the present study, we evaluate the distribution of BCs and MPs in the epididymis of transgenic CD11c-EYFP mice, in which EYFP is expressed exclusively in MPs, using antibodies against the BC marker keratin 5 (KRT5) and the macrophage marker F4/80. Immunofluorescence labeling for laminin, a basement membrane marker, showed that BCs and most MPs are located in the basal region of the epithelium. Confocal microscopy showed that in the initial segment, both BCs and MPs project intraepithelial extensions and establish a very intricate network. Flow cytometry experiments demonstrated that epididymal MPs and BCs are phenotypically distinct. BCs do not express F4/80, and MPs do not express KRT5. Therefore, despite their proximity and some morphological similarities with peritubular macrophages and dendritic cells, BCs do not belong to the MP system.

  20. Role of Somatic Testicular Cells during Mouse Spermatogenesis in Three-Dimensional Collagen Gel Culture System.

    PubMed

    Khajavi, Noushafarin; Akbari, Mohammad; Abdolsamadi, Hamid Reza; Abolhassani, Farid; Dehpour, Ahmad Reza; Koruji, Morteza; Habibi Roudkenar, Mehryar

    2014-02-03

    Spermatogonial stem cells (SSCs) are the only cell type that can restore fertility to an infertile recipient following transplantation. Much effort has been made to develop a protocol for differentiating isolated SSCs in vitro. Recently, three-dimensional (3D) culture system has been introduced as an appropriate microenvironment for clonal expansion and differentiation of SSCs. This system provides structural support and multiple options for several manipulation such as addition of different cells. Somatic cells have a critical role in stimulating spermatogenesis. They provide complex cell to cell interaction, transport proteins and produce enzymes and regulatory factors. This study aimed to optimize the culture condition by adding somatic testicular cells to the collagen gel culture system in order to induce spermatogenesis progression. In this experimental study, the disassociation of SSCs was performed by using a two-step enzymatic digestion of type I collagenase, hyaluronidase and DNase. Somatic testicular cells including Sertoli cells and peritubular cells were obtained after the second digestion. SSCs were isolated by Magnetic Activated Cell Sorting (MACS) using GDNF family receptor alpha-1 (Gfrα-1) antibody. Two experimental designs were investigated. 1. Gfrα-1 positive SSCs were cultured in a collagen solution. 2. Somatic testicular cells were added to the Gfrα-1 positive SSCs in a collagen solution. Spermatogenesis progression was determined after three weeks by staining of synaptonemal complex protein 3 (SCP3)-positive cells. Semi-quantitative Reverse Transcription PCR was undertaken for SCP3 as a meiotic marker and, Crem and Thyroid transcription factor-1 (TTF1) as post meiotic markers. For statistical analysis student t test was performed. Testicular supporter cells increased the expression of meiotic and post meiotic markers and had a positive effect on extensive colony formation. Collagen gel culture system supported by somatic testicular cells

  1. Somatostatin inhibits stem cell factor messenger RNA expression by Sertoli cells and stem cell factor-induced DNA synthesis in isolated seminiferous tubules.

    PubMed

    Goddard, I; Bauer, S; Gougeon, A; Lopez, F; Giannetti, N; Susini, C; Benahmed, M; Krantic, S

    2001-12-01

    Immature porcine Sertoli cells have been reported to be targets for the regulatory peptide somatostatin (SRIF), which inhibits the basal and FSH-induced proliferation of Sertoli cells through a decrease of cAMP production. In the present study, we show that SRIF inhibits both basal and FSH-stimulated expression of the stem cell factor (SCF), a Sertoli cell-specific gene. The SRIF-mediated inhibition of forskolin-triggered, but not of 8-bromoadenosine-cAMP-triggered, SCF mRNA expression demonstrates the involvement of adenylyl cyclase in underlying peptide actions. Moreover, these effects require functional coupling of specific plasma membrane receptors to adenylyl cyclase via inhibitory G proteins, because pertussis toxin prevents SRIF-mediated inhibition of SCF mRNA expression. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assays suggest the involvement of sst2 receptors in SRIF actions on Sertoli cells. The biological relevance of these data is supported by an SRIF-mediated decrease in SCF-induced incorporation of [(3)H]thymidine in isolated seminiferous tubules. In situ hybridization and confocal microscopy show that, in seminiferous tubules only, spermatogonia display both c-kit and sst2 receptors. Taken together, these results suggest that SCF-stimulated DNA synthesis can be inhibited by SRIF in spermatogonia, but not in Sertoli and peritubular cells. Combined RT-PCR and immunohistochemical approaches point toward spermatogonia and Leydig cells as the source of testicular SRIF. These data argue in favor of paracrine/autocrine SRIF actions in testis.

  2. Measurements of macula densa cell volume changes in isolated and perfused rabbit cortical thick ascending limb. I. Isosmotic and anisosmotic cell volume changes.

    PubMed

    González, E; Salomonsson, M; Müller-Suur, C; Persson, A E

    1988-06-01

    A method to measure time-dependent volume changes in macula densa (MD) cells is described. Cell volume is calculated from cell height measurements for which an image-splitting eyepiece is used. This paper presents the results of experiments designed to investigate the behaviour of the macula densa cells in anisosmotic media, to evaluate the cell volume response to sudden decreases in luminal or peritubular osmolarity and to examine the effect of different luminal NaCl concentrations on the steady-state isosmotic cell volume and on the regulatory volume response to anisosmotic media. The result showed that induced alteration in macula densa cell volume did not change macula densa surface area, but only cell height. The mean control cell height was 13.3 microns +/- 0.4. When MD cells were exposed to a luminal osmolarity of 180 mosM (control 300 mosM) they swelled only to 1.19 +/- 0.02 of the control value and with furosemide present to 1.13 +/- 0.02 or with low NaCl to 1.13 +/- 0.01. While after 5 min of exposure values were 1.15 +/- 0.03, 0.99 +/- 0.02 and 1.02 +/- 0.02, respectively. Addition of furosemide (10(-4) M) to the luminal perfusate (300 mosM) resulted in a rapid decrease in cell height to 0.8 +/- 0.02 in relation to control. When furosemide was removed cell volume was restituted (0.98 +/- 0.03). When luminal perfusate was replaced by mannitol and (12 mM Na+, 7 mM Cl-) cell volume decreased to 0.83 +/- 0.02 of the control value.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Overexpression of calmodulin in pancreatic beta cells induces diabetic nephropathy.

    PubMed

    Yuzawa, Yukio; Niki, Ichiro; Kosugi, Tomoki; Maruyama, Shoichi; Yoshida, Futoshi; Takeda, Motohiro; Tagawa, Yoshiaki; Kaneko, Yukiko; Kimura, Toshihide; Kato, Noritoshi; Yamamoto, Jyunichiro; Sato, Waichi; Nakagawa, Takahiko; Matsuo, Seiichi

    2008-09-01

    Recently, endothelial dysfunction induced by an uncoupling of vascular endothelial growth factor (VEGF) and nitric oxide has been implicated in the pathogenesis of diabetic nephropathy (DN). Investigating the pathogenesis of DN has been limited, however, because of the lack of animal models that mimic the human disease. In this report, pancreatic beta cell-specific calmodulin-overexpressing transgenic (CaMTg) mice, a potential new model of DN, are characterized with particular emphasis on VEGF and related molecules. CaMTg mice developed hyperglycemia at 3 wk and persistent proteinuria by 3 mo. Morphometric analysis showed considerable increases in the glomerular and mesangial areas with deposition of type IV collagen. Moreover, the pathologic hallmarks of human DN (mesangiolysis, Kimmelstiel-Wilson-like nodular lesions, exudative lesions, and hyalinosis of afferent and efferent arteries with neovascularization) were observed. In addition, increased VEGF expression was associated with an increased number of peritubular capillaries. Expression of endothelial nitric oxidase synthase was reduced and that of VEGF was markedly elevated in CaMTg mice kidney compared with nontransgenic mice. No differences in VEGF receptor-1 or VEGF receptor-2 expression were observed between CaMTg mice and nontransgenic kidneys. In summary, CaMTg mice develop most of the distinguishing lesions of human DN, and the elevated VEGF expression in the setting of diminished endothelial nitric oxide synthase expression may lead to endothelial proliferation and dysfunction. This model may prove useful in the study of the pathogenesis and treatment of DN.

  4. Myasthenia Gravis Thymus

    PubMed Central

    Leite, Maria I.; Jones, Margaret; Ströbel, Philipp; Marx, Alexander; Gold, Ralf; Niks, Erik; Verschuuren, Jan J.G.M.; Berrih-Aknin, Sonia; Scaravilli, Francesco; Canelhas, Aurea; Morgan, B. Paul; Vincent, Angela; Willcox, Nick

    2007-01-01

    In early-onset myasthenia gravis, the thymus contains lymph node-type infiltrates with frequent acetylcholine receptor (AChR)-specific germinal centers. Our recent evidence/two-step hypothesis implicates hyperplastic medullary thymic epithelial cells (expressing isolated AChR subunits) in provoking infiltration and thymic myoid cells (with intact AChR) in germinal center formation. To test this, we screened for complement attack in a wide range of typical generalized myasthenia patients. Regardless of the exact serology, thymi with sizeable infiltrates unexpectedly showed patchy up-regulation of both C5a receptor and terminal complement regulator CD59 on hyperplastic epithelial cells. These latter also showed deposits of activated C3b complement component, which appeared even heavier on infiltrating B cells, macrophages, and especially follicular dendritic cells. Myoid cells appeared particularly vulnerable to complement; few expressed the early complement regulators CD55, CD46, or CR1, and none were detectably CD59+. Indeed, when exposed to infiltrates, and especially to germinal centers, myoid cells frequently labeled for C1q, C3b (25 to 48%), or even the terminal C9, with some showing obvious damage. This early/persistent complement attack on both epithelial and myoid cells strongly supports our hypothesis, especially implicating exposed myoid cells in germinal center formation/autoantibody diversification. Remarkably, the similar changes place many apparent AChR-seronegative patients in the same spectrum as the AChR-seropositive patients. PMID:17675582

  5. Expanding the antibody-mediated component of plasma cell-rich acute rejection: A case series

    PubMed Central

    Uppin, M. S.; Gudithi, S.; Taduri, G.; Prayaga, A. K.; Raju, S. B.

    2016-01-01

    Renal allograft rejection is mediated by T-cells (T-cell mediated rejection) or by donor-specific antibodies (DSAs) (antibody mediated rejection, ABMR). Plasma cell-rich acute rejection (PCAR) is a unique entity due to its peculiar morphology and poor prognostic behavior. All allograft biopsies done at our center from January 2013 to October 2014 were reviewed, and seven were identified with a diagnosis of PCAR with antibody mediated rejection (ABMR). The allograft biopsies were classified as per the Banff 2007 schema. Immunohistochemistry with C4d, SV 40, CD3, CD20, CD138, kappa and lambda light chain was performed. Total 210 allograft biopsies were performed in the study period of which seven biopsies (3.3%) were diagnosed as PCAR with ABMR. All these were late ABMRs (more than 6 months) with median posttransplant duration of 17 months. The allograft biopsy showed features of PCAR along with glomerulitis, peritubular capillaritis, and positive C4d. DSA was positive in six patients. All the patients were treated with standard therapeutic measures of acute cellular rejection (ACR) and ABMR including steroids, plasma exchange, rituximab and intravenous immunoglobulins. All the patients had persistent graft dysfunction or graft loss on follow-up. PMID:27194831

  6. Mice spermatogonial stem cells transplantation induces macrophage migration into the seminiferous epithelium and lipid body formation: high-resolution light microscopy and ultrastructural studies.

    PubMed

    Dias, Felipe F; Chiarini-Garcia, Hélio; Parreira, Gleydes G; Melo, Rossana C N

    2011-12-01

    Transplantation of spermatogonial stem cells (SSCs), the male germline stem cells, in experimental animal models has been successfully used to study mechanisms involved in SSC self-renewal and to restore fertility. However, there are still many challenges associated with understanding the recipient immune response for SSCs use in clinical therapies. Here, we have undertaken a detailed structural study of macrophages elicited by SSCs transplantation in mice using both high-resolution light microscopy (HRLM) and transmission electron microscopy (TEM). We demonstrate that SSCs transplantation elicits a rapid and potent recruitment of macrophages into the seminiferous epithelium (SE). Infiltrating macrophages were derived from differentiation of peritubular monocyte-like cells into typical activated macrophages, which actively migrate through the SE, accumulate in the tubule lumen, and direct phagocytosis of differentiating germ cells and spermatozoa. Quantitative TEM analyses revealed increased formation of lipid bodies (LBs), organelles recognized as intracellular platforms for synthesis of inflammatory mediators and key markers of macrophage activation, within both infiltrating macrophages and Sertoli cells. LBs significantly increased in number and size in parallel to the augmented macrophage migration during different times post-transplantation. Our findings suggest that LBs may be involved with immunomodulatory mechanisms regulating the seminiferous tubule niche after SSC transplantation.

  7. Generation and characterization of polyclonal antibodies against mouse T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory domain by DNA-based immunization.

    PubMed

    Gao, Y; Cui, J; He, W; Yue, J; Yu, D; Cai, L; Xu, H; Yang, C; Chen, Z K; Zhou, H

    2014-01-01

    Mouse T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory domain (TIGIT) is a newly identified surface protein expressed in regulatory, memory, natural killer (NK), and activated T cells. Several studies indicate that mouse TIGIT is a vital immunomodulator that can control the activities of both NK and T cells and plays an important role in transplantation tolerance. In this study, we designed a vector, TIGIT-pcDNA3.1 (+), that encodes the complete coding sequence of mouse TIGIT. The vector was intramuscularly injected into rats, and then the specific antisera were harvested and purified using a protein A/G PLUS-agarose affinity column. Western blot and immunohistochemistry analyses revealed that the antibodies generated by DNA immunization can bind with the mouse TIGIT. Using these antibodies in immunoblots, TIGIT was detected in lysates of mouse organs, T cells from mouse lymph nodes, and recombinant mouse fusion protein of TIGIT and Fc fragment. Immunohistochemistry analysis of normal mouse kidney showed that immunoreactivity was located on endothelial cells of glomerular capillary loops and peritubular capillaries. Our results demonstrated that the DNA immunization of rats through intramuscular injection was a simple and easily available method of producing polyclonal antibodies that can be used to detect and analyze mouse TIGIT expression in mouse systems.

  8. Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

    PubMed Central

    Wang, Yingchun; Khan, Salman; Li, Wei; Zhang, Ping L.

    2015-01-01

    Sickle cell nephropathy (SCN) is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI). Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+) was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA) and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2) rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies. PMID:26697257

  9. Glial cell line-derived neurotrophic factor (GDNF) induced migration of spermatogonial cells in vitro via MEK and NF-kB pathways.

    PubMed

    Huleihel, M; Fadlon, E; Abuelhija, A; Piltcher Haber, E; Lunenfeld, E

    2013-01-01

    Glial cell line-derived neurotrophic factor (GDNF) regulates spermatogonial stem cell (SSC) maintenance. In the present study, we examined the levels and the cellular origin of GDNF in mouse testes during age-development, and the capacity of GDNF to induce migration of enriched GFR-α1 positive cells in vitro. The involvement of MAP kinase (MEK) and NF-kB signal pathways were examined. Our results show high levels of GDNF in testicular tissue of one-week-old mice which significantly decreased with age when examined by ELISA, real time PCR (qPCR) and immunofluorescence staining (IF) analysis. GDNF receptor (GFR-α1) expression was similar to GDNF when examined by qPCR analysis. Only Sertoli cell cultures (SCs) from one-week-old mice produced GDNF compared to SCs from older mice. However, peritubular cells from all the examined ages did not produce GDNF. The addition of recombinant GDNF (rGDNF) or supernatant from SCs from one-week-old mice to GFR-α1 positive cells induced their migration in vitro. This effect was significantly reduced by the addition of inhibitors to MEK (PD98059, U0126), NF-kB (PDTC) and IkB protease inhibitor (TPCK). Our results show for the first time the capacity of rGDNF and supernatant from SCs to induce migration of enriched GFR-α1 positive cells, and the possible involvement of MEK, NF-kB and IkB in this process. This study may suggest a novel role for GDNF in the regulation SSC niches and spermatogenesis.

  10. NF-kB overexpression and decreased immunoexpression of AR in the muscular layer is related to structural damages and apoptosis in cimetidine-treated rat vas deferens

    PubMed Central

    2013-01-01

    Background Cimetidine, histamine H2 receptors antagonist, has caused adverse effects on the male hormones and reproductive tract due to its antiandrogenic effect. In the testes, peritubular myoid cells and muscle vascular cells death has been associated to seminiferous tubules and testicular microvascularization damages, respectively. Either androgen or histamine H2 receptors have been detected in the mucosa and smooth muscular layer of vas deferens. Thus, the effect of cimetidine on this androgen and histamine-dependent muscular duct was morphologically evaluated. Methods The animals from cimetidine group (CMTG; n=5) received intraperitoneal injections of 100 mg/kg b.w. of cimetidine for 50 days; the control group (CG) received saline solution. The distal portions of vas deferens were fixed in formaldehyde and embedded in paraffin. Masson´s trichrome-stained sections were subjected to morphological and the following morphometrical analyzes: epithelial perimeter and area of the smooth muscular layer. TUNEL (Terminal deoxynucleotidyl-transferase mediated dUTP Nick End Labeling) method, NF-kB (nuclear factor kappa B) and AR (androgen receptors) immunohistochemical detection were also carried out. The birefringent collagen of the muscular layer was quantified in picrosirius red-stained sections under polarized light. The muscular layer was also evaluated under Transmission Electron Microscopy (TEM). Results In CMTG, the mucosa of vas deferens was intensely folded; the epithelial cells showed numerous pyknotic nuclei and the epithelial perimeter and the area of the muscular layer decreased significantly. Numerous TUNEL-labeled nuclei were found either in the epithelial cells, mainly basal cells, or in the smooth muscle cells which also showed typical features of apoptosis under TEM. While an enhanced NF-kB immunoexpression was found in the cytoplasm of muscle cells, a weak AR immunolabeling was detected in these cells. In CMTG, no significant difference was observed

  11. Recellularization of Well-Preserved Acellular Kidney Scaffold Using Embryonic Stem Cells

    PubMed Central

    Bonandrini, Barbara; Figliuzzi, Marina; Papadimou, Evangelia; Morigi, Marina; Perico, Norberto; Casiraghi, Federica; Sangalli, Fabio; Conti, Sara; Benigni, Ariela; Remuzzi, Giuseppe

    2014-01-01

    For chronic kidney diseases, there is little chance that the vast majority of world's population will have access to renal replacement therapy with dialysis or transplantation. Tissue engineering would help to address this shortcoming by regeneration of damaged kidney using naturally occurring scaffolds seeded with precursor renal cells. The aims of the present study were to optimize the production of three-dimensional (3D) rat whole-kidney scaffolds by shortening the duration of organ decellularization process using detergents that avoid nonionic compounds, to investigate integrity of extracellular matrix (ECM) structure and to enhance the efficacy of scaffold cellularization using physiological perfusion method. Intact rat kidneys were successfully decellularized after 17 h perfusion with sodium dodecyl sulfate. The whole-kidney scaffolds preserved the 3D architecture of blood vessels, glomeruli, and tubuli as shown by transmission and scanning electron microscopy. Micro-computerized tomography (micro-CT) scan confirmed integrity, patency, and connection of the vascular network. Collagen IV, laminin, and fibronectin staining of decellularized scaffolds were similar to those of native kidney tissues. After infusion of whole-kidney scaffolds with murine embryonic stem (mES) cells through the renal artery, and pressure-controlled perfusion with recirculating cell medium for 24 and 72 h, seeded cells were almost completely retained into the organ and uniformly distributed in the vascular network and glomerular capillaries without major signs of apoptosis. Occasionally, mES cells reached peritubular capillary and tubular compartment. We observed the loss of cell pluripotency and the start of differentiation toward meso-endodermal lineage. Our findings indicate that, with the proposed optimized protocol, rat kidneys can be efficiently decellularized to produce renal ECM scaffolds in a relatively short time, and rapid recellularization of vascular structures and

  12. Recellularization of well-preserved acellular kidney scaffold using embryonic stem cells.

    PubMed

    Bonandrini, Barbara; Figliuzzi, Marina; Papadimou, Evangelia; Morigi, Marina; Perico, Norberto; Casiraghi, Federica; Dipl, Chemistry; Sangalli, Fabio; Conti, Sara; Benigni, Ariela; Remuzzi, Andrea; Remuzzi, Giuseppe

    2014-05-01

    For chronic kidney diseases, there is little chance that the vast majority of world's population will have access to renal replacement therapy with dialysis or transplantation. Tissue engineering would help to address this shortcoming by regeneration of damaged kidney using naturally occurring scaffolds seeded with precursor renal cells. The aims of the present study were to optimize the production of three-dimensional (3D) rat whole-kidney scaffolds by shortening the duration of organ decellularization process using detergents that avoid nonionic compounds, to investigate integrity of extracellular matrix (ECM) structure and to enhance the efficacy of scaffold cellularization using physiological perfusion method. Intact rat kidneys were successfully decellularized after 17 h perfusion with sodium dodecyl sulfate. The whole-kidney scaffolds preserved the 3D architecture of blood vessels, glomeruli, and tubuli as shown by transmission and scanning electron microscopy. Micro-computerized tomography (micro-CT) scan confirmed integrity, patency, and connection of the vascular network. Collagen IV, laminin, and fibronectin staining of decellularized scaffolds were similar to those of native kidney tissues. After infusion of whole-kidney scaffolds with murine embryonic stem (mES) cells through the renal artery, and pressure-controlled perfusion with recirculating cell medium for 24 and 72 h, seeded cells were almost completely retained into the organ and uniformly distributed in the vascular network and glomerular capillaries without major signs of apoptosis. Occasionally, mES cells reached peritubular capillary and tubular compartment. We observed the loss of cell pluripotency and the start of differentiation toward meso-endodermal lineage. Our findings indicate that, with the proposed optimized protocol, rat kidneys can be efficiently decellularized to produce renal ECM scaffolds in a relatively short time, and rapid recellularization of vascular structures and

  13. Hypotonic cell volume regulation in mouse medullary thick ascending limb: effects of ADH.

    PubMed

    Hebert, S C; Sun, A

    1988-11-01

    Differential interference contrast microscopy was used in combination with standard electrophysiological techniques in the in vitro perfused mouse medullary thick ascending limb of Henle's loop (MAL) to evaluate the cell volume responses of this nephron segment during and following exposure to hypotonic media and to assess the role of antidiuretic hormone (ADH) and net salt absorption on the associated volume regulatory processes. Reductions in extracellular osmolality by 50 mosmol resulted in rapid increases in cell volume of approximately 20% with or without exposure to ADH. Cell volume recovery (volume-regulatory decrease, VRD) was much slower in the presence, than in the absence, of ADH. This hormone-mediated impairment of the VRD response could be overcome by the abolishment of net salt absorption with luminal 10(-4) M furosemide. An inverse linear relationship was observed between the rates of net salt absorption and VRD, indicating a finite ability of this nephron segment to enhance solute exit mechanisms whether induced by increases in transcellular traffic or by hypotonic cell swelling. Finally, returning to the isotonic media resulted in cell shrinkage under all conditions [+/- ADH and +(ADH and furosemide)] consistent with cell solute loss mediating VRD. However, recovery of cell volume back to the initial isotonic control value [post-VRD volume regulatory increase (VRI)] was only observed in ADH-treated tubules and was independent of net salt absorption. The post-VRD VRI response could be abolished by isohydric CO2-HCO3- removal or by addition of 10(-4) M amiloride to the peritubular medium. The latter results suggest that parallel Na+-H+ and Cl- -HCO3- exchangers located in basolateral membranes mediate the post-VRD VRI response.

  14. Functional role of hepatocyte growth factor receptor during sperm maturation.

    PubMed

    Catizone, A; Ricci, G; Galdieri, M

    2002-01-01

    Mammalian spermatozoa acquire motility and fertilizing capacity during their transit through the epididymis. Hepatocyte growth factor (HGF) is a pleiotropic cytokine with potent motogenic capacities that has been identified in different organs, including the mammalian male genital tract. In mice, HGF is present in the testis and, in large amounts, in the distal part of the epididymis. In prepuberal rats, we have demonstrated that HGF is synthesized by the peritubular myoid cells and in men, HGF is present in significant quantities in seminal plasma. It has been suggested that in mice, HGF has a role in initiating sperm motility, whereas in men, no significant correlations between HGF concentration and sperm motility have been found. In the present paper we report that in rats, HGF receptor, c-met, is expressed in testicular and epididymal spermatozoa. Through immunocytochemistry, we have found that c-met is exclusively localized on the head in testicular sperm. A different localization of c-met has been found in sperm isolated from caput and cauda epididymidis. Cells isolated from epididymal caput show a c-met localization exclusively restricted to the head in most cells. In a minority of caput epididymis spermatozoa the receptor is localized both in the cell head and along the flagellum. Spermatozoa isolated from the epididymal cauda were quite homogeneous, showing the receptor localized along the entire cell surface. We also report that HGF is synthesized and secreted by the rat epididymis as indicated by the scatter effect of epididymal cell homogenate and culture medium on MDCK cells. To clarify whether HGF is involved in the acquisition of sperm motility in the epididymis, its maintenance, or both, spermatozoa isolated from caput epididymidis have been cultured in medium alone or supplemented with HGF. The results obtained indicated that HGF has a positive effect on the maintenance of sperm motility which, in the absence of HGF, significantly decreases during

  15. Telocytes: novel interstitial cells present in the testis parenchyma of the Chinese soft-shelled turtle Pelodiscus sinensis.

    PubMed

    Yang, Ping; Ahmad, Nisar; Hunag, Yufei; Ullah, Shakeeb; Zhang, Qian; Waqas, Yasir; Liu, Yi; Li, Quanfu; Hu, Lisi; Chen, Qiusheng

    2015-12-01

    Telocytes (TCs) are novel interstitial cells that have been found in various organs, but the existence of TCs in the testes has not yet been reported. The present ultrastructural and immunohistochemical study revealed the existence of TCs and differentiate these cells from the peritubular cells (Pc) in contact with the surrounding structures in the testes. Firstly, our results confirmed the existence of two cell types surrounding seminiferous tubules; these were Pc (smooth muscle like characteristics) and TCs (as an outer layer around Pc). Telocytes and their long thin prolongations called telopodes (Tps) were detected as alternations of thin segments (podomers) and thick bead-like portions (podoms), the latter of which accommodate the mitochondria and vesicles. The spindle and irregularly shaped cell bodies were observed with small amounts of cytoplasm around them. In contrast, the processes of Pc contained abundant actin filaments with focal densities, irregular spine-like outgrowths and nuclei that exhibited irregularities similar to those of smooth muscle cells. The TCs connected with each other via homocellular and heterocellular junctions with Pc, Leydig cells and blood vessels. The Tps of the vascular TCs had bands and shed more vesicles than the other TCs. Immunohistochemistry (CD34) revealed strong positive expression within the TC cell bodies and Tps. Our data confirmed the existence and the contact of TCs with their surroundings in the testes of the Chinese soft-shelled turtle Pelodiscus sinensis, which may offer new insights for understanding the function of the testes and preventing and treating testicular disorders. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. Interference with Gsα-Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial Damage.

    PubMed

    Lachmann, Peter; Hickmann, Linda; Steglich, Anne; Al-Mekhlafi, Moath; Gerlach, Michael; Jetschin, Niels; Jahn, Steffen; Hamann, Brigitte; Wnuk, Monika; Madsen, Kirsten; Djonov, Valentin; Chen, Min; Weinstein, Lee S; Hohenstein, Bernd; Hugo, Christian P M; Todorov, Vladimir T

    2017-08-03

    Intracellular cAMP, the production of which is catalyzed by the α-subunit of the stimulatory G protein (Gsα), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gsα in JG cells and monitored them for 6 months after induction at 6 weeks of age. The knockout mapped exclusively to the JG cells of the Gsα-deficient animals. Progressive albuminuria occurred in Gsα-deficient mice. Compared with controls expressing wild-type Gsα alleles, the Gsα-deficient mice had enlarged glomeruli with mesangial expansion, injury, and FSGS at study end. Ultrastructurally, the glomerular filtration barrier of the Gsα-deficient animals featured endothelial gaps, thickened basement membrane, and fibrin-like intraluminal deposits, which are classic signs of thrombotic microangiopathy. Additionally, we found endothelial damage in peritubular capillaries and vasa recta. Because deficiency of vascular endothelial growth factor (VEGF) results in thrombotic microangiopathy, we addressed the possibility that Gsα knockout may result in impaired VEGF production. We detected VEGF expression in JG cells of control mice, and cAMP agonists regulated VEGF expression in cultured renin-producing cells. Our data demonstrate that Gsα deficiency in JG cells of adult mice results in kidney injury, and suggest that JG cells are critically involved in the maintenance and protection of the renal microvascular endothelium. Copyright © 2017 by the American Society of Nephrology.

  17. Reevaluation of erythropoietin production by the nephron.

    PubMed

    Nagai, Takanori; Yasuoka, Yukiko; Izumi, Yuichiro; Horikawa, Kahori; Kimura, Miho; Nakayama, Yushi; Uematsu, Takayuki; Fukuyama, Takashi; Yamazaki, Taiga; Kohda, Yukimasa; Hasuike, Yukiko; Nanami, Masayoshi; Kuragano, Takahiro; Kobayashi, Noritada; Obinata, Masuo; Tomita, Kimio; Tanoue, Akito; Nakanishi, Takeshi; Kawahara, Katsumasa; Nonoguchi, Hiroshi

    2014-06-27

    Erythropoietin production has been reported to occur in the peritubular interstitial fibroblasts in the kidney. Since the erythropoietin production in the nephron is controversial, we reevaluated the erythropoietin production in the kidney. We examined mRNA expressions of erythropoietin and HIF PHD2 using high-sensitive in situ hybridization system (ISH) and protein expression of HIF PHD2 using immunohistochemistry in the kidney. We further investigated the mechanism of erythropoietin production by hypoxia in vitro using human liver hepatocell (HepG2) and rat intercalated cell line (IN-IC cells). ISH in mice showed mRNA expression of erythropoietin in proximal convoluted tubules (PCTs), distal convoluted tubules (DCTs) and cortical collecting ducts (CCDs) but not in the peritubular cells under normal conditions. Hypoxia induced mRNA expression of erythropoietin largely in peritubular cells and slightly in PCTs, DCTs, and CCDs. Double staining with AQP3 or AE1 indicated that erythropoietin mRNA expresses mainly in β-intercalated or non α/non β-intercalated cells of the collecting ducts. Immunohistochemistry in rat showed the expression of HIF PHD2 in the collecting ducts and peritubular cells and its increase by anemia in peritubular cells. In IN-IC cells, hypoxia increased mRNA expression of erythropoietin, erythropoietin concentration in the medium and protein expression of HIF PHD2. These data suggest that erythropoietin is produced by the cortical nephrons mainly in the intercalated cells, but not in the peritubular cells, in normal hematopoietic condition and by mainly peritubular cells in hypoxia, suggesting the different regulation mechanism between the nephrons and peritubular cells. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. The Distribution and Density of Water Mice (Xeromys myoides) in the Maroochy River of Southeast Queensland, Australia

    PubMed Central

    Kaluza, Janina; Donald, R. Lesley; Gynther, Ian C.; Leung, Luke K-P.; Allen, Benjamin L.

    2016-01-01

    The water mouse is a small and vulnerable rodent present in coastal areas of south-west Papua New Guinea, and eastern Queensland and the Northern Territory of Australia. Current knowledge regarding the distribution of the water mouse is incomplete and the loss of one local population has been documented in southeast Queensland, a region where pressures from urban and industrial development are increasing. Water mouse populations have not been studied intensively enough to enable the primary factors responsible for the local decline to be identified. We surveyed the distribution and density of the water mouse along the Maroochy River of southeast Queensland, near the southern extent of the species’ range, to gather baseline data that may prove valuable for detecting any future decline in this population’s size or health. All areas of suitable habitat were surveyed on foot or by kayak or boat over a three-year period. We found 180 water mouse nests, of which ~94% were active. Permanent camera monitoring of one nest and limited supplementary live trapping suggested that up to three individual mice occupied active nests. Water mouse density was estimated to be 0.44 per hectare of suitable habitat along the Maroochy River. Should future monitoring reveal an adverse change in the water mouse population on the Maroochy River, a concerted effort should be made to identify contributing factors and address proximate reasons for the decline. PMID:26789521

  19. The Distribution and Density of Water Mice (Xeromys myoides) in the Maroochy River of Southeast Queensland, Australia.

    PubMed

    Kaluza, Janina; Donald, R Lesley; Gynther, Ian C; Leung, Luke K-P; Allen, Benjamin L

    2016-01-01

    The water mouse is a small and vulnerable rodent present in coastal areas of south-west Papua New Guinea, and eastern Queensland and the Northern Territory of Australia. Current knowledge regarding the distribution of the water mouse is incomplete and the loss of one local population has been documented in southeast Queensland, a region where pressures from urban and industrial development are increasing. Water mouse populations have not been studied intensively enough to enable the primary factors responsible for the local decline to be identified. We surveyed the distribution and density of the water mouse along the Maroochy River of southeast Queensland, near the southern extent of the species' range, to gather baseline data that may prove valuable for detecting any future decline in this population's size or health. All areas of suitable habitat were surveyed on foot or by kayak or boat over a three-year period. We found 180 water mouse nests, of which ~94% were active. Permanent camera monitoring of one nest and limited supplementary live trapping suggested that up to three individual mice occupied active nests. Water mouse density was estimated to be 0.44 per hectare of suitable habitat along the Maroochy River. Should future monitoring reveal an adverse change in the water mouse population on the Maroochy River, a concerted effort should be made to identify contributing factors and address proximate reasons for the decline.

  20. Secretory and basal cells of the epithelium of the tubular glands in the male Mullerian gland of the caecilian Uraeotyphlus narayani (Amphibia: Gymnophiona).

    PubMed

    George, Jancy M; Smita, Matthew; Kadalmani, Balamuthu; Girija, Ramankutty; Oommen, Oommen V; Akbarsha, Mohammad A

    2004-12-01

    Caecilians are exceptional among the vertebrates in that males retain the Mullerian duct as a functional glandular structure. The Mullerian gland on each side is formed from a large number of tubular glands connecting to a central duct, which either connects to the urogenital duct or opens directly into the cloaca. The Mullerian gland is believed to secrete a substance to be added to the sperm during ejaculation. Thus, the Mullerian gland could function as a male accessory reproductive gland. Recently, we described the male Mullerian gland of Uraeotyphlus narayani using light and transmission electron microscopy (TEM) and histochemistry. The present TEM study reports that the secretory cells of both the tubular and basal portions of the tubular glands of the male Mullerian gland of this caecilian produce secretion granules in the same manner as do other glandular epithelial cells. The secretion granules are released in the form of structured granules into the lumen of the tubular glands, and such granules are traceable to the lumen of the central duct of the Mullerian gland. This is comparable to the situation prevailing in the epididymal epithelium of several reptiles. In the secretory cells of the basal portion of the tubular glands, mitochondria are intimately associated with fabrication of the secretion granules. The structural and functional organization of the epithelium of the basal portion of the tubular glands is complicated by the presence of basal cells. This study suggests the origin of the basal cells from peritubular tissue leukocytes. The study also indicates a role for the basal cells in acquiring secretion granules from the neighboring secretory cells and processing them into lipofuscin material in the context of regression of the Mullerian gland during the period of reproductive quiescence. In these respects the basal cells match those in the epithelial lining of the epididymis of amniotes.

  1. Human adipose stromal cell therapy improves survival and reduces renal inflammation and capillary rarefaction in acute kidney injury.

    PubMed

    Collett, Jason A; Traktuev, Dmitry O; Mehrotra, Purvi; Crone, Allison; Merfeld-Clauss, Stephanie; March, Keith L; Basile, David P

    2017-07-01

    Damage to endothelial cells contributes to acute kidney injury (AKI) by causing impaired perfusion, while the permanent loss of the capillary network following AKI has been suggested to promote chronic kidney disease. Therefore, strategies to protect renal vasculature may impact both short-term recovery and long-term functional preservation post-AKI. Human adipose stromal cells (hASCs) possess pro-angiogenic and anti-inflammatory properties and therefore have been tested as a therapeutic agent to treat ischaemic conditions. This study evaluated hASC potential to facilitate recovery from AKI with specific attention to capillary preservation and inflammation. Male Sprague Dawley rats were subjected to bilateral ischaemia/reperfusion and allowed to recover for either two or seven days. At the time of reperfusion, hASCs or vehicle was injected into the suprarenal abdominal aorta. hASC-treated rats had significantly greater survival compared to vehicle-treated rats (88.7% versus 69.3%). hASC treatment showed hastened recovery as demonstrated by lower creatinine levels at 48 hrs, while tubular damage was significantly reduced at 48 hrs. hASC treatment resulted in a significant decrease in total T cell and Th17 cell infiltration into injured kidneys at 2 days post-AKI, but an increase in accumulation of regulatory T cells. By day 7, hASC-treated rats showed significantly attenuated capillary rarefaction in the cortex (15% versus 5%) and outer medulla (36% versus 18%) compared to vehicle-treated rats as well as reduced accumulation of interstitial alpha-smooth muscle actin-positive myofibroblasts. These results suggest for the first time that hASCs improve recovery from I/R-induced injury by mechanisms that contribute to decrease in inflammation and preservation of peritubular capillaries. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Plasma cell-rich rejection accompanied by acute antibody-mediated rejection in a patient with ABO-incompatible kidney transplantation.

    PubMed

    Furuya, Maiko; Yamamoto, Izumi; Kobayashi, Akimitsu; Nakada, Yasuyuki; Sugano, Naoki; Tanno, Yudo; Ohkido, Ichiro; Tsuboi, Nobuo; Yamamoto, Hiroyasu; Yokoyama, Keitaro; Yokoo, Takashi

    2014-06-01

    We report a case of plasma cell-rich rejection accompanied by acute antibody-mediated rejection in a patient with ABO-incompatible kidney transplantation. A 33-year-old man was admitted for an episode biopsy; he had a serum creatinine (S-Cr) level of 5.7 mg/dL 1 year following primary kidney transplantation. Histological features included two distinct entities: (1) a focal, aggressive tubulointerstitial inflammatory cell (predominantly plasma cells) infiltration with moderate tubulitis; and (2) inflammatory cell infiltration (including neutrophils) in peritubular capillaries. Substantial laboratory examination showed that the patient had donor-specific antibodies for DQ4 and DQ6. Considering both the histological and laboratory findings, we diagnosed him with plasma cell-rich rejection accompanied by acute antibody-mediated rejection. We started 3 days of consecutive steroid pulse therapy three times every 2 weeks for the former and plasma exchange with intravenous immunoglobulin (IVIG) for the latter histological feature. One month after treatment, a second allograft biopsy showed excellent responses to treatment for plasma cell-rich rejection, but moderate, acute antibody-mediated rejection remained. Therefore, we added plasma exchange with IVIG again. After treatment, allograft function was stable, with an S-Cr level of 2.8 mg/dL. This case report demonstrates the difficulty of the diagnosis of, and treatment for, plasma cell-rich rejection accompanied by acute antibody-mediated rejection in a patient with ABO-incompatible kidney transplantation. We also include a review of the related literature.

  3. Malignant gastrointestinal neuroectodermal tumor: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract.

    PubMed

    Stockman, David L; Miettinen, Markku; Suster, Saul; Spagnolo, Dominic; Dominguez-Malagon, Hugo; Hornick, Jason L; Adsay, Volkan; Chou, Pauline M; Amanuel, Benhur; Vantuinen, Peter; Zambrano, Eduardo V

    2012-06-01

    The clinical, histologic, immunophenotypic, ultrastructural, and molecular features of a distinctive gastrointestinal tumor are described. Sixteen patients, 8 women and 8 men aged 17 to 77 years (mean age, 42 y; 63% less than 40 y) presented with abdominal pain, intestinal obstruction, and an abdominal mass. Mean tumor size was 5.2 cm (range, 2.4 to 15.0 cm). The tumors arose in the small bowel (10), stomach (4), and colon (2) and were histologically characterized by a sheet-like or nested population of epithelioid or oval-to-spindle cells with small nucleoli and scattered mitoses. Five cases showed focal clearing of the cytoplasm. Scattered osteoclast-type multinucleated giant cells were present in 8 cases. The tumor cells were positive for S-100 protein, SOX10, and vimentin in 100% of cases, for CD56 in 70%, for synaptophysin in 56%, for NB84 in 50%, for NSE in 45%, and for neurofilament protein in 14% of cases. All cases tested were negative for specific melanocytic, gastrointestinal stromal tumors, epithelial, and myoid markers. Ultrastructural examination of 5 cases showed features of primitive neuroectodermal cells with clear secretory vesicles, dense-core granules, occasional gap junctions, and no evidence of melanogenesis. EWSR1 gene rearrangement was assessed by fluorescence in situ hybridization in 14 cases. Twelve cases (86%) showed split EWSR1 signal consistent with a chromosomal translocation involving EWSR1. One case showed extra intact signals, indicating that the nuclei possessed either extra copies of the EWSR1 gene or chromosome 22 polysomy. Only 1 case showed no involvement of the EWSR1 gene. Six cases demonstrated rearrangement of the partner fusion gene ATF1 (46%), and 3 showed rearrangement of CREB1 (23%); 2 cases lacked rearrangement of either partner gene. Clinical follow-up was available in 12 patients and ranged from 1.5 to 106 months. Six patients died of their tumors (mean survival, 32 mo; 83% less than 24 mo). At last follow-up, 4

  4. Heme oxygenase-1 modulates the expression of the anti-angiogenic chemokine CXCL-10 in renal tubular epithelial cells.

    PubMed

    Datta, Dipak; Dormond, Olivier; Basu, Aninda; Briscoe, David M; Pal, Soumitro

    2007-10-01

    The turnover and repair of peritubular capillaries is essential for the maintenance of normal renal tubular structure and function. Following injury, ineffective capillary repair/angiogenesis may result in chronic disease, whereas effective repair attenuates the injury process. Thus the process of healing in the kidney is likely dependent on an intricate balance between angiogenic and anti-angiogenic factors to maintain the renal microvasculature. We investigated the role of cytoprotective heme oxygenase-1 (HO-1) in the regulation of chemokines in human renal proximal tubular epithelial cells (RPTEC). Transfection of RPTEC with a HO-1 overexpression plasmid promoted a marked induction in the mRNA expression of the anti-angiogenic chemokine CXCL-10, along with angiogenic chemokines CXCL-8 and CCL-2. Utilizing a CXCL-10 promoter luciferase construct, we observed that HO-1-induced CXCL-10 expression is regulated at the transcriptional level. However, with increases in concentrations and time intervals of HO-1 induction, there was a marked decrease in CXCL-10 expression. Using pharmacological inhibitors, we found that HO-1-induced early robust CXCL-10 transcription is mediated through the PKC signaling pathway. To evaluate the functional significance of HO-1-induced CXCL-10 release, we cultured human vascular endothelial cells in the absence and presence of culture supernatants of the HO-1 plasmid-transfected RPTEC. We found that early (24 h) supernatants of the HO-1 plasmid-transfected cells (RPTEC) inhibited endothelial cell proliferation, and this effect was blocked by addition of a CXCL-10 neutralizing antibody. Thus HO-1 can regulate the expression of the anti-angiogenic CXCL-10 and may alter a critical balance between angiogenic vs. anti-angiogenic factors that are important to maintain renal microvasculature during injury.

  5. Enhanced homing permeability and retention of bone marrow stromal cells (BMSC) by non-invasive pulsed focused ultrasound

    PubMed Central

    Ziadloo, Ali; Burks, Scott R.; Gold, Eric M.; Lewis, Bobbi K.; Chaudhry, Aneeka; Merino, Maria J.; Frenkel, Victor; Frank, Joseph A.

    2012-01-01

    Bone marrow stromal cells (BMSC) have shown significant promise in the treatment of disease, but their therapeutic efficacy is often limited by inefficient homing of systemically-administered cells, which results in low numbers of cells accumulating at sites of pathology. BMSC home to areas of inflammation where local expression of integrins and chemokine gradients are present. We demonstrated that non-destructive pulsed focused ultrasound (pFUS) exposures that emphasize the mechanical effects of ultrasound-tissue interactions induced local and transient elevations of chemoattractants (i.e., cytokines, integrins, and growth factors) in the murine kidney. pFUS-induced upregulation of cytokines occurred through approximately 1 day post-treatment and returned to contralateral kidney levels by day 3. This window of significant increases in cytokine expression was accompanied by local increases of other trophic factors and integrins that have been shown to promote BMSC homing. When BMSC were administered intravenously following pFUS treatment to a single kidney, enhanced homing, permeability, and retention of BMSC was observed in the treated kidney versus the contralateral kidney. Histological analysis revealed up to 8 times more BMSC in the peritubular regions of the treated kidneys on days 1 and 3 post-treatment. Furthermore, cytokine levels in pFUS-treated kidneys following BMSC administration were found to be similar to controls, suggesting modulation of cytokine levels by BMSC. pFUS could potentially improve cell-based therapies as a noninvasive modality to target BMSC homing by establishing local chemoattractant gradients and increasing expression of integrins to enhance tropism of BMSC toward treated tissues. PMID:22593018

  6. Kinetics of potassium transport across single distal tubules of rat kidney

    PubMed Central

    de Mello-Aires, Margarida; Giebisch, Gerhard; Malnic, Gerhard; Curran, Peter F.

    1973-01-01

    1. The transport of potassium across the distal tubular epithelium was studied in vivo in rats on a normal potassium intake and in rats in which distal tubular potassium secretion was either stimulated by potassium loading or the I.V. administration of a 5% sodium bicarbonate solution or in which potassium secretion was suppressed by dietary deprivation of potassium or sodium. 2. 42K was used to measure unidirectional fluxes across the luminal and peritubular cell membranes and to assess the magnitude of cellular potassium partaking in the transport process. This was accomplished by the simultaneous perfusion of the peritubular capillary network with 42K-Ringer and of the distal tubular lumen with initially tracer-free solution. From the steady-state flux and the time course of tracer washout into the lumen after discontinuing the peritubular perfusion, unidirectional fluxes, rate coefficients of ion transfer and cellular transport pools could be measured. 3. Transepithelial movement of potassium involves mixing with a variable cellular potassium transport pool. The latter is significantly elevated in conditions of enhanced distal tubular potassium secretion; cellular potassium labelling is reduced in conditions in which potassium secretion has been suppressed by potassium deprivation. 4. Evidence is presented that changes in the peritubular transport pattern are primarily responsible for modifications of potassium translocation. Thus, stimulation of potassium secretion is associated with increased peritubular potassium uptake; a reduced potassium uptake across the peritubular cell membrane accounts for the fall in potassium secretion in potassium-depleted animals. Whereas passive entry of potassium across the peritubular membrane is augmented in potassium-loaded animals, the induction of metabolic alkalosis by the administration of 5% sodium bicarbonate stimulates active potassium uptake across the peritubular cell membrane. Sodium deprivation stimulates active

  7. [Differentiation of mesenchymal stem cells into vascular endothelial cells in treatment of chronic aristolochic acid nephropathy: experiment with rats].

    PubMed

    Zou, Jie; Feng, Jiang-Min; Li, Wei; Guo, Wei; Wang, Li-Ning

    2008-03-11

    To investigate the potentiality of mesenchymal stem cells (MSCs) to differentiate into vascular endothelia cells (ECs) in peritubular capillary (PTC) in chronic aristolochic acid nephropathy (CAAN). MSCs were isolated from a male Wistar rat. The surface markers were identified with flow cytometry. Thirty female Wistar rats were randomly divided into 3 equal groups: Group A, perfused intragastrically with decoction of Caulis Aristolochiae manshuriensis for 12 weeks to establish CAAN models, Group B, perfused intragastrically with decoction of Caulis Aristolochiae manshuriensis for 12 weeks to establish CAAN models and injected with the MSCs by caudal vein in the 12th week, and Group C, perfused intragastrically with drinking water for 12 weeks and then injected with normal saline by caudal vein to be used as normal controls. At week 16, specimens of blood and urine were collected to detect the blood urea nitrogen (BUN), serum creatinine (Scr) and urine protein, and then the rats were killed with their kidneys taken out. Sex-determining region of the Y chromosome-fluorescence in situ hybridization (SRY-FISH) test with carboxyfluorescein (FAM)- was used to detect the cells originated from the source of the male donors. Immunohistochemistry was used to detect CD34, marker antigen pf EC. HE and Masson staining and electron microscope were used to observe the pathology of the kidney. Immunohistochemistry and RT-PCR were used to detect the expression of vascular endothelial growth factor (VEGF). Correlation analysis was conducted to study the relationships among these indices. Y chromosome and CD34 double positive cells could be seen in the renal tissue of Group B. At week 16, the density of PTC and integrated optical density of VEGF of Group A were (5.3 +/- 0.8)/0.13 mm2 and (2.8 +/- 0.4) x 10(3) respectively, both significantly lower than those of Group B [(26.5 +/- 1.6)/0.13 mm2 and (14.7 +/- 1.7) x 10(3) respectively, both P < 0.011]. The Scr and urine protein of

  8. Mechanism of basolateral membrane H+/OH-/HCO-3 transport in the rat proximal convoluted tubule. A sodium-coupled electrogenic process

    PubMed Central

    1985-01-01

    In order to examine the mechanism of basolateral membrane H+/OH-/HCO-3 transport, a method was developed for the measurement of cell pH in the vivo doubly microperfused rat proximal convoluted tubule. A pH- sensitive fluorescein derivative, (2',7')-bis(carboxyethyl)-(5,6)- carboxyfluorescein, was loaded into cells and relative changes in fluorescence at two excitation wavelengths were followed. Calibration was accomplished using nigericin with high extracellular potassium concentrations. When luminal and peritubular fluids were pH 7.32, cell pH was 7.14 +/- 0.01. Decreasing peritubular pH from 7.32 to 6.63 caused cell pH to decrease from 7.16 +/- 0.02 to 6.90 +/- 0.03. This effect occurred at an initial rate of 2.4 +/- 0.3 pH units/min, and was inhibited by 0.5 mM SITS. Lowering the peritubular sodium concentration from 147 to 25 meq/liter caused cell pH to decrease from 7.20 +/- 0.03 to 6.99 +/- 0.01. The effect of peritubular sodium concentration on cell pH was inhibited by 0.5 mM SITS, but was unaffected by 1 mM amiloride. In addition, when peritubular pH was decreased in the total absence of luminal and peritubular sodium, the rate of cell acidification was 0.2 +/- 0.1 pH units/min, a greater than 90% decrease from that in the presence of sodium. Cell depolarization achieved by increasing the peritubular potassium concentration caused cell pH to increase, an effect that was blocked by peritubular barium or luminal and peritubular sodium removal. Lowering the peritubular chloride concentration from 128 to 0 meq/liter did not affect cell pH. These results suggest the existence of an electrogenic, sodium-coupled H+/OH- /HCO-3 transport mechanism on the basolateral membrane of the rat proximal convoluted tubule. PMID:2999293

  9. Hypoxia response and VEGF-A expression in human proximal tubular epithelial cells in stable and progressive renal disease.

    PubMed

    Rudnicki, Michael; Perco, Paul; Enrich, Julia; Eder, Susanne; Heininger, Dorothea; Bernthaler, Andreas; Wiesinger, Martin; Sarközi, Rita; Noppert, Susie-Jane; Schramek, Herbert; Mayer, Bernd; Oberbauer, Rainer; Mayer, Gert

    2009-03-01

    Proteinuria, inflammation, chronic hypoxia, and rarefaction of peritubular capillaries contribute to the progression of renal disease by affecting proximal tubular epithelial cells (PTECs). To study the transcriptional response that separates patients with a stable course from those with a progressive course of disease, we isolated PTECs by laser capture microdissection from cryocut tissue sections of patients with proteinuric glomerulopathies (stable n=20, progressive n=11) with a median clinical follow-up of 26 months. Gene-expression profiling and a systems biology analysis identified activation of intracellular vascular endothelial growth factor (VEGF) signaling and hypoxia response pathways in progressive patients, which was associated with upregulation of hypoxia-inducible-factor (HIF)-1alpha and several HIF target genes, such as transferrin, transferrin-receptor, p21, and VEGF-receptor 1, but downregulation of VEGF-A. The inverse expression levels of HIF-1alpha and VEGF-A were significantly superior in predicting clinical outcome as compared with proteinuria, renal function, and degree of tubular atrophy and interstitial fibrosis at the time of biopsy. Interactome analysis showed the association of attenuated VEGF-A expression with the downregulation of genes that usually stimulate VEGF-A expression, such as epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and HIF-2alpha. In vitro experiments confirmed the positive regulatory effect of EGF and IGF-1 on VEGF-A transcription in human proximal tubular cells. Thus, in progressive but not in stable proteinuric kidney disease, human PTECs show an attenuated VEGF-A expression despite an activation of intracellular hypoxia response and VEGF signaling pathways, which might be due to a reduced expression of positive coregulators, such as EGF and IGF-1.

  10. Influences of follicle-stimulating hormone, proteases, and antiproteases on permeability of the barrier generated by Sertoli cells in a two-chambered assembly

    SciTech Connect

    Ailenberg, M.; Fritz, I.B.

    1989-03-01

    Factors have been identified that influence the integrity of the barrier generated by Sertoli cells (SC) in culture in a two-chambered assembly. The permeability of the barrier was assessed by determining rates of equilibration of (3H)methoxyinulin or (86Rb)Cl across the Sertoli cell monolayer. The complete system consisted of a confluent monolayer of SC maintained on an extracellular matrix (Matrigel)-coated filter together with peritubular cells on the opposite side of the filter. In confirmation of previous results, levels of plasminogen activator (PA) activity secreted were increased by treatment of SC with FSH or with cAMP derivatives ((Bu)2cAMP (dbcAMP)). PA levels in the culture medium were inversely related to times required for 50% equilibration of (3H)methoxyinulin across the SC monolayer. Thus, elevated PA levels, elicited by stimulation with FSH or dbcAMP, were associated with a decreased integrity of the barrier generated by SC preparations maintained in serum-free medium in the complete system. The increase in permeability of the barrier in SC elicited by FSH dbcAMP could be prevented, however, by the addition of various antiproteases. FSH actions on barrier function were complex. Effects of FSH that favored barrier integrity were most readily detected when proteolytic activity was inhibited. The addition of intact serum increased the integrity of the barrier, but acid-treated serum depleted of antiproteases had no such effect. We advance the hypothesis that proteases are implicated in modulation of the formation and maintenance of the seminiferous tubule barrier by SC.

  11. Relationships between neurokinin receptor-expressing interstitial cells of Cajal and tachykininergic nerves in the gut.

    PubMed

    Faussone-Pellegrini, Maria-Simonetta

    2006-01-01

    The so-called interstitial cells of Cajal (ICC) are distributed throughout the muscle coat of the alimentary tract with characteristic intramural location and species-variations in structure and staining. Several ICC sub-types have been identified: ICC-DMP, ICC-MP, ICC-IM, ICC-SM. Gut motility is regulated by ICC and each sub-type is responsible for the electrical activities typical of each gut region and/or muscle layer. The interstitial position of the ICC between nerve endings and smooth muscle cells has been extensively considered. Some of these nerve endings contain tachykinins. Three distinct tachykinin receptors (NK1r, NK2r and NK3r) have been demonstrated by molecular biology. Each of them binds with different affinities to a series of tachykinins (SP, NKA and NKB). In the ileum, SP-immunoreactive (SP-IR) nerve fibers form a rich plexus at the deep muscular plexus (DMP), distributed around SP-negative cells, and ICC-DMP intensely express the SP-preferred receptor NK1r; conversely a faint NK1r-IR is detected on the ICC-MP and mainly after receptor internalization was induced by agonists. ICC-IM are never stained in laboratory mammals, while those of the human antrum are NK1r- IR. RT-PCR conducted on isolated ileal ICC-MP and gastric ICC-IM showed that these cells express NK1r and NK3r. Colonic ICC, except those in humans, do not express NK1r-IR, at least in resting conditions. Outside the gut, NK1r-IR cells were seen in the arterial wall and exocrine pancreas. In the mouse gut only, NK1r-IR is present in non-neuronal cells located within the intestinal villi, so-called myoid cells, which are c-kit-negative and alpha-smooth muscle actin-positive. Immunohistochemistry and functional studies confirmed that ICC receive input from SP-IR terminals, with differences between ICC sub-types. In the rat, very early after birth, NK1r is expressed by the ICC-DMP and SP by the related nerve varicosities. Studies on pathological conditions are few and those on mutant

  12. Anti-Angiotensin II Type 1 Receptor and Anti-Endothelial Cell Antibodies: A Cross-Sectional Analysis of Pathological Findings in Allograft Biopsies

    PubMed Central

    Philogene, Mary Carmelle; Bagnasco, Serena; Kraus, Edward S.; Montgomery, Robert A.; Dragun, Duska; Leffell, Mary S.; Zachary, Andrea A.; Jackson, Annette M.

    2017-01-01

    Background This is a cross-sectional study designed to evaluate the histologic characteristics of graft injury in the presence of anti-angiotensin II type 1 receptor antibody (AT1R-Ab) and anti-endothelial cell antibody (AECA). Methods Non-HLA antibody testing was included in the posttransplant evaluation for 70 kidney recipients. Biopsies were performed for cause for 47 patients and as protocol for the remaining 23 patients. Biopsy-proven rejection was defined according to the Banff 2009-2013 criteria. AT1R-Ab was measured on an ELISA platform. Patients were divided into 3 groups based on AT1R-Ab levels (>17, 10-17, and <10 U/ml). AECA was evaluated using an endothelial cell crossmatch (ECXM) in patients whose HLA antibody level was insufficient to cause a positive flow cytometric crossmatch. Results AT1R-Ab levels were higher in patients diagnosed with antibody mediated rejection compared to those with no rejection (P = 0.004). Glomerulitis (g) and peritubular capillaritis (ptc) scores were independently correlated with increased AT1R-Ab concentrations in the presence or absence of HLA-DSA (P = 0.007 and 0.03 for g scores; p = 0.005 and 0.03 for ptc scores). Patients with a positive ECXM had higher AT1R-Ab levels compared to those with a negative ECXM (P = 0.005). Microcirculation inflammation (MCI = g + ptc score) was higher in patients with a positive ECXM and with AT1R-Ab >17 U/ml, although this did not reach statistical significance (P = 0.07). Conclusions The data show an association between non-HLA antibodies detected in the ECXM and AT1R ELISA and microvascular injury observed in antibody mediated rejection. PMID:27222934

  13. Relationships between neurokinin receptor-expressing interstitial cells of Cajal and tachykininergic nerves in the gut

    PubMed Central

    Faussone-Pellegrini, Maria-Simonetta

    2006-01-01

    The so-called interstitial cells of Cajal (ICC) are distributed throughout the muscle coat of the alimentary tract with characteristic intramual location and species-variations in structure and staining. Several ICC sub-types have been identified: ICC-DMP, ICC-MP, ICC-IM, ICC-SM. Gut motility is regulated by ICC and each sub-type is responsible for the electrical activities typical of each gut region and/or muscle layer. The interstitial position of the ICC between nerve endings contain tachykinins. Three distinct tachykinin receptors (NK1r, NK2r and NK3r) have been demonstrated by molecular biology. Each of them binds with different affinities to a series of tachykinins (SP, NKA and NKB). In the ileum, SP-immunoreactive (SP-IR) nerve fibers form a rich plexus at the deep muscular plexus (DMP), distributed around SP-negative cells, and ICC-DMP intensely express the SP-preffered receptor NK1r; conversely a faint NK1r-IR is detected on the ICC-MP and mainly after receptor internalization was induced by agonists. ICC-IM are never stained in laboratory mammals, while those of the human, antrum are NK1r-IR. RT-PCR conducted on isolated idleal ICC-MP and gastric ICC-IM showed that these cells express NK1r and NK3r. Colonic ICC, except those in humans, do not express NK1r-IR, at least in resting conditions. Outside the gut, NK1r-IR cells were seen in the arterial wall and exocrine pancreas. In the mouse gut only, NK1r-IR is present in non-neuronal cells located within the intestinal villi, so-called myoid cells, which are c-kit-negative and α-smooth muscle actin-positive. Immunohistochemistry and functional studies confirmed that ICC receive input from SP-IR terminals, with differences between ICC sub-types. In the rat, very early after birth, NK1r is expressed by the ICC-DMP and SP by the related nerve varicosities. Studies on pathological conditions are few and those on mutant strains practically absent. It has only been reported that in the inflamed ileum of rats the

  14. Reflections on the "intrathymic pathogenesis" of myasthenia gravis.

    PubMed

    Hohlfeld, Reinhard; Wekerle, Hartmut

    2008-09-15

    The beneficial effects of thymectomy argue for a causal role of the thymus in myasthenia gravis (MG). The MG thymus contains acetylcholine receptor (AChR), which is expressed by myoid cells (whole AChR), and by medullary thymic epithelial cells (AChR subunits). The myoid cells are closely associated with antigen-presenting dendritic cells, helper T cells, and antibody-producing B cells in lymphoid follicles ("lymphofollicular hyperplasia"). Thus, all the cellular components required to initiate and maintain an autoimmune response to AChR are present in the MG thymus. It is unlikely that the cellular alterations in the thymus are secondary to an ongoing peripheral immune response, because they are absent in experimental autoimmune myasthenia gravis.

  15. Myopericytoma proliferating in an unusual anastomosing multinodular fashion.

    PubMed

    Inoue, Takuya; Misago, Noriyuki; Asami, Akihiko; Tokunaga, Osamu; Narisawa, Yutaka

    2016-05-01

    We herein describe a case of myopericytoma that proliferated in an unusual fashion. Myopericytoma is described as a group of rare, benign, dermal or subcutaneous tumors that are characterized histologically by a striking, concentric, perivascular proliferation of spindle cells and showing apparent differentiation towards perivascular myoid cells. Myopericytoma forms a morphological continuum with myofibroma/myofibromatosis, glomus tumor and angioleiomyoma. The patient was a 64-year-old woman who demonstrated a recurrent ulcer on an atrophic plaque on her left shin. A histopathological examination of the plaque demonstrated that tumor cells proliferated in an anastomosing multinodular fashion along the vessels in the dermis and subcutaneous tissue. In those nodules, there were numerous, small, concentric proliferations of myoid-appearing spindle cells around small vascular lumina. The present case is an unusual example of myopericytoma, manifesting in a characteristic anastomosing, multinodular, infiltrating fashion.

  16. Sinonasal glomangiopericytoma: case report with emphasis on the differential diagnosis.

    PubMed

    Dandekar, Monisha; McHugh, Jonathan B

    2010-10-01

    Glomangiopericytoma (sinonasal-type hemangiopericytoma) is an uncommon sinonasal neoplasm with a perivascular myoid phenotype. This tumor differs from conventional soft tissue hemangiopericytoma in location, biologic behavior, and histologic features. The proposed cell of origin is a modified perivascular glomuslike myoid cell. Glomangiopericytoma is an indolent tumor that tends to arise in the sinonasal tract of older adults and has a low malignant potential with excellent prognosis after surgical resection. Histologically, this lesion is composed of a diffuse, subepithelial proliferation of bland, uniform, closely packed spindled cells growing in a variety of patterns. A distinctive vascular network composed of variably sized vascular channels, the smaller of which demonstrate perivascular hyalinization, is often present. We report the case of a 48-year-old woman with epistaxis and nasal obstruction who was diagnosed with glomangiopericytoma and discuss the histologic differential diagnosis.

  17. Stem Cells

    MedlinePlus

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  18. Tipping the balance from angiogenesis to fibrosis in CKD

    PubMed Central

    Ballermann, Barbara J; Obeidat, Marya

    2014-01-01

    Chronic progressive renal fibrosis leads to end-stage renal failure many patients with chronic kidney disease (CKD). Loss of the rich peritubular capillary network is a prominent feature, and seems independent of the specific underlying disease. The mechanisms that contribute to peritubular capillary regression include the loss of glomerular perfusion, as flow-dependent shear forces are required to provide the survival signal for endothelial cells. Also, reduced endothelial cell survival signals from sclerotic glomeruli and atrophic or injured tubule epithelial cells contribute to peritubular capillary regression. In response to direct tubular epithelial cell injury, and the inflammatory reaction that ensues, capillary pericytes dissociate from their blood vessels, also reducing endothelial cell survival. In addition, direct inflammatory injury of capillary endothelial cells, for instance in chronic allograft nephropathy, also contributes to capillary dropout. Chronic tissue hypoxia, which ensues from the rarefaction of the peritubular capillary network, can generate both an angiogenic and a fibrogenic response. However, in CKD, the balance is strongly tipped toward fibrogenesis. Understanding the underlying mechanisms for failed angiogenesis in CKD and harnessing endothelial-specific survival and pro-angiogenic mechanisms for therapy should be our goal if we are to reduce the disease burden from CKD. PMID:26312149

  19. Cells, cells, and more cells.

    PubMed

    Bhatti, M Tariq; Gres, Katherine E; Petitto, Virginia B; Cross, Shelley Ann

    2007-01-01

    A 64-year-old woman presented with bilateral optic nerve swelling, vitreous cells, and cerebrospinal fluid monocytic pleocytosis. A chest radiograph and computed tomography demonstrated a lesion in the left lung, which histologically was confirmed to be a small-cell lung carcinoma. The serum was positive for the anti-CV2 (anti-CRMP-5) antibody. Following treatment with chemoradiation the optic nerve swelling and vitritis resolved. The differential diagnosis of uveal-meningeal diseases is discussed and the pathophysiology and clinical manifestations of paraneoplastic syndromes reviewed.

  20. T Cells

    MedlinePlus

    ... Cells Share this page Facebook Twitter Email T Cells Definition of MS Myelin Immune-Mediated Disease T ... other immune cells. Three broad categories of T cells Helper T cells augment the immune response by ...

  1. Cell and luminal activities of chloride, potassium, sodium and protons in the late distal tubule of Necturus kidney.

    PubMed

    Anagnostopoulos, T; Planelles, G

    1987-12-01

    1. Double-barrelled (selective vs. conventional) microelectrodes were used to assess the steady-state activities (a) of the ions Cl-, K+, Na+ and H+ in peritubular blood capillaries (abld) and in cell (acell) and lumen (alum) of the late distal tubule (l.d.t.) of Necturus. 2. a(cell)cl, a(lum)cl and a(bld)cl were 5.5 +/- 0.3, 11.8 +/- 1.0 and 70.5 +/- 0.1 mM, respectively. They were used to compute the chemical potentials for Cl- across the three diffusive barriers of the tissue. Basolateral and apical membrane potentials were -74.3 +/- 1.1 and -60.1 +/- 2.0 mV, respectively (cell negative); the lumen was thus negative with respect to blood, by 13.6 +/- 1.5 mV. The electrochemical potential difference (e.p.d.) for Cl- of 42 mV across the apical membrane opposes Cl- absorption, implying active apical Cl- uptake, since Cl- is known to be absorbed in the l.d.t. Basolateral Cl- exit is favoured by an e.p.d. of 10 mV. 3. a(cell)K, a(lum)K and a(bld)K were 65.8 +/- 0.8, 2.5 +/- 0.1 and 2.5 +/- 0.1 mm, respectively. The electrochemical distribution of K+ indicates that K+ absorption, if present, proceeds against an adverse apical e.p.d. of 18 mV. Basolateral K+ distribution is close to its electrochemical equilibrium, suggesting high K+ permeability at this membrane. 4. a(cell)Na was 9.0 +/- 0.4 mM, a(bld)Na 71.0 +/- 0.3 mM, and a(lum)Na was approximated at about 9 mM. Diffusive Na+ entry from lumen to cell is favoured by an e.p.d. close to 65 mV. Basolateral Na+ exit must be active, since it proceeds against an e.p.d. of 130 mV. 5. Cell, luminal and blood pH were 7.14 +/- 0.03, 6.52 +/- 0.08 and 7.37 +/- 0.04, respectively. The luminal electrochemical potential of H+ is higher than that of cell (by 91 mV) and blood (by 34 mV) indicating that proton secretion into the lumen must be active. 6. The e.p.d. of each ion across the epithelium opposes, by its orientation, the established direction of net transepithelial ion transport, suggesting that the shunt pathway may serve

  2. High levels of the extracellular matrix proteoglycan decorin are associated with inhibition of testicular function

    PubMed Central

    Adam, Marion; Urbanski, Henryk F.; Garyfallou, Vasilios T.; Welsch, Ulrich; Köhn, Frank M.; Schwarzer, J. Ullrich; Strauss, Leena; Poutanen, Matti; Mayerhofer, Artur

    2011-01-01

    Decorin (DCN), a component of the extracellular matrix of the peritubular wall and the interstitial areas of the human testis, can interact with growth factor (GF) signaling, thereby blocking downstream actions of GFs. In the present study the expression and regulation of DCN using both human testes and two experimental animal models, namely the rhesus monkey and mouse, were examined. DCN protein was present in peritubular and interstitial areas of adult human and monkey testes, while it was almost undetectable in adult wild-type mice. Interestingly, the levels and sites of testicular DCN expression in the monkeys were inversely correlated with testicular maturation markers. A strong DCN expression associated with the abundant connective tissue of the interstitial areas in the postnatal through prepubertal phases was observed. In adult and old monkeys the DCN pattern was similar to the one in normal human testes, presenting strong expression at the peritubular region. In the testes of both infertile men and in a mouse model of inflammation associated infertility (aromatase-overexpressing transgenic mice), the fibrotic changes and increased numbers of Tumor necrosis factor (TNF)-α-producing immune cells were shown to be associated with increased production of DCN. Furthermore, studies with human testicular peritubular cells isolated from fibrotic testis indicated that TNF-α significantly increased DCN production. The data, thus, show that an increased DCN level is associated with impaired testicular function, supporting our hypothesis that DCN interferes with paracrine signaling of the testis in health and disease. PMID:22413766

  3. Morphometric studies on the testis of Korean ring-necked pheasant (Phasianus colchicus karpowi) during the breeding and non-breeding seasons.

    PubMed

    Tae, H J; Jang, B G; Ahn, D C; Choi, E Y; Kang, H S; Kim, N S; Lee, J H; Park, S Y; Yang, H H; Kim, I S

    2005-10-01

    The purpose of this study was to obtain detailed quantitative information on all cell types in the testis interstitium of Korean ring-necked pheasants and to combine these data with changes in the steroidogenic function of the testis during the breeding and non-breeding seasons. For animals collected during the breeding season, their testis weights, sperm production, serum testosterone levels and leuteinizing hormone (LH)-stimulated testosterone secretion were significantly (p < 0.01) increased compared to the non-breeding season. Testes of the pheasants during the non-breeding season displayed a 98% reduction in testis volume that was associated with a decrease in the absolute volume of seminiferous tubules (98% reduction), tubular lumen (100%), interstitium (90%), blood vessels (84%), lymphatic spaces (97%), Leydig cells (79%), mesenchymal cells (51%) and myoid cells (61%) compared to the breeding season. The numbers of Leydig cells, mesenchymal cells and myoid cells per testis in the breeding season were much higher than in the non-breeding season. Although the mean volume of a Leydig cell was 74% lower in the non-breeding season, the mean volumes of myoid and mesenchymal cells remained unchanged. These results demonstrate that there are striking differences in the testicular structure of the Korean ring-necked pheasant during the breeding and non-breeding seasons. Every structural parameter of the Leydig cell was positively correlated with both testosterone serum levels and LH-stimulated testosterone secretion. The correlation of changes in hormonal status with the morphometric alterations of Leydig cells suggests that the Korean-ring necked pheasant may be used as a model to study structure-function relationships in the avian testis.

  4. Cell division

    MedlinePlus Videos and Cool Tools

    ... the first 12 hours after conception, the fertilized egg cell remains a single cell. After approximately 30 ... at the end of 3 days, the fertilized egg cell has become a berry-like structure made ...

  5. Galvanic Cells

    ERIC Educational Resources Information Center

    Young, I. G.

    1973-01-01

    Many standard physical chemistry textbooks contain ambiguities which lead to confusion about standard electrode potentials, calculating cell voltages, and writing reactions for galvanic cells. This article shows how standard electrode potentials can be used to calculate cell voltages and deduce cell reactions. (Author/RH)

  6. Stem cells.

    PubMed

    Behr, Björn; Ko, Sae Hee; Wong, Victor W; Gurtner, Geoffrey C; Longaker, Michael T

    2010-10-01

    Stem cells are self-renewing cells capable of differentiating into multiple cell lines and are classified according to their origin and their ability to differentiate. Enormous potential exists in use of stem cells for regenerative medicine. To produce effective stem cell-based treatments for a range of diseases, an improved understanding of stem cell biology and better control over stem cell fate are necessary. In addition, the barriers to clinical translation, such as potential oncologic properties of stem cells, need to be addressed. With renewed government support and continued refinement of current stem cell methodologies, the future of stem cell research is exciting and promises to provide novel reconstructive options for patients and surgeons limited by traditional paradigms.

  7. Postnatal development of epididymis and ductus deferens in the rat. A correlation between the ultrastructure of the epithelium and tubule wall, and the fluorescence-microscopic distribution of actin, myosin, fibronectin, and basement membrane.

    PubMed

    Francavilla, S; Moscardelli, S; Properzi, G; De Matteis, M A; Scorza Barcellona, P; Natali, P G; De Martino, C

    1987-08-01

    The postnatal maturation of regions of the epididymis and intragonadal segment of the deferens duct was studied in the rat by light- and transmission electron microscopy. Maturation of the genital duct starts in the distal cauda epididymidis and ductus deferens after one week of life, and one week later, in the more cranial segments of the epididymis. Epithelial principal cells and peritubular contractile cells are structurally mature 35 days after birth. The synchronous changes of these cells indicate that the same factors control their postnatal maturation. The epithelial principal cells obtain an endocytotic apparatus and long stereocilia, whereas peritubular cells acquire contractile features. These changes are associated with a progressive increase in the immunoreaction for smooth muscle actin in both cell types. Smooth muscle myosin is detected in the apical region of the epithelial cells and the peritubular cell cytoplasm by day one of postnatal development. The differentiation of contractile cells in the wall is accompanied by progressive organization of the pericellular matrix into a continuous basement membrane. Although fibronectin is visible at birth, it is gradually removed from the tubule wall.

  8. Ultrastructural pathological changes in mice kidney caused by Plasmodium berghei infection.

    PubMed

    Pulido-Méndez, M; Finol, H J; Girón, M E; Aguilar, I

    2006-01-01

    Malaria, a common health problem in certain parts of the world, has a considerable morbidity and mortality. This work reports under electron microscopy studies serious ultrastructural kidney damage such as extensive cytoplasmic vacuolation, vesiculation and autophagic vacuoles in proximal tubular cells. A thickened endothelial wall on peritubular capillary, interdigitation disorganization and significant decrease of their number in some areas were detected. Swollen rough endoplasmic reticulum, swollen mitochondria, and parasitized erythrocytes were observed. Many epithelial cells exhibited cytoplasmic areas of autophagia and a myelin-like form. A tubular cell presented severe cytoarchitecture alterations. Abundant lipid droplets were noticed. Almost total loss of interdigitations, rough endoplasmic reticulum vesiculation, peritubular capillaries with endothelial cells thickened cytoplasm, papillary processes projected to the lumen, and an inflammatory infiltrate of macrophages were also observed. These ultrastructural kidney changes could cause, on the basis of their clinical and pathologic expressions, a fat accumulation, an acute temporary reversible glomerulonephritis, a chronic progressive irreversible glomerulonephritis, and an acute renal failure (ARF).

  9. Engineering Cell-Cell Signaling

    PubMed Central

    Milano, Daniel F.; Natividad, Robert J.; Asthagiri, Anand R.

    2014-01-01

    Juxtacrine cell-cell signaling mediated by the direct interaction of adjoining mammalian cells is arguably the mode of cell communication that is most recalcitrant to engineering. Overcoming this challenge is crucial for progress in biomedical applications, such as tissue engineering, regenerative medicine, immune system engineering and therapeutic design. Here, we describe the significant advances that have been made in developing synthetic platforms (materials and devices) and synthetic cells (cell surface engineering and synthetic gene circuits) to modulate juxtacrine cell-cell signaling. In addition, significant progress has been made in elucidating design rules and strategies to modulate juxtacrine signaling based on quantitative, engineering analysis of the mechanical and regulatory role of juxtacrine signals in the context of other cues and physical constraints in the microenvironment. These advances in engineering juxtacrine signaling lay a strong foundation for an integrative approach to utilizing synthetic cells, advanced ‘chassis’ and predictive modeling to engineer the form and function of living tissues. PMID:23856592

  10. Engineering cell-cell signaling.

    PubMed

    Blagovic, Katarina; Gong, Emily S; Milano, Daniel F; Natividad, Robert J; Asthagiri, Anand R

    2013-10-01

    Juxtacrine cell-cell signaling mediated by the direct interaction of adjoining mammalian cells is arguably the mode of cell communication that is most recalcitrant to engineering. Overcoming this challenge is crucial for progress in biomedical applications, such as tissue engineering, regenerative medicine, immune system engineering and therapeutic design. Here, we describe the significant advances that have been made in developing synthetic platforms (materials and devices) and synthetic cells (cell surface engineering and synthetic gene circuits) to modulate juxtacrine cell-cell signaling. In addition, significant progress has been made in elucidating design rules and strategies to modulate juxtacrine signaling on the basis of quantitative, engineering analysis of the mechanical and regulatory role of juxtacrine signals in the context of other cues and physical constraints in the microenvironment. These advances in engineering juxtacrine signaling lay a strong foundation for an integrative approach to utilize synthetic cells, advanced 'chassis' and predictive modeling to engineer the form and function of living tissues.

  11. Fuel cells

    NASA Astrophysics Data System (ADS)

    1984-12-01

    The US Department of Energy (DOE), Office of Fossil Energy, has supported and managed a fuel cell research and development (R and D) program since 1976. Responsibility for implementing DOE's fuel cell program, which includes activities related to both fuel cells and fuel cell systems, has been assigned to the Morgantown Energy Technology Center (METC) in Morgantown, West Virginia. The total United States effort of the private and public sectors in developing fuel cell technology is referred to as the National Fuel Cell Program (NFCP). The goal of the NFCP is to develop fuel cell power plants for base-load and dispersed electric utility systems, industrial cogeneration, and on-site applications. To achieve this goal, the fuel cell developers, electric and gas utilities, research institutes, and Government agencies are working together. Four organized groups are coordinating the diversified activities of the NFCP. The status of the overall program is reviewed in detail.

  12. Cell Phones

    MedlinePlus

    ... These base stations operate at higher power than cell phones. The RF exposures people experience from base stations are typically much lower than from cell phones because base station antennas are mounted on ...

  13. The effects of an electromagnetic field on the boundary tissue of the seminiferous tubules of the rat: A light and transmission electron microscope study.

    PubMed

    Khaki, A A; Tubbs, R S; Shoja, M M; Rad, J S; Khaki, A; Farahani, R M; Zarrintan, S; Nag, T C

    2006-08-01

    Human beings are unavoidably exposed to ambient electromagnetic fields (EMF) generated from various electrical devices and from power transmission lines. Controversy exists about the effects of EMF on various organs. One of the critical issues is that EMF may adversely affect the reproductive system. In order to examine this 30 rat pups were exposed to 50 Hz EMF (non-ionising radiation) during in utero development (approximately 3 weeks) and postnatal life (5 weeks). Groups of exposed rats were subsequently left in an environment free of EMF in order to observe recovery, if any, from the changes induced by EMF on the boundary tissue of the seminiferous tubules. The materials were processed and observed under a light and a transmission electron microscope. In the experimental rats boundary tissue was found disrupted at various layers. This tissue showed infoldings, which were perhaps due to the loss of collagen and reticular fibrils from the inner and outer non-cellular layers. The outer non-cellular layer, which was thinner than that of the control, was stripped away from the myoid cell layer in multiple regions, giving a "blister-like" appearance. The myoid cells showed fewer polyribosomes, pinocytotic vesicles and glycogen granules. Most mitochondria were found to lack cristae. The connections between individual myoid cells were apparently lost. There were signs of recovery in the boundary tissue following withdrawal from EMF exposure. These results suggest that EMF exposure may cause profound changes in the boundary tissue of the seminiferous tubules. Therefore exposure to EMF may result in pathological changes that lead to subfertility and infertility.

  14. Photoelectrochemical cells

    NASA Astrophysics Data System (ADS)

    Nozik, A. J.

    1980-02-01

    The application of photoelectrochemical systems based on photoactive semiconducting electrodes to the problem of solar energy conversion and chemical synthesis is discussed. Three types of cells are described: electrochemical photovoltaic cells (wherein optical energy is converted into electrical energy); photoelectrolysis cells (wherein optical energy is converted into chemical free energy); and photocatalytic cells (wherein optical energy provides the activation energy for exoergic chemical reactions). The critical semiconductor electrode properties for these cells are the band gap, the flat-band potential, and the photoelectrochemical stability. No semiconductor electrode material is yet known for which all three parameters are simultaneously optimized. An interesting configurational variation of photoelectrolysis cells, labelled 'photochemical diodes', is described. These diodes comprise cells that have been collapsed into monolithic particles containing no external wires. Recent advances in several areas of photoelectrochemical systems are also described.

  15. Types of Stem Cells

    MedlinePlus

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  16. Electrolytic cell

    NASA Astrophysics Data System (ADS)

    Bullock, J. S.; Hale, B. D.

    1984-09-01

    An apparatus is described for the separation of the anolyte and the catholyte during electrolysis. The electrolyte flows through an electrolytic cell between the oppositely charged electrodes. The cell is equipped with a wedge-shaped device, the tapered end is located between the electrodes on the effluent side of the cell. The wedge diverts the flow of the electrolyte to either side of the wedge, substantially separating the anolyte and the catholyte.

  17. Cell Chauvinism

    ERIC Educational Resources Information Center

    Keller, Dolores Elaine

    1972-01-01

    Indicates that biological terminology, such as mother cell'' and labels of sex factors in bacteria, reflect discrimination against females by reinforcing perpetuation of stereotyped gender roles. (AL)

  18. Cell Migration

    PubMed Central

    Trepat, Xavier; Chen, Zaozao; Jacobson, Ken

    2015-01-01

    Cell migration is fundamental to establishing and maintaining the proper organization of multicellular organisms. Morphogenesis can be viewed as a consequence, in part, of cell locomotion, from large-scale migrations of epithelial sheets during gastrulation, to the movement of individual cells during development of the nervous system. In an adult organism, cell migration is essential for proper immune response, wound repair, and tissue homeostasis, while aberrant cell migration is found in various pathologies. Indeed, as our knowledge of migration increases, we can look forward to, for example, abating the spread of highly malignant cancer cells, retarding the invasion of white cells in the inflammatory process, or enhancing the healing of wounds. This article is organized in two main sections. The first section is devoted to the single-cell migrating in isolation such as occurs when leukocytes migrate during the immune response or when fibroblasts squeeze through connective tissue. The second section is devoted to cells collectively migrating as part of multicellular clusters or sheets. This second type of migration is prevalent in development, wound healing, and in some forms of cancer metastasis. PMID:23720251

  19. Cell Chauvinism

    ERIC Educational Resources Information Center

    Keller, Dolores Elaine

    1972-01-01

    Indicates that biological terminology, such as mother cell'' and labels of sex factors in bacteria, reflect discrimination against females by reinforcing perpetuation of stereotyped gender roles. (AL)

  20. Anatomy and cytology of the thymus in juvenile Australian lungfish, Neoceratodus forsteri

    PubMed Central

    Mohammad, M G; Chilmonczyk, S; Birch, D; Aladaileh, S; Raftos, D; Joss, J

    2007-01-01

    The anatomy, histology and ultrastructure of the thymus of a dipnoan, the Australian lungfish, Neoceratodus forsteri, was studied by light and transmission electron microscopy. The thymic tissue showed clear demarcation into a cortex and medulla with ample vascularization. Large cells including foamy and giant multinucleated cells with periodic acid Schiff/Alcian blue positive staining properties were localized mainly in the medulla. The major cellular components were epithelial cells and lymphoid cells. The epithelial cells were classified by location and ultrastructure into six sub-populations: capsular cells, cortical and medullary reticular cells, perivascular endothelial cells, intermediate cells, nurse-like cells and Hassall-like corpuscles. Myoid cells were found mainly in the cortico-medullary boundary and medulla. Macrophages and secretory-like cells were also present. These findings will provide a base of knowledge about the cellular immune system of lungfish. PMID:17944863

  1. Unit Cells

    ERIC Educational Resources Information Center

    Olsen, Robert C.; Tobiason, Fred L.

    1975-01-01

    Describes the construction of unit cells using clear plastic cubes which can be disassembled, and one inch cork balls of various colors, which can be cut in halves, quarters, or eighths, and glued on the inside face of the cube, thus simulating a unit cell. (MLH)

  2. Unit Cells

    ERIC Educational Resources Information Center

    Olsen, Robert C.; Tobiason, Fred L.

    1975-01-01

    Describes the construction of unit cells using clear plastic cubes which can be disassembled, and one inch cork balls of various colors, which can be cut in halves, quarters, or eighths, and glued on the inside face of the cube, thus simulating a unit cell. (MLH)

  3. Fuel Cells

    ERIC Educational Resources Information Center

    Hawkins, M. D.

    1973-01-01

    Discusses the theories, construction, operation, types, and advantages of fuel cells developed by the American space programs. Indicates that the cell is an ideal small-scale power source characterized by its compactness, high efficiency, reliability, and freedom from polluting fumes. (CC)

  4. Fuel Cells

    ERIC Educational Resources Information Center

    Hawkins, M. D.

    1973-01-01

    Discusses the theories, construction, operation, types, and advantages of fuel cells developed by the American space programs. Indicates that the cell is an ideal small-scale power source characterized by its compactness, high efficiency, reliability, and freedom from polluting fumes. (CC)

  5. Host cells and cell banking.

    PubMed

    Stacey, Glyn N; Merten, Otto-Wilhelm

    2011-01-01

    Gene therapy based on the use of viral vectors is entirely dependent on the use of animal cell lines, mainly of mammalian origin, but also of insect origin. As for any biotechnology product for clinical use, viral -vectors have to be produced with cells derived from an extensively characterized cell bank to maintain the appropriate standard for assuring the lowest risk for the patients to be treated. Although many different cell types and lines have been used for the production of viral vectors, HEK293 cells or their derivatives have been extensively used for production of different vector types: adenovirus, oncorectrovirus, lentivirus, and AAV vectors, because of their easy handling and the possibility to grow them adherently in serum-containing medium as well as in suspension in serum-free culture medium. Despite this, these cells are not necessarily the best for the production of a given viral vector, and there are many other cell lines with significant advantages including superior growth and/or production characteristics, which have been tested and also used for the production of clinical vector batches. This chapter presents basic -considerations concerning the characterization of cell banks, in the first part, and, in the second part, practically all cell lines (at least when public information was available) established and developed for the production of the most important viral vectors (adenoviral, oncoretroviral, lentiviral, AAV, baculovirus).

  6. Cell polarity

    PubMed Central

    Romereim, Sarah M

    2011-01-01

    Despite extensive genetic analysis of the dynamic multi-phase process that transforms a small population of lateral plate mesoderm into the mature limb skeleton, the mechanisms by which signaling pathways regulate cellular behaviors to generate morphogenetic forces are not known. Recently, a series of papers have offered the intriguing possibility that regulated cell polarity fine-tunes the morphogenetic process via orienting cell axes, division planes and cell movements. Wnt5a-mediated non-canonical signaling, which may include planar cell polarity, has emerged as a common thread in the otherwise distinct signaling networks that regulate morphogenesis in each phase of limb development. These findings position the limb as a key model to elucidate how global tissue patterning pathways direct local differences in cell behavior that, in turn, generate growth and form. PMID:22064549

  7. Fuel cells 101

    SciTech Connect

    Hirschenhofer, J.H.

    1999-07-01

    This paper discusses the various types of fuel cells, the importance of cell voltage, fuel processing for natural gas, cell stacking, fuel cell plant description, advantages and disadvantages of the types of fuel cells, and applications. The types covered include: polymer electrolyte fuel cell, alkaline fuel cell, phosphoric acid fuel cell; molten carbonate fuel cell, and solid oxide fuel cell.

  8. Prenatal development of the bovine epididymis: light microscopical, glycohistochemical and immunohistochemical studies.

    PubMed

    Alkafafy, Mohamed; Sinowatz, Fred

    2012-11-01

    Prenatal development of the epididymis was studied in bovine fetuses ranging from 10 to 90cm crown-rump length (CRL) (75-285 pcd). The studies aimed to apply both glycohistochemistry and immunohistochemistry for the detection of the differentiation of the developing prenatal epididymis. Both conventional histological and histochemical techniques were applied on paraffin sections of the epididymis from different fetal stages. Establishment of the urogenital junction between the extra-testicular rete testis and the mesonephric duct, via the growing efferent ductules (ductuli efferentes) was first evident in fetuses with 10cm CRL. At the fetal age of 110 pcd (24cm CRL), the mesonephric duct began to lengthen and coil forming three distinct regions (caput, corpus and cauda). In addition to the macroscopical modifications in the extra-testicular excurrent duct system, histological differentiation involved both the tubular epithelial and the peritubular mesenchymal cells. The epithelium lining the efferent ductules was differentiated into ciliated and non-ciliated columnar cells. The simple epithelium of the epididymal duct increased in height and developed stereocilia on the apical surface. Additionally, some basal cells first appeared at 185 pcd (56cm CRL), within the epithelium lining the cauda only. Lectin histochemistry (WGA, PNA, GSA-I) showed early immunostaining in epithelium of the efferent ductules and in peritubular mesenchymal structures. Immunoreactivity for different proteins (S-100, fibroblast growth factor-1 and factor-2, angiotensin converting enzyme, laminin, alpha-smooth muscle actin) was evident, both in the epithelial and in the peritubular mesenchymal cells as early as at 75 pcd. On the basis of our histochemical observations, we conclude that both glycohistochemistry and immunohistochemistry are useful tools to demonstrate that the differentiation in the peritubular structures and efferent ductular epithelium begins earlier than other components.

  9. 9. ENGINE TEST CELL BUILDING INTERIOR. CELL ACCESS ELEVATOR, CELLS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. ENGINE TEST CELL BUILDING INTERIOR. CELL ACCESS ELEVATOR, CELLS 2 AND 4, BASEMENT LEVEL. LOOKING SOUTHEAST. - Fairchild Air Force Base, Engine Test Cell Building, Near intersection of Arnold Street & George Avenue, Spokane, Spokane County, WA

  10. Bi-Cell Unit for Fuel Cell.

    DTIC Science & Technology

    The patent concerns a bi-cell unit for a fuel cell . The bi-cell unit is comprised of two electrode packs. Each of the electrode packs includes an...invention relates in general to a bi-cell unit for a fuel cell and in particular, to a bi-cell unit for a hydrazine-air fuel cell .

  11. Electrochemical cell

    DOEpatents

    Redey, L.I.; Vissers, D.R.; Prakash, J.

    1996-07-16

    An electrochemical cell is described having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm{sup 3}; the cell can be 90% recharged in three hours and can operate at temperatures below 160 C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6{times}10{sup 4}cm{sup 2}/g of Ni. 6 figs.

  12. Electrochemical cell

    DOEpatents

    Redey, L.I.; Vissers, D.R.; Prakash, J.

    1994-02-01

    An electrochemical cell is described having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm[sup 3]; the cell can be 90% recharged in three hours and can operate at temperatures below 160 C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6[times]10[sup 4] cm[sup 2]/g of Ni. 8 figures.

  13. T Cells

    MedlinePlus

    ... Cells d What Causes MS? Disproved Theories Viruses Clusters d Who Gets MS? Pediatric MS African Americans ... Learn More Relapsing-remitting MS (RRMS) Learn More Clusters Learn More Viruses Learn More Disproved Theories Learn ...

  14. Electrochemical cell

    DOEpatents

    Redey, Laszlo I.; Vissers, Donald R.; Prakash, Jai

    1994-01-01

    An electrochemical cell having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm.sup.3 ; the cell can be 90% recharged in three hours and can operate at temperatures below 160.degree. C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6.times.10.sup.4 cm.sup.2 /g of Ni.

  15. Electrochemical cell

    DOEpatents

    Redey, Laszlo I.; Vissers, Donald R.; Prakash, Jai

    1996-01-01

    An electrochemical cell having a bimodal positive electrode, a negative electrode of an alkali metal, and a compatible electrolyte including an alkali metal salt molten at the cell operating temperature. The positive electrode has an electrochemically active layer of at least one transition metal chloride at least partially present as a charging product, and additives of bromide and/or iodide and sulfur in the positive electrode or the electrolyte. Electrode volumetric capacity is in excess of 400 Ah/cm.sup.3 ; the cell can be 90% recharged in three hours and can operate at temperatures below 160.degree. C. There is also disclosed a method of reducing the operating temperature and improving the overall volumetric capacity of an electrochemical cell and for producing a positive electrode having a BET area greater than 6.times.10.sup.4 cm.sup.2 /g of Ni.

  16. Electrochemical cell

    DOEpatents

    Redey, Laszlo I.; Vissers, Donald R.; Prakash, Jai

    1994-01-01

    An electrochemical cell having an alkali metal negative electrode such as sodium and a positive electrode including Ni or transition metals, separated by a .beta." alumina electrolyte and NaAlCl.sub.4 or other compatible material. Various concentrations of a bromine, iodine and/or sulfur containing additive and pore formers are disclosed, which enhance cell capacity and power. The pore formers may be the ammonium salts of carbonic acid or a weak organic acid or oxamide or methylcellulose.

  17. Electrochemical cell

    SciTech Connect

    Maloney, D.E.

    1984-04-24

    A process and cell for electrolysis of alkali metal halides, especially sodium chloride, are described, wherein the anolyte and catholyte compartments are separated by a fluorinated ion-exchange membrane whose surface facing the catholyte compartment is of a polymer having carboxylic functionality and which has a roughness which does not exceed 1.5 microns. Such a cell and process operate at high current efficiency, low voltage and low power consumption.

  18. Solar Cells

    NASA Technical Reports Server (NTRS)

    1983-01-01

    The Heat Exchanger Method (HEM) produces high efficiency crystal ingots in an automated well-insulated furnace offering low equipment, labor and energy costs. The "grown" silicon crystals are used to make solar cells, or photovoltaic cells which convert sunlight directly into electricity. The HEM method is used by Crystal Systems, Inc. and was developed under a NASA/Jet Propulsion Laboratory contract. The square wafers which are the result of the process are sold to companies manufacturing solar panels.

  19. Load cell

    DOEpatents

    Spletzer, Barry L.

    2001-01-01

    A load cell combines the outputs of a plurality of strain gauges to measure components of an applied load. Combination of strain gauge outputs allows measurement of any of six load components without requiring complex machining or mechanical linkages to isolate load components. An example six axis load cell produces six independent analog outputs which can be combined to determine any one of the six general load components.

  20. Load cell

    DOEpatents

    Spletzer, Barry L.

    1998-01-01

    A load cell combines the outputs of a plurality of strain gauges to measure components of an applied load. Combination of strain gauge outputs allows measurement of any of six load components without requiring complex machining or mechanical linkages to isolate load components. An example six axis load cell produces six independent analog outputs, each directly proportional to one of the six general load components.

  1. The in vitro growth and characterization of the skeletal muscle component of Wilms' tumor.

    PubMed Central

    Garvin, A. J.; Surrette, F.; Hintz, D. S.; Rudisill, M. T.; Sens, M. A.; Sens, D. A.

    1985-01-01

    Skeletal muscle differentiation within a Wilms' tumor is a well-documented histopathologic entity thought to occur at a relatively low incidence and influence prognosis. A serum-free hormonally defined growth medium has been developed, allowing the long-term growth of the skeletal muscle component of Wilms' tumors. Eight Wilms' tumors have been grown under these conditions. Three cases grew a homogeneous population of cells which ultrastructurally displayed all stages of myogenesis through myotubule formation. They also possessed immunoreactivity for skeletal muscle myosin and myoglobin and synthesized the M and B subunits of creatine kinase. Of interest was the finding that the ability to yield skeletal muscle cultures was limited to those cases which exhibited skeletal muscle fibers in vivo. This technique is also a very sensitive marker for identifying Wilms' tumors possessing a myoid component. A second serum-free hormonally defined medium has also been developed that supports the long-term culture of a unique cell type from Wilms' tumors which contain a myoid component. These cells are spindle-shaped and exhibit all of the characteristics of early myoblasts. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 7 Figures 8 and 9 p307-a PMID:2998192

  2. Pericyte antigens in angiomyolipoma and PEComa family tumors.

    PubMed

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Scott, Michelle A; Asatrian, Greg; Barnhill, Raymond; Lugassy, Claire; Soo, Chia; Ting, Kang; Peault, Bruno; Dry, Sarah M; James, Aaron W

    2015-08-01

    Perivascular epithelioid cell tumors (PEComas) are an uncommon family of soft tissue tumors with dual myoid-melanocytic differentiation. Although PEComa family tumors commonly demonstrate a perivascular growth pattern, pericyte antigen expression has not yet been examined among this unique tumor group. Previously, we demonstrated that a subset of perivascular soft tissue tumors exhibit a striking pericytic immunophenotype, with diffuse expression of αSMA, CD146, and PDGFRβ. Here, we describe the presence of pericyte antigens across a diverse group of PEComa family tumors (n = 19 specimens). Results showed that pericyte antigens differed extensively by histological appearance. Typical angiomyolipoma (AML) specimens showed variable expression of pericyte antigens among both perivascular and myoid-appearing cells. In contrast, AML specimens with a predominant spindled morphology showed diffuse expression of pericyte markers, including αSMA, CD146, and PDGFRβ. AML samples with predominant epithelioid morphology showed a marked reduction in or the absence of immunoreactivity for pericyte markers. Lymphangiomyoma samples showed more variable and partial pericyte marker expression. In summary, pericyte antigen expression is variable among PEComa family tumors and largely varies by tumor morphology. Pericytic marker expression in PEComa may represent a true pericytic cell of origin, or alternatively aberrant pericyte marker adoption. Markers of pericytic differentiation may be of future diagnostic utility for the evaluation of mesenchymal tumors, or identify actionable signaling pathways for future therapeutic intervention.

  3. Air cell

    NASA Astrophysics Data System (ADS)

    Okamura, Okiyoshi; Wakasa, Masayuki; Tamanoi, Yoshihito

    1991-04-01

    The present invention relates to an air cell. This air cell provides a compact light-weight power source for model aircraft permitting them to fly for an extended period so that they may be used for such practical purposes as crop dusting, surveying, and photographing. The cell is comprised of a current collector so disposed between a magnesium, zinc, or aluminum alloy cathode and a petroleum graphite anode that it is in contact with the anode. The anode is formed by adding polytetrafluoroethylene dispersion liquid in a mixture of active carbon and graphite powder, pouring the mixture into a mold and heating it to form the anode. It is fabricated by a plurality of anode sections and is formed with at least one hole so that it can provide a cell which is compact in size and light in weight yet is capable of generating a high output. The anode, the cathode, and a separator are wetted by an electrolytic liquid. The electrolyte is continuously supplied through the life of the cell.

  4. Electrochemical cell

    DOEpatents

    Redey, Laszlo I.; Myles, Kevin M.; Vissers, Donald R.; Prakash, Jai

    1996-01-01

    An electrochemical cell with a positive electrode having an electrochemically active layer of at least one transition metal chloride. A negative electrode of an alkali metal and a compatible electrolyte including an alkali metal salt molten at cell operating temperature is included in the cell. The electrolyte is present at least partially as a corrugated .beta." alumina tube surrounding the negative electrode interior to the positive electrode. The ratio of the volume of liquid electrolyte to the volume of the positive electrode is in the range of from about 0.1 to about 3. A plurality of stacked electrochemical cells is disclosed each having a positive electrode, a negative electrode of an alkali metal molten at cell operating temperature, and a compatible electrolyte. The electrolyte is at least partially present as a corrugated .beta." alumina sheet separating the negative electrode and interior to the positive electrodes. The alkali metal is retained in a porous electrically conductive ceramic, and seals for sealing the junctures of the electrolyte and the adjacent electrodes at the peripheries thereof.

  5. Electrochemical cell

    DOEpatents

    Nagy, Zoltan; Yonco, Robert M.; You, Hoydoo; Melendres, Carlos A.

    1992-01-01

    An electrochemical cell has a layer-type or sandwich configuration with a Teflon center section that houses working, reference and counter electrodes and defines a relatively narrow electrolyte cavity. The center section is surrounded on both sides with thin Teflon membranes. The membranes are pressed in place by a pair of Teflon inner frames which are in turn supported by a pair of outer metal frames. The pair of inner and outer frames are provided with corresponding, appropriately shaped slits that are in plane generally transverse to the plane of the working electrode and permit X-ray beams to enter and exit the cell through the Teflon membranes that cover the slits so that the interface between the working electrode and the electrolyte within the cell may be analyzed by transmission geometry. In one embodiment, the center section consists of two parts, one on top of the other. Alternatively, the center section of the electrochemical cell may consist of two intersliding pieces or may be made of a single piece of Teflon sheet material. The electrolyte cavity is shaped so that the electrochemical cell can be rotated 90.degree. in either direction while maintaining the working and counter electrodes submerged in the electrolyte.

  6. Electrochemical cell

    DOEpatents

    Nagy, Z.; Yonco, R.M.; You, H.; Melendres, C.A.

    1992-08-25

    An electrochemical cell has a layer-type or sandwich configuration with a Teflon center section that houses working, reference and counter electrodes and defines a relatively narrow electrolyte cavity. The center section is surrounded on both sides with thin Teflon membranes. The membranes are pressed in place by a pair of Teflon inner frames which are in turn supported by a pair of outer metal frames. The pair of inner and outer frames are provided with corresponding, appropriately shaped slits that are in plane generally transverse to the plane of the working electrode and permit X-ray beams to enter and exit the cell through the Teflon membranes that cover the slits so that the interface between the working electrode and the electrolyte within the cell may be analyzed by transmission geometry. In one embodiment, the center section consists of two parts, one on top of the other. Alternatively, the center section of the electrochemical cell may consist of two intersliding pieces or may be made of a single piece of Teflon sheet material. The electrolyte cavity is shaped so that the electrochemical cell can be rotated 90[degree] in either direction while maintaining the working and counter electrodes submerged in the electrolyte. 5 figs.

  7. Electrochemical cell

    DOEpatents

    Redey, L.I.; Myles, K.M.; Vissers, D.R.; Prakash, J.

    1996-07-02

    An electrochemical cell is described with a positive electrode having an electrochemically active layer of at least one transition metal chloride. A negative electrode of an alkali metal and a compatible electrolyte including an alkali metal salt molten at cell operating temperature is included in the cell. The electrolyte is present at least partially as a corrugated {beta}{double_prime} alumina tube surrounding the negative electrode interior to the positive electrode. The ratio of the volume of liquid electrolyte to the volume of the positive electrode is in the range of from about 0.1 to about 3. A plurality of stacked electrochemical cells is disclosed each having a positive electrode, a negative electrode of an alkali metal molten at cell operating temperature, and a compatible electrolyte. The electrolyte is at least partially present as a corrugated {beta}{double_prime} alumina sheet separating the negative electrode and interior to the positive electrodes. The alkali metal is retained in a porous electrically conductive ceramic, and seals for sealing the junctures of the electrolyte and the adjacent electrodes at the peripheries thereof. 8 figs.

  8. Cell Phones

    PubMed Central

    Sansone, Lori A.

    2013-01-01

    Cell phones are a relatively novel and evolving technology. While the potential benefits of this technology continue to emerge, so do the potential psychosocial risks. For example, one psychosocial risk is user stress, which appears to be related to feeling compelled to promptly respond to cell-phone activity in order to maintain spontaneity and access with others. Other potential psychosocial risks include disruptions in sleep; the user’s risk of exposure to cyberbullying, particularly the unwanted exposure of photographs and/or videos of the victim; and overuse, particularly among adolescents. With regard to the latter phenomenon, the boundaries among overuse, misuse, dependence, and addiction are not scientifically clear. Therefore, while cell phones are a convenient and expedient technology, they are not without their potential psychosocial hazards. PMID:23439568

  9. Electrochemical cell

    DOEpatents

    Kaun, Thomas D.

    1984-01-01

    An improved secondary electrochemical cell is disclosed having a negative electrode of lithium aluminum, a positive electrode of iron sulfide, a molten electrolyte of lithium chloride and potassium chloride, and the combination that the fully charged theoretical capacity of the negative electrode is in the range of 0.5-1.0 that of the positive electrode. The cell thus is negative electrode limiting during discharge cycling. Preferably, the negative electrode contains therein, in the approximate range of 1-10 volume % of the electrode, an additive from the materials of graphitized carbon, aluminum-iron alloy, and/or magnesium oxide.

  10. Electrochemical cell

    DOEpatents

    Redey, L.I.; Vissers, D.R.; Prakash, J.

    1994-08-23

    An electrochemical cell is described having an alkali metal negative electrode such as sodium and a positive electrode including Ni or transition metals, separated by a [beta] alumina electrolyte and NaAlCl[sub 4] or other compatible material. Various concentrations of a bromine, iodine and/or sulfur containing additive and pore formers are disclosed, which enhance cell capacity and power. The pore formers may be the ammonium salts of carbonic acid or a weak organic acid or oxamide or methylcellulose. 6 figs.

  11. Electrochemical cell

    DOEpatents

    Kaun, T.D.

    An improved secondary electrochemical cell is disclosed having a negative electrode of lithium aluminum, a positive electrode of iron sulfide, a molten electrolyte of lithium chloride and potassium chloride, and the combination that the fully charged theoretical capacity of the negative electrode is in the range of 0.5 to 1.0 that of the positive electrode. The cell thus is negative electrode limiting during discharge cycling. Preferably, the negative electrode contains therein, in the approximate range of 1 to 10 volume % of the electrode, an additive from the materials of graphitized carbon, aluminum-iron alloy, and/or magnesium oxide.

  12. Cell Libraries

    NASA Technical Reports Server (NTRS)

    1994-01-01

    A NASA contract led to the development of faster and more energy efficient semiconductor materials for digital integrated circuits. Gallium arsenide (GaAs) conducts electrons 4-6 times faster than silicon and uses less power at frequencies above 100-150 megahertz. However, the material is expensive, brittle, fragile and has lacked computer automated engineering tools to solve this problem. Systems & Processes Engineering Corporation (SPEC) developed a series of GaAs cell libraries for cell layout, design rule checking, logic synthesis, placement and routing, simulation and chip assembly. The system is marketed by Compare Design Automation.

  13. Fine structure of the retinal photoreceptors of the tiger salamander (Ambystoma tigrinum).

    PubMed

    Braekevelt, C R

    1993-04-01

    The retinal photoreceptors of the tiger salamander (Ambystoma tigrinum) have been studied by light and electron microscopy in both light- and dark-adaptation. Rods and cones are present in this duplex retina in a ratio of about 20:1. As in other urodele species these photoreceptors are very large cells. The rod outer segment is composed of bi-membranous discs of uniform diameter displaying several very deep incisures. The rod inner segment displays an ellipsoid of mitochondria and a myoid region which changes in diameter during the lighting cycle indicating that rods undergo photomechanical movements. Rod nuclei are located at all levels of the outer nuclear layer and rod spherules are large and display several invaginated and superficial synaptic sites. Cone photoreceptors while large cells are smaller than the rods. They show a smaller tapering outer segment, a large distal ellipsoid of mitochondria and a prominent paraboloid of glycogen but no oil droplet within the inner segment. Judging by the width of the myoid region which remains similar throughout the lighting cycle, cones in this species show no retino-motor responses. Cone nuclei are less electron dense than rods and are also located at all levels of the outer nuclear layer. The cone synaptic pedicle is larger than that of the rods and also shows several invaginated and superficial synaptic sites.

  14. Stem Cell Information: Glossary

    MedlinePlus

    ... a fluid-filled cavity (the blastocoel ), and a cluster of cells on the interior (the inner cell ... the female body. Inner cell mass (ICM) —The cluster of cells inside the blastocyst . These cells give ...

  15. Photoelectrodialytic cell

    DOEpatents

    Murphy, G.W.

    1983-09-13

    A multicompartment photoelectrodialytic demineralization cell is provided with a buffer compartment interposed between the product compartment and a compartment containing an electrolyte solution. Semipermeable membranes separate the buffer compartment from the product and electrolyte compartments. The buffer compartment is flushed to prevent leakage of the electrolyte compartment from entering the product compartment. 3 figs.

  16. Photovoltaic cell

    DOEpatents

    Gordon, Roy G.; Kurtz, Sarah

    1984-11-27

    In a photovoltaic cell structure containing a visibly transparent, electrically conductive first layer of metal oxide, and a light-absorbing semiconductive photovoltaic second layer, the improvement comprising a thin layer of transition metal nitride, carbide or boride interposed between said first and second layers.

  17. Potent Cells

    ERIC Educational Resources Information Center

    Liu, Dennis

    2007-01-01

    It seems hard to believe that Dolly the cloned sheep was born 10 years ago, kindling furious arguments over the prospects and ethics of cloning a human. Today, the controversy over cloning is entwined, often confused, with concerns over the use of human embryonic stem cells. Most people are unclear what cloning is, and they know even less when it…

  18. Potent Cells

    ERIC Educational Resources Information Center

    Liu, Dennis

    2007-01-01

    It seems hard to believe that Dolly the cloned sheep was born 10 years ago, kindling furious arguments over the prospects and ethics of cloning a human. Today, the controversy over cloning is entwined, often confused, with concerns over the use of human embryonic stem cells. Most people are unclear what cloning is, and they know even less when it…

  19. Nonaqueous cell

    SciTech Connect

    Brand, L.E.; Chi, I.; Granstaff, S.M. Jr.; Vyas, B.

    1988-06-28

    A nonaqueous cell is described comprising lithium negative electrode, positive electrode comprising active material and electrolyte comprising solvent and current carrying species characterized in that the solvent comprises at least 15 mole percent ethylene carbonate, at least 15 mole percent propylene carbonate and at least 15 mole percent polyethylene glycol dialkyl ether.

  20. 19. Oblique, typical cell (south cells) from rear of cell; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Oblique, typical cell (south cells) from rear of cell; view to north, 65mm lens with electronic flash illumination. - Tule Lake Project Jail, Post Mile 44.85, State Route 139, Newell, Modoc County, CA

  1. Cell Proliferation, Cell Death, and Size Regulation

    DTIC Science & Technology

    1998-10-01

    Cell Death , and Size Regulation PRINCIPAL INVESTIGATOR: Nicholas E. Baker, Ph.D. CONTRACTING ORGANIZATION: Albert Einstein College of Medicine of Yeshiva...SUBTITLE 5. FUNDING NUMBERS Cell Proliferation, Cell Death , and Size Regulation DAMD17-97-1-7034 6. AUTHOR(S) Nicholas E. Baker, Ph.D. 7. PERFORMING...Contains unpublished data 5 CELL PROLIFERATION, CELL DEATH , AND SIZE REGULATION INTRODUCTION Cell proliferation and cell death come to attention through

  2. Coupled water transport by rat proximal tubule.

    PubMed

    Green, R; Giebisch, G; Unwin, R; Weinstein, A M

    1991-12-01

    Simultaneous microperfusion of proximal tubules and peritubular capillaries in kidneys of rats anesthetized with Inactin was used to examine water reabsorption by this epithelium. Osmolality of the luminal solution was varied with changes in NaCl concentration and by the addition of raffinose. Capillary perfusates contained either low (2 g/dl) or high (16 g/dl) concentrations of albumin. We used low-bicarbonate perfusates for both lumen and capillary so that we might apply the nonequilibrium thermodynamic model of transport for a single solute (NaCl) to interpret our observations. Linear regression with the volume flux equation Jv = -Lp delta II - Lp sigma delta C + Jav (where Jv is volume flux, Lp is hydraulic conductance, delta II is oncotic force, sigma is osmotic reflection coefficient, delta C is salt concentration difference, and Jav is the component of Jv not attributed to transepithelial hydrostatic or osmotic forces) revealed a tubule water permeability (Pf = 0.11 +/- 0.01 cm/s) and a sigma (0.74 +/- 0.08) in agreement with previous determinations. These transport parameters were unaffected by changes in peritubular protein. We also found that Jav was substantial, approximately three-fourths of the rate of isotonic transport under these perfusion conditions. Further, this component of water transport nearly doubled with the transition from low- to high-protein peritubular capillary perfusion. When expressed as a capacity for water reabsorption against an osmotic gradient, the salt concentration differences required to null volume flux were 13.2 +/- 2.4 and 29.4 +/- 4.0 mosmol/kgH2O under low and high peritubular protein. Our data suggest that this protein effect is, most likely, an increase in solute transport by the tubule epithelial cells.

  3. Electrochemical cell

    SciTech Connect

    Walsh, F.M.

    1986-12-23

    This patent describes an electrochemical cell having a metal anode wherein the metal is selected from zinc and cadmium; a bromine cathode; and an aqueous electrolyte containing a metal bromide, the metal bromide having the same metal as the metal of the anode. The improvement described here comprises: a bromine complexing agent in the aqueous metal bromide electrolyte, the complexing agent consisting solely of a quaternary ammonium salt of an N-organo substituted alpha amino acid, ester, or betaine.

  4. Basolateral membrane Na/base cotransport is dependent on CO2/HCO3 in the proximal convoluted tubule

    PubMed Central

    1987-01-01

    The mechanism of basolateral membrane base transport was examined in the in vitro microperfused rabbit proximal convoluted tubule (PCT) in the absence and presence of ambient CO2/HCO3- by means of the microfluorometric measurement of cell pH. The buffer capacity of the cells measured using rapid NH3 washout was 42.8 +/- 5.6 mmol.liter-1.pH unit-1 in the absence and 84.6 +/- 7.3 mmol.liter-1.pH unit-1 in the presence of CO2/HCO3-. In the presence of CO2/HCO3-, lowering peritubular pH from 7.4 to 6.8 acidified the cell by 0.30 pH units and lowering peritubular Na from 147 to 0 mM acidified the cell by 0.25 pH units. Both effects were inhibited by peritubular 4-acetamido-4'- isothiocyanostilbene-2,2'-disulfonate (SITS). In the absence of exogenous CO2/HCO3-, lowering peritubular pH from 7.4 to 6.8 acidified the cell by 0.25 pH units and lowering peritubular Na from 147 to 0 mM decreased cell pH by 0.20 pH units. Lowering bath pH from 7.4 to 6.8 induced a proton flux of 643 +/- 51 pmol.mm-1.min-1 in the presence of exogenous CO2/HCO3- and 223 +/- 27 pmol.mm-1.min-1 in its absence. Lowering bath Na from 147 to 0 mM induced proton fluxes of 596 +/- 77 pmol.mm-1.min-1 in its absence. The cell acidification induced by lowering bath pH or bath Na in the absence of CO2/HCO3- was inhibited by peritubular SITS or by acetazolamide, whereas peritubular amiloride had no effect. In the absence of exogenous CO2/HCO3-, cyanide blocked the cell acidification induced by bath Na removal, but was without effect in the presence of exogenous CO2/HCO3-. We reached the following conclusions. (a) The basolateral Na/base n greater than 1 cotransporter in the rabbit PCT has an absolute requirement for CO2/HCO3-. (b) In spite of this CO2 dependence, in the absence of exogenous CO2/HCO3-, metabolically produced CO2/HCO3- is sufficient to keep the transporter running at 30% of its control rate in the presence of ambient CO2/HCO3- . (c) There is no apparent amiloride-sensitive Na/H antiporter on

  5. Eukaryotic cells and their cell bodies: Cell Theory revised.

    PubMed

    Baluska, Frantisek; Volkmann, Dieter; Barlow, Peter W

    2004-07-01

    Cell Theory, also known as cell doctrine, states that all eukaryotic organisms are composed of cells, and that cells are the smallest independent units of life. This Cell Theory has been influential in shaping the biological sciences ever since, in 1838/1839, the botanist Matthias Schleiden and the zoologist Theodore Schwann stated the principle that cells represent the elements from which all plant and animal tissues are constructed. Some 20 years later, in a famous aphorism Omnis cellula e cellula, Rudolf Virchow annunciated that all cells arise only from pre-existing cells. General acceptance of Cell Theory was finally possible only when the cellular nature of brain tissues was confirmed at the end of the 20th century. Cell Theory then rapidly turned into a more dogmatic cell doctrine, and in this form survives up to the present day. In its current version, however, the generalized Cell Theory developed for both animals and plants is unable to accommodate the supracellular nature of higher plants, which is founded upon a super-symplasm of interconnected cells into which is woven apoplasm, symplasm and super-apoplasm. Furthermore, there are numerous examples of multinucleate coenocytes and syncytia found throughout the eukaryote superkingdom posing serious problems for the current version of Cell Theory. To cope with these problems, we here review data which conform to the original proposal of Daniel Mazia that the eukaryotic cell is composed of an elemental Cell Body whose structure is smaller than the cell and which is endowed with all the basic attributes of a living entity. A complement to the Cell Body is the Cell Periphery Apparatus, which consists of the plasma membrane associated with other periphery structures. Importantly, boundary structures of the Cell Periphery Apparatus, although capable of some self-assembly, are largely produced and maintained by Cell Body activities and can be produced from it de novo. These boundary structures serve not only as

  6. Dry cell battery poisoning

    MedlinePlus

    Acidic dry cell batteries contain: Manganese dioxide Ammonium chloride Alkaline dry cell batteries contain: Sodium hydroxide Potassium hydroxide Lithium dioxide dry cell batteries contain: Manganese dioxide

  7. Red blood cells, multiple sickle cells (image)

    MedlinePlus

    Sickle cell anemia is an inherited disorder in which abnormal hemoglobin (the red pigment inside red blood cells) is produced. The abnormal hemoglobin causes red blood cells to assume a sickle shape, like the ones seen in this photomicrograph.

  8. Antiparietal cell antibody test

    MedlinePlus

    APCA; Anti-gastric parietal cell antibody; Atrophic gastritis - anti-gastric parietal cell antibody; Gastric ulcer - anti-gastric parietal cell antibody; Pernicious anemia - anti-gastric parietal cell antibody; Vitamin B12 - anti-gastric ...

  9. Stem Cell Basics

    MedlinePlus

    ... healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of ... as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates ...

  10. Murine Mueller cells are progenitor cells for neuronal cells and fibrous tissue cells

    SciTech Connect

    Florian, Christian; Langmann, Thomas; Weber, Bernhard H.F.; Morsczeck, Christian

    2008-09-19

    Mammalian Mueller cells have been reported to possess retinal progenitor cell properties and generate new neurons after injury. This study investigates murine Mueller cells under in vitro conditions for their capability of dedifferentiation into retinal progenitor cells. Mueller cells were isolated from mouse retina, and proliferating cells were expanded in serum-containing medium. For dedifferentiation, the cultured cells were transferred to serum-replacement medium (SRM) at different points in time after their isolation. Interestingly, early cell passages produced fibrous tissue in which extracellular matrix proteins and connective tissue markers were differentially expressed. In contrast, aged Mueller cell cultures formed neurospheres in SRM that are characteristic for neuronal progenitor cells. These neurospheres differentiated into neuron-like cells after cultivation on laminin/ornithine cell culture substrate. Here, we report for the first time that murine Mueller cells can be progenitors for both, fibrous tissue cells and neuronal cells, depending on the age of the cell culture.

  11. Giant Cell Arteritis

    MedlinePlus

    ... Patient / Caregiver Diseases & Conditions Giant Cell Arteritis Giant Cell Arteritis Fast Facts Giant cell arteritis (GCA) is ... polymyalgia rheumatica (also called PMR). What is giant cell arteritis? GCA is a type of vasculitis or ...

  12. CORONAL CELLS

    SciTech Connect

    Sheeley, N. R. Jr.; Warren, H. P. E-mail: harry.warren@nrl.navy.mil

    2012-04-10

    We have recently noticed cellular features in Fe XII 193 A images of the 1.2 MK corona. They occur in regions bounded by a coronal hole and a filament channel, and are centered on flux elements of the photospheric magnetic network. Like their neighboring coronal holes, these regions have minority-polarity flux that is {approx}0.1-0.3 times their flux of majority polarity. Consequently, the minority-polarity flux is 'grabbed' by the majority-polarity flux to form low-lying loops, and the remainder of the network flux escapes to connect with its opposite-polarity counterpart in distant active regions of the Sun. As these regions are carried toward the limb by solar rotation, the cells disappear and are replaced by linear plumes projecting toward the limb. In simultaneous views from the Solar Terrestrial Relations Observatory and Solar Dynamics Observatory spacecraft, these plumes project in opposite directions, extending away from the coronal hole in one view and toward the hole in the other view, suggesting that they are sky-plane projections of the same radial structures. We conclude that these regions are composed of closely spaced radial plumes, extending upward like candles on a birthday cake and visible as cells when seen from above. We suppose that a coronal hole has this same discrete, cellular magnetic structure, but that it is not seen until the encroachment of opposite-polarity flux closes part or all of the hole.

  13. Ion Channels, Cell Volume, Cell Proliferation and Apoptotic Cell Death

    NASA Astrophysics Data System (ADS)

    Lang, Florian; Gulbins, Erich; Szabo, Ildiko; Vereninov, Alexey; Huber, Stephan M.

    At some stage cell proliferation requires an increase in cell volume and a typical hallmark of apoptotic cell death is cell shrinkage. The respective alterations of cell volume are accomplished by altered regulation of ion transport including ion channels. Thus, cell proliferation and apoptosis are both paralleled by altered activity of ion channels, which play an active part in these fundamental cellular mechanisms. Activation of anion channels allows exit of Cl?, osmolyte and HCO3 ? leading to cell shrinkage and acidification of the cytosol. K+ exit through K+ channels leads to cell shrinkage and a decrease in intracellular K+ concentration. K+ channel activity is further important for maintenance of the cell membrane potential - a critical determinant of Ca2+ entry through Ca2+ channels. Cytosolic Ca2+ may both activate mechanisms required for cell proliferation and stimulate enzymes executing apoptosis. The effect of enhanced cytosolic Ca2+ activity depends on the magnitude and temporal organisation of Ca2+ entry. Moreover, a given ion channel may support both cell proliferation and apoptosis, and specific ion channel blockers may abrogate both fundamental cellular mechanisms, depending on cell type, regulatory environment and condition of the cell. Clearly, further experimental effort is needed to clarify the role of ion channels in the regulation of cell proliferation and apoptosis.

  14. Molluscan cells in culture: primary cell cultures and cell lines

    PubMed Central

    Yoshino, T. P.; Bickham, U.; Bayne, C. J.

    2013-01-01

    In vitro cell culture systems from molluscs have significantly contributed to our basic understanding of complex physiological processes occurring within or between tissue-specific cells, yielding information unattainable using intact animal models. In vitro cultures of neuronal cells from gastropods show how simplified cell models can inform our understanding of complex networks in intact organisms. Primary cell cultures from marine and freshwater bivalve and gastropod species are used as biomonitors for environmental contaminants, as models for gene transfer technologies, and for studies of innate immunity and neoplastic disease. Despite efforts to isolate proliferative cell lines from molluscs, the snail Biomphalaria glabrata Say, 1818 embryonic (Bge) cell line is the only existing cell line originating from any molluscan species. Taking an organ systems approach, this review summarizes efforts to establish molluscan cell cultures and describes the varied applications of primary cell cultures in research. Because of the unique status of the Bge cell line, an account is presented of the establishment of this cell line, and of how these cells have contributed to our understanding of snail host-parasite interactions. Finally, we detail the difficulties commonly encountered in efforts to establish cell lines from molluscs and discuss how these difficulties might be overcome. PMID:24198436

  15. DNA-cell conjugates

    DOEpatents

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2016-05-03

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  16. Indium phosphide solar cells

    NASA Technical Reports Server (NTRS)

    Weinberg, Irving

    1991-01-01

    The direction for InP solar cell research; reduction of cell cost; increase of cell efficiency; measurements needed to better understand cell performance; n/p versus p/n; radiation effects; major problems in cell contacting; and whether the present level of InP solar cell research in the USA should be maintained, decreased, or increased were considered.

  17. [Primary malignant mesenchymoma of the lung].

    PubMed

    Kodolova, I M; Kogan, E A; Sekamova, S M; Iashunskaia, N Ia

    1988-01-01

    A case of a primary malignant mesenchymoma of the lung with elements of rhabdomyo-, leiomyo-, osteo-, fibro- and lipo-sarcoma is described. The tumor developed in a man of 58 with a long history of smoking, complaints of chest pains and cough with scanty sputum expectoration. The neoplastic process involved the upper lobe of the left lung and microscopically contained smooth muscle, endothelial, fibroblast-like cells, multinuclear giant cells resembling osteoclasts, strips of osteoid-like hyalinized connective tissue. Electron-microscopic examination revealed myoid-type cells with clusters of myofilaments and Z-type material, cells resembling fibroblasts, osteoclasts and lipocytes. It is suggested that there should be a common histogenesis of primary lung sarcomas arising from a stem cell precursor of mesenchymal origin in lung stroma, bronchial and vascular walls, pleura.

  18. Can mesenchymal cells undergo collective cell migration?

    PubMed Central

    Theveneau, Eric

    2011-01-01

    Cell migration is critical for proper development of the embryo and is also used by many cell types to perform their physiological function. For instance, cell migration is essential for immune cells to monitor the body and for epithelial cells to heal a wound whereas, in cancer cells, acquisition of migratory capabilities is a critical step toward malignancy. Migratory cells are often categorized into two groups: (1) mesenchymal cells, produced by an epithelium-to-mesenchyme transition, that undergo solitary migration and (2) epithelial-like cells which migrate collectively. However, on some occasions, mesenchymal cells may travel in large, dense groups and exhibit key features of collectively migrating cells such as coordination and cooperation. Here, using data published on neural crest cells, a highly invasive mesenchymal cell population that extensively migrate throughout the embryo, we explore the idea that mesenchymal cells, including cancer cells, might be able to undergo collective cell migration under certain conditions and discuss how they could do so. PMID:22274714

  19. Cell cycle regulation in hematopoietic stem cells.

    PubMed

    Pietras, Eric M; Warr, Matthew R; Passegué, Emmanuelle

    2011-11-28

    Hematopoietic stem cells (HSCs) give rise to all lineages of blood cells. Because HSCs must persist for a lifetime, the balance between their proliferation and quiescence is carefully regulated to ensure blood homeostasis while limiting cellular damage. Cell cycle regulation therefore plays a critical role in controlling HSC function during both fetal life and in the adult. The cell cycle activity of HSCs is carefully modulated by a complex interplay between cell-intrinsic mechanisms and cell-extrinsic factors produced by the microenvironment. This fine-tuned regulatory network may become altered with age, leading to aberrant HSC cell cycle regulation, degraded HSC function, and hematological malignancy.

  20. Fuel cell

    SciTech Connect

    Struthers, R.C.

    1983-06-28

    An improved fuel cell comprising an anode section including an anode terminal, an anode fuel, and an anolyte electrolyte, a cathode section including a cathode terminal, an electron distributor and a catholyte electrolyte, an ion exchange section between the anode and cathode sections and including an ionolyte electrolyte, ion transfer membranes separating the ionolyte from the anolyte and the catholyte and an electric circuit connected with and between the terminals conducting free electrons from the anode section and delivering free electrons to the cathode section, said ionolyte receives ions of one polarity moving from the anolyte through the membrane related thereto preventing chemical equilibrium in the anode section and sustaining chemical reaction and the generating of free electrons therein, said ions received by the ionolyte from the anolyte release different ions from the ionolyte which move through the membrane between the ionolyte and catholyte and which add to the catholyte.

  1. Photoelectrochemical cell

    DOEpatents

    Rauh, R. David; Boudreau, Robert A.

    1983-06-14

    A photoelectrochemical cell comprising a sealed container having a light-transmitting window for admitting light into the container across a light-admitting plane, an electrolyte in the container, a photoelectrode in the container having a light-absorbing surface arranged to receive light from the window and in contact with the electrolyte, the surface having a plurality of spaced portions oblique to the plane, each portion having dimensions at least an order of magnitude larger than the maximum wavelength of incident sunlight, the total surface area of the surface being larger than the area of the plane bounded by the container, and a counter electrode in the container in contact with the electrolyte.

  2. CellTracks: Cell analysis system for rare cell detection

    NASA Astrophysics Data System (ADS)

    Kagan, Michael T.; Trainer, Michael N.; Bendele, Teresa; Rao, Chandra; Horton, Allen; Tibbe, Arjan G.; Greve, Jan; Terstappen, Leon W. M. M.

    2002-06-01

    The CellTracks system is a Compact Disk-based cell analyzer that, similar to flow cytometry, differentiates cells that are aligned while passing through focused laser beams. In CellTracks, only immuno-magnetically labeled cells are aligned and remain in position for further analysis. This feature is important in those cases were the cells are relatively infrequent. Epithelium derived tumor cells in peripheral blood are extremely rare but can be present in the blood of cancer patients. The certainty that an event present in a gate is, indeed, an epithelial cell with the assumed characteristics diminishes with the number of events in the analysis gate. Additional and preferably independent information on the individual events aids in the correct classification of the event as an epithelium derived tumor cell. Epithelial cells are immuno-magnetically selected from 7.5 mL of blood and magnetically aligned in the sample chamber between a series of parallel thin film nickel lines. The CD head scans along all nickel lines and captures the fluorescence signals of the objects between the lines. Objects that immuno-phenotypically classify as epithelial tumor cells are revisited for imaging to determine if the identified objects indeed classify as epithelial tumors cells or as debris derived from epithelial cells.

  3. NKT Cell Responses to B Cell Lymphoma

    PubMed Central

    Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B.; Page, Carly; Younger, Kenisha M.; Tiper, Irina V.; Frieman, Matthew; Kimball, Amy S.; Webb, Tonya J.

    2014-01-01

    Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma. PMID:24955247

  4. Integrated circuit cell library

    NASA Technical Reports Server (NTRS)

    Whitaker, Sterling R. (Inventor); Miles, Lowell H. (Inventor)

    2005-01-01

    According to the invention, an ASIC cell library for use in creation of custom integrated circuits is disclosed. The ASIC cell library includes some first cells and some second cells. Each of the second cells includes two or more kernel cells. The ASIC cell library is at least 5% comprised of second cells. In various embodiments, the ASIC cell library could be 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 95% or more comprised of second cells.

  5. Automated Cell-Cutting for Cell Cloning

    NASA Astrophysics Data System (ADS)

    Ichikawa, Akihiko; Tanikawa, Tamio; Matsukawa, Kazutsugu; Takahashi, Seiya; Ohba, Kohtaro

    We develop an automated cell-cutting technique for cell cloning. Animal cells softened by the cytochalasin treatment are injected into a microfluidic chip. The microfluidic chip contains two orthogonal channels: one microchannel is wide, used to transport cells, and generates the cutting flow; the other is thin and used for aspiration, fixing, and stretching of the cell. The injected cell is aspirated and stretched in the thin microchannel. Simultaneously, the volumes of the cell before and after aspiration are calculated; the volumes are used to calculate the fluid flow required to aspirate half the volume of the cell into the thin microchannel. Finally, we apply a high-speed flow in the orthogonal microchannel to bisect the cell. This paper reports the cutting process, the cutting system, and the results of the experiment.

  6. Thymoma related myasthenia gravis in humans and potential animal models.

    PubMed

    Marx, Alexander; Porubsky, Stefan; Belharazem, Djeda; Saruhan-Direskeneli, Güher; Schalke, Berthold; Ströbel, Philipp; Weis, Cleo-Aron

    2015-08-01

    Thymoma-associated Myasthenia gravis (TAMG) is one of the anti-acetylcholine receptor MG (AChR-MG) subtypes. The clinico-pathological features of TAMG and its pathogenesis are described here in comparison with pathogenetic models suggested for the more common non-thymoma AChR-MG subtypes, early onset MG and late onset MG. Emphasis is put on the role of abnormal intratumorous T cell selection and activation, lack of intratumorous myoid cells and regulatory T cells as well as deficient expression of the autoimmune regulator (AIRE) by neoplastic thymic epithelial cells. We review spontaneous and genetically engineered thymoma models in a spectrum of animals and the extensive clinical and immunological overlap between canine, feline and human TAMG. Finally, limitations and perspectives of the transplantation of human and murine thymoma tissue into nude mice, as potential models for TAMG, are addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Electrochemical cell

    SciTech Connect

    Notten, P.H.L.

    1991-12-10

    This patent describes an electrochemical cell comprising a negative electrode. It comprises an electrochemical active material consisting of an intermetallic compound of the formula AB{sub m}C{sub n} wherein m plus n is between 4.8 and 5.4, n has a value of up to 0.6 and greater than 0, A is a Mischmetall or at least one element of the group consisting of Y, Ti, Hf, Zr, Ca, Th, La and the remaining rare earth metals, B is at least two elements selected from the group consisting of Ni, Co, Cu, Fe and Mn and C consists of at least one element selected from the group consisting of Al, Cr, and Si, and has a CaCu{sub 5} structure, and a catalytic material at the surface of which hydrogen exhibits a large electrochemical activity, the catalytic material having a composition of formula DE{sub 3} wherein D is at least one element selected from the group consisting of Cr, Mo and W and E is at least one element selected from the group consisting of Ni and Co.

  8. Cell tracking for cell image analysis

    NASA Astrophysics Data System (ADS)

    Bise, Ryoma; Sato, Yoichi

    2017-04-01

    Cell image analysis is important for research and discovery in biology and medicine. In this paper, we present our cell tracking methods, which is capable of obtaining fine-grain cell behavior metrics. In order to address difficulties under dense culture conditions, where cell detection cannot be done reliably since cell often touch with blurry intercellular boundaries, we proposed two methods which are global data association and jointly solving cell detection and association. We also show the effectiveness of the proposed methods by applying the method to the biological researches.

  9. Tumor cell "dead or alive": caspase and survivin regulate cell death, cell cycle and cell survival.

    PubMed

    Suzuki, A; Shiraki, K

    2001-04-01

    Cell death and cell cycle progression are two sides of the same coin, and these two different phenomenons are regulated moderately to maintain the cellular homeostasis. Tumor is one of the disease states produced as a result of the disintegrated regulation and is characterized as cells showing an irreversible progression of cell cycle and a resistance to cell death signaling. Several investigations have been performed for the understanding of cell death or cell cycle, and cell death research has remarkably progressed in these 10 years. Caspase is a nomenclature referring to ICE/CED-3 cysteine proteinase family and plays a central role during cell death. Recently, several investigations raised some possible hypotheses that caspase is also involved in cell cycle regulation. In this issue, therefore, we review the molecular basis of cell death and cell cycle regulated by caspase in tumor, especially hepatocellular carcinoma cells.

  10. Fuel cell arrangement

    DOEpatents

    Isenberg, Arnold O.

    1987-05-12

    A fuel cell arrangement is provided wherein cylindrical cells of the solid oxide electrolyte type are arranged in planar arrays where the cells within a plane are parallel. Planes of cells are stacked with cells of adjacent planes perpendicular to one another. Air is provided to the interior of the cells through feed tubes which pass through a preheat chamber. Fuel is provided to the fuel cells through a channel in the center of the cell stack; the fuel then passes the exterior of the cells and combines with the oxygen-depleted air in the preheat chamber.

  11. Fuel cell arrangement

    DOEpatents

    Isenberg, A.O.

    1987-05-12

    A fuel cell arrangement is provided wherein cylindrical cells of the solid oxide electrolyte type are arranged in planar arrays where the cells within a plane are parallel. Planes of cells are stacked with cells of adjacent planes perpendicular to one another. Air is provided to the interior of the cells through feed tubes which pass through a preheat chamber. Fuel is provided to the fuel cells through a channel in the center of the cell stack; the fuel then passes the exterior of the cells and combines with the oxygen-depleted air in the preheat chamber. 3 figs.

  12. Nanostructured Solar Cells.

    PubMed

    Chen, Guanying; Ning, Zhijun; Ågren, Hans

    2016-08-09

    We are glad to announce the Special Issue "Nanostructured Solar Cells", published in Nanomaterials. This issue consists of eight articles, two communications, and one review paper, covering major important aspects of nanostructured solar cells of varying types. From fundamental physicochemical investigations to technological advances, and from single junction solar cells (silicon solar cell, dye sensitized solar cell, quantum dots sensitized solar cell, and small molecule organic solar cell) to tandem multi-junction solar cells, all aspects are included and discussed in this issue to advance the use of nanotechnology to improve the performance of solar cells with reduced fabrication costs.

  13. Sickle Cell Anemia

    MedlinePlus

    Sickle cell anemia is a disease in which your body produces abnormally shaped red blood cells. The cells are shaped like a crescent or sickle. They don' ... problem causes sickle cell anemia. People with the disease are born with two sickle cell genes, one ...

  14. Cell death pathways in directly irradiated cells and cells exposed to medium from irradiated cells.

    PubMed

    Jella, Kishore Kumar; Garcia, Amaya; McClean, Brendan; Byrne, Hugh J; Lyng, Fiona M

    2013-03-01

    The aim of this study was to compare levels of apoptosis, necrosis, mitotic cell death and senescence after treatment with both direct radiation and irradiated cell conditioned medium. Human keratinocytes (HaCaT cell line) were irradiated (0.005, 0.05 and 0.5 Gy) using a cobalt 60 teletherapy unit. For bystander experiments, the medium was harvested from donor HaCaT cells 1 hour after irradiation and transferred to recipient HaCaT cells. Clonogenic assay, apoptosis, necrosis, mitotic cell death, senescence and cell cycle analysis were measured in both directly irradiated cells and bystander cells A reduction in cell survival was observed for both directly irradiated cells and irradiated cell conditioned medium (ICCM)-treated cells. Early apoptosis and necrosis was observed predominantly after direct irradiation. An increase in the number of cells in G2/M phase was observed at 6 and 12 h which led to mitotic cell death after 72 h following direct irradiation and ICCM treatment. No senescence was observed in the HaCaT cell line following either direct irradiation or treatment with ICCM. This study has shown that directly irradiated cells undergo apoptosis, necrosis and mitotic cell death whereas ICCM-treated cells predominantly undergo mitotic cell death.

  15. Deformability of Tumor Cells versus Blood Cells

    PubMed Central

    Shaw Bagnall, Josephine; Byun, Sangwon; Begum, Shahinoor; Miyamoto, David T.; Hecht, Vivian C.; Maheswaran, Shyamala; Stott, Shannon L.; Toner, Mehmet; Hynes, Richard O.; Manalis, Scott R.

    2015-01-01

    The potential for circulating tumor cells (CTCs) to elucidate the process of cancer metastasis and inform clinical decision-making has made their isolation of great importance. However, CTCs are rare in the blood, and universal properties with which to identify them remain elusive. As technological advancements have made single-cell deformability measurements increasingly routine, the assessment of physical distinctions between tumor cells and blood cells may provide insight into the feasibility of deformability-based methods for identifying CTCs in patient blood. To this end, we present an initial study assessing deformability differences between tumor cells and blood cells, indicated by the length of time required for them to pass through a microfluidic constriction. Here, we demonstrate that deformability changes in tumor cells that have undergone phenotypic shifts are small compared to differences between tumor cell lines and blood cells. Additionally, in a syngeneic mouse tumor model, cells that are able to exit a tumor and enter circulation are not required to be more deformable than the cells that were first injected into the mouse. However, a limited study of metastatic prostate cancer patients provides evidence that some CTCs may be more mechanically similar to blood cells than to typical tumor cell lines. PMID:26679988

  16. Making new beta cells from stem cells.

    PubMed

    Colman, Alan

    2004-06-01

    In 2000, Shapiro et al. provided compelling "proof of principle" data showing that the transplantation of human islets, purified from cadaveric material, could restore severely diabetic, Type 1 patients to insulin independence. This demonstration prompted renewed efforts to find an alternative and sustainable source of surrogate islet cells for cell therapy. Experiments involving adult ductal and liver "stem" cells, or embryonic stem cells, are prominent amongst these endeavors and are reviewed in this article. Whilst there are many published claims to success in converting ES cells into insulin secreting, glucose responsive cells, all require careful reinterpretation in the light of findings that cells can adsorb insulin present in growth media. It is likely that work with adult cells is less prone to this potential artifact and significant progress has been made in producing insulin-secreting cells. Assessment of in vivo function in the surrogate cells is most frequently made using cell transplantation into toxin-induced, diabetic mice, but this model is rarely used to maximal advantage. In many cases, it remains unclear whether reductions in the hyperglycemia result from insulin secretion from the transplanted cells or are due to recovery of endogenous islet function. In this latter context, experiments are reviewed where endogenous stimulation of recovery is engendered even by irradiated donor cells.

  17. Cell culture purity issues and DFAT cells

    SciTech Connect

    Wei, Shengjuan; Bergen, Werner G.; Zan, Linsen; Dodson, Michael V.

    2013-04-12

    Highlights: •DFAT cells are progeny cells derived from dedifferentiated mature adipocytes. •Common problems in this research is potential cell contamination of initial cultures. •The initial cell culture purity is crucial in DFAT cell research field. -- Abstract: Dedifferentiation of mature adipocytes, in vitro, has been pursued/documented for over forty years. The subsequent progeny cells are named dedifferentiated adipocyte-derived progeny cells (DFAT cells). DFAT cells are proliferative and likely to possess mutilineage potential. As a consequence, DFAT cells and their progeny/daughter cells may be useful as a potential tool for various aspects of tissue engineering and as potential vectors for the alleviation of several disease states. Publications in this area have been increasing annually, but the purity of the initial culture of mature adipocytes has seldom been documented. Consequently, it is not always clear whether DFAT cells are derived from dedifferentiated mature (lipid filled) adipocytes or from contaminating cells that reside in an impure culture.

  18. Electrochemical cell

    SciTech Connect

    Heuts, J.J.F.; Frens, G.

    1987-10-27

    An electrochemical cell is described comprising a negative electrode. The electrochemically active material consists of an intermetallic compound forming a hydride with hydrogen, which compound has the CaCu/sub 5/-structure and the compositional formula AB/sub m/C/sub n/, where m+n is between 4.8 and 5.4, and where n is between 0.05 and 0.6. A consists of Mischmetall or of at least one element selected from the group consisting of Y, Ti, Hf, Zr, Ca, Th, La and the remaining rare earth metals, in which the total atomic quantities of the elements Y, Ti, Hf and Zr may not be more than 40% of A. B consists of two or more elements selected from the group consisting of Ni, Co, Cu, Fe and Mn, the maximum atomic quantity per gram atom of A is being for Ni:3.5, for Co:3.5, for Cu:3.5, for Fe:2.0 and for Mn:1.0. C consists of at least one element selected from the group consisting of Al, Cr and Si in the following atomic quantities: Al:0.05-0.6, Cr:0.05-0.5 and Si:0.05-0.5, characterized in that the electrochemically active material of the negative electrode also comprises an intermetallic compound forming a hydride with hydrogen, of the compositional formula DNihd pE/sub q/ in an amount from 5 to 45% by weight calculated on the total amount of electrochemically active material, where p+q is between 4.8 and 5.4, where p is between 3.5 and 5.4, where q has a value from 0 to 1.5. D is selected from the group formed by La and Mischmetall, and E consists of one or more elements selected from the group consisting of Co, Cr, Mn and Cu.

  19. Fuel cell-fuel cell hybrid system

    DOEpatents

    Geisbrecht, Rodney A.; Williams, Mark C.

    2003-09-23

    A device for converting chemical energy to electricity is provided, the device comprising a high temperature fuel cell with the ability for partially oxidizing and completely reforming fuel, and a low temperature fuel cell juxtaposed to said high temperature fuel cell so as to utilize remaining reformed fuel from the high temperature fuel cell. Also provided is a method for producing electricity comprising directing fuel to a first fuel cell, completely oxidizing a first portion of the fuel and partially oxidizing a second portion of the fuel, directing the second fuel portion to a second fuel cell, allowing the first fuel cell to utilize the first portion of the fuel to produce electricity; and allowing the second fuel cell to utilize the second portion of the fuel to produce electricity.

  20. Red blood cells, sickle cell (image)

    MedlinePlus

    ... is an inherited blood disease in which the red blood cells produce abnormal pigment (hemoglobin). The abnormal hemoglobin causes deformity of the red blood cells into crescent or sickle-shapes, as seen in ...

  1. Cell culture purity issues and DFAT cells.

    PubMed

    Wei, Shengjuan; Bergen, Werner G; Hausman, Gary J; Zan, Linsen; Dodson, Michael V

    2013-04-12

    Dedifferentiation of mature adipocytes, in vitro, has been pursued/documented for over forty years. The subsequent progeny cells are named dedifferentiated adipocyte-derived progeny cells (DFAT cells). DFAT cells are proliferative and likely to possess mutilineage potential. As a consequence, DFAT cells and their progeny/daughter cells may be useful as a potential tool for various aspects of tissue engineering and as potential vectors for the alleviation of several disease states. Publications in this area have been increasing annually, but the purity of the initial culture of mature adipocytes has seldom been documented. Consequently, it is not always clear whether DFAT cells are derived from dedifferentiated mature (lipid filled) adipocytes or from contaminating cells that reside in an impure culture.

  2. Mammary stem cells have myoepithelial cell properties

    PubMed Central

    Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

    2014-01-01

    Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

  3. Cell Membrane Softening in Cancer Cells

    NASA Astrophysics Data System (ADS)

    Schmidt, Sebastian; Händel, Chris; Käs, Josef

    Biomechanical properties are useful characteristics and regulators of the cell's state. Current research connects mechanical properties of the cytoskeleton to many cellular processes but does not investigate the biomechanics of the plasma membrane. We evaluated thermal fluctuations of giant plasma membrane vesicles, directly derived from the plasma membranes of primary breast and cervical cells and observed a lowered rigidity in the plasma membrane of malignant cells compared to non-malignant cells. To investigate the specific role of membrane rigidity changes, we treated two cell lines with the Acetyl-CoA carboxylase inhibitor Soraphen A. It changed the lipidome of cells and drastically increased membrane stiffness by up regulating short chained membrane lipids. These altered cells had a decreased motility in Boyden chamber assays. Our results indicate that the thermal fluctuations of the membrane, which are much smaller than the fluctuations driven by the cytoskeleton, can be modulated by the cell and have an impact on adhesion and motility.

  4. Beta Cell Breakthroughs

    MedlinePlus

    ... says Douglas Melton, PhD, a biologist at the Harvard Stem Cell Institute. Fluctuating blood glucose levels do ... journal Cell, Melton reported that his team at Harvard managed to turn human stem cells into beta ...

  5. Sickle cell test

    MedlinePlus

    The sickle cell test looks for the abnormal hemoglobin in the blood that causes the disease sickle ... done to tell if a person has abnormal hemoglobin that causes sickle cell disease and sickle cell ...

  6. [Pancreatic cancer stem cell].

    PubMed

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2015-05-01

    Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.

  7. Closed Large Cell Clouds

    Atmospheric Science Data Center

    2013-04-19

    article title:  Closed Large Cell Clouds in the South Pacific     ... unperturbed by cyclonic or frontal activity. When the cell centers are cloudy and the main sinking motion is concentrated at cell ...

  8. Liver cancer stem cells.

    PubMed

    Sell, Stewart; Leffert, Hyam L

    2008-06-10

    In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas (HCC) arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells? For many years the finding of preneoplastic nodules in the liver during experimental induction of HCCs by chemicals was interpreted to support the hypothesis that HCC arose by dedifferentiation of mature liver cells. More recently, recognition of the role of small oval cells in the carcinogenic process led to a new hypothesis that HCC arises by maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties (ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.

  9. Inside the Cell

    MedlinePlus

    ... Business Basics Describes functions shared by virtually all cells: making fuel and proteins, transporting materials and disposing of wastes. » more Chapter 3: On the Job: Cellular Specialties Explains how cells specialize. Features a number of cell types: nerves, ...

  10. Sickle cell anemia - resources

    MedlinePlus

    Resources - sickle cell anemia ... The following organizations are good resources for information on sickle cell anemia : American Sickle Cell Anemia Association -- www.ascaa.org National Heart, Blood, and Lung Institute -- www. ...

  11. Lung cancer - small cell

    MedlinePlus

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  12. Fuel cells: A survey

    NASA Technical Reports Server (NTRS)

    Crowe, B. J.

    1973-01-01

    A survey of fuel cell technology and applications is presented. The operating principles, performance capabilities, and limitations of fuel cells are discussed. Diagrams of fuel cell construction and operating characteristics are provided. Photographs of typical installations are included.

  13. Advances in cell culture

    SciTech Connect

    Maramorosch, K. )

    1987-01-01

    This book presents papers on advances in cell culture. Topics covered include: Genetic changes in the influenza viruses during growth in cultured cells; The biochemistry and genetics of mosquito cells in culture; and Tree tissue culture applications.

  14. Kidney cell electrophoresis

    NASA Technical Reports Server (NTRS)

    Todd, P.

    1979-01-01

    A kidney cell electrophoresis technique is described in four parts: (1) the development and testing of electrophoresis solutions; (2) optimization of freezing and thawing; (3) procedures for evaluation of separated kidney cells; and (4) electrophoretic mobility characteristics of kidney cells.

  15. Kidney cell electrophoresis

    NASA Technical Reports Server (NTRS)

    Todd, P.

    1980-01-01

    The following aspects of kidney cell electrophoresis are discussed: (1) the development and testing of electrophoresis solutions; (2) optimization of freezing and thawing; (3) procedures for evaluation of separated kidney cells; and (4) electrophoretic mobility characterization of kidney cells.

  16. CellFinder: a cell data repository.

    PubMed

    Stachelscheid, Harald; Seltmann, Stefanie; Lekschas, Fritz; Fontaine, Jean-Fred; Mah, Nancy; Neves, Mariana; Andrade-Navarro, Miguel A; Leser, Ulf; Kurtz, Andreas

    2014-01-01

    CellFinder (http://www.cellfinder.org) is a comprehensive one-stop resource for molecular data characterizing mammalian cells in different tissues and in different development stages. It is built from carefully selected data sets stemming from other curated databases and the biomedical literature. To date, CellFinder describes 3394 cell types and 50 951 cell lines. The database currently contains 3055 microscopic and anatomical images, 205 whole-genome expression profiles of 194 cell/tissue types from RNA-seq and microarrays and 553 905 protein expressions for 535 cells/tissues. Text mining of a corpus of >2000 publications followed by manual curation confirmed expression information on ∼900 proteins and genes. CellFinder's data model is capable to seamlessly represent entities from single cells to the organ level, to incorporate mappings between homologous entities in different species and to describe processes of cell development and differentiation. Its ontological backbone currently consists of 204 741 ontology terms incorporated from 10 different ontologies unified under the novel CELDA ontology. CellFinder's web portal allows searching, browsing and comparing the stored data, interactive construction of developmental trees and navigating the partonomic hierarchy of cells and tissues through a unique body browser designed for life scientists and clinicians.

  17. CellFinder: a cell data repository

    PubMed Central

    Stachelscheid, Harald; Seltmann, Stefanie; Lekschas, Fritz; Fontaine, Jean-Fred; Mah, Nancy; Neves, Mariana; Andrade-Navarro, Miguel A.; Leser, Ulf; Kurtz, Andreas

    2014-01-01

    CellFinder (http://www.cellfinder.org) is a comprehensive one-stop resource for molecular data characterizing mammalian cells in different tissues and in different development stages. It is built from carefully selected data sets stemming from other curated databases and the biomedical literature. To date, CellFinder describes 3394 cell types and 50 951 cell lines. The database currently contains 3055 microscopic and anatomical images, 205 whole-genome expression profiles of 194 cell/tissue types from RNA-seq and microarrays and 553 905 protein expressions for 535 cells/tissues. Text mining of a corpus of >2000 publications followed by manual curation confirmed expression information on ∼900 proteins and genes. CellFinder’s data model is capable to seamlessly represent entities from single cells to the organ level, to incorporate mappings between homologous entities in different species and to describe processes of cell development and differentiation. Its ontological backbone currently consists of 204 741 ontology terms incorporated from 10 different ontologies unified under the novel CELDA ontology. CellFinder’s web portal allows searching, browsing and comparing the stored data, interactive construction of developmental trees and navigating the partonomic hierarchy of cells and tissues through a unique body browser designed for life scientists and clinicians. PMID:24304896

  18. Glial cells: Old cells with new twists

    PubMed Central

    Ndubaku, Ugo; de Bellard, Maria Elena

    2008-01-01

    Summary Based on their characteristics and function – migration, neural protection, proliferation, axonal guidance and trophic effects – glial cells may be regarded as probably the most versatile cells in our body. For many years, these cells were considered as simply support cells for neurons. Recently, it has been shown that they are more versatile than previously believed – as true stem cells in the nervous system – and are important players in neural function and development. There are several glial cell types in the nervous system: the two most abundant are oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. Although both of these cells are responsible for myelination, their developmental origins are quite different. Oligodendrocytes originate from small niche populations from different regions of the central nervous system, while Schwann cells develop from a stem cell population (the neural crest) that gives rise to many cell derivatives besides glia and which is a highly migratory group of cells. PMID:18068219

  19. Cell Proliferation, Cell Death, and Size Regulation

    DTIC Science & Technology

    2000-10-01

    generated in part by apoptosis of excess cells during development. We identified a mutation named pineapple eye (pie ) that has too few cells in the...predicted to encode a novel 582 amino acid protein, perhaps interacting with molybdopterin. It is possible that the pie gene encodes a novel enzyme protecting against cell death during growth and development.

  20. Snail modulates cell metabolism in MDCK cells

    SciTech Connect

    Haraguchi, Misako; Indo, Hiroko P.; Iwasaki, Yasumasa; Iwashita, Yoichiro; Fukushige, Tomoko; Majima, Hideyuki J.; Izumo, Kimiko; Horiuchi, Masahisa; Kanekura, Takuro; Furukawa, Tatsuhiko; Ozawa, Masayuki

    2013-03-22

    Highlights: ► MDCK/snail cells were more sensitive to glucose deprivation than MDCK/neo cells. ► MDCK/snail cells had decreased oxidative phosphorylation, O{sub 2} consumption and ATP content. ► TCA cycle enzyme activity, but not expression, was lower in MDCK/snail cells. ► MDCK/snail cells showed reduced PDH activity and increased PDK1 expression. ► MDCK/snail cells showed reduced expression of GLS2 and ACLY. -- Abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP{sup +}-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of

  1. Sertoli cells as biochambers

    NASA Technical Reports Server (NTRS)

    Cameron, Don F. (Inventor); Sanberg, Paul R. (Inventor); Saporta, Samuel (Inventor); Hushen, Joelle J. (Inventor)

    2004-01-01

    According to the present invention, there is provided a biological chamber system having a biochamber defined by outer walls of Sertoli cells. Also provided is a transplantation facilitator including a biochamber. A method of making biochambers by co-culturing facilitator cells and therapeutic cells and then aggregating the facilitator celes is also provided. Also provided is a method of transplanting cells by incorporating transplant cells into a biochamber and transplanting the biochamber containing the transplant cells.

  2. Stem Cell Sciences plc.

    PubMed

    Daniels, Sebnem

    2006-09-01

    Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

  3. Snail modulates cell metabolism in MDCK cells.

    PubMed

    Haraguchi, Misako; Indo, Hiroko P; Iwasaki, Yasumasa; Iwashita, Yoichiro; Fukushige, Tomoko; Majima, Hideyuki J; Izumo, Kimiko; Horiuchi, Masahisa; Kanekura, Takuro; Furukawa, Tatsuhiko; Ozawa, Masayuki

    2013-03-22

    Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of key enzymes. This results in enhanced glucose dependency and leads to cell death under low-glucose conditions. On the other hand, the reduced requirements for oxygen and nutrients from the surrounding environment, might confer the resistance to cell death induced by hypoxia and malnutrition. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Nanostructured Solar Cells

    PubMed Central

    Chen, Guanying; Ning, Zhijun; Ågren, Hans

    2016-01-01

    We are glad to announce the Special Issue “Nanostructured Solar Cells”, published in Nanomaterials. This issue consists of eight articles, two communications, and one review paper, covering major important aspects of nanostructured solar cells of varying types. From fundamental physicochemical investigations to technological advances, and from single junction solar cells (silicon solar cell, dye sensitized solar cell, quantum dots sensitized solar cell, and small molecule organic solar cell) to tandem multi-junction solar cells, all aspects are included and discussed in this issue to advance the use of nanotechnology to improve the performance of solar cells with reduced fabrication costs.

  5. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2009-01-23

    We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

  6. Heterostructure solar cells

    NASA Technical Reports Server (NTRS)

    Chang, K. I.; Yeh, Y. C. M.; Iles, P. A.; Morris, R. K.

    1987-01-01

    The performance of gallium arsenide solar cells grown on Ge substrates is discussed. In some cases the substrate was thinned to reduce overall cell weight with good ruggedness. The conversion efficiency of 2 by 2 cm cells under AMO reached 17.1 percent with a cell thickness of 6 mils. The work described forms the basis for future cascade cell structures, where similar interconnecting problems between the top cell and the bottom cell must be solved. Applications of the GaAs/Ge solar cell in space and the expected payoffs are discussed.

  7. Gaucher cell, photomicrograph (image)

    MedlinePlus

    Gaucher disease is called a "lipid storage disease" where abnormal amounts of lipids called "glycosphingolipids" are stored in special cells called reticuloendothelial cells. Classically, the nucleus is ...

  8. Human memory B cells.

    PubMed

    Seifert, M; Küppers, R

    2016-12-01

    A key feature of the adaptive immune system is the generation of memory B and T cells and long-lived plasma cells, providing protective immunity against recurring infectious agents. Memory B cells are generated in germinal center (GC) reactions in the course of T cell-dependent immune responses and are distinguished from naive B cells by an increased lifespan, faster and stronger response to stimulation and expression of somatically mutated and affinity matured immunoglobulin (Ig) genes. Approximately 40% of human B cells in adults are memory B cells, and several subsets were identified. Besides IgG(+) and IgA(+) memory B cells, ∼50% of peripheral blood memory B cells express IgM with or without IgD. Further smaller subpopulations have additionally been described. These various subsets share typical memory B cell features, but likely also fulfill distinct functions. IgM memory B cells appear to have the propensity for refined adaptation upon restimulation in additional GC reactions, whereas reactivated IgG B cells rather differentiate directly into plasma cells. The human memory B-cell pool is characterized by (sometimes amazingly large) clonal expansions, often showing extensive intraclonal IgV gene diversity. Moreover, memory B-cell clones are frequently composed of members of various subsets, showing that from a single GC B-cell clone a variety of memory B cells with distinct functions is generated. Thus, the human memory B-cell compartment is highly diverse and flexible. Several B-cell malignancies display features suggesting a derivation from memory B cells. This includes a subset of chronic lymphocytic leukemia, hairy cell leukemia and marginal zone lymphomas. The exposure of memory B cells to oncogenic events during their generation in the GC, the longevity of these B cells and the ease to activate them may be key determinants for their malignant transformation.

  9. The plastic liver: differentiated cells, stem cells, every cell?

    PubMed Central

    Hindley, Christopher J.; Mastrogiovanni, Gianmarco; Huch, Meritxell

    2014-01-01

    The liver is capable of full regeneration following several types and rounds of injury, ranging from hepatectomy to toxin-mediated damage. The source of this regenerative capacity has long been a hotly debated topic. The damage response that occurs when hepatocyte proliferation is impaired is thought to be mediated by oval/dedifferentiated progenitor cells, which replenish the hepatocyte and ductal compartments of the liver. Recently, reports have questioned whether these oval/progenitor cells truly serve as the facultative stem cell of the liver following toxin-mediated damage. In this issue of the JCI, Kordes and colleagues use lineage tracing to follow transplanted rat hepatic stellate cells, a resident liver mesenchymal cell population, in hosts that have suffered liver damage. Transplanted stellate cells repopulated the damaged rat liver by contributing to the oval cell response. These data establish yet another cell type of mesenchymal origin as the progenitor for the oval/ductular response in the rat. The lack of uniformity between different damage models, the extent of the injury to the liver parenchyma, and potential species-specific differences might be at the core of the discrepancy between different studies. Taken together, these data imply a considerable degree of plasticity in the liver, whereby several cell types can contribute to regeneration. PMID:25401467

  10. Accessory cells for β-cell transplantation.

    PubMed

    Staels, W; De Groef, S; Heremans, Y; Coppens, V; Van Gassen, N; Leuckx, G; Van de Casteele, M; Van Riet, I; Luttun, A; Heimberg, H; De Leu, N

    2016-02-01

    Despite recent advances, insulin therapy remains a treatment, not a cure, for diabetes mellitus with persistent risk of glycaemic alterations and life-threatening complications. Restoration of the endogenous β-cell mass through regeneration or transplantation offers an attractive alternative. Unfortunately, signals that drive β-cell regeneration remain enigmatic and β-cell replacement therapy still faces major hurdles that prevent its widespread application. Co-transplantation of accessory non-islet cells with islet cells has been shown to improve the outcome of experimental islet transplantation. This review will highlight current travails in β-cell therapy and focuses on the potential benefits of accessory cells for islet transplantation in diabetes.

  11. [Exosomes and Immune Cells].

    PubMed

    Seo, Naohiro

    2017-05-01

    In addition to the cytokines and cytotoxic granules, exosomes have been known as the intercellular communicator and cytotoxic missile of immune cells for the past decade. It has been well known that mature dendritic cell(DC)-derived exosomes participate in the T cell and natural killer(NK)cell activation, while immature DCs secrete tolerogenic exosomes for regulatory T(Treg)cell generation. Treg cell-derived EVs act as a suppressor against pathogenic type-1 T helper(Th1)cell responses. CD8+ T cells produce tumoricidal exosomes for preventing tumor invasion and metastasis transiently after T cell receptor(TCR)-mediated stimulation. Thus, immune cells produce functional exosomes in the activation state- and/or differentiation stage-dependent manner. In this review, the role of immune cell-derived exosomes will be introduced, focusing mainly on immune reaction against tumor.

  12. Cell mechanics: a dialogue

    NASA Astrophysics Data System (ADS)

    Tao, Jiaxiang; Li, Yizeng; Vig, Dhruv K.; Sun, Sean X.

    2017-03-01

    Under the microscope, eukaryotic animal cells can adopt a variety of different shapes and sizes. These cells also move and deform, and the physical mechanisms driving these movements and shape changes are important in fundamental cell biology, tissue mechanics, as well as disease biology. This article reviews some of the basic mechanical concepts in cells, emphasizing continuum mechanics description of cytoskeletal networks and hydrodynamic flows across the cell membrane. We discuss how cells can generate movement and shape changes by controlling mass fluxes at the cell boundary. These mass fluxes can come from polymerization/depolymerization of actin cytoskeleton, as well as osmotic and hydraulic pressure-driven flow of water across the cell membrane. By combining hydraulic pressure control with force balance conditions at the cell surface, we discuss a quantitative mechanism of cell shape and volume control. The broad consequences of this model on cell mechanosensation and tissue mechanics are outlined.

  13. Cell mechanics: a dialogue.

    PubMed

    Tao, Jiaxiang; Li, Yizeng; Vig, Dhruv K; Sun, Sean X

    2017-03-01

    Under the microscope, eukaryotic animal cells can adopt a variety of different shapes and sizes. These cells also move and deform, and the physical mechanisms driving these movements and shape changes are important in fundamental cell biology, tissue mechanics, as well as disease biology. This article reviews some of the basic mechanical concepts in cells, emphasizing continuum mechanics description of cytoskeletal networks and hydrodynamic flows across the cell membrane. We discuss how cells can generate movement and shape changes by controlling mass fluxes at the cell boundary. These mass fluxes can come from polymerization/depolymerization of actin cytoskeleton, as well as osmotic and hydraulic pressure-driven flow of water across the cell membrane. By combining hydraulic pressure control with force balance conditions at the cell surface, we discuss a quantitative mechanism of cell shape and volume control. The broad consequences of this model on cell mechanosensation and tissue mechanics are outlined.

  14. Cell mechanics: a dialogue

    PubMed Central

    Tao, Jiaxiang; Li, Yizeng; Vig, Dhruv K; Sun, Sean X

    2017-01-01

    Under the microscope, eukaryotic animal cells can adopt a variety of different shapes and sizes. These cells also move and deform, and the physical mechanisms driving these movements and shape changes are important in fundamental cell biology, tissue mechanics, as well as disease biology. This article reviews some of the basic mechanical concepts in cells, emphasizing continuum mechanics description of cytoskeletal networks and hydrodynamic flows across the cell membrane. We discuss how cells can generate movement and shape changes by controlling mass fluxes at the cell boundary. These mass fluxes can come from polymerization/depolymerization of actin cytoskeleton, as well as osmotic and hydraulic pressure-driven flow of water across the cell membrane. By combining hydraulic pressure control with force balance conditions at the cell surface, we discuss a quantitative mechanism of cell shape and volume control. The broad consequences of this model on cell mechanosensation and tissue mechanics are outlined. PMID:28129208

  15. Cell surface engineering of mesenchymal stem cells.

    PubMed

    Sarkar, Debanjan; Zhao, Weian; Gupta, Ashish; Loh, Wei Li; Karnik, Rohit; Karp, Jeffrey M

    2011-01-01

    By leveraging the capacity to promote regeneration, stem cell therapies offer enormous hope for solving some of the most tragic illnesses, diseases, and tissue defects world-wide. However, a significant barrier to the effective implementation of cell therapies is the inability to target a large quantity of viable cells with high efficiency to tissues of interest. Systemic infusion is desired as it minimizes the invasiveness of cell therapy, and maximizes practical aspects of repeated doses. However, cell types such as mesenchymal stem cells exhibit a poor homing capability or lose their capacity to home following culture expansion (i.e. FASEB J 21:3197-3207, 2007; Circulation 108:863-868, 2003; Stroke: A Journal of Cerebral Circulation 32:1005-1011; Blood 104:3581-3587, 2004). To address this challenge, we have developed a simple platform technology to chemically attach cell adhesion molecules to the cell surface to improve the homing efficiency to specific tissues. This chemical approach involves a stepwise process including (1) treatment of cells with sulfonated biotinyl-N-hydroxy-succinimide to introduce biotin groups on the cell surface, (2) addition of streptavidin that binds to the biotin on the cell surface and presents unoccupied binding sites, and (3) attachment of biotinylated targeting ligands that promote adhesive interactions with vascular endothelium. Specifically, in our model system, a biotinylated cell rolling ligand, sialyl Lewisx (SLeX), found on the surface of leukocytes (i.e., the active site of the P-selectin glycoprotein ligand (PSGL-1)), is conjugated on MSC surface. The SLeX engineered MSCs exhibit a rolling response on a P-selectin coated substrate under shear stress conditions. This indicates that this approach can be used to potentially target P-selectin expressing endothelium in the more marrow or at sites of inflammation. Importantly, the surface modification has no adverse impact on MSCs' native phenotype including their multilineage

  16. Resident vascular progenitor cells.

    PubMed

    Torsney, Evelyn; Xu, Qingbo

    2011-02-01

    Homeostasis of the vessel wall is essential for maintaining its function, including blood pressure and patency of the lumen. In physiological conditions, the turnover rate of vascular cells, i.e. endothelial and smooth muscle cells, is low, but markedly increased in diseased situations, e.g. vascular injury after angioplasty. It is believed that mature vascular cells have an ability to proliferate to replace lost cells normally. On the other hand, recent evidence indicates stem/progenitor cells may participate in vascular repair and the formation of neointimal lesions in severely damaged vessels. It was found that all three layers of the vessels, the intima, media and adventitia, contain resident progenitor cells, including endothelial progenitor cells, mesenchymal stromal cells, Sca-1+ and CD34+ cells. Data also demonstrated that these resident progenitor cells could differentiate into a variety of cell types in response to different culture conditions. However, collective data were obtained mostly from in vitro culture assays and phenotypic marker studies. There are many unanswered questions concerning the mechanism of cell differentiation and the functional role of these cells in vascular repair and the pathogenesis of vascular disease. In the present review, we aim to summarize the data showing the presence of the resident progenitor cells, to highlight possible signal pathways orchestrating cell differentiation toward endothelial and smooth muscle cells, and to discuss the data limitations, challenges and controversial issues related to the role of progenitors. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

  17. Structural alterations in the seminiferous tubules of rats treated with immunosuppressor tacrolimus

    PubMed Central

    Caneguim, Breno H; Cerri, Paulo S; Spolidório, Luís C; Miraglia, Sandra M; Sasso-Cerri, Estela

    2009-01-01

    Background Tacrolimus (FK-506) is an immunosuppressant that binds to a specific immunophilin, resulting in the suppression of the cellular immune response during transplant rejection. Except for some alterations in the spermatozoa, testicular morphological alterations have not been described in rats treated with tacrolimus. In the present study, we purpose to evaluate if the treatment with tacrolimus at long term of follow-up interferes in the integrity of the seminiferous tubules. Methods Rats aging 42-day-old received daily subcutaneous injections of 1 mg/kg/day of tacrolimus during 30 (T-30) and 60 (T-60) days; the rats from control groups (C-30 and C-60) received saline solution. The left testes were fixed in 4% formaldehyde and embedded in glycol methacrylate for morphological and morphometric analyses while right testes were fixed in Bouin's liquid and embedded in paraffin for detection of cell death by the TUNEL method. The epithelial and total tubular areas as well as the stages of the seminiferous epithelium and the number of spermatocytes, spermatids and Sertoli cells (SC) per tubule were obtained. Results In the treated groups, seminiferous tubules irregularly outlined showed disarranged cellular layers and loss of germ cells probably due to cell death, which was revealed by TUNEL method. In addition to germ cells, structural alterations in the SC and folding of the peritubular tissue were usually observed. The morphometric results revealed significant decrease in the number of SC, spermatocytes, spermatids and significant reduction in the epithelial and total tubular areas. Conclusion Tacrolimus induces significant histopathological disorders in the seminiferous tubules, resulting in spermatogenic damage and reduction in the number of Sertoli cells. A careful evaluation of the peritubular components will be necessary to clarify if these alterations are related to the effect of FK-506 on the peritubular tissue. PMID:19243597

  18. Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

    SciTech Connect

    Felthaus, O.; Ettl, T.; Gosau, M.; Driemel, O.; Brockhoff, G.; Reck, A.; Zeitler, K.; Hautmann, M.; Reichert, T.E.; Schmalz, G.; Morsczeck, C.

    2011-04-01

    Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simple method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.

  19. Stem cell therapy without the cells

    PubMed Central

    Maguire, Greg

    2013-01-01

    As an example of the burgeoning importance of stem cell therapy, this past month the California Institute for Regenerative Medicine (CIRM) has approved $70 million to create a new network of stem cell clinical trial centers. Much work in the last decade has been devoted to developing the use of autologous and allogeneic adult stem cell transplants to treat a number of conditions, including heart attack, dementia, wounds, and immune system-related diseases. The standard model teaches us that adult stem cells exists throughout most of the body and provide a means to regenerate and repair most tissues through replication and differentiation. Although we have often witnessed the medical cart placed in front of the scientific horse in the development of stem cell therapies outside of academic circles, great strides have been made, such as the use of purified stem cells1 instead of whole bone marrow transplants in cancer patients, where physicians avoid re-injecting the patients with their own cancer cells.2 We most often think of stem cell therapy acting to regenerate tissue through replication and then differentiation, but recent studies point to the dramatic effects adult stem cells exert in the repair of various tissues through the release of paracrine and autocrine substances, and not simply through differentiation. Indeed, up to 80% of the therapeutic effect of adult stem cells has been shown to be through paracrine mediated actions.3 That is, the collected types of molecules released by the stem cells, called the secretome, or stem cell released molecules (SRM), number in the 100s, including proteins, microRNA, growth factors, antioxidants, proteasomes, and exosomes, and target a multitude of biological pathways through paracrine actions. The composition of the different molecule types in SRM is state dependent, and varies with cell type and conditions such as age and environment. PMID:24567776

  20. Dummy Cell Would Improve Performance Of Fuel-Cell Stack

    NASA Technical Reports Server (NTRS)

    Suljak, G. T.

    1993-01-01

    Interposition of dummy cell between stack of alkaline fuel cells and accessory section of fuel-cell powerplant proposed to overcome operational deficiencies plaguing end-most active cell. Cell in combination with additional hydrogen/coolant separator plate keeps end cell warmer and drier. End cell 96th in stack of fuel cells.

  1. Specific cell cycle synchronization with butyrate and cell cycle analysis

    USDA-ARS?s Scientific Manuscript database

    Synchronized cells have been invaluable for many kinds of cell cycle and cell proliferation studies. Butyrate induces cell cycle arrest and apoptosis in MDBK cells. To explore the possibility of using butyrate-blocked cells to obtain synchronized cells, we investigated the property of the cell cyc...

  2. Dummy Cell Would Improve Performance Of Fuel-Cell Stack

    NASA Technical Reports Server (NTRS)

    Suljak, G. T.

    1993-01-01

    Interposition of dummy cell between stack of alkaline fuel cells and accessory section of fuel-cell powerplant proposed to overcome operational deficiencies plaguing end-most active cell. Cell in combination with additional hydrogen/coolant separator plate keeps end cell warmer and drier. End cell 96th in stack of fuel cells.

  3. Nanocomposite Photoelectrochemical Cells

    NASA Technical Reports Server (NTRS)

    Narayan, Sri R.; Kindler, Andrew; Whitacre, Jay F.

    2007-01-01

    Improved, solid-state photoelectrochemical cells for converting solar radiation to electricity have been proposed. (In general, photoelectrochemical cells convert incident light to electricity through electrochemical reactions.) It is predicted that in comparison with state-of-the-art photoelectrochemical cells, these cells will be found to operate with greater solar-to-electric energy-conversion efficiencies.

  4. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    SciTech Connect

    Varga, Nora; Vereb, Zoltan; Rajnavoelgyi, Eva; Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs; Apati, Agota

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  5. Chromosomal differentiation of cells

    SciTech Connect

    1993-12-31

    Chapter 16, discusses the chromosomal differentiation of cells. The chromosomes of differentiated cells have been much less studies than those of meristematic or germline cells, probably because such cells do not usually divide spontaneously. However, in many cases they can be induced to undergo mitosis. 26 refs., 2 figs.

  6. Dictyostelium cell death

    PubMed Central

    Levraud, Jean-Pierre; Adam, Myriam; Luciani, Marie-Françoise; de Chastellier, Chantal; Blanton, Richard L.; Golstein, Pierre

    2003-01-01

    Cell death in the stalk of Dictyostelium discoideum, a prototypic vacuolar cell death, can be studied in vitro using cells differentiating as a monolayer. To identify early events, we examined potentially dying cells at a time when the classical signs of Dictyostelium cell death, such as heavy vacuolization and membrane lesions, were not yet apparent. We observed that most cells proceeded through a stereotyped series of differentiation stages, including the emergence of “paddle” cells showing high motility and strikingly marked subcellular compartmentalization with actin segregation. Paddle cell emergence and subsequent demise with paddle-to-round cell transition may be critical to the cell death process, as they were contemporary with irreversibility assessed through time-lapse videos and clonogenicity tests. Paddle cell demise was not related to formation of the cellulose shell because cells where the cellulose-synthase gene had been inactivated underwent death indistinguishable from that of parental cells. A major subcellular alteration at the paddle-to-round cell transition was the disappearance of F-actin. The Dictyostelium vacuolar cell death pathway thus does not require cellulose synthesis and includes early actin rearrangements (F-actin segregation, then depolymerization), contemporary with irreversibility, corresponding to the emergence and demise of highly polarized paddle cells. PMID:12654899

  7. Molten carbonate fuel cell

    DOEpatents

    Kaun, Thomas D.; Smith, James L.

    1987-01-01

    A molten electrolyte fuel cell with an array of stacked cells and cell enclosures isolating each cell except for access to gas manifolds for the supply of fuel or oxidant gas or the removal of waste gas, the cell enclosures collectively providing an enclosure for the array and effectively avoiding the problems of electrolyte migration and the previous need for compression of stack components, the fuel cell further including an inner housing about and in cooperation with the array enclosure to provide a manifold system with isolated chambers for the supply and removal of gases. An external insulated housing about the inner housing provides thermal isolation to the cell components.

  8. Individual cell sorting.

    PubMed

    Stovel, R T; Sweet, R G

    1979-01-01

    Current cell sorting machines do not preserve the individual identity of processed cells; after analysis, the cells are assigned to a subpopulation where they are pooled with other similar cells. This paper reports progress on a system that sorts cells individually to precise locations on a microscope slide and preserves them for further observation with a light microscope while recording flow measurement data for each cell. Various electronic and mechanical modifications to an existing sorting machine are described that increase drop placement accuracy and permit individual cell sorting.

  9. Stem Cell Organoid Engineering

    PubMed Central

    Yin, Xiaolei; Mead, Benjamin E.; Safaee, Helia; Langer, Robert; Karp, Jeffrey M.; Levy, Oren

    2016-01-01

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies. PMID:26748754

  10. Cytokinesis in animal cells.

    PubMed

    D'Avino, Pier Paolo; Giansanti, Maria Grazia; Petronczki, Mark

    2015-02-13

    Cell division ends with the physical separation of the two daughter cells, a process known as cytokinesis. This final event ensures that nuclear and cytoplasmic contents are accurately partitioned between the two nascent cells. Cytokinesis is one of the most dramatic changes in cell shape and requires an extensive reorganization of the cell's cytoskeleton. Here, we describe the cytoskeletal structures, factors, and signaling pathways that orchestrate this robust and yet highly dynamic process in animal cells. Finally, we discuss possible future directions in this growing area of cell division research and its implications in human diseases, including cancer.

  11. Cell tracking using nanoparticles.

    PubMed

    Vaccaro, Dennis E; Yang, Meiheng; Weinberg, James S; Reinhardt, Christopher P; Groman, Ernest V

    2008-09-01

    Tracking cells in regenerative medicine is becoming increasingly important for basic cell therapy science, for cell delivery optimization and for accurate biodistribution studies. This report describes nanoparticles that utilize stable-isotope metal labels for multiple detection technologies in preclinical studies. Cells labeled with nanoparticles can be imaged by electron microscopy, fluorescence, and magnetic resonance. The nanoparticle-labeled cells can be quantified by neutron activation, thereby allowing, with the use of standard curves, the determination of the number of labeled cells in tissue samples from in vivo sources. This report describes the characteristics of these nanoparticles and methods for using these nanoparticles to label and track cells.

  12. Fluorescence activated cell sorting.

    NASA Technical Reports Server (NTRS)

    Bonner, W. A.; Hulett, H. R.; Sweet, R. G.; Herzenberg, L. A.

    1972-01-01

    An instrument has been developed for sorting biological cells. The cells are rendered differentially fluorescent and incorporated into a small liquid stream illuminated by a laser beam. The cells pass sequentially through the beam, and fluorescent light from the cells gives rise to electrical signals. The stream is broken into a series of uniform size drops downstream of the laser. The cell signals are used to give appropriate electrostatic charges to drops containing the cells. The drops then pass between two charged plates and are deflected to appropriate containers. The system has proved capable of providing fractions containing large numbers of viable cells highly enriched in a particular functional type.

  13. Molten carbonate fuel cell

    DOEpatents

    Kaun, T.D.; Smith, J.L.

    1986-07-08

    A molten electrolyte fuel cell is disclosed with an array of stacked cells and cell enclosures isolating each cell except for access to gas manifolds for the supply of fuel or oxidant gas or the removal of waste gas. The cell enclosures collectively provide an enclosure for the array and effectively avoid the problems of electrolyte migration and the previous need for compression of stack components. The fuel cell further includes an inner housing about and in cooperation with the array enclosure to provide a manifold system with isolated chambers for the supply and removal of gases. An external insulated housing about the inner housing provides thermal isolation to the cell components.

  14. Engineering Stem Cell Organoids.

    PubMed

    Yin, Xiaolei; Mead, Benjamin E; Safaee, Helia; Langer, Robert; Karp, Jeffrey M; Levy, Oren

    2016-01-07

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies.

  15. Fuel cells seminar

    SciTech Connect

    1996-12-01

    This year`s meeting highlights the fact that fuel cells for both stationary and transportation applications have reached the dawn of commercialization. Sales of stationary fuel cells have grown steadily over the past 2 years. Phosphoric acid fuel cell buses have been demonstrated in urban areas. Proton-exchange membrane fuel cells are on the verge of revolutionizing the transportation industry. These activities and many more are discussed during this seminar, which provides a forum for people from the international fuel cell community engaged in a wide spectrum of fuel cell activities. Discussions addressing R&D of fuel cell technologies, manufacturing and marketing of fuel cells, and experiences of fuel cell users took place through oral and poster presentations. For the first time, the seminar included commercial exhibits, further evidence that commercial fuel cell technology has arrived. A total of 205 papers is included in this volume.

  16. Modeling collective cell motility

    NASA Astrophysics Data System (ADS)

    Rappel, Wouter-Jan

    Eukaryotic cells often move in groups, a critical aspect of many biological and medical processes including wound healing, morphogenesis and cancer metastasis. Modeling can provide useful insights into the fundamental mechanisms of collective cell motility. Constructing models that incorporate the physical properties of the cells, however, is challenging. Here, I discuss our efforts to build a comprehensive cell motility model that includes cell membrane properties, cell-substrate interactions, cell polarity, and cell-cell interaction. The model will be applied to a variety of systems, including motion on micropatterned substrates and the migration of border cells in Drosophila. This work was supported by NIH Grant No. P01 GM078586 and NSF Grant No. 1068869.

  17. Chicken NK cell receptors.

    PubMed

    Straub, Christian; Neulen, Marie-Luise; Sperling, Beatrice; Windau, Katharina; Zechmann, Maria; Jansen, Christine A; Viertlboeck, Birgit C; Göbel, Thomas W

    2013-11-01

    Natural killer cells are innate immune cells that destroy virally infected or transformed cells. They recognize these altered cells by a plethora of diverse receptors and thereby differ from other lymphocytes that use clonally distributed antigen receptors. To date, several receptor families that play a role in either activating or inhibiting NK cells have been identified in mammals. In the chicken, NK cells have been functionally and morphologically defined, however, a conclusive analysis of receptors involved in NK cell mediated functions has not been available. This is partly due to the low frequencies of NK cells in blood or spleen that has hampered their intensive characterization. Here we will review recent progress regarding the diverse NK cell receptor families, with special emphasis on novel families identified in the chicken genome with potential as chicken NK cell receptors.

  18. Innate Memory T cells

    PubMed Central

    Jameson, Stephen C.; Lee, You Jeong; Hogquist, Kristin A.

    2015-01-01

    Memory T cells are usually considered to be a feature of a successful immune response against a foreign antigen, and such cells can mediate potent immunity. However, in mice, alternative pathways have been described, through which naïve T cells can acquire the characteristics and functions of memory T cells without encountering specific foreign antigen or the typical signals required for conventional T cell differentiation. Such cells reflect a response to the internal rather the external environment, and hence such cells are called innate memory T cells. In this review, we describe how innate memory subsets were identified, the signals that induce their generation and their functional properties and potential role in the normal immune response. The existence of innate memory T cells in mice raises questions about whether parallel populations exist in humans, and we discuss the evidence for such populations during human T cell development and differentiation. PMID:25727290

  19. Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia

    MedlinePlus

    ... and Hairy Cell Leukemia: Introduction Request Permissions Leukemia - B-cell Prolymphocytic Leukemia and Hairy Cell Leukemia: Introduction ... t k e P Types of Cancer Leukemia - B-cell Prolymphocytic Leukemia and Hairy Cell Leukemia Guide ...

  20. [Cell cycle regulation in cancer stem cells].

    PubMed

    Takeishi, Shoichiro

    2015-05-01

    In addition to the properties of self-renewal and multipotency, cancer stem cells share the characteristics of their distinct cell cycle status with somatic stem cells. Cancer stem cells (CSCs) are maintained in a quiescent state with this characteristic conferring resistance to anticancer therapies that target dividing cells. Elucidation of the mechanisms of CSC quiescence might therefore be expected to provide further insight into CSC behaviors and lead to the elimination of cancer. This review summarizes several key regulators of the cell cycle in CSCs as well as attempts to define future challenges in this field, especially from the point of view of the application of our current understandings to the clinical medicine.

  1. Space solar cell research

    NASA Technical Reports Server (NTRS)

    Flood, Dennis J.

    1989-01-01

    A brief overview is given of the scope of the NASA space solar cell research and development program. Silicon cells, gallium arsenide cells, indium phosphide cells, and superlattice solar cells are addressed, indicating the state of the art of each type in outer space and their advantages and drawbacks for use in outer space. Contrasts between efficiency in space and on earth are pointed out.

  2. Space solar cell research

    NASA Technical Reports Server (NTRS)

    Flood, Dennis J.

    1989-01-01

    A brief overview is given of the scope of the NASA space solar cell research and development program. Silicon cells, gallium arsenide cells, indium phosphide cells, and superlattice solar cells are addressed, indicating the state of the art of each type in outer space and their advantages and drawbacks for use in outer space. Contrasts between efficiency in space and on earth are pointed out.

  3. Kidney cell electrophoresis

    NASA Technical Reports Server (NTRS)

    Todd, P. W.

    1985-01-01

    Tasks were undertaken in support of two objectives. They are: (1) to carry out electrophoresis experiments on cells in microgravity; and (2) assess the feasibility of using purified kidney cells from embryonic kidney cultures as a source of important cell products. Investigations were carried out in the following areas: (1) ground based electrophoresis technology; (2) cell culture technology; (3) electrophoresis of cells; (4) urokinase assay research; (5) zero-g electrophoresis; and (6) flow cytometry.

  4. Technology Status: Fuel Cells and Electrolysis Cells

    NASA Technical Reports Server (NTRS)

    Mcbryar, H.

    1978-01-01

    The status of the baselined shuttle fuel cell as well as the acid membrane fuel cell and space-oriented water electrolysis technologies are presented. The more recent advances in the alkaline fuel cell technology area are the subject of a companion paper. A preliminary plan for the focusing of these technologies towards regenerative energy storage applications in the multi-hundred kilowatt range is also discussed.

  5. B cell helper assays.

    PubMed

    Abrignani, Sergio; Tonti, Elena; Casorati, Giulia; Dellabona, Paolo

    2009-01-01

    Activation, proliferation and differentiation of naïve B lymphocytes into memory B cells and plasma cells requires engagement of the B cell receptor (BCR) coupled to T-cell help (1, 2). T cells deliver help in cognate fashion when they are activated upon recognition of specific MHC-peptide complexes presented by B cells. T cells can also deliver help in a non-cognate or bystander fashion, when they do not find specific MHC-peptide complexes on B cells and are activated by alternative mechanisms. T-cell dependent activation of B cells can be studied in vitro by experimental models called "B cell helper assays" that are based on the co-culture of B cells with activated T cells. These assays allow to decipher the molecular bases for productive T-dependent B cell responses. We show here examples of B cell helper assays in vitro, which can be reproduced with any subset of T lymphocytes that displays the appropriate helper signals.

  6. Screening of solar cells

    NASA Technical Reports Server (NTRS)

    Appelbaum, J.; Chait, A.; Thompson, D. A.

    1993-01-01

    Because solar cells in a production batch are not identical, screening is performed to obtain similar cells for aggregation into arrays. A common technique for screening is based on a single operating point of the I-V characteristic of the cell, usually the maximum power point. As a result, inferior cell matching may occur at the actual operating points. Screening solar cells based on the entire I-V characteristic will inherently result in more similar cells in the array. An array consisting of more similar cells is likely to have better overall characteristics and more predictable performance. Solar cell screening methods and cell ranking are discussed. The concept of a mean cell is defined as a cell 'best' representing all the cells in the production batch. The screening and ranking of all cells are performed with respect to the mean cell. The comparative results of different screening methods are illustrated on a batch of 50 silicon cells of the Space Station Freedom.

  7. Visualization of Cell-Cell Interaction Contacts

    PubMed Central

    2011-01-01

    T-cell activation requires interactions of T-cell antigen receptors (TCR) and peptides presented by major histocompatibility complex molecules (MHCp) in an adhesive junction between the T-cell and antigen-presenting cell (APC). Stable junctions with bull's eye supramolecular activation clusters (SMACs) have been defined as immunological synapses. The term synapse works in this case because it joins roots for “same” and “fasten,” which could be translated as “fasten in the same place.” These structures maintain T-cell-APC interaction and allow directed secretion. We have proposed that SMACs are not really clusters, but are analogous to higher order membrane-cytoskeleton zones involved in amoeboid locomotion including a substrate testing lamellipodium, an adhesive lamella and anti-adhesive uropod. Since T-cells can also integrate signaling during locomotion over antigen presenting cells, it is important to consider adhesive junctions maintained as cells move past each other. This combination of movement (kine-) and fastening (-apse) can be described as a kinapse or moving junction. Synapses and kinapses operate in different stages of T-cell priming. Optimal effector functions may also depend upon cyclical use of synapses and kinapses. Visualization of these structures in vitro and in vivo presents many distinct challenges that will be discussed in this paper. PMID:22299060

  8. Analytical pyrolysis of cells and cell fragments

    SciTech Connect

    Faix, O.; Bertelt, E.

    1995-12-01

    Wood of spruce, beech and birch was disintegrated without chemical pretreatment after 10 minutes of steaming at 110{degrees}C in a laboratory defibrator. Fibers, vessels, and fragments of secondary wall were separated by wet screening. A hydrocylon was used for separation of middle lamellae. By using analytical pyrolysis-GC/MS, parenchymatic cells were found to be richer in lignin than the other cells. The lignin content of middle lamellae was 35% (beech, spruce) and 39% (birch). In agreement with the literature, the S/G ratios of the vessels and middle lamellae was lower than those of the other cells and cell fragments.

  9. Liver cell adenoma and liver cell adenomatosis

    PubMed Central

    Barthelmes, Ludger

    2005-01-01

    During the last three decades liver cell adenoma and liver cell adenomatosis have emerged as new clinical entities in hepato-logical practice due to the widespread use of oral contraceptives and increased imaging of the liver. On review of published series there is evidence that 10% of liver cell adenomas progress to hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision biopsy, and the preferred treatment modality is resection of the liver cell adenoma to prevent bleeding and malignant transformation. In liver cell adenomatosis, the association with oral contraceptive use is not as high as in solitary liver cell adenomas. The risk of malignant transformation is not increased compared with solitary liver cell adenomas. Treatment consists of close monitoring and imaging, resection of superficially located, large (>4 cm) or growing liver cell adenomas. Liver transplantation is the last resort in case of substantive concern about malignant transformation or for large, painful adenomas in liver cell adenomatosis after treatment attempts by liver resection. PMID:18333188

  10. Effect of IgA deposits on the glomerular mesangium in Berger's disease.

    PubMed

    Sinniah, R; Churg, J

    1983-01-01

    In mesangial IgA glomerulonephritis (Berger's disease), the immunoproteins appeared to gain access from the capillary lumen to the mesangium via endothelial fenestrae or via channels between the endothelial cells. The deposits are transported into the deeper mesangium by a process of inhibition or diffusion, with the matrix acting as the head. There are no true channels or grooves in the mesangial matrix for the transport of the immunoproteins. The contractility of the glomerular myoid fibrils may account for the movement of deposits to the hilus for possible removal. There was partial dissolution of the deposits in the mesangial matrix accompanied by loosening of the matrix. No evidence was found for any significant intracellular phagocytosis and digestion. The mesangial deposits directly or indirectly stimulated the cellular hypertrophy and hyperplasia and increased deposition of mesangial matrix. This was accompanied by formation of collagen fibrils within the thickened matrix and led to atrophy of the mesangial cells and sclerosis of the glomeruli.

  11. DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment.

    PubMed

    Petzoldt, Astrid G; Coutelis, Jean-Baptiste; Géminard, Charles; Spéder, Pauline; Suzanne, Magali; Cerezo, Delphine; Noselli, Stéphane

    2012-05-01

    In bilateria, positioning and looping of visceral organs requires proper left-right (L/R) asymmetry establishment. Recent work in Drosophila has identified a novel situs inversus gene encoding the unconventional type ID myosin (MyoID). In myoID mutant flies, the L/R axis is inverted, causing reversed looping of organs, such as the gut, spermiduct and genitalia. We have previously shown that MyoID interacts physically with β-Catenin, suggesting a role of the adherens junction in Drosophila L/R asymmetry. Here, we show that DE-Cadherin co-immunoprecipitates with MyoID and is required for MyoID L/R activity. We further demonstrate that MyoIC, a closely related unconventional type I myosin, can antagonize MyoID L/R activity by preventing its binding to adherens junction components, both in vitro and in vivo. Interestingly, DE-Cadherin inhibits MyoIC, providing a protective mechanism to MyoID function. Conditional genetic experiments indicate that DE-Cadherin, MyoIC and MyoID show temporal synchronicity for their function in L/R asymmetry. These data suggest that following MyoID recruitment by β-Catenin at the adherens junction, DE-Cadherin has a twofold effect on Drosophila L/R asymmetry by promoting MyoID activity and repressing that of MyoIC. Interestingly, the product of the vertebrate situs inversus gene inversin also physically interacts with β-Catenin, suggesting that the adherens junction might serve as a conserved platform for determinants to establish L/R asymmetry both in vertebrates and invertebrates.

  12. Bioelectrochemistry of cell surfaces

    NASA Astrophysics Data System (ADS)

    Dolowy, Krzysztof

    This paper deals with processes and phenomena of cell surface bioelectrochemistry in which charges do not move across the cell membrane. First, electrochemical properties of the cell membrane and the cell medium interface are described, and different electric potentials present in biological systems are defined. Methods of cell electrophoresis are then discussed. It is shown that none of the simple electrochemical models of the cell membrane can explain the dependence of cell electrophoretic mobility upon ionic strength and other electrochemical properties of the cell membrane, such as the difference in cell membrane charge as determined electrochemically and biochemically, or the effect of neuraminidase, pH, or membrane potential change on cell electrophoretic mobility. Thus, it is apparent that conclusions drawn from electrophoretic mobility data on the basis of simple models are false. The more complex multilayer-electrochemical model of the cell membrane is then described and shown to explain most electrochemical properties of the cell membrane. Next, different electrochemical techniques that were applied to study cell surfaces are described. It is shown that colloid titration, isoelectric focusing, and partition of cells between two immiscible phases is dependent not only on electrical properties of the cell membrane, but also on the energy of adsorption at cell surfaces of organic molecules used in these methods. Powder electrodes, cell polarography, conductometric titration, and Donnan potential methods are described and it is shown that these methods also produce results of doubtful value and are also often misinterpreted. The contact potential difference method produces results difficult to interpret and only electro-osmotic measurements and potential sensitive molecules are valuable methods. The colloid particle interaction theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO) as applied to cell interactions is discussed. It is shown that the

  13. Mast cells enhance T cell activation: Importance of mast cell-derived TNF

    NASA Astrophysics Data System (ADS)

    Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

    2005-05-01

    Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response

  14. Single cell mechanics of keratinocyte cells.

    PubMed

    Lulevich, Valentin; Yang, Hsin-ya; Isseroff, R Rivkah; Liu, Gang-yu

    2010-11-01

    Keratinocytes represent the major cell type of the uppermost layer of human skin, the epidermis. Using AFM-based single cell compression, the ability of individual keratinocytes to resist external pressure and global rupturing forces is investigated and compared with various cell types. Keratinocytes are found to be 6-70 times stiffer than other cell types, such as white blood, breast epithelial, fibroblast, or neuronal cells, and in contrast to other cell types they retain high mechanic strength even after the cell's death. The absence of membrane rupturing peaks in the force-deformation profiles of keratinocytes and their high stiffness during a second load cycle suggests that their unique mechanical resistance is dictated by the cytoskeleton. A simple analytical model enables the quantification of Young's modulus of keratinocyte cytoskeleton, as high as 120-340 Pa. Selective disruption of the two major cytoskeletal networks, actin filaments and microtubules, does not significantly affect keratinocyte mechanics. F-actin is found to impact cell deformation under pressure. During keratinocyte compression, the plasma membrane stretches to form peripheral blebs. Instead of blebbing, cells with depolymerized F-actin respond to pressure by detaching the plasma membrane from the cytoskeleton underneath. On the other hand, the compression force of keratinocytes expressing a mutated keratin (cell line, KEB-7) is 1.6-2.2 times less than that for the control cell line that has normal keratin networks. Therefore, we infer that the keratin intermediate filament network is responsible for the extremely high keratinocyte stiffness and resilience. This could manifest into the rugged protective nature of the human epidermis.

  15. Quantitative Characterization of Cell Behaviors through Cell Cycle Progression via Automated Cell Tracking

    PubMed Central

    Wang, Yuliang; Jeong, Younkoo; Jhiang, Sissy M.; Yu, Lianbo; Menq, Chia-Hsiang

    2014-01-01

    Cell behaviors are reflections of intracellular tension dynamics and play important roles in many cellular processes. In this study, temporal variations in cell geometry and cell motion through cell cycle progression were quantitatively characterized via automated cell tracking for MCF-10A non-transformed breast cells, MCF-7 non-invasive breast cancer cells, and MDA-MB-231 highly metastatic breast cancer cells. A new cell segmentation method, which combines the threshold method and our modified edge based active contour method, was applied to optimize cell boundary detection for all cells in the field-of-view. An automated cell-tracking program was implemented to conduct live cell tracking over 40 hours for the three cell lines. The cell boundary and location information was measured and aligned with cell cycle progression with constructed cell lineage trees. Cell behaviors were studied in terms of cell geometry and cell motion. For cell geometry, cell area and cell axis ratio were investigated. For cell motion, instantaneous migration speed, cell motion type, as well as cell motion range were analyzed. We applied a cell-based approach that allows us to examine and compare temporal variations of cell behavior along with cell cycle progression at a single cell level. Cell body geometry along with distribution of peripheral protrusion structures appears to be associated with cell motion features. Migration speed together with motion type and motion ranges are required to distinguish the three cell-lines examined. We found that cells dividing or overlapping vertically are unique features of cell malignancy for both MCF-7 and MDA-MB-231 cells, whereas abrupt changes in cell body geometry and cell motion during mitosis are unique to highly metastatic MDA-MB-231 cells. Taken together, our live cell tracking system serves as an invaluable tool to identify cell behaviors that are unique to malignant and/or highly metastatic breast cancer cells. PMID:24911281

  16. Microscale Fuel Cells

    SciTech Connect

    Holladay, Jamie D.; Viswanathan, Vish V.

    2005-11-03

    Perhaprs some of the most innovative work on fuel cells has been the research dedicated to applying silicon fabrication techniques to fuel cells technology creating low power microscale fuel cells applicable to microelectro mechanical systems (MEMS), microsensors, cell phones, PDA’s, and other low power (0.001 to 5 We) applications. In this small power range, fuel cells offer the decoupling of the energy converter from the energy storage which may enable longer operating times and instant or near instant charging. To date, most of the microscale fuel cells being developed have been based on proton exchange membrane fuel cell technology (PEMFC) or direct methanol fuel cell (DMFC) technology. This section will discuss requirements and considerations that need to be addressed in the development of microscale fuel cells, as well as some proposed designs and fabrication strategies.

  17. Bacterial Cell Wall Components

    NASA Astrophysics Data System (ADS)

    Ginsberg, Cynthia; Brown, Stephanie; Walker, Suzanne

    Bacterial cell-surface polysaccharides cells are surrounded by a variety of cell-surface structures that allow them to thrive in extreme environments. Components of the cell envelope and extracellular matrix are responsible for providing the cells with structural support, mediating intercellular communication, allowing the cells to move or to adhere to surfaces, protecting the cells from attack by antibiotics or the immune system, and facilitating the uptake of nutrients. Some of the most important cell wall components are polysaccharide structures. This review discusses the occurrence, structure, function, and biosynthesis of the most prevalent bacterial cell surface polysaccharides: peptidoglycan, lipopolysaccharide, arabinogalactan, and lipoarabinomannan, and capsular and extracellular polysaccharides. The roles of these polysaccharides in medicine, both as drug targets and as therapeutic agents, are also described.

  18. Plant stem cell niches.

    PubMed

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  19. Tetraspanins in Cell Migration

    PubMed Central

    Jiang, Xupin; Zhang, Jiaping; Huang, Yuesheng

    2015-01-01

    Tetraspanins are a superfamily of small transmembrane proteins that are expressed in almost all eukaryotic cells. Through interacting with one another and with other membrane and intracellular proteins, tetraspanins regulate a wide range of proteins such as integrins, cell surface receptors, and signaling molecules, and thereby engage in diverse cellular processes ranging from cell adhesion and migration to proliferation and differentiation. In particular, tetraspanins modulate the function of proteins involved in all determining factors of cell migration including cell–cell adhesion, cell–ECM adhesion, cytoskeletal protrusion/contraction, and proteolytic ECM remodeling. We herein provide a brief overview of collective in vitro and in vivo studies of tetraspanins to illustrate their regulatory functions in the migration and trafficking of cancer cells, vascular endothelial cells, skin cells (keratinocytes and fibroblasts), and leukocytes. We also discuss the involvement of tetraspanins in various pathologic and remedial processes that rely on cell migration and their potential value as targets for therapeutic intervention. PMID:26091149

  20. The cytoskeletal proteins in the contractile tissues of the testis and its excurrent ducts of the passerine bird, Masked Weaver (Ploceus velatus).

    PubMed

    Ozegbe, P C; Aire, T A; Deokar, M S

    2012-02-01

    The cellular composition of the testicular capsule, seminiferous peritubular tissue, the epithelia as well as periductal muscle cell layers of the excurrent ducts was studied, in sexually mature and active Masked Weaver (Ploceus velatus) birds of the passerine family, Ploceidae. Ultrastructure of the contractile cells in the testicular capsule, peritubular and periductal tissues showed that these cells were smooth muscles of typical morphological characteristics. Variability in the immunohistochemical co-expression of microfilaments and intermediate filaments in the different tissues was evident. Actin and desmin proteins were co-expressed immunohistochemically in the testicular capsule and seminiferous peritubular smooth muscle layer. Actin was singly and very weakly expressed in the rete testis epithelium while cytokeratins and desmin were co-expressed in the epithelium of the excurrent ducts. The periductal muscle layer of all ducts of the epididymis, the ductus deferens as well as the seminal glomus, strongly co-expressed actin and desmin. Vimentin was absent in all cells and tissue types studied. There is clear evidence that the tissues of the male gonad and its excurrent ducts in the Masked Weaver, as has been reported for members of the Galloanserae and Ratitae, contain well-formed contractile tissues whose function would include the transportation of luminal through-flow from the testis into, and through, its excurrent ducts. The microtubule helix in the head and of the mid-piece, of elongating spermatids, as well as of the mature spermatozoa in the various excurrent ducts, including some spermatozoa in the seminal glomus, also co-expressed these three proteins.

  1. Apigenin inhibits renal cell carcinoma cell proliferation.

    PubMed

    Meng, Shuai; Zhu, Yi; Li, Jiang-Feng; Wang, Xiao; Liang, Zhen; Li, Shi-Qi; Xu, Xin; Chen, Hong; Liu, Ben; Zheng, Xiang-Yi; Xie, Li-Ping

    2017-03-21

    Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor activity in several cancer types. The present study evaluated the effects and mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose- and time-dependent manner. A comet assay suggested that apigenin caused DNA damage in ACHN cells, especially at higher doses, and induced G2/M phase cell cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)-mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53 dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell xenograft mouse model. Apigenin treatment reduced tumor growth and volume in vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors derived from apigenin-treated mice. These findings suggest that apigenin exposure induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis, which collectively suppress ACHN RCC cell proliferation in vitro and in vivo. Given its antitumor effects and low in vivo toxicity, apigenin is a highly promising agent for treatment of RCC.

  2. Mechanical guidance through cell-cell and cell-surface contact during multicellular streaming

    NASA Astrophysics Data System (ADS)

    Wang, Chenlu; Driscoll, Meghan; Gupta, Satyandra K.; Parent, Carole; Losert, Wolfgang

    2014-03-01

    During collective cell migration, mechanical forces arise from the extracellular matrix (ECM) through cell-surface contact and from other cells through cell-cell contact. These forces regulate the motion of migrating cell groups. To determine how these mechanical interactions balance during cell migration, we measured the shape dynamics of Dictyostelium discoideum cells at the multicellular streaming stage. We found that cells can coordinate their motion by synchronizing protrusion waves that travel along their membranes when they form proper cell-cell adhesion and cell-surface adhesion. In addition, our experiments on live actin labeled cells show that intracellular actin polymerization actively responds to the change of cell-cell/surface adhesion and helps to stabilize multicellular migration streams. Our finding suggests that the coordination of motion between neighboring cells in collective migration requires a balance between cell-cell adhesion and cell-surface adhesion, and that the cell cytoskeleton plays an important role in this balance.

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

    PubMed Central

    Liu, Quanwen; Shen, Yi; Chen, Jiarong; Ding, Jie; Tang, Zihua; Zhang, Cui; Chen, Jianling; Li, Liang; Chen, Ping; Wang, Jinfu

    2016-01-01

    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. PMID:27057177

  4. Thin cells for space

    NASA Technical Reports Server (NTRS)

    Storti, G.; Wohlgemuth, J.; Wrigley, C.

    1979-01-01

    Research and pilot line production efforts directed towards the fabrication of high efficiency ultrathin silicon solar cells (50 micrometers) are reported. Conventional ultrathin cells with air-mass-zero (AM0) efficiencies exceeding 14% and coplanar back contact cells with AM0 efficiencies up to 11.7% were developed. The primary mechanisms limiting efficiency were determined in both types of cells, and they are discussed within the context of further improving efficiency. Results of pilot line production of conventional ultrathin cells are also presented. Average AM0 efficiencies of 12% were readily achieved for 2000 cell production runs.

  5. Microfluidics for manipulating cells.

    PubMed

    Mu, Xuan; Zheng, Wenfu; Sun, Jiashu; Zhang, Wei; Jiang, Xingyu

    2013-01-14

    Microfluidics, a toolbox comprising methods for precise manipulation of fluids at small length scales (micrometers to millimeters), has become useful for manipulating cells. Its uses range from dynamic management of cellular interactions to high-throughput screening of cells, and to precise analysis of chemical contents in single cells. Microfluidics demonstrates a completely new perspective and an excellent practical way to manipulate cells for solving various needs in biology and medicine. This review introduces and comments on recent achievements and challenges of using microfluidics to manipulate and analyze cells. It is believed that microfluidics will assume an even greater role in the mechanistic understanding of cell biology and, eventually, in clinical applications.

  6. Natural Killer Cell Memory

    PubMed Central

    O’Sullivan, Timothy E.; Sun, Joseph C.; Lanier, Lewis L.

    2015-01-01

    Natural killer (NK) cells have historically been considered short-lived cytolytic cells that can rapidly respond against pathogens and tumors in an antigen-independent manner, and then undergo cell death. Recently, however, NK cells have been shown to possess traits of adaptive immunity, and can acquire immunological memory in a similar manner to T and B cells. In this review, we discuss evidence for NK cell memory and the mechanisms involved in the generation and survival of these innate lymphocytes. PMID:26488815

  7. Cytokinesis in Animal Cells

    PubMed Central

    D’Avino, Pier Paolo; Giansanti, Maria Grazia; Petronczki, Mark

    2015-01-01

    Cell division ends with the physical separation of the two daughter cells, a process known as cytokinesis. This final event ensures that nuclear and cytoplasmic contents are accurately partitioned between the two nascent cells. Cytokinesis is one of the most dramatic changes in cell shape and requires an extensive reorganization of the cell’s cytoskeleton. Here, we describe the cytoskeletal structures, factors, and signaling pathways that orchestrate this robust and yet highly dynamic process in animal cells. Finally, we discuss possible future directions in this growing area of cell division research and its implications in human diseases, including cancer. PMID:25680833

  8. Alloreactive T cell clones.

    PubMed

    Fitch, F W

    1984-01-01

    T cell clones are useful models for studying lymphocyte function both at the level of the individual cell and in interacting systems. Murine cytolytic and non- cytolyic T cell clones have been obtained with relative ease, and the particular procedure used to derive and maintain T cell clones may influence profoundly the characteristics of the resulting cells. The method of choice depends on the specific question to be asked. Although some clones have characteristics that would have been expected on the basis of results observed with bulk cell populations, other clones have rather unexpected properties. Although most T cell clones appear to be either cytolytic or non-cytolytic, this distinction is not always absolute. A high proportion of both cytolytic and non-cytolytic T cell clones have dual reactivity. This is true for cells which by other criteria appear to be true clones. The frequency of such cells is high enough to suggest that most if not all T cells may have reactivity for more than one antigenic determinant or that antigenic determinants recognized by T cells are shared widely and unexpectedly. It is not clear whether one or two different antigen receptors account for such dual reactivity. The nature of the T cell receptor for antigen remains obscure. T cell clones, because of their homogeneous nature, should make it easier to answer these important immunological questions. Although it remains to be determined how many distinct molecules account for the numerous biological activities found in the culture supernatants from antigen-stimulated T cell clones, it is clear that these factors influence several different types of cells that are involved directly and indirectly in immune responses. IL-2 stimulates both cytolytic and non-cytolytic T cells to proliferate. BCSF causes polyclonal activation of B cells, and there may be other factors which influence B cell responses to antigenic stimulation. IL-3 apparently stimulates maturation of immature T cells

  9. Assessment of pancreas cells

    NASA Technical Reports Server (NTRS)

    Vanoss, C. J.

    1978-01-01

    Pancreatic islets were obtained from guinea pig pancreas by the collagenase method and kept alive in tissue culture prior to further studies. Pancreas cell morphology was studied by standard histochemical techniques using light microscopy. Preparative vertical electrophoresis-levitation of dispersed fetal guinea pig pancreas cells was conducted in phosphate buffer containing a heavy water (D20) gradient which does not cause clumping of cells or alter the osmolarity of the buffers. The faster migrating fractions tended to be enriched in beta-cell content. Alpha and delta cells were found to some degree in most fractions. A histogram showing the cell count distribution is included.

  10. Natural Killer Cell Memory.

    PubMed

    O'Sullivan, Timothy E; Sun, Joseph C; Lanier, Lewis L

    2015-10-20

    Natural killer (NK) cells have historically been considered short-lived cytolytic cells that can rapidly respond against pathogens and tumors in an antigen-independent manner and then undergo cell death. Recently, however, NK cells have been shown to possess traits of adaptive immunity and can acquire immunological memory in a manner similar to that of T and B cells. In this review, we discuss evidence of NK cell memory and the mechanisms involved in the generation and survival of these innate lymphocytes.

  11. Pluripotent stem cells for Schwann cell engineering.

    PubMed

    Ma, Ming-San; Boddeke, Erik; Copray, Sjef

    2015-04-01

    Tissue engineering of Schwann cells (SCs) can serve a number of purposes, such as in vitro SC-related disease modeling, treatment of peripheral nerve diseases or peripheral nerve injury, and, potentially, treatment of CNS diseases. SCs can be generated from autologous stem cells in vitro by recapitulating the various stages of in vivo neural crest formation and SC differentiation. In this review, we survey the cellular and molecular mechanisms underlying these in vivo processes. We then focus on the current in vitro strategies for generating SCs from two sources of pluripotent stem cells, namely embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Different methods for SC engineering from ESCs and iPSCs are reviewed and suggestions are proposed for optimizing the existing protocols. Potential safety issues regarding the clinical application of iPSC-derived SCs are discussed as well. Lastly, we will address future aspects of SC engineering.

  12. Alternative Cell Death Pathways and Cell Metabolism

    PubMed Central

    Fulda, Simone

    2013-01-01

    While necroptosis has for long been viewed as an accidental mode of cell death triggered by physical or chemical damage, it has become clear over the last years that necroptosis can also represent a programmed form of cell death in mammalian cells. Key discoveries in the field of cell death research, including the identification of critical components of the necroptotic machinery, led to a revised concept of cell death signaling programs. Several regulatory check and balances are in place in order to ensure that necroptosis is tightly controlled according to environmental cues and cellular needs. This network of regulatory mechanisms includes metabolic pathways, especially those linked to mitochondrial signaling events. A better understanding of these signal transduction mechanisms will likely contribute to open new avenues to exploit our knowledge on the regulation of necroptosis signaling for therapeutic application in the treatment of human diseases. PMID:23401689

  13. T helper cell cytotoxicity

    SciTech Connect

    Penna, A.; Glasebrook, A.

    1986-03-01

    It has recently been shown that helper T cells (Lyt2/sup -/, L3T4/sup +/) can express cytolytic activity when activated by antigen (Ag). The authors have studied the phenomenon of T helper cell cytotoxicity using cloned lines of Ag-reactive T cells and T hybrids. Cytotoxicity was determined by coculture of T cells with /sup 51/Cr-labelled Ag presenting cells (APC) and/or non-APC (bystander cells). A high frequency of Ag-specific L3T4/sup +/ T cell clones (> 90%) and hybrids (> 50%) were found to be cytotoxic. Cytotoxicity as determined by /sup 51/Cr release was maximal at 20 hr with little or no cytotoxicity detectable at 6 hr. Target cells, either APC or bystander cells, were killed provided the T cells were stimulated by Ag. Not all of the B cells used as APC were susceptible targets even if able to promote bystander killing. Monoclonal antibodies directed against L3T4, LFA-1 and T cell receptor molecules were able to block the cytotoxicity indicating a requirement for specific activation of the T cells. Cyclosporin A (CsA) reduced the cytotoxic activity of helper T hybrids and clones, while it did not affect the cytotoxic activity of Lyt2/sup +/, L3T4/sup -/ cytolytic T cell (CTL) clones. The delayed expression of cytotoxic activity, the lysis of bystander cells and inhibition by CsA suggest that the cytolytic mechanism is mediated by a soluble factor and different from the cytolytic mechanism of CTL. The phenomenon of cytotoxic T helper cells may be relevant to suppression of B cell immune responses in vivo.

  14. Colorectal cancer stem cells.

    PubMed

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  15. The cell cycle as a brake for β-cell regeneration from embryonic stem cells.

    PubMed

    El-Badawy, Ahmed; El-Badri, Nagwa

    2016-01-13

    The generation of insulin-producing β cells from stem cells in vitro provides a promising source of cells for cell transplantation therapy in diabetes. However, insulin-producing cells generated from human stem cells show deficiency in many functional characteristics compared with pancreatic β cells. Recent reports have shown molecular ties between the cell cycle and the differentiation mechanism of embryonic stem (ES) cells, assuming that cell fate decisions are controlled by the cell cycle machinery. Both β cells and ES cells possess unique cell cycle machinery yet with significant contrasts. In this review, we compare the cell cycle control mechanisms in both ES cells and β cells, and highlight the fundamental differences between pluripotent cells of embryonic origin and differentiated β cells. Through critical analysis of the differences of the cell cycle between these two cell types, we propose that the cell cycle of ES cells may act as a brake for β-cell regeneration. Based on these differences, we discuss the potential of modulating the cell cycle of ES cells for the large-scale generation of functionally mature β cells in vitro. Further understanding of the factors that modulate the ES cell cycle will lead to new approaches to enhance the production of functional mature insulin-producing cells, and yield a reliable system to generate bona fide β cells in vitro.

  16. Single-cell growth analysis in a mixed cell culture

    NASA Astrophysics Data System (ADS)

    Ando, Jun; Bato, Mary Grace P.; Daria, Vincent Ricardo

    2008-06-01

    We perform single cell analysis of cell growth in a mixed cell culture. Two species of yeast cells: Saccharomyces cerevisiae and Candida albicans, are optically trapped using focused continuous-wave near infrared laser. Cell growth for both cells is inhibited only when the two species of cells are in contact with each other. This indicates cell-cell interaction mediated cell growth inhibition mechanism. Single cell level analysis of cell growth studied here contributes to the further understanding of yeast growth arrest in a mixed yeast culture.

  17. Giant Cell Arteritis

    MedlinePlus

    Giant cell arteritis is a disorder that causes inflammation of your arteries, usually in the scalp, neck, and arms. ... arteries, which keeps blood from flowing well. Giant cell arteritis often occurs with another disorder called polymyalgia ...

  18. Regulatory T cells.

    PubMed

    Thompson, Claire; Powrie, Fiona

    2004-08-01

    Regulatory T (TR) cells are a subset of T cells that function to control immune responses. Different populations of TR cells have been described, including thymically derived CD4(+)CD25+ TR cells and Tr1 cells induced in the periphery through exposure to antigen. A transcription factor, Foxp3, has been identified that is essential for CD4(+)CD25+ TR cell development and function. There is now evidence that transforming growth factor-beta might play a role in this pathway. CD4(+)CD25+ TR cells proliferate extensively in vivo in an antigen-specific manner, and can respond to both self and foreign peptides. By suppressing excessive immune responses, TR cells play a key role in the maintenance of self-tolerance, thus preventing autoimmune disease, as well as inhibiting harmful inflammatory diseases such as asthma and inflammatory bowel disease.

  19. Stem Cell Transplant

    MedlinePlus

    ... transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or ... A bone marrow transplant is also called a stem cell transplant. A bone marrow transplant may be necessary ...

  20. Red blood cell production

    MedlinePlus

    ... to one part of the body or another. Red blood cells are an important element of blood. Their job ... is carried to and eliminated by the lungs. Red blood cells are formed in the red bone marrow of ...

  1. Odontogenic ghost cell tumour with clear cell components: clear cell odontogenic ghost cell tumour?

    PubMed

    Yoon, Jung Hoon; Ahn, Sang Gun; Kim, Su Gwan; Kim, Jin

    2004-07-01

    A case of odontogenic ghost cell tumour (OGCT) with clear cell components was encountered in the mandible of a 63-year-old man. The tumour revealed ameloblastomatous-type epithelial components accompanied by clusters of ghost cells and dentinoid juxtaposed to the odontogenic epithelium. In addition, some areas of the tumour tissue showed sheets and islands of clear, glycogen containing epithelial cells, which were separated by a thin fibrous connective tissue stroma. Both ameloblastic and clear cells exhibited positive immunoreactivities for cytokeratin 19 and AE1/3. It is not known whether this tumour represents a clear cell change of a pre-existing OGCT or a separate and distinct neoplasm derived de novo from the odontogenic epithelium. This tumour was given the term 'clear cell OGCT' because it captures the clear cell components, which is one of the most prominent distinguishing features of the tumour.

  2. White Blood Cell Count

    MedlinePlus

    ... limited. Home Visit Global Sites Search Help? White Blood Cell Count Share this page: Was this page helpful? ... Count; Leukocyte Count; White Count Formal name: White Blood Cell Count Related tests: Complete Blood Count , Blood Smear , ...

  3. Single-cell nanosurgery.

    PubMed

    Zeigler, Maxwell B; Chiu, Daniel T

    2013-01-01

    This chapter explains the steps necessary to perform laser surgery upon single adherent mammalian cells, where individual organelles are extracted from the cells by optical tweezers and the cells are monitored post-surgery to check their viability. Single-cell laser nanosurgery is used in an increasing range of methodologies because it offers great flexibility. Its main advantages are (a) there is not any physical contact with the cells so they remain in a sterile environment, (b) high spatial selectivity so that single organelles can be extracted from specific areas of individual cells, (c) the method can be conducted in the cell's native media, and (d) in comparison to other techniques that target single cells, such as micromanipulators, laser nanosurgery has a comparatively high throughput.

  4. Fluorescence Live Cell Imaging

    PubMed Central

    Ettinger, Andreas

    2014-01-01

    Fluorescence microscopy of live cells has become an integral part of modern cell biology. Fluorescent protein tags, live cell dyes, and other methods to fluorescently label proteins of interest provide a range of tools to investigate virtually any cellular process under the microscope. The two main experimental challenges in collecting meaningful live cell microscopy data are to minimize photodamage while retaining a useful signal-to-noise ratio, and to provide a suitable environment for cells or tissues to replicate physiological cell dynamics. This chapter aims to give a general overview on microscope design choices critical for fluorescence live cell imaging that apply to most fluorescence microscopy modalities, and on environmental control with a focus on mammalian tissue culture cells. In addition, we provide guidance on how to design and evaluate fluorescent protein constructs by spinning disk confocal microscopy. PMID:24974023

  5. Cell phone explosion.

    PubMed

    Atreya, Alok; Kanchan, Tanuj; Nepal, Samata; Pandey, Bhuwan Raj

    2016-03-01

    Cell phone explosions and resultant burn injuries are rarely reported in the scientific literature. We report a case of cell phone explosion that occurred when a young male was listening to music while the mobile was plugged in for charging.

  6. FUEL CELL ELECTRODE MATERIALS

    DTIC Science & Technology

    FUEL CELL ELECTRODE MATERIALS. RAW MATERIAL SELECTION INFLUENCES POLARIZATION BUT IS NOT A SINGLE CONTROLLING FACTOR. AVAILABLE...DATA INDICATES THAT AN INTERRELATIONSHIP OF POROSITY, AVERAGE PORE VOLUME, AND PERMEABILITY CONTRIBUTES TO ELECTRODE FUEL CELL BEHAVIOR.

  7. Sickle Cell Information Center

    MedlinePlus

    ... procedure for stem cell transplantation from healthy, ... NYT, Nature, Wash Post, SciAm, CNN - Google Custom Search Sickle ... summarizing medical research on sickle-cell anemia. NYT, Nature, Wash Post, SciAm, CNN - Google Custom Search Genetic ...

  8. Learn About Stem Cells

    MedlinePlus

    ... to survive, including the umbilical cord and the placenta that nourishes the developing fetus. Basic cell biology ... types but cannot generate support structures like the placenta and umbilical cord. Other cells are multipotent, meaning ...

  9. Sickle Cell Disease

    MedlinePlus

    ... About Us Overview of CDC’s work. Advancements in Sickle Cell Disease New supplement from the American Journal of Preventive Medicine describes the state of sickle cell disease related care in the United States. Read Supplement ...

  10. Stem cells remember their grade.

    PubMed

    Lo Celso, Cristina; Scadden, David T

    2007-08-16

    The stem cell state is understood based on what cells do in performance assays, crude measures of a highly refined state. In this issue of Cell Stem Cell, Dykstra et al. (2007) reveal stem cell gradation and the extent to which that gradation is retained in stem cell daughters of hematopoietic stem cells.

  11. Diagram of Cell to Cell Communication

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Diagram depicts the importance of cell-cell communication as central to the understanding of cancer growth and progression, the focus of the NASA bioreactor demonstration system (BDS-05) investigation. Microgravity studies will allow us to unravel the signaling and communication between these cells with the host and potential development of therapies for the treatment of cancer metastasis. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: Emory University.

  12. Cell-cell connectivity: desmosomes and disease.

    PubMed

    Brooke, Matthew A; Nitoiu, Daniela; Kelsell, David P

    2012-01-01

    Cell-cell connectivity is an absolute requirement for the correct functioning of cells, tissues and entire organisms. At the level of the individual cell, direct cell-cell adherence and communication is mediated by the intercellular junction complexes: desmosomes, adherens, tight and gap junctions. A broad spectrum of inherited, infectious and auto-immune diseases can affect the proper function of intercellular junctions and result in either diseases affecting specific individual tissues or widespread syndromic conditions. A particularly diverse group of diseases result from direct or indirect disruption of desmosomes--a consequence of their importance in tissue integrity, their extensive distribution, complex structure, and the wide variety of functions their components accomplish. As a consequence, disruption of desmosomal assembly, structure or integrity disrupts not only their intercellular adhesive function but also their functions in cell communication and regulation, leading to such diverse pathologies as cardiomyopathy, epidermal and mucosal blistering, palmoplantar keratoderma, woolly hair, keratosis, epidermolysis bullosa, ectodermal dysplasia and alopecia. Here, as well as describing the importance of the other intercellular junctions, we focus primarily on the desmosome, its structure and its role in disease. We will examine the various pathologies that result from impairment of desmosome function and thereby demonstrate the importance of desmosomes to tissues and to the organism as a whole.

  13. Germ Cell Differentiation from Pluripotent Cells

    PubMed Central

    Medrano, Jose V.; Pera, Renee A. Reijo; Simón, Carlos

    2014-01-01

    Infertility is a medical condition with an increasing impact in Western societies with causes linked to toxins, genetics, and aging (primarily delay of motherhood). Within the different pathologies that can lead to infertility, poor quality or reduced quantity of gametes plays an important role. Gamete donation and therefore demand on donated sperm and eggs in fertility clinics is increasing. It is hoped that a better understanding of the conditions related to poor gamete quality may allow scientists to design rational treatments. However, to date, relatively little is known about human germ cell development in large part due to the inaccessibility of human development to molecular genetic analysis. It is hoped that pluripotent human embryonic stem cells and induced pluripotent stem cells may provide an accessible in vitro model to study germline development; these cells are able to differentiate to cells of all three primary embryonic germ layers, as well as to germ cells in vitro. We review the state of the art in germline differentiation from pluripotent stem cells. PMID:23329632

  14. Diagram of Cell to Cell Communication

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Diagram depicts the importance of cell-cell communication as central to the understanding of cancer growth and progression, the focus of the NASA bioreactor demonstration system (BDS-05) investigation. Microgravity studies will allow us to unravel the signaling and communication between these cells with the host and potential development of therapies for the treatment of cancer metastasis. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: Emory University.

  15. Cell cycle regulates cell type in the Arabidopsis sepal.

    PubMed

    Roeder, Adrienne H K; Cunha, Alexandre; Ohno, Carolyn K; Meyerowitz, Elliot M

    2012-12-01

    The formation of cellular patterns during development requires the coordination of cell division with cell identity specification. This coordination is essential in patterning the highly elongated giant cells, which are interspersed between small cells, in the outer epidermis of the Arabidopsis thaliana sepal. Giant cells undergo endocycles, replicating their DNA without dividing, whereas small cells divide mitotically. We show that distinct enhancers are expressed in giant cells and small cells, indicating that these cell types have different identities as well as different sizes. We find that members of the epidermal specification pathway, DEFECTIVE KERNEL1 (DEK1), MERISTEM LAYER1 (ATML1), Arabidopsis CRINKLY4 (ACR4) and HOMEODOMAIN GLABROUS11 (HDG11), control the identity of giant cells. Giant cell identity is established upstream of cell cycle regulation. Conversely, endoreduplication represses small cell identity. These results show not only that cell type affects cell cycle regulation, but also that changes in the cell cycle can regulate cell type.

  16. Fuel cells feasibility

    NASA Technical Reports Server (NTRS)

    Schonfeld, D.; Charng, T.

    1981-01-01

    The technical and economic status of fuel cells is assessed with emphasis on their potential benefits to the Deep Space Network. The fuel cell, what it is, how it operates, and what its outputs are, is reviewed. Major technical problems of the fuel cell and its components are highlighted. Due to these problems and economic considerations it is concluded that fuel cells will not become commercially viable until the early 1990s.

  17. Increased voltage photovoltaic cell

    NASA Technical Reports Server (NTRS)

    Ross, B.; Bickler, D. B.; Gallagher, B. D. (Inventor)

    1985-01-01

    A photovoltaic cell, such as a solar cell, is provided which has a higher output voltage than prior cells. The improved cell includes a substrate of doped silicon, a first layer of silicon disposed on the substrate and having opposite doping, and a second layer of silicon carbide disposed on the first layer. The silicon carbide preferably has the same type of doping as the first layer.

  18. Regenerative fuel cells

    NASA Technical Reports Server (NTRS)

    Swette, Larry L.; Kackley, Nancy D.; Laconti, Anthony B.

    1992-01-01

    A development status evaluation is presented for moderate-temperature, single-unit, regenerative fuel cells using either alkaline or solid polymer proton-exchange membrane (PEM) electrolytes. Attention is given to the results thus far obtained for Pt, Ir, Rh, and Na(x)Pt3O4 catalysts. Alkaline electrolyte tests have been performed on a half-cell basis with a floating-electrode cell; PEM testing has been with complete fuel cells, using Nafion 117.

  19. Regenerative fuel cells

    NASA Astrophysics Data System (ADS)

    Swette, Larry L.; Kackley, Nancy D.; Laconti, Anthony B.

    A development status evaluation is presented for moderate-temperature, single-unit, regenerative fuel cells using either alkaline or solid polymer proton-exchange membrane (PEM) electrolytes. Attention is given to the results thus far obtained for Pt, Ir, Rh, and Na(x)Pt3O4 catalysts. Alkaline electrolyte tests have been performed on a half-cell basis with a floating-electrode cell; PEM testing has been with complete fuel cells, using Nafion 117.

  20. Cross Cell Sandwich Core

    NASA Technical Reports Server (NTRS)

    Ford, Donald B. (Inventor)

    2004-01-01

    A sandwich core comprises two faceplates separated by a plurality of cells. The cells are comprised of walls positioned at oblique angles relative to a perpendicular axis extending through the faceplates. The walls preferably form open cells and are constructed from open cells and are constructed from rows of ribbons. The walls may be obliquely angled relative to more than one plane extending through the perpendicular axis.

  1. Clonogenic Assay: Adherent Cells

    PubMed Central

    Rafehi, Haloom; Orlowski, Christian; Georgiadis, George T.; Ververis, Katherine; El-Osta, Assam; Karagiannis, Tom C.

    2011-01-01

    The clonogenic (or colony forming) assay has been established for more than 50 years; the original paper describing the technique was published in 19561. Apart from documenting the method, the initial landmark study generated the first radiation-dose response curve for X-ray irradiated mammalian (HeLa) cells in culture1. Basically, the clonogenic assay enables an assessment of the differences in reproductive viability (capacity of cells to produce progeny; i.e. a single cell to form a colony of 50 or more cells) between control untreated cells and cells that have undergone various treatments such as exposure to ionising radiation, various chemical compounds (e.g. cytotoxic agents) or in other cases genetic manipulation. The assay has become the most widely accepted technique in radiation biology and has been widely used for evaluating the radiation sensitivity of different cell lines. Further, the clonogenic assay is commonly used for monitoring the efficacy of radiation modifying compounds and for determining the effects of cytotoxic agents and other anti-cancer therapeutics on colony forming ability, in different cell lines. A typical clonogenic survival experiment using adherent cells lines involves three distinct components, 1) treatment of the cell monolayer in tissue culture flasks, 2) preparation of single cell suspensions and plating an appropriate number of cells in petri dishes and 3) fixing and staining colonies following a relevant incubation period, which could range from 1-3 weeks, depending on the cell line. Here we demonstrate the general procedure for performing the clonogenic assay with adherent cell lines with the use of an immortalized human keratinocyte cell line (FEP-1811)2. Also, our aims are to describe common features of clonogenic assays including calculation of the plating efficiency and survival fractions after exposure of cells to radiation, and to exemplify modification of radiation-response with the use of a natural antioxidant

  2. [Hairy cell leukemia].

    PubMed

    Dietrich, S; Andrulis, M; Zenz, T

    2015-04-01

    Hairy cell leukemia was initially described as a distinct entity in 1958. It is rare B-cell malignancy characterized by an indolent course. Advances in the treatment and understanding of the biology of hairy cell leukemia have made the disease exquisitely amenable to treatment. This review summarizes the present understanding of hairy cell leukemia with a particular focus on the development of novel and targeted approaches to treatment.

  3. Fish Stem Cell Cultures

    PubMed Central

    Hong, Ni; Li, Zhendong; Hong, Yunhan

    2011-01-01

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on “Fish Stem Cells and Nuclear Transfer”, we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer. PMID:21547056

  4. Kidney Cell Electrophoresis

    NASA Technical Reports Server (NTRS)

    Todd, P.

    1985-01-01

    Materials and procedures for microgravity electrophoresis of living human embryonic kidney cells were evaluated, ground support in the form of analytical cell electrophoresis and flow cytometry was provided and cells returned from space flight were analyzed. Preflight culture media, electrophoresis buffer, fraction collection media, temperature profiles, and urokinase assay procedures were tested prior to flight. Electrophoretic mobility distributions of aliquots of the cell population to be fractionated in flight were obtained. The protocol established and utilized is given.

  5. Fuel cell status, 1994

    NASA Astrophysics Data System (ADS)

    Hirschenhofer, John H.

    1994-11-01

    Fuel cells are increasingly being used for commercial purposes in various countries worldwide because of their high efficiency environmental benefits. Among the nations which are pioneering the use of fuel cells are Australia, the United States, England, Japan, Germany, Netherlands, Belgium and Canada. These countries use fuel cells to augment the capacity of and improve the reliability of power plants fueled by natural gas.

  6. Cell phones and cancer

    MedlinePlus

    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of ...

  7. Adventures with Cell Phones

    ERIC Educational Resources Information Center

    Kolb, Liz

    2011-01-01

    Teachers are finding creative ways to turn the basic cell phone from a digital distraction into a versatile learning tool. In this article, the author explains why cell phones are important in learning and suggests rather than banning them that they be integrated into learning. She presents activities that can be done on a basic cell phone with a…

  8. Solar Photovoltaic Cells.

    ERIC Educational Resources Information Center

    Mickey, Charles D.

    1981-01-01

    Reviews information on solar radiation as an energy source. Discusses these topics: the key photovoltaic material; the bank theory of solids; conductors, semiconductors, and insulators; impurity semiconductors; solid-state photovoltaic cell operation; limitations on solar cell efficiency; silicon solar cells; cadmium sulfide/copper (I) sulfide…

  9. Photoelectrochemical Solar Cells.

    ERIC Educational Resources Information Center

    McDevitt, John T.

    1984-01-01

    This introduction to photoelectrochemical (PEC) cells reviews topics pertaining to solar energy conversion and demonstrates the ease with which a working PEC cell can be prepared with n-type silicon as the photoanode and a platinum counter electrode (both immersed in ethanolic ferrocene/ferricenium solutions). Experiments using the cell are…

  10. Solar Photovoltaic Cells.

    ERIC Educational Resources Information Center

    Mickey, Charles D.

    1981-01-01

    Reviews information on solar radiation as an energy source. Discusses these topics: the key photovoltaic material; the bank theory of solids; conductors, semiconductors, and insulators; impurity semiconductors; solid-state photovoltaic cell operation; limitations on solar cell efficiency; silicon solar cells; cadmium sulfide/copper (I) sulfide…

  11. Islet Cell Transplantation

    MedlinePlus

    ... person who has type 1 diabetes must take insulin daily to live. Transplanted islet cells, however, can take over the work of the destroyed cells. The beta cells in these islets will begin to make and release insulin. Researchers hope islet transplantation will help people with ...

  12. Reprogramming of somatic cells.

    PubMed

    Rajasingh, Johnson

    2012-01-01

    Reprogramming of adult somatic cells into pluripotent stem cells may provide an attractive source of stem cells for regenerative medicine. It has emerged as an invaluable method for generating patient-specific stem cells of any cell lineage without the use of embryonic stem cells. A revolutionary study in 2006 showed that it is possible to convert adult somatic cells directly into pluripotent stem cells by using a limited number of pluripotent transcription factors and is called as iPS cells. Currently, both genomic integrating viral and nonintegrating nonviral methods are used to generate iPS cells. However, the viral-based technology poses increased risk of safety, and more studies are now focused on nonviral-based technology to obtain autologous stem cells for clinical therapy. In this review, the pros and cons of the present iPS cell technology and the future direction for the successful translation of this technology into the clinic are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Mesothelial cell transplantation.

    PubMed

    Witkowicz, Joanna

    2008-05-01

    Mesothelial cells are an integral part of the peritoneum and play an important role in maintaining its structural and functional properties. In the recent years a number of studies on mesothelial cells have been performed to evaluate the localization, secretional properties and the ability of regeneration and transdifferentiation of these cells. They are also involved in the repair of the peritoneum damage following surgery or peritonitis. Mesothelial cells produce several cytokines, growth factors and extracellular matrix components, possessing anti-inflammatory and immunomodulatory properties. Because of their plasticity, these cells are able to form a new cell type like fibroblast, endothelial and smooth muscle cell, chondrocyte, osteoblast, adipocyte or neuron. The first step involves mesothelial cell transdifferentiation into progenitor cells with the capacity of further differentiation. In this paper the current knowledge concerning the mesothelial cell differentiation and transplantation has been reviewed. Own mesothelial cells of a patient are used in transplantation. They are sampled, cultured in vitro and then they can be used in the prevention and treatment of post-operative abdominal adhesions, incisional hernias, repair of peritoneal membrane of patients on long-term peritoneal dialysis, the prevention of ischemic myocardial damage, nerve regeneration and genetically modified recombinant protein secretion. Inevitably, more potential applications of transplanted mesothelial cell will be available over the next few years.

  14. Cell Culture Made Easy.

    ERIC Educational Resources Information Center

    Dye, Frank J.

    1985-01-01

    Outlines steps to generate cell samples for observation and experimentation. The procedures (which use ordinary laboratory equipment) will establish a short-term primary culture of normal mammalian cells. Information on culture vessels and cell division and a list of questions to generate student interest and involvement in the topics are…

  15. Mammalian Cell Culture Simplified.

    ERIC Educational Resources Information Center

    Moss, Robert; Solomon, Sondra

    1991-01-01

    A tissue culture experiment that does not require elaborate equipment and that can be used to teach sterile technique, the principles of animal cell line maintenance, and the concept of cell growth curves is described. The differences between cancerous and normal cells can be highlighted. The procedure is included. (KR)

  16. Photoelectrochemical Solar Cells.

    ERIC Educational Resources Information Center

    McDevitt, John T.

    1984-01-01

    This introduction to photoelectrochemical (PEC) cells reviews topics pertaining to solar energy conversion and demonstrates the ease with which a working PEC cell can be prepared with n-type silicon as the photoanode and a platinum counter electrode (both immersed in ethanolic ferrocene/ferricenium solutions). Experiments using the cell are…

  17. Biomarkers of cell senescence

    DOEpatents

    Dirmi, Goberdhan P.; Campisi, Judith; Peacocke, Monica

    1996-01-01

    The present invention provides a biomarker system for the in vivo and in vitro assessment of cell senescence. In the method of the present invention, .beta.-galactosidase activity is utilized as a means by which cell senescence may be assessed either in in vitro cell cultures or in vivo.

  18. Biomarkers of cell senescence

    DOEpatents

    Dimri, Goberdhan P.; Campisi, Judith; Peacocke, Monica

    1998-01-01

    The present invention provides a biomarker system for the in vivo and in vitro assessment of cell senescence. In the method of the present invention, .beta.-galactosidase activity is utilized as a means by which cell senescence may be assessed either in vitro cell cultures or in vivo.

  19. Lithium Cell Reactions.

    DTIC Science & Technology

    1985-02-01

    Page 1. INVESTIGATION OF CHEMICAL, ELECTROCHEMICAL AND PARASITIC REACTIONS IN LITHIUM - THIONYL CHLORIDE CELLS ....... ................. 1 1.1 INTRODUCTION...OF LITHIUM - THIONYL CHLORIDE CELLS. ................ 56 1.4.1 Carbon Limited Overdischarge...............56 1.4.1.1 Background... LITHIUM THIONYL - CHLORIDE CELLS. .. ............ ...... 101 1.5.1 Background. ....... ............ .... 101 1.5.2 Microphotography

  20. Adventures with Cell Phones

    ERIC Educational Resources Information Center

    Kolb, Liz

    2011-01-01

    Teachers are finding creative ways to turn the basic cell phone from a digital distraction into a versatile learning tool. In this article, the author explains why cell phones are important in learning and suggests rather than banning them that they be integrated into learning. She presents activities that can be done on a basic cell phone with a…

  1. B cells flying solo.

    PubMed

    Groom, Joanna; Mackay, Fabienne

    2008-01-01

    Systemic autoimmunity such as systemic lupus erythematosus (SLE) is associated with the loss of B-cell tolerance, B-cell dysregulation and autoantibody production. While some autoantibodies may contribute to the pathology seen with SLE, numerous studies have shown that dysregulation of T-cell function is another critical aspect driving disease. The positive results obtained in clinical trials using T-cell- or B-cell-specific treatments have suggested that cooperation between T and B cells probably underlies disease progression in many patients. A similar cooperative mechanism seemed to explain SLE developing in mice overexpressing the B-cell-activating factor from the tumor necrosis factor family (BAFF). However, surprisingly, T-cell-deficient BAFF transgenic (Tg) mice develop SLE similar to T-cell-sufficient BAFF Tg mice, and the disease was linked to innate activation of B cells and production of proinflammatory autoantibody isotypes. In conclusion, dysregulated innate activation of B cells alone can drive disease independently of T cells, and as such this aspect represents a new pathogenic mechanism in autoimmunity.

  2. Biomarkers of cell senescence

    DOEpatents

    Dirmi, G.P.; Campisi, J.; Peacocke, M.

    1996-02-13

    The present invention provides a biomarker system for the in vivo and in vitro assessment of cell senescence. In the method of the present invention, {beta}-galactosidase activity is utilized as a means by which cell senescence may be assessed either in in vitro cell cultures or in vivo. 1 fig.

  3. Biomarkers of cell senescence

    DOEpatents

    Dimri, G.P.; Campisi, J.; Peacocke, M.

    1998-08-18

    The present invention provides a biomarker system for the in vivo and in vitro assessment of cell senescence. In the method of the present invention, {beta}-galactosidase activity is utilized as a means by which cell senescence may be assessed either in vitro cell cultures or in vivo. 1 fig.

  4. Rapidly refuelable fuel cell

    DOEpatents

    Joy, Richard W.

    1983-01-01

    This invention is directed to a metal-air fuel cell where the consumable metal anode is movably positioned in the cell and an expandable enclosure, or bladder, is used to press the anode into contact with separating spacers between the cell electrodes. The bladder may be depressurized to allow replacement of the anode when consumed.

  5. Cell Culture Made Easy.

    ERIC Educational Resources Information Center

    Dye, Frank J.

    1985-01-01

    Outlines steps to generate cell samples for observation and experimentation. The procedures (which use ordinary laboratory equipment) will establish a short-term primary culture of normal mammalian cells. Information on culture vessels and cell division and a list of questions to generate student interest and involvement in the topics are…

  6. Mammalian Cell Culture Simplified.

    ERIC Educational Resources Information Center

    Moss, Robert; Solomon, Sondra

    1991-01-01

    A tissue culture experiment that does not require elaborate equipment and that can be used to teach sterile technique, the principles of animal cell line maintenance, and the concept of cell growth curves is described. The differences between cancerous and normal cells can be highlighted. The procedure is included. (KR)

  7. Cell-cell connection to cardiac disease.

    PubMed

    Sheikh, Farah; Ross, Robert S; Chen, Ju

    2009-08-01

    Intercalated disks (ICDs) are highly organized cell-cell adhesion structures, which connect cardiomyocytes to one another. They are composed of three major complexes: desmosomes, fascia adherens, and gap junctions. Desmosomes and fascia adherens junction are necessary for mechanically coupling and reinforcing cardiomyocytes, whereas gap junctions are essential for rapid electrical transmission between cells. Because human genetics and mouse models have revealed that mutations and/or deficiencies in various ICD components can lead to cardiomyopathies and arrhythmias, considerable attention has focused on the biologic function of the ICD. This review will discuss recent scientific developments related to the ICD and focus on its role in regulating cardiac muscle structure, signaling, and disease.

  8. Mesangial cells initiate compensatory tubular cell hypertrophy.

    PubMed

    Sinuani, I; Beberashvili, I; Averbukh, Z; Cohn, M; Gitelman, I; Weissgarten, J

    2010-01-01

    Unilateral nephrectomy results in compensatory renal growth, in which both the size and the functional capacity of the remaining kidney are increased. The functional adaptation to the removal of the contralateral kidney consists mostly of an increase in the glomerular filtration rate of the remaining kidney, and hypertrophy of cells comprising the nephron, mainly of the proximal tubular cells. Although the phenomenon of single kidney hypertrophy has been known for the past thousand years and despite intensive research over the past century, the mechanism of this process still remains unclear. The present article reviews the role of mesangial cells in compensatory renal hypertrophy. 2010 S. Karger AG, Basel.

  9. Molecular Mechanisms of HTLV-1 Cell-to-Cell Transmission

    PubMed Central

    Gross, Christine; Thoma-Kress, Andrea K.

    2016-01-01

    The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1), a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood products, semen, and breast milk. In vivo, HTLV-1 preferentially infects CD4+ T-cells, and to a lesser extent, CD8+ T-cells, dendritic cells, and monocytes. Efficient infection of CD4+ T-cells requires cell-cell contacts while cell-free virus transmission is inefficient. Two types of cell-cell contacts have been described to be critical for HTLV-1 transmission, tight junctions and cellular conduits. Further, two non-exclusive mechanisms of virus transmission at cell-cell contacts have been proposed: (1) polarized budding of HTLV-1 into synaptic clefts; and (2) cell surface transfer of viral biofilms at virological synapses. In contrast to CD4+ T-cells, dendritic cells can be infected cell-free and, to a greater extent, via viral biofilms in vitro. Cell-to-cell transmission of HTLV-1 requires a coordinated action of steps in the virus infectious cycle with events in the cell-cell adhesion process; therefore, virus propagation from cell-to-cell depends on specific interactions between cellular and viral proteins. Here, we review the molecular mechanisms of HTLV-1 transmission with a focus on the HTLV-1-encoded proteins Tax and p8, their impact on host cell factors mediating cell-cell contacts, cytoskeletal remodeling, and thus, virus propagation. PMID:27005656

  10. The thymus in myasthenia gravis. Changes typical for the human disease are absent in experimental autoimmune myasthenia gravis of the Lewis rat.

    PubMed Central

    Meinl, E.; Klinkert, W. E.; Wekerle, H.

    1991-01-01

    In human myasthenia gravis (MG) formation of autoantibodies against acetylcholine receptor (AChR) is commonly associated with thymic changes termed lymphofollicular hyperplasia (LFH). To learn whether the thymic lesions of human MG are primary changes in the autoimmune pathogenesis, or rather secondary events caused by peripheral autoimmunization, the authors compared the pathologic changes of MG thymuses with the thymuses of Lewis rats with experimental autoimmune myasthenia gravis (EAMG). EAMG was induced either actively by immunization with AChR, or transferred passively with monoclonal antibodies (mAb) binding to AChR. The clinical diagnosis of EAMG was confirmed by electromyography. Germinal centers, which are typical for human MG thymuses, were not detectable in the thymus of EAMG rats. Scattered B cells were seen as normal components of the thymic medulla. In EAMG their number was not augmented, nor were they accumulated focally. The perivascular spaces (PVS) were not distended and the amount of reticulin was not increased. Thymic myoid cells were identified in EAMG as well as in control thymuses; their cellular microenvironment was inconspicuous. Both in normal and in EAMG thymuses, a subpopulation of myoid cells expressed the main immunogenic region of the AChR. Heavily affected rats showed a severe cortical involution, but no specific changes of the medulla. The fact that none of the thymic lesions characteristic for human MG was found in EAMG is compatible with the concept that the thymic changes in MG are primary events in the autoimmune pathogenesis of this disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1951638

  11. Stochastic elimination of cancer cells.

    PubMed Central

    Michor, Franziska; Nowak, Martin A; Frank, Steven A; Iwasa, Yoh

    2003-01-01

    Tissues of multicellular organisms consist of stem cells and differentiated cells. Stem cells divide to produce new stem cells or differentiated cells. Differentiated cells divide to produce new differentiated cells. We show that such a tissue design can reduce the rate of fixation of mutations that increase the net proliferation rate of cells. It has, however, no consequence for the rate of fixation of neutral mutations. We calculate the optimum relative abundance of stem cells that minimizes the rate of generating cancer cells. There is a critical fraction of stem cell divisions that is required for a stochastic elimination ('wash out') of cancer cells. PMID:14561289

  12. Killer cells in atherosclerosis.

    PubMed

    Kyaw, Tin; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex

    2017-05-05

    Cytotoxic lymphocytes (killer cells) play a critical role in host defence mechanisms, protecting against infections and in tumour surveillance. They can also exert detrimental effects in chronic inflammatory disorders and in autoimmune diseases. Tissue cell death and necrosis are prominent features of advanced atherosclerotic lesions including vulnerable/unstable lesions which are largely responsible for most heart attacks and strokes. Evidence for accumulation of killer cells in both human and mouse lesions together with their cytotoxic potential strongly suggest that these cells contribute to cell death and necrosis in lesions leading to vulnerable plaque development and potentially plaque rupture. Killer cells can be divided into two groups, adaptive and innate immune cells depending on whether they require antigen presentation for activation. Activated killer cells detect damaged or stressed cells and kill by cytotoxic mechanisms that include perforin, granzymes, TRAIL or FasL and in some cases TNF-α. In this review, we examine current knowledge on killer cells in atherosclerosis, including CD8 T cells, CD28- CD4 T cells, natural killer cells and γδ-T cells, mechanisms responsible for their activation, their migration to developing lesions and effector functions. We also discuss pharmacological strategies to prevent their deleterious vascular effects by preventing/limiting their cytotoxic effects within atherosclerotic lesions as well as potential immunomodulatory therapies that might better target lesion-resident killer cells, to minimise any compromise of the immune system, which could result in increased susceptibility to infections and reductions in tumour surveillance. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Cell-ECM traction force modulates endogenous tension at cell-cell contacts.

    PubMed

    Maruthamuthu, Venkat; Sabass, Benedikt; Schwarz, Ulrich S; Gardel, Margaret L

    2011-03-22

    Cells in tissues are mechanically coupled both to the ECM and neighboring cells, but the coordination and interdependency of forces sustained at cell-ECM and cell-cell adhesions are unknown. In this paper, we demonstrate that the endogenous force sustained at the cell-cell contact between a pair of epithelial cells is approximately 100 nN, directed perpendicular to the cell-cell interface and concentrated at the contact edges. This force is stably maintained over time despite significant fluctuations in cell-cell contact length and cell morphology. A direct relationship between the total cellular traction force on the ECM and the endogenous cell-cell force exists, indicating that the cell-cell tension is a constant fraction of the cell-ECM traction. Thus, modulation of ECM properties that impact cell-ECM traction alters cell-cell tension. Finally, we show in a minimal model of a tissue that all cells experience similar forces from the surrounding microenvironment, despite differences in the extent of cell-ECM and cell-cell adhesion. This interdependence of cell-cell and cell-ECM forces has significant implications for the maintenance of the mechanical integrity of tissues, mechanotransduction, and tumor mechanobiology.

  14. [Cell transplant and regenerative stem cell therapy].

    PubMed

    Prosper, F

    2008-01-01

    The derivation of the first human embryonic stem cell lines as well as the notion of the unexpected plasticity and potential of the adult stem cells has significantly impacted the biomedical research. Many of the tissues long believe to lack any regenerative capacity has demonstrated otherwise. Patients alike physicians expectations for treatment of incurable diseases have also fuelled this field and in occasions have led to unrealistic expectations. In the next pages I review some of the tissue specific stem cells that have been used either in preclinical models or even in clinical research. Despite the effort of numerous investigators, more questions that answers remain in the field of cell therapy and only careful and independent -not biased- research will allow us to translate some of this findings into clinical application.

  15. Skeletal muscle satellite cells

    NASA Technical Reports Server (NTRS)

    Schultz, E.; McCormick, K. M.

    1994-01-01

    Evidence now suggests that satellite cells constitute a class of myogenic cells that differ distinctly from other embryonic myoblasts. Satellite cells arise from somites and first appear as a distinct myoblast type well before birth. Satellite cells from different muscles cannot be functionally distinguished from one another and are able to provide nuclei to all fibers without regard to phenotype. Thus, it is difficult to ascribe any significant function to establishing or stabilizing fiber type, even during regeneration. Within a muscle, satellite cells exhibit marked heterogeneity with respect to their proliferative behavior. The satellite cell population on a fiber can be partitioned into those that function as stem cells and those which are readily available for fusion. Recent studies have shown that the cells are not simply spindle shaped, but are very diverse in their morphology and have multiple branches emanating from the poles of the cells. This finding is consistent with other studies indicating that the cells have the capacity for extensive migration within, and perhaps between, muscles. Complexity of cell shape usually reflects increased cytoplasmic volume and organelles including a well developed Golgi, and is usually associated with growing postnatal muscle or muscles undergoing some form of induced adaptive change or repair. The appearance of activated satellite cells suggests some function of the cells in the adaptive process through elaboration and secretion of a product. Significant advances have been made in determining the potential secretion products that satellite cells make. The manner in which satellite cell proliferative and fusion behavior is controlled has also been studied. There seems to be little doubt that cellcell coupling is not how satellite cells and myofibers communicate. Rather satellite cell regulation is through a number of potential growth factors that arise from a number of sources. Critical to the understanding of this form

  16. Cell and gene therapy.

    PubMed

    Rao, Rajesh C; Zacks, David N

    2014-01-01

    Replacement or repair of a dysfunctional gene combined with promoting cell survival is a two-pronged approach that addresses an unmet need in the therapy of retinal degenerative diseases. In this chapter, we discuss various strategies toward achieving both goals: transplantation of wild-type cells to replace degenerating cells and to rescue gene function, sequential gene and cell therapy, and in vivo reprogramming of rods to cones. These approaches highlight cutting-edge advances in cell and gene therapy, and cellular lineage conversion in order to devise new therapies for various retinal degenerative diseases.

  17. Making Ultrathin Solar Cells

    NASA Technical Reports Server (NTRS)

    Cogan, George W.; Christel, Lee A.; Merchant, J. Thomas; Gibbons, James F.

    1991-01-01

    Process produces extremely thin silicon solar cells - only 50 micrometers or less in thickness. Electrons and holes have less opportunity to recombine before collected at cell surfaces. Efficiency higher and because volume of silicon small, less chance of radiation damage in new cells. Initial steps carried out at normal thickness to reduce breakage and avoid extra cost of special handling. Cells then thinned mechanically and chemically. Final cell includes reflective layer on back surface. Layer bounces unabsorbed light back into bulk silicon so it absorbs and produces useful electrical output.

  18. Nail stem cells.

    PubMed

    Sellheyer, Klaus

    2013-03-01

    Our knowledge on stem cells of the hair follicle has increased exponentially after the bulge was characterized as the stem cell niche two decades ago. In contrast, little is known about stem cells in the nail unit. Whereas hair follicles are plentiful and easy to access, the human body has only twenty nails and they are rarely biopsied. Therefore, examining fetal material offers unique advantages. In the following mini-review, our current knowledge on nail stem cells is summarized and analogies to the hair follicle stem cells are drawn.

  19. The microbial cell cycle

    SciTech Connect

    Nurse, P.; Streiblova, E.

    1984-01-01

    This book concentrates on the major problems of cell cycle control in microorganisms. A wide variety of microorganisms, ranging from bacteria and yeasts to hyphal fungi, algae, and ciliates are analyzed, with emphasis on the basic similarities among the organisms. Different ways of looking at cell cycle control which emphasize aspects of the problem such as circadian rhythms, limit cycle oscillators, and cell size models, are considered. New approaches such as the study of cell cycle mutants, and cloning of cell cycle control genes are also presented.

  20. Transparent ultraviolet photovoltaic cells.

    PubMed

    Yang, Xun; Shan, Chong-Xin; Lu, Ying-Jie; Xie, Xiu-Hua; Li, Bing-Hui; Wang, Shuang-Peng; Jiang, Ming-Ming; Shen, De-Zhen

    2016-02-15

    Photovoltaic cells have been fabricated from p-GaN/MgO/n-ZnO structures. The photovoltaic cells are transparent to visible light and can transform ultraviolet irradiation into electrical signals. The efficiency of the photovoltaic cells is 0.025% under simulated AM 1.5 illumination conditions, while it can reach 0.46% under UV illumination. By connecting several such photovoltaic cells in a series, light-emitting devices can be lighting. The photovoltaic cells reported in this Letter may promise the applications in glass of buildings to prevent UV irradiation and produce power for household appliances in the future.

  1. Fuel Cell Handbook update

    SciTech Connect

    Owens, W.R.; Hirschenhofer, J.H.; Engleman, R.R. Jr.; Stauffer, D.B.

    1993-11-01

    The objective of this work was to update the 1988 version of DOE`s Fuel Cell Handbook. Significant developments in the various fuel cell technologies required revisions to reflect state-of-the-art configurations and performance. The theoretical presentation was refined in order to make the handbook more useful to both the casual reader and fuel cell or systems analyst. In order to further emphasize the practical application of fuel cell technologies, the system integration information was expanded. In addition, practical elements, such as suggestions and guidelines to approximate fuel cell performance, were provided.

  2. Stem Cells and Aging.

    PubMed

    Koliakos, George

    2017-02-01

    The article is a presentation at the 4th Conference of ESAAM, which took place on October 30-31, 2015, in Athens, Greece. Its purpose was not to cover all aspects of cellular aging but to share with the audience of the Conference, in a 15-minute presentation, current knowledge about the rejuvenating and repairing somatic stem cells that are distinct from other stem cell types (such as embryonic or induced pluripotent stem cells), emphasize that our body in old age cannot take advantage of these rejuvenating cells, and provide some examples of novel experimental stem cell applications in the field of rejuvenation and antiaging biomedical research.

  3. Making Ultrathin Solar Cells

    NASA Technical Reports Server (NTRS)

    Cogan, George W.; Christel, Lee A.; Merchant, J. Thomas; Gibbons, James F.

    1991-01-01

    Process produces extremely thin silicon solar cells - only 50 micrometers or less in thickness. Electrons and holes have less opportunity to recombine before collected at cell surfaces. Efficiency higher and because volume of silicon small, less chance of radiation damage in new cells. Initial steps carried out at normal thickness to reduce breakage and avoid extra cost of special handling. Cells then thinned mechanically and chemically. Final cell includes reflective layer on back surface. Layer bounces unabsorbed light back into bulk silicon so it absorbs and produces useful electrical output.

  4. Mast cell activation disorders.

    PubMed

    Akin, Cem

    2014-01-01

    Disorders associated with mast cell activation range from relatively common IgE-mediated disease and chronic urticaria to rarer conditions such as mastocytosis or monoclonal mast cell activation disorder. Mast cell activation disorders can be mechanistically classified into primary (associated with abnormal production of mast cells that carry pathologic markers of clonality), secondary (normal mast cells activated in reaction to a microenvironmental trigger), and idiopathic (no etiology is found). Clinical presentations, diagnostic criteria as well as general principles of a stepwise therapy approach are discussed.

  5. Aging changes in lymphopoietic and myelopoietic organs of the annual cyprinodont fish, Nothobranchius guentheri.

    PubMed

    Cooper, E L; Zapata, A; Garcia Barrutia, M; Ramirez, J A

    1983-01-01

    The thymus of aging annual, cyprinodont fish, Nothobranchius guentheri and Cynolebias adloffi begins to undergo senescent changes at approximately four months. At this time, the histopathology reveals increased amounts of connective tissue, epithelial cysts and myoid cells, but decreased numbers of thymocytes. At 12 months, of the 50 fish observed at 10 stages from day 15 and 1, 2, 4, 6, 8, 9, 10, 11, 12 months the maximum time of senescence, there was an increased incidence of tumors in the oral cavity, connective tissue, kidney and liver in all 5 fish. At least in the kidney, the malignant transformation was classified as nodular-type histiocytic lymphoma. It is of interest that development of these tumors occurs during peak senescent changes in the thymus, supporting the view that as fish age, accompanied by atrophy of the thymus, the immune system is less vigorous and there is an increase in the incidence of cancer.

  6. Cell-cell and intracellular lactate shuttles.

    PubMed

    Brooks, George A

    2009-12-01

    Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously in diverse cells under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of the cell-cell shuttles include lactate exchanges between between white-glycolytic and red-oxidative fibres within a working muscle bed, and between working skeletal muscle and heart, brain, liver and kidneys. Examples of intracellular lactate shuttles include lactate uptake by mitochondria and pyruvate for lactate exchange in peroxisomes. Lactate for pyruvate exchanges affect cell redox state, and by itself lactate is a ROS generator. In vivo, lactate is a preferred substrate and high blood lactate levels down-regulate the use of glucose and free fatty acids (FFA). As well, lactate binding may affect metabolic regulation, for instance binding to G-protein receptors in adipocytes inhibiting lipolysis, and thus decreasing plasma FFA availability. In vitro lactate accumulation upregulates expression of MCT1 and genes coding for other components of the mitochondrial reticulum in skeletal muscle. The mitochondrial reticulum in muscle and mitochondrial networks in other aerobic tissues function to establish concentration and proton gradients necessary for cells with high mitochondrial densities to oxidize lactate. The presence of lactate shuttles gives rise to the realization that glycolytic and oxidative pathways should be viewed as linked, as opposed to alternative, processes, because lactate, the product of one pathway, is the substrate for the other.

  7. Fuel Cell/Electrochemical Cell Voltage Monitor

    NASA Technical Reports Server (NTRS)

    Vasquez, Arturo

    2012-01-01

    A concept has been developed for a new fuel cell individual-cell-voltage monitor that can be directly connected to a multi-cell fuel cell stack for direct substack power provisioning. It can also provide voltage isolation for applications in high-voltage fuel cell stacks. The technology consists of basic modules, each with an 8- to 16-cell input electrical measurement connection port. For each basic module, a power input connection would be provided for direct connection to a sub-stack of fuel cells in series within the larger stack. This power connection would allow for module power to be available in the range of 9-15 volts DC. The relatively low voltage differences that the module would encounter from the input electrical measurement connection port, coupled with the fact that the module's operating power is supplied by the same substack voltage input (and so will be at similar voltage), provides for elimination of high-commonmode voltage issues within each module. Within each module, there would be options for analog-to-digital conversion and data transfer schemes. Each module would also include a data-output/communication port. Each of these ports would be required to be either non-electrical (e.g., optically isolated) or electrically isolated. This is necessary to account for the fact that the plurality of modules attached to the stack will normally be at a range of voltages approaching the full range of the fuel cell stack operating voltages. A communications/ data bus could interface with the several basic modules. Options have been identified for command inputs from the spacecraft vehicle controller, and for output-status/data feeds to the vehicle.

  8. Stress and stem cells.

    PubMed

    Tower, John

    2012-01-01

    The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress.

  9. Parameterization of solar cells

    NASA Technical Reports Server (NTRS)

    Appelbaum, J.; Chait, A.; Thompson, D.

    1992-01-01

    The aggregation (sorting) of the individual solar cells into an array is commonly based on a single operating point on the current-voltage (I-V) characteristic curve. An alternative approach for cell performance prediction and cell screening is provided by modeling the cell using an equivalent electrical circuit, in which the parameters involved are related to the physical phenomena in the device. These analytical models may be represented by a double exponential I-V characteristic with seven parameters, by a double exponential model with five parameters, or by a single exponential equation with four or five parameters. In this article we address issues concerning methodologies for the determination of solar cell parameters based on measured data points of the I-V characteristic, and introduce a procedure for screening of solar cells for arrays. We show that common curve fitting techniques, e.g., least squares, may produce many combinations of parameter values while maintaining a good fit between the fitted and measured I-V characteristics of the cell. Therefore, techniques relying on curve fitting criteria alone cannot be directly used for cell parameterization. We propose a consistent procedure which takes into account the entire set of parameter values for a batch of cells. This procedure is based on a definition of a mean cell representing the batch, and takes into account the relative contribution of each parameter to the overall goodness of fit. The procedure is demonstrated on a batch of 50 silicon cells for Space Station Freedom.

  10. PURE CULTURES OF CELLS

    PubMed Central

    Carrel, Alexis

    1912-01-01

    In experiment I a group of ameboid cells was isolated from a culture of cardiac muscle sixty-three days old, and cultivated in plasma. After several passages, they formed a dense tissue from which ameboid cells radiated. The culture was divided into two parts. The part cultivated in plasma alone kept its morphological characters and continued to produce ameboid cells. The part cultivated upon silk in plasma became modified; the cells lost their ameboid characters, and were transformed into large elongated cells which were united in chains, or interlaced to form a network. In experiment II the round cells taken from a culture of connective tissue seventy-four days old multiplied rapidly. They transformed themselves into elongated cells and produced, after a few passages, a mass of dense connective tissue. From the tissue a large number of elongated cells were constantly growing. In both experiments the tissues originated from the ameboid or round cells extirpated from cultures that were sixty-three and seventy-four days old respectively. These cultures were still growing actively thirty and forty days later; that is, more than one hundred days after the extirpation of the original fragments from the organism. These experiments show that from old cultures it is possible to isolate and propagate cells that belong to a definite type. A tissue, formed by a pure strain of cells, can be obtained in this way, and this new method may be of value in cytological investigations. PMID:19867562

  11. Islet cell development.

    PubMed

    Rojas, Anabel; Khoo, Adrian; Tejedo, Juan R; Bedoya, Francisco J; Soria, Bernat; Martín, Franz

    2010-01-01

    Over the last years, there has been great success in driving stem cells toward insulin-expressing cells. However, the protocols developed to date have some limitations, such as low reliability and low insulin production. The most successful protocols used for generation of insulin-producing cells from stem cells mimic in vitro pancreatic organogenesis by directing the stem cells through stages that resemble several pancreatic developmental stages. Islet cell fate is coordinated by a complex network of inductive signals and regulatory transcription factors that, in a combinatorial way, determine pancreatic organ specification, differentiation, growth, and lineage. Together, these signals and factors direct the progression from multipotent progenitor cells to mature pancreatic cells. Later in development and adult life, several of these factors also contribute to maintain the differentiated phenotype of islet cells. A detailed understanding of the processes that operate in the pancreas during embryogenesis will help us to develop a suitable source of cells for diabetes therapy. In this chapter, we will discuss the main transcription factors involved in pancreas specification and beta-cell formation.

  12. Programmed cell death.

    PubMed

    Samuilov, V D; Oleskin, A V; Lagunova, E M

    2000-08-01

    This paper reviews data on programmed cell death (apoptosis) in animals and plants. Necrosis is a pathological scenario of cell death, which entails an inflammatory response in animal tissues. Apoptosis results in the disintegration of animal/plant cells into membrane vesicles enclosing the intracellular content, which are thereupon engulfed by adjacent or specialized cells (phagocytes) in animals. Plants lack such specialized cells, and plant cell walls prevent phagocytosis. The paper considers the main molecular mechanisms of apoptosis in animals and the pathways of activation of caspases, evolutionarily conserved cysteine proteases. A self-contained section concerns itself with the process of programmed cell death (PCD) in microorganisms including: 1) cell death in the myxomycete Dictyostelium discoideum and the parasitic flagellate Trypanosoma cruzi; 2) PCD in genetically manipulated yeast expressing the proapoptotic Bax and Bak proteins; 3) the death of a part of a prokaryotic cell population upon the depletion of nutrient resources or under stress; 4) the elimination of cells after a loss of a plasmid encoding a stable cytotoxic agent in combination with an unstable antidote; and 5) PCD in phage-infected bacterial cells.

  13. Freezing human ES cells.

    PubMed

    Trish, Erin; Dimos, John; Eggan, Kevin

    2006-10-12

    Here we demonstrate how our lab freezes HuES human embryonic stem cell lines. A healthy, exponentially expanding culture is washed with PBS to remove residual media that could otherwise quench the Trypsin reaction. Warmed 0.05% Trypsin-EDTA is then added to cover the cells, and the plate allowed to incubate for up to 5 mins at room temperature. During this time cells can be observed rounding, and colonies lifting off the plate surface. Gentle repeated pipetting will remove cells and colonies from the plate surface. Trypsinized cells are placed in a standard conical tube containing pre-warmed hES cell media to quench remaining trypsin, and then spun. Cells are resuspended growth media at a concentration of approximately one million cells in one mL of media, a concentration such that one frozen aliquot is sufficient to resurrect a culture on a 10 cm plate. After cells are adequately resuspended, ice cold freezing media is added at equal volume. Cell suspensions are mixed thoroughly, aliquoted into freezing vials, and allowed to slowly freeze to -80 C over 24 hours. Frozen cells can then moved to the vapor phase of liquid nitrogen for long term storage, or remain at -80 for approximately six months.

  14. Chlorophyll sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Glenn, D. F.

    1984-06-01

    The photovoltaic properties of the green plant pigment chlorophyll-a (Chl-a) were investigated in photoelectrochemical and solid state solar cells. Both types of cells utilized a thin film of Chl-a electro-deposited on a SnO2 optically transparent electrode. Solid state cells were fabricated by vapor depositing a thin layer of metal on top of the Chl-A to produce a SnO2/Chl-a/metal sandwich cell. Photoelectrochemical cells were assembled by immersing the SnO2/Chl-a electrode in an aqueous electrolyte solution along with a counter electrode. Both types of Chl-a cells were generally characterized by a strong dependence of he photoactivity on the other cell components and a surprisingly large photovoltage. Photoelectrochemical cells of SnO2/l-a/aq.AlCl3 were seen to produce photovoltages as high as 1.1 V and photocurrents of 1.1 micro A/sq cm while a solid state cell of SnO2/Chl-a/Al could produce 1.4 V and an initial photocurrent of 200 micro A/sq cm. This photoactivity was strongly time dependent in both configurations. Despite this fact, these cells are the most powerful Chl-a sensitized solar cells yet reported.

  15. Hematopoietic Stem Cells Therapies.

    PubMed

    Chivu-Economescu, Mihaela; Rubach, Martin

    2017-01-01

    Stem cell-based therapies are recognized as a new way to treat various diseases and injuries, with a wide range of health benefits. The goal is to heal or replace diseased or destroyed organs or body parts with healthy new cells provided by stem cell transplantation. The current practical form of stem cell therapy is the hematopoietic stem cells transplant applied for the treatment of hematological disorders. There are over 2100 clinical studies in progress concerning hematopoietic stem cell therapies. All of them are using hematopoietic stem cells to treat various diseases like: cancers, leukemia, lymphoma, cardiac failure, neural disorders, auto-immune diseases, immunodeficiency, metabolic or genetic disorders. Several challenges are to be addressed prior to developing and applying large scale cell therapies: 1) to explain and control the mechanisms of differentiation and development toward a specific cell type needed to treat the disease, 2) to obtain a sufficient number of desired cell type for transplantation, 3) to overcome the immune rejection and 4) to show that transplanted cells fulfill their normal functions in vivo after transplants.

  16. Stress and stem cells

    PubMed Central

    Tower, John

    2013-01-01

    The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress. PMID:23799624

  17. Cell biology. Metabolic control of cell death.

    PubMed

    Green, Douglas R; Galluzzi, Lorenzo; Kroemer, Guido

    2014-09-19

    Beyond their contribution to basic metabolism, the major cellular organelles, in particular mitochondria, can determine whether cells respond to stress in an adaptive or suicidal manner. Thus, mitochondria can continuously adapt their shape to changing bioenergetic demands as they are subjected to quality control by autophagy, or they can undergo a lethal permeabilization process that initiates apoptosis. Along similar lines, multiple proteins involved in metabolic circuitries, including oxidative phosphorylation and transport of metabolites across membranes, may participate in the regulated or catastrophic dismantling of organelles. Many factors that were initially characterized as cell death regulators are now known to physically or functionally interact with metabolic enzymes. Thus, several metabolic cues regulate the propensity of cells to activate self-destructive programs, in part by acting on nutrient sensors. This suggests the existence of "metabolic checkpoints" that dictate cell fate in response to metabolic fluctuations. Here, we discuss recent insights into the intersection between metabolism and cell death regulation that have major implications for the comprehension and manipulation of unwarranted cell loss.

  18. Biosensing with cell phones.

    PubMed

    Preechaburana, Pakorn; Suska, Anke; Filippini, Daniel

    2014-07-01

    Continued progress in cell-phone devices has made them powerful mobile computers, equipped with sophisticated, permanent physical sensors embedded as the default configuration. By contrast, the incorporation of permanent biosensors in cell-phone units has been prevented by the multivocal nature of the stimuli and the reactions involved in biosensing and chemical sensing. Biosensing with cell phones entails the complementation of biosensing devices with the physical sensors and communication and processing capabilities of modern cell phones. Biosensing, chemical-sensing, environmental-sensing, and diagnostic capabilities would thus be supported and run on the residual capacity of existing cell-phone infrastructure. The technologies necessary to materialize such a scenario have emerged in different fields and applications. This article addresses the progress on cell-phone biosensing, the specific compromises, and the blend of technologies required to craft biosensing on cell phones.

  19. Myosins in cell junctions

    PubMed Central

    Liu, Katy C.; Cheney, Richard E.

    2012-01-01

    The development of cell-cell junctions was a fundamental step in metazoan evolution, and human health depends on the formation and function of cell junctions. Although it has long been known that actin and conventional myosin have important roles in cell junctions, research has begun to reveal the specific functions of the different forms of conventional myosin. Exciting new data also reveals that a growing number of unconventional myosins have important roles in cell junctions. Experiments showing that cell junctions act as mechanosensors have also provided new impetus to understand the functions of myosins and the forces they exert. In this review we will summarize recent developments on the roles of myosins in cell junctions. PMID:22954512

  20. Overview of Cell Synchronization.

    PubMed

    Banfalvi, Gaspar

    2017-01-01

    The widespread interest in cell synchronization is maintained by the studies of control mechanism involved in cell cycle regulation. During the synchronization distinct subpopulations of cells are obtained representing different stages of the cell cycle. These subpopulations are then used to study regulatory mechanisms of the cycle at the level of macromolecular biosynthesis (DNA synthesis, gene expression, protein synthesis), protein phosphorylation, development of new drugs, etc. Although several synchronization methods have been described, it is of general interest that scientists get a compilation and an updated view of these synchronization techniques. This introductory chapter summarizes: (1) the basic concepts and principal criteria of cell cycle synchronizations, (2) the most frequently used synchronization methods, such as physical fractionation (flow cytometry, dielectrophoresis, cytofluorometric purification), chemical blockade, (3) synchronization of embryonic cells, (4) synchronization at low temperature, (5) comparison of cell synchrony techniques, (6) synchronization of unicellular organisms, and (7) the effect of synchronization on transfection.

  1. Cell sorting apparatus

    NASA Technical Reports Server (NTRS)

    Yen, Shiao-Ping S. (Inventor); Rembaum, Alan (Inventor); Molday, Robert S. (Inventor)

    1980-01-01

    Polymeric functional microspheres containing metal or metal compounds are formed by addition polymerization of a covalently bondable olefinic monomer such as hydroxyethylmethacrylate in the presence of finely divided metal or metal oxide particles, such as iron, gold, platinum or magnetite, which are embedded in the resulting microspheres. The microspheres can be covalently bonded to chemotherapeutic agents, antibodies, or other proteins providing a means for labeling or separating labeled cells. Labeled cells or microspheres can be concentrated at a specific body location such as in the vicinity of a malignant tumor by applying a magnetic field to the location and then introducing the magnetically attractable microspheres or cells into the circulatory system of the subject. Labeled cells can be separated from a cell mixture by applying a predetermined magnetic field to a tube in which the mixture is flowing. After collection of the labeled cells, the magnetic field is discontinued and the labeled sub-cell population recovered.

  2. Intraoperative Stem Cell Therapy

    PubMed Central

    Coelho, Mónica Beato; Cabral, Joaquim M.S.; Karp, Jeffrey M.

    2013-01-01

    Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium. PMID:22809140

  3. Cell viability assays: introduction.

    PubMed

    Stoddart, Martin J

    2011-01-01

    The measurement of cell viability plays a fundamental role in all forms of cell culture. Sometimes it is the main purpose of the experiment, such as in toxicity assays. Alternatively, cell viability can be used to -correlate cell behaviour to cell number, providing a more accurate picture of, for example, anabolic -activity. There are wide arrays of cell viability methods which range from the most routine trypan blue dye exclusion assay to highly complex analysis of individual cells, such as using RAMAN microscopy. The cost, speed, and complexity of equipment required will all play a role in determining the assay used. This chapter aims to provide an overview of many of the assays available today.

  4. Cell Factory Engineering.

    PubMed

    Davy, Anne Mathilde; Kildegaard, Helene Faustrup; Andersen, Mikael Rørdam

    2017-03-22

    Rational approaches to modifying cells to make molecules of interest are of substantial economic and scientific interest. Most of these efforts aim at the production of native metabolites, expression of heterologous biosynthetic pathways, or protein expression. Reviews of these topics have largely focused on individual strategies or cell types, but collectively they fall under the broad umbrella of a growing field known as cell factory engineering. Here we condense >130 reviews and key studies in the art into a meta-review of cell factory engineering. We identified 33 generic strategies in the field, all applicable to multiple types of cells and products, and proven successful in multiple major cell types. These apply to three major categories: production of native metabolites and/or bioactives, heterologous expression of biosynthetic pathways, and protein expression. This meta-review provides general strategy guides for the broad range of applications of rational engineering of cell factories. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Natural killer cell deficiency.

    PubMed

    Orange, Jordan S

    2013-09-01

    Natural killer (NK) cells are part of the innate immune defense against infection and cancer and are especially useful in combating certain viral pathogens. The utility of NK cells in human health has been underscored by a growing number of persons who are deficient in NK cells and/or their functions. This can be in the context of a broader genetically defined congenital immunodeficiency, of which there are more than 40 presently known to impair NK cells. However, the abnormality of NK cells in certain cases represents the majority immunologic defect. In aggregate, these conditions are termed NK cell deficiency. Recent advances have added clarity to this diagnosis and identified defects in 3 genes that can cause NK cell deficiency, as well as some of the underlying biology. Appropriate consideration of these diagnoses and patients raises the potential for rational therapeutic options and further innovation.

  6. Human regulatory B cells control the TFH cell response.

    PubMed

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (TFH) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of TFH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on TFH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate TFH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing TFH cell maturation. In cocultures they differentiated B cells into CD138(+) plasma and IgD(-)CD27(+) memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented TFH cell development. Added to TFH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3(+)CXCR5(+)PD-1(+) follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on TFH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control TFH cell maturation, expand follicular regulatory T cells, and inhibit the TFH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the TFH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Nevoid basal cell carcinoma syndrome

    MedlinePlus

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic condition. The gene linked to the syndrome is known as PTCH (" ...

  8. Sickle Cell Crisis (For Teens)

    MedlinePlus

    ... Surgery? A Week of Healthy Breakfasts Shyness Sickle Cell Crisis (Pain Crisis) KidsHealth > For Teens > Sickle Cell ... drepanocíticas (Crisis de dolor) What Is a Sickle Cell Crisis? Sickle cell disease changes the shape of ...

  9. High Red Blood Cell Count

    MedlinePlus

    Symptoms High red blood cell count By Mayo Clinic Staff A high red blood cell count is an increase in oxygen-carrying cells in your bloodstream. Red blood cells transport oxygen from your lungs to tissues throughout ...

  10. Membrane Cells for Brine Electrolysis.

    ERIC Educational Resources Information Center

    Tingle, M.

    1982-01-01

    Membrane cells were developed as alternatives to mercury and diaphragm cells for the electrolysis of brine. Compares the three types of cells, focusing on the advantages and disadvantages of membrane cells. (JN)

  11. Cutaneous hamartoma with pagetoid cells.

    PubMed

    Piérard-Franchimont, C; Dosal, F L; Estrada, J A; Piérard, G E

    1991-04-01

    We report an unusual cutaneous hamartoma with pagetoid cells characterized by the presence of intraepidermal cells resembling Toker's cells of the nipple. These cells were EMA positive and could be related to the histogenesis of some Paget's disease.

  12. Membrane Cells for Brine Electrolysis.

    ERIC Educational Resources Information Center

    Tingle, M.

    1982-01-01

    Membrane cells were developed as alternatives to mercury and diaphragm cells for the electrolysis of brine. Compares the three types of cells, focusing on the advantages and disadvantages of membrane cells. (JN)

  13. Cell-to-cell binding induced by different lectins.

    PubMed

    Rutishauser, U; Sachs, L

    1975-05-01

    The cell-to-cell binding induced by concanavalin A (Con A) and the lectins from wheatgerm, soybean, and waxbean has been analyzed by measuring the ability of single cells to bind to lectin-coated cells immobilized on nylon fibers. The cells used were lymphoma, myeloid leukemia, and normal fibroblast cells. With all lectins, cell-to-cell binding was inhibited if both cells were prefixed with glutaraldehyde. However, in most cases cell-to-cell binding was enhanced when only the lectin-coated cell was prefixed. With normal fibroblasts, treatment of either one or both cells with trypsin enhanced the cell-to-cell binding induced by Con A and the wheatgerm lectin. Neuraminidase, which increases the number of receptors for soybean agglutinin, increased cell-to-cell binding only if both cells were treated. Although cell-to-cell binding induced by the lectins from soybean and wheatgerm could be partially reversed by the appropriate competitive saccharide inhibitor, binding induced by Con A could not be reversed. The experiments indicate that cell-to-cell binding induced by a lectin can be prevented by an insufficient density of receptors for the lectin, insufficient receptor mobility, or induced clustering of receptors. These effects can explain the differences in cell-to-cell binding and agglutination observed with different cell types and lectins. They also suggest that cell-to-cell binding induced by different lectins with a variety of cell types is initiated by a mechanism involving the alignment of complementary receptors on the colliding cells for the formation of multiple cell-to-lectin-to-cell bridges.

  14. Markers of Endothelial-to-Mesenchymal Transition: Evidence for Antibody-Endothelium Interaction during Antibody-Mediated Rejection in Kidney Recipients.

    PubMed

    Xu-Dubois, Yi-Chun; Peltier, Julie; Brocheriou, Isabelle; Suberbielle-Boissel, Caroline; Djamali, Arjang; Reese, Shannon; Mooney, Nuala; Keuylian, Zela; Lion, Julien; Ouali, Nacéra; Levy, Pierre P; Jouanneau, Chantal; Rondeau, Eric; Hertig, Alexandre

    2016-01-01

    Antibody-mediated rejection (ABMR) is a leading cause of allograft loss. Treatment efficacy depends on accurate diagnosis at an early stage. However, sensitive and reliable markers of antibody-endothelium interaction during ABMR are not available for routine use. Using immunohistochemistry, we retrospectively studied the diagnostic value of three markers of endothelial-to-mesenchymal transition (EndMT), fascin1, vimentin, and heat shock protein 47, for ABMR in 53 renal transplant biopsy specimens, including 20 ABMR specimens, 24 cell-mediated rejection specimens, and nine normal grafts. We validated our results in an independent set of 74 unselected biopsy specimens. Endothelial cells of the peritubular capillaries in grafts with ABMR expressed fascin1, vimentin, and heat shock protein 47 strongly, whereas those from normal renal grafts did not. The level of EndMT marker expression was significantly associated with current ABMR criteria, including capillaritis, glomerulitis, peritubular capillary C4d deposition, and donor-specific antibodies. These markers allowed us to identify C4d-negative ABMR and to predict late occurrence of disease. EndMT markers were more specific than capillaritis for the diagnosis and prognosis of ABMR and predicted late (up to 4 years after biopsy) renal graft dysfunction and proteinuria. In the independent set of 74 renal graft biopsy specimens, the EndMT markers for the diagnosis of ABMR had a sensitivity of 100% and a specificity of 85%. Fascin1 expression in peritubular capillaries was also induced in a rat model of ABMR. In conclusion, EndMT markers are a sensitive and reliable diagnostic tool for detecting endothelial activation during ABMR and predicting late loss of allograft function.

  15. Nestin(+) cells direct inflammatory cell migration in atherosclerosis.

    PubMed

    Del Toro, Raquel; Chèvre, Raphael; Rodríguez, Cristina; Ordóñez, Antonio; Martínez-González, José; Andrés, Vicente; Méndez-Ferrer, Simón

    2016-09-02

    Atherosclerosis is a leading death cause. Endothelial and smooth muscle cells participate in atherogenesis, but it is unclear whether other mesenchymal cells contribute to this process. Bone marrow (BM) nestin(+) cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestin(+) cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestin(+) cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestin(+) cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestin(+) stromal cells increase ∼30 times and contribute to the atheroma plaque. Mcp1 deletion in nestin(+) cells-but not in endothelial cells only- increases circulating inflammatory cells, but decreases their aortic infiltration, delaying atheroma plaque formation and aortic valve calcification. Therefore, nestin expression marks cells that regulate inflammatory cell migration during atherosclerosis.

  16. Mechanics and regulation of cell shape during the cell cycle.

    PubMed

    Clark, Andrew G; Paluch, Ewa

    2011-01-01

    Many cell types undergo dramatic changes in shape throughout the cell cycle. For individual cells, a tight control of cell shape is crucial during cell division, but also in interphase, for example during cell migration. Moreover, cell cycle-related cell shape changes have been shown to be important for tissue morphogenesis in a number of developmental contexts. Cell shape is the physical result of cellular mechanical properties and of the forces exerted on the cell. An understanding of the causes and repercussions of cell shape changes thus requires knowledge of both the molecular regulation of cellular mechanics and how specific changes in cell mechanics in turn effect global shape changes. In this chapter, we provide an overview of the current knowledge on the control of cell morphology, both in terms of general cell mechanics and specifically during the cell cycle.

  17. Cell-to-cell transmission can overcome multiple donor and target cell barriers imposed on cell-free HIV.

    PubMed

    Zhong, Peng; Agosto, Luis M; Ilinskaya, Anna; Dorjbal, Batsukh; Truong, Rosaline; Derse, David; Uchil, Pradeep D; Heidecker, Gisela; Mothes, Walther

    2013-01-01

    Virus transmission can occur either by a cell-free mode through the extracellular space or by cell-to-cell transmission involving direct cell-to-cell contact. The factors that determine whether a virus spreads by either pathway are poorly understood. Here, we assessed the relative contribution of cell-free and cell-to-cell transmission to the spreading of the human immunodeficiency virus (HIV). We demonstrate that HIV can spread by a cell-free pathway if all the steps of the viral replication cycle are efficiently supported in highly permissive cells. However, when the cell-free path was systematically hindered at various steps, HIV transmission became contact-dependent. Cell-to-cell transmission overcame barriers introduced in the donor cell at the level of gene expression and surface retention by the restriction factor tetherin. Moreover, neutralizing antibodies that efficiently inhibit cell-free HIV were less effective against cell-to-cell transmitted virus. HIV cell-to-cell transmission also efficiently infected target T cells that were relatively poorly susceptible to cell-free HIV. Importantly, we demonstrate that the donor and target cell types influence critically the extent by which cell-to-cell transmission can overcome each barrier. Mechanistically, cell-to-cell transmission promoted HIV spread to more cells and infected target cells with a higher proviral content than observed for cell-free virus. Our data demonstrate that the frequently observed contact-dependent spread of HIV is the result of specific features in donor and target cell types, thus offering an explanation for conflicting reports on the extent of cell-to-cell transmission of HIV.

  18. Comparative retinal anatomy in four species of elasmobranch.

    PubMed

    Schieber, Nicole L; Collin, Shaun P; Hart, Nathan S

    2012-04-01

    Using both light and transmission electron microscopy, we examined the retinal anatomy of four elasmobranch species with differing ecologies: the bull shark Carcharhinus leucas, Port Jackson shark Heterodontus portusjacksoni, epaulette shark Hemiscyllium ocellatum and pink whipray Himantura fai. Their retinas are typical of other vertebrates, having three nuclear and two synaptic layers, but are characterised by very large horizontal cells, low densities of ganglion cells (many of which are displaced to the inner nuclear and inner plexiform layers) and the presence of numerous myelinated axons within the nerve fibre layer. Carcharhinus leucas, H. fai and H. ocellatum have duplex retinas containing both rods and single cones. The peak ratio of rods to cones is much lower in C. leucas (4:1) and H. fai (3:1) compared to H. ocellatum (19:1), reflecting differences in diel activity patterns. No cones were observed in the retina of H. portusjacksoni, which is strongly nocturnal. The cones of H. fai lack a distinct myoid and their nuclei are located in a discrete layer sclerad to the external limiting membrane (ELM), whereas those of C. leucas and H. ocellatum have an obvious myoid, and their nuclei are located vitread to the ELM. No double/twin cones were observed in any species. Incorporating data from other studies, there is a clear correlation between rod outer segment volume and visual ecology in elasmobranchs, with smaller volumes found in partly diurnal pelagic species and larger volumes in benthic nocturnal species. This trend may reflect fundamental differences in visual temporal resolution between active and more sedentary species. Copyright © 2011 Wiley Periodicals, Inc.

  19. NKT cells in leishmaniasis.

    PubMed

    Zamora-Chimal, Jaime; Hernández-Ruiz, Joselín; Becker, Ingeborg

    2017-04-01

    The role of NKT cells in the resistance or susceptibility towards Leishmania infections remains to be defined, since controversial data persist. The response of these cells seems to depend on many variables such as the infection site, the number of infecting parasites, the virulence of the strain and the Leishmania species. We here revise the activation pathways leading to NKT cell activation. NKT cells can be activated by the direct pathway, in which Leishmania glycolipids are presented by CD1d molecules on antigen presenting cells, such as dendritic cells (DC), leading to the secretion of diverse cytokines by NKT. NKT cells can also be activated by the indirect pathway, in which Leishmania glycolipids, such as LPG, stimulate TLR2 in DC, inducing their IL-12 production, which in turn activates NKT cells. The review further analyzes the role of NKT cells in disease development, both in humans as in mouse models. Finally we propose the activation of NKT cells for controlling Leishmania infections. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Nanofluidic fuel cell

    NASA Astrophysics Data System (ADS)

    Lee, Jin Wook; Kjeang, Erik

    2013-11-01

    Fuel cells are gaining momentum as a critical component in the renewable energy mix for stationary, transportation, and portable power applications. State-of-the-art fuel cell technology benefits greatly from nanotechnology applied to nanostructured membranes, catalysts, and electrodes. However, the potential of utilizing nanofluidics for fuel cells has not yet been explored, despite the significant opportunity of harnessing rapid nanoscale reactant transport in close proximity to the reactive sites. In the present article, a nanofluidic fuel cell that utilizes fluid flow through nanoporous media is conceptualized and demonstrated for the first time. This transformative concept captures the advantages of recently developed membraneless and catalyst-free fuel cell architectures paired with the enhanced interfacial contact area enabled by nanofluidics. When compared to previously reported microfluidic fuel cells, the prototype nanofluidic fuel cell demonstrates increased surface area, reduced activation overpotential, superior kinetic characteristics, and moderately enhanced fuel cell performance in the high cell voltage regime with up to 14% higher power density. However, the expected mass transport benefits in the high current density regime were constrained by high ohmic cell resistance, which could likely be resolved through future optimization studies.

  1. Mast Cell Function

    PubMed Central

    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

  2. CELL RESPIRATION STUDIES

    PubMed Central

    Daland, Geneva A.; Isaacs, Raphael

    1927-01-01

    1. The oxygen consumption of blood of normal individuals, when the hemoglobin is saturated with oxygen, is practically zero within the limits of experimental error of the microspirometer used. 2. The oxygen consumed in a microspirometer by the blood of patients with chronic myelogenous leucemia with a high white blood cell count, and of one with leucocytosis from sepsis, was proportional to the number of adult polymorphonuclear neutrophils in the blood. 3. No correlation could be made between the rate of oxygen absorption and the total number of white blood cells in the blood, or the total number of immature cells, or the number of red blood cells, or the amount of oxyhemoglobin. 4. The blood of patients with chronic myelogenous leucemia continued to use oxygen in the microspirometer longer than that of normal individuals, and the hemoglobin, in the leucemic bloods, became desaturated even though exposed to air. 5. In blood in which the bulk. of the cells were immature and the mature cells few, the oxygen consumption was lower than in blood in which the mature cells predominated. The rate of oxygen consumption of the immature cells was relatively low as compared to the mature. 6. The slower rate of oxygen absorption by the immature leucocytes in chronic myelogenous leucemia as compared to the mature cells, places them, in accord with Warburg's reports, in the class of the malignant tissues in this respect rather than in the group of young or embryonic cells. PMID:19869329

  3. Reflections on cell competition.

    PubMed

    Baillon, Ludovic; Basler, Konrad

    2014-08-01

    Cell competition is a process by which otherwise viable cells are actively eliminated due to the presence of more competitive cells. It is a conserved phenomenon and occurs in various developmental and experimental contexts. Competitive elimination represents a safeguard mechanism that potentiates animal development. However, the process can also be hijacked, for example, by cancer cells to promote and sustain malignancy. One of the challenges facing the field is that the term "cell competition" is used to describe a variety of phenomena whose relatedness is under debate. The goals of this review are to provide an overview of the literature on cell competition-like phenomena, highlight where there are discrepancies, and, when possible, provide alternative interpretations to reconcile the dissonance. Central to this is a comparison of the various models of cell competition. With our critical examination we seek to draw attention to future prospects in the field of cell competition. We believe that the elucidation of the interplay between loser and winner cells in the process of cell competition will provide new targets for the development of cancer therapeutics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Single cell wound repair

    PubMed Central

    Abreu-Blanco, Maria Teresa; Verboon, Jeffrey M

    2011-01-01

    Cell wounding is a common event in the life of many cell types, and the capacity of the cell to repair day-to-day wear-and-tear injuries, as well as traumatic ones, is fundamental for maintaining tissue integrity. Cell wounding is most frequent in tissues exposed to high levels of stress. Survival of such plasma membrane disruptions requires rapid resealing to prevent the loss of cytosolic components, to block Ca2+ influx and to avoid cell death. In addition to patching the torn membrane, plasma membrane and cortical cytoskeleton remodeling are required to restore cell function. Although a general understanding of the cell wound repair process is in place, the underlying mechanisms of each step of this response are not yet known. We have developed a model to study single cell wound repair using the early Drosophila embryo. Our system combines genetics and live imaging tools, allowing us to dissect in vivo the dynamics of the single cell wound response. We have shown that cell wound repair in Drosophila requires the coordinated activities of plasma membrane and cytoskeleton components. Furthermore, we identified an unexpected role for E-cadherin as a link between the contractile actomyosin ring and the newly formed plasma membrane plug. PMID:21922041

  5. T Cells in Fish

    PubMed Central

    Nakanishi, Teruyuki; Shibasaki, Yasuhiro; Matsuura, Yuta

    2015-01-01

    Cartilaginous and bony fish are the most primitive vertebrates with a thymus, and possess T cells equivalent to those in mammals. There are a number of studies in fish demonstrating that the thymus is the essential organ for development of T lymphocytes from early thymocyte progenitors to functionally competent T cells. A high number of T cells in the intestine and gills has been reported in several fish species. Involvement of CD4+ and CD8α+ T cells in allograft rejection and graft-versus-host reaction (GVHR) has been demonstrated using monoclonal antibodies. Conservation of CD4+ helper T cell functions among teleost fishes has been suggested in a number studies employing mixed leukocyte culture (MLC) and hapten/carrier effect. Alloantigen- and virus-specific cytotoxicity has also been demonstrated in ginbuna and rainbow trout. Furthermore, the important role of cell-mediated immunity rather than humoral immunity has been reported in the protection against intracellular bacterial infection. Recently, the direct antibacterial activity of CD8α+, CD4+ T-cells and sIgM+ cells in fish has been reported. In this review, we summarize the recent progress in T cell research focusing on the tissue distribution and function of fish T cells. PMID:26426066

  6. Simple Cell Balance Circuit

    NASA Technical Reports Server (NTRS)

    Johnson, Steven D.; Byers, Jerry W.; Martin, James A.

    2012-01-01

    A method has been developed for continuous cell voltage balancing for rechargeable batteries (e.g. lithium ion batteries). A resistor divider chain is provided that generates a set of voltages representing the ideal cell voltage (the voltage of each cell should be as if the cells were perfectly balanced). An operational amplifier circuit with an added current buffer stage generates the ideal voltage with a very high degree of accuracy, using the concept of negative feedback. The ideal voltages are each connected to the corresponding cell through a current- limiting resistance. Over time, having the cell connected to the ideal voltage provides a balancing current that moves the cell voltage very close to that ideal level. In effect, it adjusts the current of each cell during charging, discharging, and standby periods to force the cell voltages to be equal to the ideal voltages generated by the resistor divider. The device also includes solid-state switches that disconnect the circuit from the battery so that it will not discharge the battery during storage. This solution requires relatively few parts and is, therefore, of lower cost and of increased reliability due to the fewer failure modes. Additionally, this design uses very little power. A preliminary model predicts a power usage of 0.18 W for an 8-cell battery. This approach is applicable to a wide range of battery capacities and voltages.

  7. The Chlamydomonas cell cycle.

    PubMed

    Cross, Frederick R; Umen, James G

    2015-05-01

    The position of Chlamydomonas within the eukaryotic phylogeny makes it a unique model in at least two important ways: as a representative of the critically important, early-diverging lineage leading to plants; and as a microbe retaining important features of the last eukaryotic common ancestor (LECA) that has been lost in the highly studied yeast lineages. Its cell biology has been studied for many decades and it has well-developed experimental genetic tools, both classical (Mendelian) and molecular. Unlike land plants, it is a haploid with very few gene duplicates, making it ideal for loss-of-function genetic studies. The Chlamydomonas cell cycle has a striking temporal and functional separation between cell growth and rapid cell division, probably connected to the interplay between diurnal cycles that drive photosynthetic cell growth and the cell division cycle; it also exhibits a highly choreographed interaction between the cell cycle and its centriole-basal body-flagellar cycle. Here, we review the current status of studies of the Chlamydomonas cell cycle. We begin with an overview of cell-cycle control in the well-studied yeast and animal systems, which has yielded a canonical, well-supported model. We discuss briefly what is known about similarities and differences in plant cell-cycle control, compared with this model. We next review the cytology and cell biology of the multiple-fission cell cycle of Chlamydomonas. Lastly, we review recent genetic approaches and insights into Chlamydomonas cell-cycle regulation that have been enabled by a new generation of genomics-based tools. © 2015 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  8. Biology of Schwann cells.

    PubMed

    Kidd, Grahame J; Ohno, Nobuhiko; Trapp, Bruce D

    2013-01-01

    The fundamental roles of Schwann cells during peripheral nerve formation and regeneration have been recognized for more than 100 years, but the cellular and molecular mechanisms that integrate Schwann cell and axonal functions continue to be elucidated. Derived from the embryonic neural crest, Schwann cells differentiate into myelinating cells or bundle multiple unmyelinated axons into Remak fibers. Axons dictate which differentiation path Schwann cells follow, and recent studies have established that axonal neuregulin1 signaling via ErbB2/B3 receptors on Schwann cells is essential for Schwann cell myelination. Extracellular matrix production and interactions mediated by specific integrin and dystroglycan complexes are also critical requisites for Schwann cell-axon interactions. Myelination entails expansion and specialization of the Schwann cell plasma membrane over millimeter distances. Many of the myelin-specific proteins have been identified, and transgenic manipulation of myelin genes have provided novel insights into myelin protein function, including maintenance of axonal integrity and survival. Cellular events that facilitate myelination, including microtubule-based protein and mRNA targeting, and actin based locomotion, have also begun to be understood. Arguably, the most remarkable facet of Schwann cell biology, however, is their vigorous response to axonal damage. Degradation of myelin, dedifferentiation, division, production of axonotrophic factors, and remyelination all underpin the substantial regenerative capacity of the Schwann cells and peripheral nerves. Many of these properties are not shared by CNS fibers, which are myelinated by oligodendrocytes. Dissecting the molecular mechanisms responsible for the complex biology of Schwann cells continues to have practical benefits in identifying novel therapeutic targets not only for Schwann cell-specific diseases but other disorders in which axons degenerate.

  9. Successful differentiation to T cells, but unsuccessful B-cell generation, from B-cell-derived induced pluripotent stem cells.

    PubMed

    Wada, Haruka; Kojo, Satoshi; Kusama, Chie; Okamoto, Naoki; Sato, Yorino; Ishizuka, Bunpei; Seino, Ken-ichiro

    2011-01-01

    Forced expression of certain transcription factors in somatic cells results in generation of induced pluripotent stem (iPS) cells, which differentiate into various cell types. We investigated T-cell and B-cell lineage differentiation from iPS cells in vitro. To evaluate the impact of iPS cell source, murine splenic B-cell-derived iPS (B-iPS) cells were generated after retroviral transduction of four transcription factors (Oct4, Sox2, Klf4 and c-Myc). B-iPS cells were identical to embryonic stem (ES) cells and mouse embryonic fibroblast (MEF)-derived iPS cells in morphology, ES cell marker expression as well as teratoma and chimera mouse formation. Both B-iPS and MEF-derived iPS cells differentiated into lymphocytes in OP9 co-culture systems. Both efficiently differentiated into T-cell lineage that produced IFN-γ on T-cell receptor stimulation. However, iPS cells including B-iPS cells were relatively resistant to B-cell lineage differentiation. One of the reasons of the failure of B-cell lineage differentiation seemed due to a defect of Pax5 expression in the differentiated cells. Therefore, current in vitro differentiation systems using iPS cells are sufficient for inducing T-cell but not B-cell lineage.

  10. Cell Research and Technology Workshop

    NASA Technical Reports Server (NTRS)

    Hutchby, J.

    1985-01-01

    Four major areas in solar cell research and technology were considered. The areas were: (1) the silicon cell; (2) the GaAs cell; (3) the multibandgap cell; and (4) novel ideas. In each area material research issues, cell research issues, and the cell technology that needs development are considered.

  11. Cell-Substrate Adhesion by Amoeboid Cells

    NASA Astrophysics Data System (ADS)

    Flanders, Bret; Panta, Krishna

    Amoeboid migration is a rapid (10 μm min-1) mode of migration that some tumor cells exhibit. To permit such rapid movement, the adhesive contacts between the cell and the substrate must be relatively short-lived and weak. In this study, we investigate the basic adhesive character of amoeboid cells (D. discoideum) in contact with silanized glass substrates. We observe the initiation and spreading of the adhesive contacts that these cells establish as they settle under gravity onto the substrate and relax towards mechanical equilibrium. The use of interference reflection microscopy and cellular tethering measurements have allowed us to determine the basic adhesive properties of the cell: the membrane-medium interfacial energy; the bending modulus; the equilibrium contact angle; and the work of adhesion. We find the time scale on which settling occurs to be longer than expected. Implications of these results on adhesion and migration will be discussed. The authors are grateful for support from NSF (CBET-1451903) and NIH (1R21EY026392).

  12. New Cell Sources for T Cell Engineering and Adoptive Immunotherapy

    PubMed Central

    Themeli, Maria; Rivière, Isabelle; Sadelain, Michel

    2017-01-01

    The promising clinical results obtained with engineered T cells, including chimeric antigen receptor (CAR) therapy, call for further advancements to facilitate and broaden their applicability. One potentially beneficial innovation is to exploit new T cell sources that reduce the need for autologous cell manufacturing and enable cell transfer across histocompatibility barriers. Here we review emerging T cell engineering approaches that utilize alternative T cell sources, which include virus-specific or T cell receptor-less allogeneic T cells, expanded lymphoid progenitors, and induced pluripotent stem cell (iPSC)-derived T lymphocytes. The latter offer the prospect for true off-the-shelf, genetically enhanced, histocompatible cell therapy products. PMID:25842976

  13. Isolation of rare cancer cells from blood cells using dielectrophoresis.

    PubMed

    Salmanzadeh, Alireza; Sano, Michael B; Shafiee, Hadi; Stremler, Mark A; Davalos, Rafael V

    2012-01-01

    In this study, we investigate the application of contactless dielectrophoresis (cDEP) for isolating cancer cells from blood cells. Devices with throughput of 0.2 mL/hr (equivalent to sorting 3×10(6) cells per minute) were used to trap breast cancer cells while allowing blood cells through. We have shown that this technique is able to isolate cancer cells in concentration as low as 1 cancer cell per 10(6) hematologic cells (equivalent to 1000 cancer cells in 1 mL of blood). We achieved 96% trapping of the cancer cells at 600 kHz and 300 V(RMS).

  14. Embryonic stem cell-somatic cell fusion and postfusion enucleation.

    PubMed

    Sumer, Huseyin; Verma, Paul J

    2015-01-01

    Embryonic stem (ES) cells are able to reprogram somatic cells following cell fusion. The resulting cell hybrids have been shown to have similar properties to pluripotent cells. It has also been shown that transcriptional changes can occur in a heterokaryon, without nuclear hybridization. However it is unclear whether these changes can be sustained following removal of the dominant ES nucleus. In this chapter, methods are described for the cell fusion of mouse tetraploid ES cells with somatic cells and enrichment of the resulting heterokaryons. We next describe the conditions for the differential removal of the ES cell nucleus, allowing for the recovery of somatic cells.

  15. Solar cell shingle

    NASA Technical Reports Server (NTRS)

    Forestieri, A. F.; Ratajczak, A. F.; Sidorak, L. G. (Inventor)

    1977-01-01

    A solar cell shingle was made of an array of solar cells on a lower portion of a substantially rectangular shingle substrate made of fiberglass cloth or the like. The solar cells may be encapsulated in flourinated ethylene propylene or some other weatherproof translucent or transparent encapsulant to form a combined electrical module and a roof shingle. The interconnected solar cells were connected to connectors at the edge of the substrate through a connection to a common electrical bus or busses. An overlap area was arranged to receive the overlap of a cooperating similar shingle so that the cell portion of the cooperating shingle may overlie the overlap area of the roof shingle. Accordingly, the same shingle serves the double function of an ordinary roof shingle which may be applied in the usual way and an array of cooperating solar cells from which electrical energy may be collected.

  16. Stochasticity and Cell Fate

    PubMed Central

    Losick, Richard; Desplan, Claude

    2008-01-01

    Summary Fundamental to living cells is the capacity to differentiate into subtypes with specialized attributes. Understanding the way cells acquire their fates is a major challenge in developmental biology. How cells adopt a particular fate is usually thought of as being deterministic, and in the large majority of cases it is. That is, cells acquire their fate by virtue of their lineage or their proximity to an inductive signal from another cell. In some cases, however, and in organisms ranging from bacteria to humans, cells choose one or another pathway of differentiation stochastically without apparent regard to environment or history. Stochasticity has important mechanistic requirements as we discuss. We will also speculate on why stochasticity is advantageous, and even critical in some circumstances, to the individual, the colony, or the species. PMID:18388284

  17. Amorphous silicon solar cells

    NASA Astrophysics Data System (ADS)

    Takahashi, K.; Konagai, M.

    The fabrication, performance, and applications of a-Si solar cells are discussed, summarizing the results of recent experimental investigations and trial installations. Topics examined include the fundamental principles and design strategies of solar power installations; the characteristics of monocrystalline-Si solar cells; techniques for reducing the cost of solar cells; independent, linked, and hybrid solar power systems; proposed satellite solar power systems; and the use of solar cells in consumer appliances. Consideration is given to the history of a-Si, a-Si fabrication techniques, quality criteria for a-Si films, solar cells based on a-Si, and techniques for increasing the efficiency and lowering the cost of a-Si solar cells. Graphs, diagrams, drawings, and black-and-white and color photographs are provided.

  18. Dot junction solar cells

    NASA Technical Reports Server (NTRS)

    Daud, T.; Crotty, G. T.

    1986-01-01

    A design of solar cells with reduced junction area on the cell surface is investigated for reduction of saturation current and increase in open-circuit voltage. Equidiameter dot junctions distributed across the surface of the cell offer an efficient alternative, with variations in dot diameter and in the spacing between dots giving the required variations in the ratio of junction area to total surface area. A simplified analysis for short-circuit current and other cell parameters, which enables cell design optimization, is presented. Experimental solar-cell performance results, as functions of different area ratios, are presented and compared with the model. It is shown that saturation current reduction is possible for achieving efficiencies as high as 18 percent in flat-plate terrestrial applications.

  19. Melanoma stem cells.

    PubMed

    Roesch, Alexander

    2015-02-01

    The cancer stem cell concept significantly broadens our understanding of melanoma biology. However, this concept should be regarded as an integral part of a holistic cancer model that also includes the genetic evolution of tumor cells and the variability of cell phenotypes within a dynamic tumor microenvironment. The biologic complexity and methodological difficulties in identifying cancer stem cells and their biomarkers are currently impeding the direct translation of experimental findings into clinical practice. Nevertheless, it is these methodological shortcomings that provide a new perspective on the phenotypic heterogeneity and plasticity of melanoma with important consequences for future therapies. The development of new combination treatment strategies, particularly with regard to overcoming treatment resistance, could significantly benefit from targeted elimination of cell subpopulations with cancer stem cell properties. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  20. Cell Therapy in Dermatology

    PubMed Central

    Petrof, Gabriela; Abdul-Wahab, Alya; McGrath, John A.

    2014-01-01

    Harnessing the regenerative capacity of keratinocytes and fibroblasts from human skin has created new opportunities to develop cell-based therapies for patients. Cultured cells and bioengineered skin products are being used to treat patients with inherited and acquired skin disorders associated with defective skin, and further clinical trials of new products are in progress. The capacity of extracutaneous sources of cells such as bone marrow is also being investigated for its plasticity in regenerating skin, and new strategies, such as the derivation of inducible pluripotent stem cells, also hold great promise for future cell therapies in dermatology. This article reviews some of the preclinical and clinical studies and future directions relating to cell therapy in dermatology, particularly for inherited skin diseases associated with fragile skin and poor wound healing. PMID:24890834