Breast carcinoma with a predominant duct-replacing component and chondroid matrix production.

PubMed

Tajima, Shogo; Koda, Kenji

2016-12-01

Breast carcinomas that produce chondroid matrix are extremely rare. If the carcinoma is invasive, it is classified as a matrix-producing carcinoma (MPC). Herein, we present a case of a breast carcinoma, which showed duct-replacing growth with chondroid matrix production. A 63-year-old woman underwent fine needle aspiration cytology for suspected malignancy, based on radiological findings. Cellular components showed sufficient atypia to allow a diagnosis of malignancy. A partial mastectomy was performed, and no mass-forming lesion was apparent in the surgically resected specimen. Histopathological examination showed that the carcinoma produced chondroid matrix and grew replacing ducts, which were associated with a small amount of an obvious invasive component without matrix production. Some parts of the duct-replacing component might take the form of expansile invasion due to the absence of residual duct-lining myoepithelial cells; it is difficult to decide whether the duct-replacing component is invasive or not. However, regarding a few tumor nests, they would be recognized as MPC-like intraductal components because of the focal presence of myoepithelial cells around them. Hence, this carcinoma could not be definitely diagnosed as a MPC, even though we believe they are closely related. This is the first reported case of a breast carcinoma displaying duct-replacing growth with chondroid matrix production.

Recellularization via the bile duct supports functional allogenic and xenogenic cell growth on a decellularized rat liver scaffold.

PubMed

Hassanein, Wessam; Uluer, Mehmet C; Langford, John; Woodall, Jhade D; Cimeno, Arielle; Dhru, Urmil; Werdesheim, Avraham; Harrison, Joshua; Rivera-Pratt, Carlos; Klepfer, Stephen; Khalifeh, Ali; Buckingham, Bryan; Brazio, Philip S; Parsell, Dawn; Klassen, Charlie; Drachenberg, Cinthia; Barth, Rolf N; LaMattina, John C

2017-01-02

Recent years have seen a proliferation of methods leading to successful organ decellularization. In this experiment we examine the feasibility of a decellularized liver construct to support growth of functional multilineage cells. Bio-chamber systems were used to perfuse adult rat livers with 0.1% SDS for 24 hours yielding decellularized liver scaffolds. Initially, we recellularized liver scaffolds using a human tumor cell line (HepG2, introduced via the bile duct). Subsequent studies were performed using either human tumor cells co-cultured with human umbilical vein endothelial cells (HUVECs, introduced via the portal vein) or rat neonatal cell slurry (introduced via the bile duct). Bio-chambers were used to circulate oxygenated growth medium via the portal vein at 37C for 5-7 days. Human HepG2 cells grew readily on the scaffold (n = 20). HepG2 cells co-cultured with HUVECs demonstrated viable human endothelial lining with concurrent hepatocyte growth (n = 10). In the series of neonatal cell slurry infusion (n = 10), distinct foci of neonatal hepatocytes were observed to repopulate the parenchyma of the scaffold. The presence of cholangiocytes was verified by CK-7 positivity. Quantitative albumin measurement from the grafts showed increasing albumin levels after seven days of perfusion. Graft albumin production was higher than that observed in traditional cell culture. This data shows that rat liver scaffolds support human cell ingrowth. The scaffold likewise supported the engraftment and survival of neonatal rat liver cell slurry. Recellularization of liver scaffolds thus presents a promising model for functional liver engineering.

The GDNF Target Vsnl1 Marks the Ureteric Tip

PubMed Central

Ola, Roxana; Jakobson, Madis; Kvist, Jouni; Perälä, Nina; Kuure, Satu; Braunewell, Karl-Heinz; Bridgewater, Darren; Rosenblum, Norman D.; Chilov, Dmitri; Immonen, Tiina; Sainio, Kirsi

2011-01-01

Glial cell line-derived neurotrophic factor (GDNF) is indispensable for ureteric budding and branching. If applied exogenously, GDNF promotes ectopic ureteric buds from the Wolffian duct. Although several downstream effectors of GDNF are known, the identification of early response genes is incomplete. Here, microarray screening detected several GDNF-regulated genes in the Wolffian duct, including Visinin like 1 (Vsnl1), which encodes a neuronal calcium-sensor protein. We observed renal Vsnl1 expression exclusively in the ureteric epithelium, but not in Gdnf-null kidneys. In the tissue culture of Gdnf-deficient kidney primordium, exogenous GDNF and alternative bud inducers (FGF7 and follistatin) restored Vsnl1 expression. Hence, Vsnl1 characterizes the tip of the ureteric bud epithelium regardless of the inducer. In the tips, Vsnl1 showed a mosaic expression pattern that was mutually exclusive with β-catenin transcriptional activation. Vsnl1 was downregulated in both β-catenin-stabilized and β-catenin-deficient kidneys. Moreover, in a mouse collecting duct cell line, Vsnl1 compromised β-catenin stability, suggesting a counteracting relationship between Vsnl1 and β-catenin. In summary, Vsnl1 marks ureteric bud tips in embryonic kidneys, and its mosaic pattern demonstrates a heterogeneity of cell types that may be critical for normal ureteric branching. PMID:21289216

Efficient and Controlled Generation of 2D and 3D Bile Duct Tissue from Human Pluripotent Stem Cell-Derived Spheroids.

PubMed

Tian, Lipeng; Deshmukh, Abhijeet; Ye, Zhaohui; Jang, Yoon-Young

2016-08-01

While in vitro liver tissue engineering has been increasingly studied during the last several years, presently engineered liver tissues lack the bile duct system. The lack of bile drainage not only hinders essential digestive functions of the liver, but also leads to accumulation of bile that is toxic to hepatocytes and known to cause liver cirrhosis. Clearly, generation of bile duct tissue is essential for engineering functional and healthy liver. Differentiation of human induced pluripotent stem cells (iPSCs) to bile duct tissue requires long and/or complex culture conditions, and has been inefficient so far. Towards generating a fully functional liver containing biliary system, we have developed defined and controlled conditions for efficient 2D and 3D bile duct epithelial tissue generation. A marker for multipotent liver progenitor in both adult human liver and ductal plate in human fetal liver, EpCAM, is highly expressed in hepatic spheroids generated from human iPSCs. The EpCAM high hepatic spheroids can, not only efficiently generate a monolayer of biliary epithelial cells (cholangiocytes), in a 2D differentiation condition, but also form functional ductal structures in a 3D condition. Importantly, this EpCAM high spheroid based biliary tissue generation is significantly faster than other existing methods and does not require cell sorting. In addition, we show that a knock-in CK7 reporter human iPSC line generated by CRISPR/Cas9 genome editing technology greatly facilitates the analysis of biliary differentiation. This new ductal differentiation method will provide a more efficient method of obtaining bile duct cells and tissues, which may facilitate engineering of complete and functional liver tissue in the future.

Acoustic radiation from lined, unflanged ducts: Acoustic source distribution program

NASA Technical Reports Server (NTRS)

Beckemeyer, R. J.; Sawdy, D. T.

1971-01-01

An acoustic radiation analysis was developed to predict the far-field characteristics of fan noise radiated from an acoustically lined unflanged duct. This analysis is comprised of three modular digital computer programs which together provide a capability of accounting for the impedance mismatch at the duct exit plane. Admissible duct configurations include circular or annular, with or without an extended centerbody. This variation in duct configurations provides a capability of modeling inlet and fan duct noise radiation. The computer programs are described in detail.

Organization of tubules in the human caput epididymidis and the ultrastructure of their epithelia.

PubMed

Yeung, C H; Cooper, T G; Bergmann, M; Schulze, H

1991-07-01

The structure of the human caput epididymidis was examined by gross morphological and light and electron microscopic techniques. There were at least seven types of tubules, each characterized by a different epithelium. These tubules were connected with one another by at least eight types of junctions to form a network. Most of the caput epididymidis was composed of efferent ducts. Within these, five types of tubules, each with a different ciliated epithelium, were found in different regions; and four types of junctions between the efferent ducts and the epididymal tubule were observed. The efferent ducts left the testis, initially as parallel straight tubules containing both ciliated and non-ciliated cells in an epithelium of irregular height. Each efferent duct then coiled tortuously into lobules that folded over one another. These efferent ducts then branched out as thin tubules to join a network of dark tubules which were lined by a regular epithelium containing prominently vacuolated, non-ciliated cells. These tubules anastomosed via common cavities characterized by a ciliated cuboidal epithelium and sometimes joined tubules exhibiting a non-vacuolated ciliated epithelium. The latter, as well as typical efferent ducts, made connection with the epididymis proper in both end-to-end and end-to-side junctions. In the more distal junctions with the epididymis, the efferent ducts joined to a transitional epididymal ductule before joining to the side of the epididymis proper. Post-junctional epithelia in the beginning of the epididymis occasionally contained patches of cells characteristic of efferent ducts. Tall cells with long stereocilia constituted a discontinuous "initial segment"-like region of the epididymis. This is the most detailed study so far of the epithelia and the tubule organization in the caput epididymidis of any species, and most of the results are reported for the first time for the human. Although the pattern of the tubule network resembles that of some domestic species, the rich variety of epithelia has not been appreciated before.

Investigation of the tone-burst tube for duct lining attenuation measurement

NASA Technical Reports Server (NTRS)

Soffel, A. R.; Morrow, P. F.

1972-01-01

The tone burst technique makes practical the laboratory evaluation of potential inlet and discharge duct treatments. Tone burst apparatus requires only simple machined parts and standard components. Small, simply made, lining samples are quickly and easily installed in the system. Two small electromagnetric loudspeaker drivers produce peak sound pressure level of over 166 db in the 3-square-inch sample duct. Air pump available in most laboratories can produce air flows of over plus and minus Mach 0.3 in the sample duct. The technique uses short shaped pulses of sound propagated down a progressive wave tube containing the sample duct. The peak pressure level output of the treated duct is compared with the peak pressure level output of a substituted reference duct. The difference between the levels is the attenuation or insertion loss of the treated duct. Evaluations of resonant absorber linings by the tone burst technique check attenuation values predicted by empirical formulas based on full scale ducts.

CXCL12 Chemokine Expression Suppresses Human Pancreatic Cancer Growth and Metastasis

PubMed Central

Roy, Ishan; Zimmerman, Noah P.; Mackinnon, A. Craig; Tsai, Susan; Evans, Douglas B.; Dwinell, Michael B.

2014-01-01

Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites. PMID:24594697

Stem cell marker prominin-1/AC133 is expressed in duct cells of the adult human pancreas.

PubMed

Lardon, Jessy; Corbeil, Denis; Huttner, Wieland B; Ling, Zhidong; Bouwens, Luc

2008-01-01

Many efforts are spent in identifying stem cells in adult pancreas because these could provide a source of beta cells for cell-based therapy of type 1 diabetes. Prominin-1, particularly its specific glycosylation-dependent AC133 epitope, is expressed on stem/progenitor cells of various human tissues and can be used to isolate them. We, therefore, examined its expression in adult human pancreas. To detect prominin-1 protein, monoclonal antibody CD133/1 (AC133 clone), which recognizes the AC133 epitope, and the alphahE2 antiserum, which is directed against the human prominin-1 polypeptide, were used. Prominin-1 RNA expression was analyzed by real-time polymerase chain reaction. We report that all duct-lining cells of the pancreas express prominin-1. Most notably, the cells that react with the alphahE2 antiserum also react with the AC133 antibody. After isolation and culture of human exocrine cells, we found a relative increase in prominin-1 expression both at protein and RNA expression level, which can be explained by an enrichment of cells with ductal phenotype in these cultures. Our data show that pancreatic duct cells express prominin-1 and surprisingly reveal that its particular AC133 epitope is not an exclusive stem and progenitor cell marker.

Membrane covered duct lining for high-frequency noise attenuation: prediction using a Chebyshev collocation method.

PubMed

Huang, Lixi

2008-11-01

A spectral method of Chebyshev collocation with domain decomposition is introduced for linear interaction between sound and structure in a duct lined with flexible walls backed by cavities with or without a porous material. The spectral convergence is validated by a one-dimensional problem with a closed-form analytical solution, and is then extended to the two-dimensional configuration and compared favorably against a previous method based on the Fourier-Galerkin procedure and a finite element modeling. The nonlocal, exact Dirichlet-to-Neumann boundary condition is embedded in the domain decomposition scheme without imposing extra computational burden. The scheme is applied to the problem of high-frequency sound absorption by duct lining, which is normally ineffective when the wavelength is comparable with or shorter than the duct height. When a tensioned membrane covers the lining, however, it scatters the incident plane wave into higher-order modes, which then penetrate the duct lining more easily and get dissipated. For the frequency range of f=0.3-3 studied here, f=0.5 being the first cut-on frequency of the central duct, the membrane cover is found to offer an additional 0.9 dB attenuation per unit axial distance equal to half of the duct height.

Noise radiation directivity from a wind-tunnel inlet with inlet vanes and duct wall linings

NASA Technical Reports Server (NTRS)

Soderman, P. T.; Phillips, J. D.

1986-01-01

The acoustic radiation patterns from a 1/15th scale model of the Ames 80- by 120-Ft Wind Tunnel test section and inlet have been measured with a noise source installed in the test section. Data were acquired without airflow in the duct. Sound-absorbent inlet vanes oriented parallel to each other, or splayed with a variable incidence relative to the duct long axis, were evaluated along with duct wall linings. Results show that splayed vans tend to spread the sound to greater angles than those measured with the open inlet. Parallel vanes narrowed the high-frequency radiation pattern. Duct wall linings had a strong effect on acoustic directivity by attenuating wall reflections. Vane insertion loss was measured. Directivity results are compared with existing data from square ducts. Two prediction methods for duct radiation directivity are described: one is an empirical method based on the test data, and the other is a analytical method based on ray acoustics.

Induction of insulin-producing cells from human pancreatic progenitor cells.

PubMed

Noguchi, H; Naziruddin, B; Shimoda, M; Fujita, Y; Chujo, D; Takita, M; Peng, H; Sugimoto, K; Itoh, T; Tamura, Y; Olsen, G S; Kobayashi, N; Onaca, N; Hayashi, S; Levy, M F; Matsumoto, S

2010-01-01

We previously established a mouse pancreatic stem cell line without genetic manipulation. In this study, we sought to identify and isolate human pancreatic stem/progenitor cells. We also tested whether growth factors and protein transduction of pancreatic and duodenal homeobox factor-1 (PDX-1) and BETA2/NeuroD into human pancreatic stem/progenitor cells induced insulin or pancreas-related gene expressions. Human pancreata from brain-dead donors were used for islet isolation with the standard Ricordi technique modified by the Edmonton protocol. The cells from a duct-rich population were cultured in several media, based on those designed for mouse pancreatic or for human embryonic stem cells. To induce cell differentiation, cells were cultured for 2 weeks with exendin-4, nicotinamide, keratinocyte growth factor, PDX-1 protein, or BETA2/NeuroD protein. The cells in serum-free media showed morphologies similar to a mouse pancreatic stem cell line, while the cells in the medium for human embryonic stem cells formed fibroblast-like morphologies. The nucleus/cytoplasm ratios of the cells in each culture medium decreased during the culture. The cells stopped dividing after 30 days, suggesting that they had entered senescence. The cells treated with induction medium differentiated into insulin-producing cells, expressing pancreas-related genes. Duplications of cells from a duct-rich population were limited. Induction therapy with several growth factors and transduction proteins might provide a potential new strategy for induction of transplantable insulin-producing cells. Copyright 2010 Elsevier Inc. All rights reserved.

Localization of S-100 proteins in the testis and epididymis of poultry and rabbits

PubMed Central

Abd-Elmaksoud, Ahmed; Marei, Hany E. S.

2014-01-01

The present investigation was conducted to demonstrate S-100 protein in the testis and epididymis of adult chickens, Sudani ducks, pigeons, and rabbits. This study may represent the first indication for the presence of S-100 in the male reproductive organs of these species and might therefore serve as a milestone for further reports. In the testis of chickens, pigeons and rabbits, intense S-100 was seen in Sertoli cells. S-100 was also seen in the endothelial lining of blood vessels in rabbit testis. On the contrary, no S-100 reaction was detected in the Sertoli cells of Sudani ducks. In epididymis, the localization of S-100 had varied according to species studied; it was seen in the basal cells (BC) of epididymal duct in duck, non-ciliated cells of the distal efferent ductules in pigeons and ciliated cells of the efferent ductules and BC of rabbit epididymis. Conversely, S-100 specific staining was not detected in the epithelial lining of the rooster and pigeon epididymal duct as well as the principal cells of the rabbit epididymis. In conclusion, the distribution of the S-100 proteins in the testis and epididymis might point out to its roles in the male reproduction. PMID:25276477

Experimental models to study cholangiocyte biology

PubMed Central

Tietz, Pamela S.; Chen, Xian-Ming; Gong, Ai-Yu; Huebert, Robert C.; Masyuk, Anatoliy; Masyuk, Tatyana; Splinter, Patrick L.; LaRusso, Nicholas F.

2002-01-01

Cholangiocytes-the epithelial cells which line the bile ducts-are increasingly recognized as important transporting epithelia actively involved in the absorption and secretion of water, ions, and solutes. This recognition is due in part to the recent development of new experimental models. New biologic concepts have emerged including the identification and topography of receptors and flux proteins on the apical and/or basolateral membrane which are involved in the molecular mechanisms of ductal bile secretion. Individually isolated and/or perfused bile duct units from livers of rats and mice serve as new, physiologically relevant in vitro models to study cholangiocyte transport. Biliary tree dimensions and novel insights into anatomic remodeling of proliferating bile ducts have emerged from three-dimensional reconstruction using CT scanning and sophisticated software. Moreover, new pathologic concepts have arisen regarding the interaction of cholangiocytes with pathogens such as Cryptosporidium parvum. These concepts and associated methodologies may provide the framework to develop new therapies for the cholangiopathies, a group of important hepatobiliary diseases in which cholangiocytes are the target cell. PMID:11833061

Ultra structural changes occurring in duct ectasia and periductal mastitis and their significance in etiopathogenesis.

PubMed

Ramalingam, Kirithiga; Vuthaluru, Seenu; Srivastava, Anurag; Dinda, Amit Kumar; Dhar, Anita

2017-01-01

Duct ectasia (DE) and periductal mastitis (PDM) are the most common benign breast conditions seen in women. The etiopathogenesis of these entities is still not clear and most of the theories regarding the causation are based on the histological features as seen on light microscopy. The ultramicroscopic features associated with these conditions that may give more insight to the etiopathogenesis are unknown. To study the ultrastructural changes occurring in mammary duct cones in patients with DE and PDM using Transmission Electron Microscopic (TEM). Major ducts removed by radical duct excision from 21 patients with final histopathological diagnosis of DE and PDM were subjected to TEM study with 2 normal duct samples as controls. The TEM features of DE were denudation of the epithelial cells with focal loss of microvilli, widening of the inter-epithelial junctions with focal disruption of the T bars, periductal collagenisation without inflammation, and features suggestive of Epithelial Mesenchymal Transition (EMT). PDM features are intact epithelial lining with proliferative epithelium and periductal collagenisation with inflammation. Based on the TEM findings, we suggest that DE and PDM are two different entities. EMT a novel finding observed in DE in this study.

Ultra structural changes occurring in duct ectasia and periductal mastitis and their significance in etiopathogenesis

PubMed Central

Ramalingam, Kirithiga; Vuthaluru, Seenu; Srivastava, Anurag; Dinda, Amit Kumar; Dhar, Anita

2017-01-01

Introduction Duct ectasia (DE) and periductal mastitis (PDM) are the most common benign breast conditions seen in women. The etiopathogenesis of these entities is still not clear and most of the theories regarding the causation are based on the histological features as seen on light microscopy. The ultramicroscopic features associated with these conditions that may give more insight to the etiopathogenesis are unknown. Aim To study the ultrastructural changes occurring in mammary duct cones in patients with DE and PDM using Transmission Electron Microscopic (TEM). Method Major ducts removed by radical duct excision from 21 patients with final histopathological diagnosis of DE and PDM were subjected to TEM study with 2 normal duct samples as controls. Results The TEM features of DE were denudation of the epithelial cells with focal loss of microvilli, widening of the inter-epithelial junctions with focal disruption of the T bars, periductal collagenisation without inflammation, and features suggestive of Epithelial Mesenchymal Transition (EMT). PDM features are intact epithelial lining with proliferative epithelium and periductal collagenisation with inflammation. Conclusions Based on the TEM findings, we suggest that DE and PDM are two different entities. EMT a novel finding observed in DE in this study. PMID:28273122

The PPARδ ligand GW501516 reduces growth but not apoptosis in mouse inner medullary collecting duct cells.

PubMed

Clark, Jordan; Nasrallah, Rania; Hébert, Richard L

2009-01-01

The collecting duct (CD) expresses considerable amounts of PPARδ. While its role is unknown in the CD, in other renal cells it has been shown to regulate both growth and apoptosis. We thus hypothesized that PPARδ reduces apoptotic responses and stimulates cell growth in the mouse CD, and examined the effect of GW501516, a synthetic PPARδ ligand, on these responses in mouse IMCD-K2 cells. High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability. Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels. These results show that a PPARδ ligand inhibits growth but does not affect anisomycin-apoptosis in a mouse IMCD cell line. This could have therapeutic implications for renal diseases associated with increased CD growth responses.

Characterization of Insulin-Immunoreactive Cells and Endocrine Cells Within the Duct System of the Adult Human Pancreas.

PubMed

Li, Rong; Zhang, Xiaoxi; Yu, Lan; Zou, Xia; Zhao, Hailu

2016-01-01

The adult pancreatic duct system accommodates endocrine cells that have the potential to produce insulin. Here we report the characterization and distribution of insulin-immunoreactive cells and endocrine cells within the ductal units of adult human pancreas. Sequential pancreas sections from 12 nondiabetic adults were stained with biomarkers of ductal epithelial cells (cytokeratin 19), acinar cells (amylase), endocrine cells (chromogranin A; neuron-specific enolase), islet hormones (insulin, glucagon, somatostatin, pancreatic polypeptide), cell proliferation (Ki-67), and neogenesis (CD29). The number of islet hormone-immunoreactive cells increased from large ducts to the terminal branches. The insulin-producing cells outnumbered endocrine cells reactive for glucagon, somatostatin, or pancreatic polypeptide. The proportions of insulin-immunoreactive count compared with local islets (100% as a baseline) were 1.5% for the main ducts, 7.2% for interlobular ducts, 24.8% for intralobular ducts, 67.9% for intercalated ducts, and 348.9% for centroacinar cells. Both Ki-67- and CD29-labeled cells were predominantly localized in the terminal branches around the islets. The terminal branches also showed cells coexpressing islet hormones and cytokeratin 19. The adult human pancreatic ducts showed islet hormone-producing cells. The insulin-reactive cells predominantly localized in terminal branches where they may retain potential capability for β-cell neogenesis.

MTA1 regulation of ERβ pathway in salivary gland carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohshiro, Kazufumi, E-mail: bcmkxo@gwu.edu; Kumar, Rakesh

Abstracts: Although Metastatic-tumor antigen 1 (MTA1) is differentially expressed in metastatic cancer and coregulates the status and activity of nuclear receptors, its role upon estrogen receptor β (ERβ) – a potent tumor suppressor, remains poorly understood. Here we investigated whether MTA1 regulates the expression and functions of ERβ, an ER isoform predominantly expressed in salivary gland cancer cells. We found that the depletion of the endogenous MTA1 in the HSG and HSY salivary duct carcinoma cell lines enhances the expression of ERβ while MTA1 overexpression augmented the expression of ERβ in salivary duct carcinoma cells. Furthermore, MTA1 knockdown inhibited themore » proliferations and invasion of HSG and HSY cells. The noted ERβ downregulation by MTA1 overexpression involves the process of proteasomal degradation, as a proteasome inhibitor could block it. In addition, both MTA1 knockdown and ERβ overexpression attenuated the cell migration and inhibited the ERK1/2 signaling in the both cell lines. These findings imply that MTA1 dysregulation in a subset of salivary gland cancer might promote aggressive phenotypes by compromising the tumor suppressor activity of ERβ, and hence, MTA1-ERβ axis might serve a new therapeutic target for the salivary gland cancer. - Highlights: • MTA1 silencing upregulates ERβ expression in salivary gland carcinoma cells. • MTA1 overexpression downregulates ERβ expression via proteasomal degradation. • Upregulation of ERβ expression inhibits cell migration and ERK signaling. • MTA1 knockdown inhibits cell proliferation and invasion.« less

Farnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.

PubMed

Xu, Sujuan; Huang, Shizheng; Luan, Zhilin; Chen, Tingyue; Wei, Yuanyi; Xing, Miaomiao; Li, Yaqing; Du, Chunxiu; Wang, Bing; Zheng, Feng; Wang, Nanping; Guan, Youfei; Gustafsson, Jan-Åke; Zhang, Xiaoyan

2018-05-22

Hypertonicity in renal medulla is critical for the kidney to produce concentrated urine. Renal medullary cells have to survive high medullary osmolarity during antidiuresis. Previous study reported that farnesoid X receptor (FXR), a nuclear receptor transcription factor activated by endogenous bile acids, increases urine concentrating ability by up-regulating aquaporin 2 expression in medullary collecting duct cells (MCDs). However, whether FXR is also involved in the maintenance of cell survival of MCDs under dehydration condition and hypertonic stress remains largely unknown. In the present study, we demonstrate that 24-hours water restriction selectively up-regulated renal medullary expression of FXR with little MCD apoptosis in wild-type mice. In contrast, water deprivation caused a massive apoptosis of MCDs in both global FXR gene-deficient mice and collecting duct-specific FXR knockout mice. In vitro studies showed that hypertonicity significantly increased FXR and tonicity response enhancer binding protein (TonEBP) expression in mIMCD3 cell line and primary cultured MCDs. Activation and overexpression of FXR markedly increased cell viability and decreased cell apoptosis under hyperosmotic conditions. In addition, FXR can increase gene expression and nuclear translocation of TonEBP. We conclude that FXR protects MCDs from hypertonicity-induced cell injury very likely via increasing TonEBP expression and nuclear translocation. This study provides insights into the molecular mechanism by which FXR enhances urine concentration via maintaining cell viability of MCDs under hyperosmotic condition.

Credit BG. View looking northeast down from the tower onto ...

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

Credit BG. View looking northeast down from the tower onto the two horizontal test stations at Test Stand "D." Station Dy is at the far left (Dy vacuum cell out of view), with in-line exhaust gas cooling sections and steam-driven "air ejector" (or evacuator) discharging engine exhausts to the east. The Dd cell is visible at the lower left, and the Dd exhaust train has the same functions as at Dy. The spherical tank is an electrically heated "accumulator" which supplies steam to the ejectors at Dv, Dd, and Dy stations. Other large piping delivered cooling water to the horizontal train cooling sections. The horizontal duct at the "Y" branch in the Dd train connects the Dd ejector to the Dv and Cv vacuum duct system (a blank can be bolted into this duct to isolate the Dd system). The shed roof for the Dpond test station appears at bottom center of this image. The open steel frame to the lower left of the image supports a hoist and crane for installing or removing test engines from the Dd test cell - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

A quasi-one-dimensional theory of sound propagation in lined ducts with mean flow

NASA Astrophysics Data System (ADS)

Dokumaci, Erkan

2018-04-01

Sound propagation in ducts with locally-reacting liners has received the attention of many authors proposing two- and three-dimensional solutions of the convected wave equation and of the Pridmore-Brown equation. One-dimensional lined duct models appear to have received less attention. The present paper proposes a quasi-one-dimensional theory for lined uniform ducts with parallel sheared mean flow. The basic assumption of the theory is that the effects of refraction and wall compliance on the fundamental mode remain within ranges in which the acoustic fluctuations are essentially uniform over a duct section. This restricts the model to subsonic low Mach numbers and Helmholtz numbers of less than about unity. The axial propagation constants and the wave transfer matrix of the duct are given by simple explicit expressions and can be applied with no-slip, full-slip or partial slip boundary conditions. The limitations of the theory are discussed and its predictions are compared with the fundamental mode solutions of the convected wave equation, the Pridmore-Brown equation and measurements where available.

Role of medullary progenitor cells in epithelial cell migration and proliferation

PubMed Central

Chen, Dong; Chen, Zhiyong; Zhang, Yuning; Park, Chanyoung; Al-Omari, Ahmed

2014-01-01

This study is aimed at characterizing medullary interstitial progenitor cells and to examine their capacity to induce tubular epithelial cell migration and proliferation. We have isolated a progenitor cell side population from a primary medullary interstitial cell line. We show that the medullary progenitor cells (MPCs) express CD24, CD44, CXCR7, CXCR4, nestin, and PAX7. MPCs are CD34 negative, which indicates that they are not bone marrow-derived stem cells. MPCs survive >50 passages, and when grown in epithelial differentiation medium develop phenotypic characteristics of epithelial cells. Inner medulla collecting duct (IMCD3) cells treated with conditioned medium from MPCs show significantly accelerated cell proliferation and migration. Conditioned medium from PGE2-treated MPCs induce tubule formation in IMCD3 cells grown in 3D Matrigel. Moreover, most of the MPCs express the pericyte marker PDGFR-b. Our study shows that the medullary interstitium harbors a side population of progenitor cells that can differentiate to epithelial cells and can stimulate tubular epithelial cell migration and proliferation. The findings of this study suggest that medullary pericyte/progenitor cells may play a critical role in collecting duct cell injury repair. PMID:24808539

Serine protease activity in m-1 cortical collecting duct cells.

PubMed

Liu, Lian; Hering-Smith, Kathleen S; Schiro, Faith R; Hamm, L Lee

2002-04-01

An apical serine protease, channel-activating protease 1 (CAP1), augments sodium transport in A6 cells. Prostasin, a novel serine protease originally purified from seminal fluid, has been proposed to be the mammalian ortholog of CAP1. We have recently found functional evidence for a similar protease activity in the M-1 cortical collecting duct cell line. The purposes of the present studies were to determine whether prostasin (or CAP1) is present in collecting duct cells by use of mouse M-1 cells, to sequence mouse prostasin, and to further characterize the identity of the serine protease activity and additional functional features in M-1 cells. Using mouse expressed sequence tag sequences that are highly homologous to the published human prostasin sequence as templates, reverse transcription-polymerase chain reaction and RACE (rapid amplification of cDNA ends) were used to sequence mouse prostasin mRNA, which shows 99% identical to published mouse CAP1 sequence. A single 1800-bp transcript was found by Northern analysis, and this was not altered by aldosterone. Equivalent short-circuit current (I(eq)), which represents sodium transport in these cells, dropped to 59+/-3% of control value within 1 hour of incubation with aprotinin, a serine protease inhibitor. Trypsin increased the I(eq) in aprotinin-treated cells to the value of the control group within 5 minutes. Application of aprotinin not only inhibited amiloride sensitive I(eq) but also reduced transepithelial resistance (R(te)) to 43+/-2%, an effect not expected with simple inhibition of sodium channels. Trypsin partially reversed the effect of aprotinin on R(te). Another serine protease inhibitor, soybean trypsin inhibitor (STI), decreased I(eq) in M-1 cells. STI inhibited I(eq) gradually over 6 hours, and the inhibition of I(eq) by 2 inhibitors was additive. STI decreased transepithelial resistance much less than did aprotinin. Neither aldosterone nor dexamethasone significantly augmented protease activity or prostasin mRNA levels, and in fact, dexamethasone decreased prostasin mRNA expression. In conclusion, although prostasin is present in M-1 cells and probably augments sodium transport in these cells, serine proteases probably have other effects (eg, resistance) in the collecting duct in addition to effects on sodium channels. Steroids do not alter these effects in M-1 cells. Additional proteases are likely also present in mouse collecting duct cells.

[Mucous retention cysts of the minor salivary glands. A specific type of mucocele].

PubMed

Kakarantza-Angelopoulou, E; Triantaphyllou, A

1989-08-01

The mucous retention cyst of the minor salivary glands represent a specific type of oral mucocele which is lined by epithelium. It is caused probably from partial or complete obstruction of a duct. It affects older patients (over 40 years of age) most commonly women and it is located in different sites than the ordinary mucocele. In this paper we studied the histologic and histochemical features of four cases. The lining epithelium varied from cuboidal to columnar or flattened. Among the cells of the lining epithelium oncocytes were observed.

Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells.

PubMed

Kojima, Takashi; Takasawa, Akira; Kyuno, Daisuke; Ito, Tatsuya; Yamaguchi, Hiroshi; Hirata, Koichi; Tsujiwaki, Mitsuhiro; Murata, Masaki; Tanaka, Satoshi; Sawada, Norimasa

2011-10-01

The novel tight junction protein marvelD3 contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain like occludin and tricellulin. However, little is yet known about the detailed role and regulation of marvelD3 in normal epithelial cells and cancer cells, including pancreatic cancer. In the present study, we investigated marvelD3 expression in well and poorly differentiated human pancreatic cancer cell lines and normal pancreatic duct epithelial cells in which the hTERT gene was introduced into human pancreatic duct epithelial cells in primary culture, and the changes of marvelD3 during Snail-induced epithelial-mesenchymal transition (EMT) under hypoxia, TGF-β treatment and knockdown of FOXA2 in well differentiated pancreatic cancer HPAC cells. MarvelD3 was transcriptionally downregulated in poorly differentiated pancreatic cancer cells and during Snail-induced EMT of pancreatic cancer cells in which Snail was highly expressed and the fence function downregulated, whereas it was maintained in well differentiated human pancreatic cancer cells and normal pancreatic duct epithelial cells. Depletion of marvelD3 by siRNAs in HPAC cells resulted in downregulation of barrier functions indicated as a decrease in transepithelial electric resistance and an increase of permeability to fluorescent dextran tracers, whereas it did not affect fence function of tight junctions. In conclusion, marvelD3 is transcriptionally downregulated in Snail-induced EMT during the progression for the pancreatic cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

PubMed Central

Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

2016-01-01

The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

Deep proteomic profiling of vasopressin-sensitive collecting duct cells. I. Virtual Western blots and molecular weight distributions.

PubMed

Yang, Chin-Rang; Tongyoo, Pumipat; Emamian, Milad; Sandoval, Pablo C; Raghuram, Viswanathan; Knepper, Mark A

2015-12-15

The mouse mpkCCD cell line is a continuous cultured epithelial cell line with characteristics of renal collecting duct principal cells. This line is widely used to study epithelial transport and its regulation. To provide a data resource useful for experimental design and interpretation in studies using mpkCCD cells, we have carried out "deep" proteomic profiling of these cells using three levels of fractionation (differential centrifugation, SDS-PAGE, and HPLC) followed by tandem mass spectrometry to identify and quantify proteins. The analysis of all resulting samples generated 34.6 gigabytes of spectral data. As a result, we identified 6,766 proteins in mpkCCD cells at a high level of stringency. These proteins are expressed over eight orders of magnitude of protein abundance. The data are provided to users as a public data base (https://helixweb.nih.gov/ESBL/Database/mpkFractions/). The mass spectrometry data were mapped back to their gel slices to generate "virtual Western blots" for each protein. For most of the 6,766 proteins, the apparent molecular weight from SDS-PAGE agreed closely with the calculated molecular weight. However, a substantial fraction (>15%) of proteins was found to run aberrantly, with much higher or much lower mobilities than predicted. These proteins were analyzed to identify mechanisms responsible for altered mobility on SDS-PAGE, including high or low isoelectric point, high or low hydrophobicity, physiological cleavage, residence in the lysosome, posttranslational modifications, and expression of alternative isoforms due to alternative exon usage. Additionally, this analysis identified a previously unrecognized isoform of aquaporin-2 with apparent molecular mass <20 kDa. Copyright © 2015 the American Physiological Society.

Deep proteomic profiling of vasopressin-sensitive collecting duct cells. I. Virtual Western blots and molecular weight distributions

PubMed Central

Yang, Chin-Rang; Tongyoo, Pumipat; Emamian, Milad; Sandoval, Pablo C.; Raghuram, Viswanathan

2015-01-01

The mouse mpkCCD cell line is a continuous cultured epithelial cell line with characteristics of renal collecting duct principal cells. This line is widely used to study epithelial transport and its regulation. To provide a data resource useful for experimental design and interpretation in studies using mpkCCD cells, we have carried out “deep” proteomic profiling of these cells using three levels of fractionation (differential centrifugation, SDS-PAGE, and HPLC) followed by tandem mass spectrometry to identify and quantify proteins. The analysis of all resulting samples generated 34.6 gigabytes of spectral data. As a result, we identified 6,766 proteins in mpkCCD cells at a high level of stringency. These proteins are expressed over eight orders of magnitude of protein abundance. The data are provided to users as a public data base (https://helixweb.nih.gov/ESBL/Database/mpkFractions/). The mass spectrometry data were mapped back to their gel slices to generate “virtual Western blots” for each protein. For most of the 6,766 proteins, the apparent molecular weight from SDS-PAGE agreed closely with the calculated molecular weight. However, a substantial fraction (>15%) of proteins was found to run aberrantly, with much higher or much lower mobilities than predicted. These proteins were analyzed to identify mechanisms responsible for altered mobility on SDS-PAGE, including high or low isoelectric point, high or low hydrophobicity, physiological cleavage, residence in the lysosome, posttranslational modifications, and expression of alternative isoforms due to alternative exon usage. Additionally, this analysis identified a previously unrecognized isoform of aquaporin-2 with apparent molecular mass <20 kDa. PMID:26310816

Physiology of Cholangiocytes

PubMed Central

Tabibian, James H.; Masyuk, Anatoliy I.; Masyuk, Tetyana V.; O’Hara, Steven P.; LaRusso, Nicholas F.

2013-01-01

Cholangiocytes are epithelial cells that line the intra- and extrahepatic ducts of the biliary tree. The main physiologic function of cholangiocytes is modification of hepatocyte-derived bile, an intricate process regulated by hormones, peptides, nucleotides, neurotransmitters, and other molecules through intracellular signaling pathways and cascades. The mechanisms and regulation of bile modification are reviewed herein. PMID:23720296

Cuticular Poroma: A Poroma Mostly Composed of Cuticular Cells (Cuticuloma).

PubMed

Alegría-Landa, Victoria; Kutzner, Heinz; Requena, Luis

2017-12-28

Poromas are benign cutaneous adnexal neoplasms with differentiation toward excretory ducts of eccrine and apocrine glands. They are mainly composed of solid aggregates of small, monomorphous, round, and basophilic poroid cells, with a lower proportion of larger, squamous, eosinophilic cuticular cells, which are lining ductal structures with an eosinophilic luminal cuticle. In most cases of poromas, cuticular cells represent a small proportion of the neoplastic aggregates. We report 2 poromas mostly composed of cuticular cells, and on the basis of these findings, we have named cuticuloma to this histopathologic variant of poroma.

Taurine zinc solid dispersions enhance bile-incubated L02 cell viability and improve liver function by inhibiting ERK2 and JNK phosphorylation during cholestasis.

PubMed

Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lai, Xiaofang; Xu, Donghui

2016-07-29

Dietary intakes of taurine and zinc are associated with decreased risk of liver disease. In this study, solid dispersions (SDs) of a taurine zinc complex on hepatic injury were examined in vitro using the immortalized human hepatocyte cell line L02 and in a rat model of bile duct ligation. Sham-operated and bile duct ligated Sprague-Dawley rats were treated with the vehicle alone or taurine zinc (40, 80, 160mg/kg) for 17days. Bile duct ligation significantly increased blood lipid levels, and promoted hepatocyte apoptosis, inflammation and compensatory biliary proliferation. In vitro, incubation with bile significantly reduced L02 cell viability; this effect was significantly attenuated by pretreatment with SP600125 (a JNK inhibitor) and enhanced when co-incubated with taurine zinc SDs. In vivo, administration of taurine zinc SDs decreased serum alanine aminotransferase and aspartate aminotransferase activities in a dose-dependent manner and attenuated the increases in serum total bilirubin, total cholesterol and low density lipoprotein cholesterol levels after bile duct ligation. Additionally, taurine zinc SDs downregulated the expression of interleukin-1β and inhibited the phosphorylation of Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase2 (ERK2) in the liver after bile duct ligation. Moreover, taurine zinc SDs had more potent blood lipid regulatory and anti-apoptotic effects than the physical mixture of taurine and zinc acetate. Therefore, we speculate that taurine zinc SDs protect liver function at least in part via a mechanism linked to reduce phosphorylation of JNK and ERK2, which suppresses inflammation, apoptosis and cholangiocyte proliferation during cholestasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM.

PubMed

Hayward, A R; Levy, J; Facchetti, F; Notarangelo, L; Ochs, H D; Etzioni, A; Bonnefoy, J Y; Cosyns, M; Weinberg, A

1997-01-15

We report an association between X-linked immunodeficiency with hyper-IgM (XHIM) and carcinomas affecting the liver, pancreas, biliary tree, and associated neuroectodermal endocrine cells. The tumors were fatal in eight of nine cases and in most instances were preceded by chronic cholangiopathy and/or cirrhosis. An additional group of subjects with XHIM had chronic inflammation of the liver or bile ducts but no malignancy. Many patients with XHIM were infected with cryptosporidia. CD40 is normally expressed on regenerating or inflammed bile duct epithelium. A CD40+ hepatocellular carcinoma cell line, HepG2, susceptible to cryptosporidia and CMV infection became resistant when cell surface CD40 was cross-linked by a CD40 ligand fusion protein. Apoptosis was triggered in HepG2 cells if protein synthesis was blocked by cycloheximide or if the cells were infected by cryptosporidia. Ligation of CD40 on biliary epithelium may contribute to defense against infection by intracellular pathogens. We propose that the CD40 ligand mutations that cause XHIM deprive the biliary epithelium of one line of defense against intracellular pathogens and that malignant transformation in the biliary tree follows chronic infection or inflammation. The resulting tumors may then progress without check by an effective immune response. Patients with XHIM who have abnormal liver function tests should be considered at increased risk for cholangiopathy or malignancy.

Sound propagation in and radiation from acoustically lined flow ducts: A comparison of experiment and theory

NASA Technical Reports Server (NTRS)

Plumblee, H. E., Jr.; Dean, P. D.; Wynne, G. A.; Burrin, R. H.

1973-01-01

The results of an experimental and theoretical study of many of the fundamental details of sound propagation in hard wall and soft wall annular flow ducts are reported. The theory of sound propagation along such ducts and the theory for determining the complex radiation impedance of higher order modes of an annulus are outlined, and methods for generating acoustic duct modes are developed. The results of a detailed measurement program on propagation in rigid wall annular ducts with and without airflow through the duct are presented. Techniques are described for measuring cut-on frequencies, modal phase speed, and radial and annular mode shapes. The effects of flow velocity on cut-on frequencies and phase speed are measured. Comparisons are made with theoretical predictions for all of the effects studies. The two microphone method of impedance is used to measure the effects of flow on acoustic liners. A numerical study of sound propagation in annular ducts with one or both walls acoustically lined is presented.

[Expression of calponin and P63 in human submandibular glands].

PubMed

Lu, Yu-he; Gao, Yan

2007-02-01

To observe the expression of new myoepithelial cell markers calponin and P63 in human submandibular glands. Calponin and P63 antigen in routinely processed human submandibular gland tissues were immunohistochemically demonstrated by monoclonal antibodies to calponin and P63. Calponin expressed around all acinus and intercalated ducts as linear or punctuate pattern. Positive staining was also noted in peripheral area of some thin striated ducts that connect to intercalated ducts. Subulate or trigonal calponin expression was sometimes seen between the duct dells of striated ducts. P63 expressed mainly in the nucleus of the basal cells of excretory duct. Calponin is an ideal gland. P63 labels mainly the basal cells of excretory duct. marker for myoepithelial cells of human submandibular

Widespread porokeratotic adnexal ostial nevus: clinical features and proposal of a new name unifying porokeratotic eccrine ostial and dermal duct nevus and porokeratotic eccrine and hair follicle nevus.

PubMed

Goddard, Deborah S; Rogers, Maureen; Frieden, Ilona J; Krol, Alfons L; White, Clifton R; Jayaraman, Anu G; Robinson-Bostom, Leslie; Bruckner, Anna L; Ruben, Beth S

2009-12-01

Porokeratotic eccrine ostial and dermal duct nevus and a similar condition, porokeratotic eccrine and hair follicle nevus, are rare disorders of keratinization with eccrine and hair follicle involvement. We describe the clinical features in 5 patients, all of whom had widespread skin involvement following the lines of Blaschko. Two patients presented with erosions in the newborn period as the initial manifestation of their disease; one had an associated structural anomaly, unilateral breast hypoplasia; and one adult had malignant transformation in the nevus with development of multifocal squamous cell carcinomas. Three patients had histologic involvement of both acrosyringia and acrotrichia. Based on the observation of overlapping histologic features, we propose the name "porokeratotic adnexal ostial nevus" to incorporate the previously described entities porokeratotic eccrine ostial and dermal duct nevus and porokeratotic eccrine and hair follicle nevus.

Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation.

PubMed

Omenetti, Alessia; Yang, Liu; Li, Yin-Xiong; McCall, Shannon J; Jung, Youngmi; Sicklick, Jason K; Huang, Jiawen; Choi, Steve; Suzuki, Ayako; Diehl, Anna Mae

2007-05-01

In bile duct-ligated (BDL) rodents, as in humans with chronic cholangiopathies, biliary obstruction triggers proliferation of bile ductular cells that are surrounded by fibrosis produced by adjacent myofibroblastic cells in the hepatic mesenchyme. The proximity of the myofibroblasts and cholangiocytes suggests that mesenchymal-epithelial crosstalk promotes the fibroproliferative response to cholestatic liver injury. Studying BDL mice, we found that bile duct obstruction induces activity of the Hedgehog (Hh) pathway, a system that regulates the viability and differentiation of various progenitors during embryogenesis. After BDL, many bile ductular cells and fibroblastic-appearing cells in the portal stroma express Hh ligands, receptor and/or target genes. Transwell cocultures of an immature cholangiocyte line that expresses the Hh receptor, Patched (Ptc), with liver myofibroblastic cells demonstrated that both cell types produced Hh ligands that enhanced each other's viability and proliferation. Further support for the concept that Hh signaling modulates the response to BDL was generated by studying PtcLacZ mice, which have an impaired ability to constrain Hh signaling due to a heterozygous deficiency of Ptc. After BDL, PtcLacZ mice upregulated fibrosis gene expression earlier than wild-type controls and manifested an unusually intense ductular reaction, more expanded fibrotic portal areas, and a greater number of lobular necrotic foci. Our findings reveal that adult livers resurrect developmental signaling systems, such as the Hh pathway, to guide remodeling of the biliary epithelia and stroma after cholestatic injury.

Design and performance of duct acoustic treatment

NASA Technical Reports Server (NTRS)

Motsinger, R. E.; Kraft, R. E.

1991-01-01

The procedure for designing acoustic treatment panels used to line the walls of aircraft engine ducts and for estimating the resulting suppression of turbofan engine duct noise is discussed. This procedure is intended to be used for estimating noise suppression of existing designs or for designing new acoustic treatment panels and duct configurations to achieve desired suppression levels.

Ultrastructure of the salivary glands in Lithobius forficatus (Myriapoda, Chilopoda, Lithobiidae) according to seasonal and circadian rhythms.

PubMed

Kamińska, K; Włodarczyk, A; Sonakowska, L; Ostróżka, A; Marchewka, A; Rost-Roszkowska, M

2016-11-01

The salivary glands (mandibular epidermal glands) of adult males and females of Lithobius forficatus (Myriapoda, Chilopoda) were isolated during spring, summer and autumn. In addition, the organs were isolated at different times of the day - at about 12:00 (noon) and about 00:00 (midnight). The ultrastructure of these organs depending on seasonal and circadian rhythms was analyzed using transmission and scanning electron microscopy and histochemical methods. The paired salivary glands of L. forficatus are situated in the vicinity of the foregut and they are formed by numerous acini that are surrounded by the fat body, hemocytes and tracheolae. The salivary glands are composed of a terminal acinar component and a system of tubular ducts that are lined with a cuticle. The glandular part is composed of secretory epithelial cells that are at various stages of their secretory activity. The saliva that is produced by the secretory cells of the acini is secreted into the salivary ducts, which are lined with a simple epithelium that is based on the non-cellular basal lamina. The ultrastructural variations suggest that salivary glands function differently depending on seasonal rhythms and prepare the animal for overwintering. Therefore, the salivary glands of the centipedes that were analyzed participate in the accumulation of proteins, lipids and polysaccharides during the spring, summer and autumn. Subtle differences in the ultrastructure of the secretory cells of the salivary glands during the circadian cycle must be related to the physiological reactions of the organism. The salivary ducts showed no differences in the specimens that were analyzed during the day/night cycle or during the seasonal cycle. Copyright © 2016 Elsevier Ltd. All rights reserved.

Continued Expression of GATA3 Is Necessary for Cochlear Neurosensory Development

PubMed Central

Duncan, Jeremy S.; Fritzsch, Bernd

2013-01-01

Hair cells of the developing mammalian inner ear are progressively defined through cell fate restriction. This process culminates in the expression of the bHLH transcription factor Atoh1, which is necessary for differentiation of hair cells, but not for their specification. Loss of several genes will disrupt ear morphogenesis or arrest of neurosensory epithelia development. We previously showed in null mutants that the loss of the transcription factor, Gata3, results specifically in the loss of all cochlear neurosensory development. Temporal expression of Gata3 is broad from the otic placode stage through the postnatal ear. It therefore remains unclear at which stage in development Gata3 exerts its effect. To better understand the stage specific effects of Gata3, we investigated the role of Gata3 in cochlear neurosensory specification and differentiation utilizing a LoxP targeted Gata3 line and two Cre lines. Foxg1Cre∶Gata3f/f mice show recombination of Gata3 around E8.5 but continue to develop a cochlear duct without differentiated hair cells and spiral ganglion neurons. qRT-PCR data show that Atoh1 was down-regulated but not absent in the duct whereas other hair cell specific genes such as Pou4f3 were completely absent. In addition, while Sox2 levels were lower in the Foxg1Cre:Gata3f/f cochlea, Eya1 levels remained normal. We conclude that Eya1 is unable to fully upregulate Atoh1 or Pou4f3, and drive differentiation of hair cells without Gata3. Pax2-Cre∶Gata3f/f mice show a delayed recombination of Gata3 in the ear relative to Foxg1Cre:Gata3f/f. These mice exhibited a cochlear duct containing patches of partially differentiated hair cells and developed only few and incorrectly projecting spiral ganglion neurons. Our conditional deletion studies reveal a major role of Gata3 in the signaling of prosensory genes and in the differentiation of cochlear neurosenory cells. We suggest that Gata3 may act in combination with Eya1, Six1, and Sox2 in cochlear prosensory gene signaling. PMID:23614009

Silver zeolite antimicrobial activity in aluminium heating, ventilation and air conditioning system ducts.

PubMed

Rizzetto, R; Mansi, A; Panatto, D; Rizzitelli, E; Tinteri, C; Sasso, T; Gasparini, R; Crovari, P

2008-03-01

Air pollution in confined environments is a serious health problem, in that most people spend long periods indoors (in homes, offices, classrooms etc.). Some people (children, the elderly, heart disease patients, asthmatic or allergic subjects) are at greater risk because of their conditions of frailty. The growing use of air-conditioning systems in many public and private buildings aggravates this health risk, especially when these systems are not correctly installed or regularly serviced. The aim of our study was to verify the capacity of Ag+ ions to stop the growth of bacteria and moulds inside the ducts of Heating, Ventilation and Air Conditioning system ducts (HVAC) systems when these ducts were lined with active Ag+ ions zeolite-coated panels. A Y-shaped HVAC model with two branches was used; one branch was made of traditional galvanized iron, as was the whole system, while the other was lined with active Ag+ zeolite-coated polyurethane panels. During the test, samples of dust present inside both ducts were collected and seeded in liquid and solid media to detect bacteria and moulds. The presence of bacteria was also sought in the air emerging from the outlets of both ducts. Tests made on samples of particulate collected from the two different ducts revealed a lower total bacterial load in the samples collected from the Ag+ zeolite-coated duct than in the samples from the traditional Zn galvanized duct. In addition, the values of bacterial load found in the air emerging from the Ag+ ions zeolite-lined duct were 5 times lower than those found in the air from the traditional galvanized iron duct. The utilization of Ag+ zeolite-coated panels in air-conditioning systems could improve the quality of the emerging air in comparison with traditional installations in galvanized iron. This innovation could prove particularly advantageous in the event of accidents during the installation of air-conditioning systems or of contaminated aerosols coming from outside.

[Ultrastructure of nephridial systems in cyclophyllidean cestoda: Catenotaenia pusilla (Goeze, 1782), Hymenolepis diminuta (Rudolphi, 1819) and Inermicapsifer madagascariensis (Davaine, 1870) Baer, 1956].

PubMed

Swiderski, Z; Euzet, L; Schönenberger, N

1975-01-01

Electron microscopic study of nephridial systems in three cyclophyllidean cestodes indicates a resemblance in their ultrastructure. The walls of longitudinal, transverse and collecting ducts show a very similar pattern of organization. The surface of the anucleate epithelium lining the ducts is developed into microvilli. A relatively thick layer of fibrillar tissue underlies the basal membrane of the microvillar epithelium. The nucleated portions or "pericaryons", situated between the parenchymal cells, are directly connected with epithelium by cytoplasmic prolongations. The canalicular lumen extends through a single series of cells curved into a ring. The epithelial surface of the canalicular wall is developed into short, densly staining microvilli and the immediately underlying fibrillar tissue appears very compact. The cilia were never observed in any of the above ducts. The ultrastructure of protonephridia proper is comparable with those already described in other cestodes. There is a close association between the flame-cell and the cancalicular ending, enlarged into a nephridial funnel. A single row of nephridial rods of the flame-cell is surrounded by a row of digitiform prolongations of the nephridial funnel border. The prolongations alternate with the rods and their interlocking pattern appears clearly in cross-sections. A series of minute pores or "nephrostomes" providing a direct contact between the nephridial chamber and intercellular space of the paranchyma was shown. The problem of classification and definition between the "closed" protonephridia and open metanephridia is discussed. The structural unity of protonephridia in different groupes of Platyhelminthes is reviewed. The different number of flagella within the "flames" of different cestodes is compared and analyzed. The ultrastructural characteristics of duct-wall epithelium provides some confirmation of its high metabolic activity.

27. DUCT LINES AND HOLES TO BE LEFT IN TRANSFORMER ...

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

27. DUCT LINES AND HOLES TO BE LEFT IN TRANSFORMER ROOM AND GALLERY, MENTONE, MAR. 13, 1904. R.S. MASSON, CONSULTING ELECTRICAL ENGINEER, SAN FRANCISCO AND LOS ANGELES. SCE drawing no. 52319. - Santa Ana River Hydroelectric System, SAR-3 Powerhouse, San Bernardino National Forest, Redlands, San Bernardino County, CA

Pipe crawler development for duct elbow removal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zollinger, W.T.; Treanor, R.C.

1992-01-01

This paper describes the development of equipment for removing an elbow in a 36 inch diameter ventilation line by cutting from the inside. Radiation levels, high air flow and physical constraints preclude any manual rework of the ventilation system. A remotely operated pipe crawler was developed. Testing has been performed in a full-scale mockup which models the ventilation duct configuration with the exception of radiation levels. The results gathered from the testing are discussed, and illustrate the strengths and weaknesses of the crawler and plasma arc torch system. To date, the equipment has successfully completed the tasks of maneuvering throughmore » the duct geometry, performing the two required cuts, and backing out of the duct mockup. The elbow successfully fell away from the main duct, showing that the line would be clear of obstructions.« less

Pipe crawler development for duct elbow removal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zollinger, W.T.; Treanor, R.C.

1992-11-01

This paper describes the development of equipment for removing an elbow in a 36 inch diameter ventilation line by cutting from the inside. Radiation levels, high air flow and physical constraints preclude any manual rework of the ventilation system. A remotely operated pipe crawler was developed. Testing has been performed in a full-scale mockup which models the ventilation duct configuration with the exception of radiation levels. The results gathered from the testing are discussed, and illustrate the strengths and weaknesses of the crawler and plasma arc torch system. To date, the equipment has successfully completed the tasks of maneuvering throughmore » the duct geometry, performing the two required cuts, and backing out of the duct mockup. The elbow successfully fell away from the main duct, showing that the line would be clear of obstructions.« less

A role for gamma-glutamyl transpeptidase and the amino acid transport system xc- in cystine transport by a human pancreatic duct cell line.

PubMed Central

Sweiry, J H; Sastre, J; Viña, J; Elsässer, H P; Mann, G E

1995-01-01

1. The roles of the gamma-glutamyl cycle and the anionic amino acid transport system xc- in mediating L-cystine uptake were investigated in cultured human pancreatic duct PaTu 8902 cells. This cell line exhibits morphological features of normal pancreatic duct cells and expresses gamma-glutamyl transpeptidase (gamma-GT, EC 2.3.2.2), an enzyme involved in the metabolism and regulation of intracellular glutathione (GSH). 2. Uptake of L-cystine (10 microM) was linear for up to 10 min, temperature dependent, Na+ independent, saturable (Michaelis-Menten constant (Km), 86 +/- 25 microM; maximal velocity (Vmax), 109 +/- 33 nmol (mg protein)-1 h-1) and reduced by 80-90% by a 50-fold excess concentration of L-glutamate and L-homocysteic acid, but not L-aspartate. These transport properties resemble those described for system xc-, which exchanges cystine for intracellular glutamate. 3. Acivicin, a known inhibitor of gamma-GT, decreased gamma-GT activity from 2.58 +/- 0.96 to 0.97 +/- 0.11 mU (mg protein)-1 and decreased the initial rates of L-cystine and L-glutamine uptake by 41-55%. Anthglutin (1-gamma-L-glutamyl-2-(2-carboxyphenylhyl)hydrazine), a structurally different inhibitor of gamma-GT, also caused a concentration-dependent (0.01-1 mM) decrease in gamma-GT activity and L-cystine uptake. 4. Neither acivicin nor anthglutin inhibited the uptake of L-glutamate, a poor substrate for gamma-GT. 5. In the presence of a 500-fold excess concentration of glutamate, which should abolish entry of cystine via system xc-, the remaining fraction of cystine transport was inhibited by 50% by acivicin, suggesting that transport is, in part, dependent on the activity of gamma-GT. 6. Cystine transport was also 60-80% inhibited by a series of gamma-glutamyl amino acids (5 mM) including gamma-glutamyl-glutamate, gamma-glutamyl-glutamine and gamma-glutamyl-glycine. alpha-Dipeptides inhibited cystine transport by only 6-22%. 7. These findings demonstrate that in human pancreatic duct PaTu 8902 cells, cystine uptake is mediated by system xc- (50-60%) and the gamma-glutamyl cycle. Our results provide the first evidence linking gamma-GT with cystine transport in human epithelial cells and are of relevance in view of the importance of cystine as a sulphur amino acid source for GSH synthesis in cells exposed to oxidative stress. Images Figure 1 PMID:7658371

An experimental study on neural crest migration in Barbus conchonius (Cyprinidae, Teleostei), with special reference to the origin of the enteroendocrine cells.

PubMed

Lamers, C H; Rombout, J W; Timmermans, L P

1981-04-01

A neural crest transplantation technique is described for fish. As in other classes of vertebrates, two pathways of neural crest migration can be distinguished: a lateroventral pathway between somites and ectoderm, and a medioventral pathway between somites and neural tube/notochord. In this paper evidence is presented for a neural crest origin of spinal ganglion cells and pigment cells, and indication for such an origin is obtained for sympathetic and enteric ganglion cells and for cells that are probably homologues to adrenomedullary and paraganglion cells in the future kidney area. The destiny of neural crest cells near the developing lateral-line sense organs is discussed. When grafted into the yolk, neural crest cells or neural tube cells appear to differentiate into 'periblast cells'; this suggests a highly activating influence of the yolk. Many neural crest cells are found around the urinary ducts and, when grafted below the notochord, even within the urinary duct epithelium. These neural crest cells do not invade the gut epithelium, even when grafted adjacent to the developing gut. Consequently enteroendocrine cells in fish are not likely to have a trunk- or rhombencephalic neural crest origin. Another possible origin of these cells will be proposed.

Coexistence of mucous retention cyst and basal cell adenoma arising from the lining epithelium of the cyst. Report of two cases.

PubMed

Antoniades, D; Epivatianos, A; Markopoulos, A; Kolokotronis, A; Zaraboukas, T

2009-01-01

To report 2 cases of coexisting mucous retention cyst and basal cell adenoma arising from the lining epithelium of the cyst. Two cases of painless swellings, well-demarcated, soft to palpation, and located in the submucosa of the upper lip were clinically examined with the provisional diagnosis of mucocele or salivary gland tumor. Histological examination showed the presence of a large unilocular cystic cavity in many parts surrounded by single or bilayered lining epithelium composed of flattened to cuboidal cells, and in other parts surrounded by projections of cells arranged in a trabecular pattern far into the cystic cavity. The trabeculae were composed of basal and low columnar cells that sometimes formed small duct-like structures. Immunohistochemistry showed that the lining epithelium of the cystic cavity and the cells of the projections expressed cytokeratin 7 and high-molecular-weight cytokeratins. The cells of the projections were weakly positive for S-100 protein and negative for vimentin and alpha-smooth muscle actin. Based on the results, a diagnosis of coexisting mucous retention cysts and basal cell adenomas arising from the lining epithelium of cysts was made. The coexistence of mucous retention cysts and basal cell adenomas arising from the lining epithelium of the cyst is reported. Copyright 2009 S. Karger AG, Basel.

Advances in cholangiocyte immunobiology

PubMed Central

Syal, Gaurav; Fausther, Michel

2012-01-01

Cholangiocytes, or bile duct epithelia, were once thought to be the simple lining of the conduit system comprising the intra- and extrahepatic bile ducts. Growing experimental evidence demonstrated that cholangiocytes are in fact the first line of defense of the biliary system against foreign substances. Experimental advances in recent years have unveiled previously unknown roles of cholangiocytes in both innate and adaptive immune responses. Cholangiocytes can release inflammatory modulators in a regulated fashion. Moreover, they express specialized pattern-recognizing molecules that identify microbial components and activate intracellular signaling cascades leading to a variety of downstream responses. The cytokines secreted by cholangiocytes, in conjunction with the adhesion molecules expressed on their surface, play a role in recruitment, localization, and modulation of immune responses in the liver and biliary tract. Cholangiocyte survival and function is further modulated by cytokines and inflammatory mediators secreted by immune cells and cholangiocytes themselves. Because cholangiocytes act as professional APCs via expression of major histocompatibility complex antigens and secrete antimicrobial peptides in bile, their role in response to biliary infection is critical. Finally, because cholangiocytes release mediators critical to myofibroblastic differentiation of portal fibroblasts and hepatic stellate cells, cholangiocytes may be essential in the pathogenesis of biliary cirrhosis. PMID:22961800

Advances in cholangiocyte immunobiology.

PubMed

Syal, Gaurav; Fausther, Michel; Dranoff, Jonathan A

2012-11-15

Cholangiocytes, or bile duct epithelia, were once thought to be the simple lining of the conduit system comprising the intra- and extrahepatic bile ducts. Growing experimental evidence demonstrated that cholangiocytes are in fact the first line of defense of the biliary system against foreign substances. Experimental advances in recent years have unveiled previously unknown roles of cholangiocytes in both innate and adaptive immune responses. Cholangiocytes can release inflammatory modulators in a regulated fashion. Moreover, they express specialized pattern-recognizing molecules that identify microbial components and activate intracellular signaling cascades leading to a variety of downstream responses. The cytokines secreted by cholangiocytes, in conjunction with the adhesion molecules expressed on their surface, play a role in recruitment, localization, and modulation of immune responses in the liver and biliary tract. Cholangiocyte survival and function is further modulated by cytokines and inflammatory mediators secreted by immune cells and cholangiocytes themselves. Because cholangiocytes act as professional APCs via expression of major histocompatibility complex antigens and secrete antimicrobial peptides in bile, their role in response to biliary infection is critical. Finally, because cholangiocytes release mediators critical to myofibroblastic differentiation of portal fibroblasts and hepatic stellate cells, cholangiocytes may be essential in the pathogenesis of biliary cirrhosis.

Acoustic power balance in lined ducts

NASA Technical Reports Server (NTRS)

Eversman, W.

1979-01-01

It is shown that the two common definitions of acoustic energy density and intensity in uniform unlined ducts carrying uniform flow are compatible to the extent that both energy densities can be used in an appropriate variational principle to derive the convected wave equation. When the duct walls are lined both energy densities must be modified to account for the wall energy density. This results in a new energy conservation equation which utilizes a modified definition of axial power and accounts for wall dissipation. Computations in specific cases demonstrate the validity of the modified acoustic energy relation.

Turbofan Duct Propagation Model

NASA Technical Reports Server (NTRS)

Lan, Justin H.; Posey, Joe W. (Technical Monitor)

2001-01-01

The CDUCT code utilizes a parabolic approximation to the convected Helmholtz equation in order to efficiently model acoustic propagation in acoustically treated, complex shaped ducts. The parabolic approximation solves one-way wave propagation with a marching method which neglects backwards reflected waves. The derivation of the parabolic approximation is presented. Several code validation cases are given. An acoustic lining design process for an example aft fan duct is discussed. It is noted that the method can efficiently model realistic three-dimension effects, acoustic lining, and flow within the computational capabilities of a typical computer workstation.

Aldosterone does not alter endothelin B receptor signaling in the inner medullary collecting duct.

PubMed

Ramkumar, Nirupama; Stuart, Deborah; Yang, Tianxin; Kohan, Donald E

2017-03-01

Recent studies suggest that aldosterone-mediated sulfenic acid modification of the endothelin B receptor (ETB) promotes renal injury in an ischemia/reperfusion model through reduced ETB-stimulated nitric oxide production. Similarly, aldosterone inactivation of ETB signaling promotes pulmonary artery hypertension. Consequently, we asked whether aldosterone inhibits collecting duct ETB signaling; this could promote fluid retention since CD ETB exerts natriuretic and diuretic effects. A mouse inner medullary collecting duct cell line (IMCD3) was treated with aldosterone for 48 h followed by sarafotoxin-6c, an ETB-selective agonist, and extracellular signal-related kinase 1/2 (ERK) phosphorylation assessed. S6c increased the phospho/total-ERK ratio similarly in control and aldosterone-treated cells (aldosterone alone increased phospho/total-ERK). Since cultured IMCD cell lines lack ETB inhibited AVP signaling, the effect of S6c on AVP-stimulated cAMP in acutely isolated IMCD was assessed. Rats (have much higher CD ETB expression than mice) were exposed to 3 days of a normal or low Na + diet, or low Na + diet + desoxycorticosterone acetate. S6c inhibited AVP-stimulated cAMP in rat IMCD by the same degree in the high mineralocorticoid groups compared to controls. Finally, S6c-stimulated cGMP accumulation in cultured IMCD, or S6c-stimulated nitric oxide or cGMP in acutely isolated IMCD, was not affected by prior aldosterone exposure. These findings provide evidence that aldosterone does not modify ETB effects on ERK phosphorylation, AVP-dependent cAMP inhibition, or NO/cGMP accumulation in the IMCD Thus, while aldosterone can inhibit endothelial cell ETB activity to promote hypertension and injury, this response does not appear to occur in the IMCD. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Studies on sperm storage in the vas deferens of the spinifex hopping mouse (Notomys alexis).

PubMed

Peirce, E J; Moore, H D M; Leigh, C M; Breed, W G

2003-02-01

The cauda epididymidis, with its relatively cool temperature (32-35 degrees C), is considered to be the main site of sperm storage in male mammals. However, in the adult male spinifex hopping mouse, Notomys alexis, similar numbers of spermatozoa are found in the vas deferens to those in the cauda epididymidis. The present study shows that, unlike in the laboratory mouse in which spermatozoa of the vas deferens are found mainly in the epididymal region of the duct, spermatozoa in the hopping mouse are localized mainly to the middle and urethral regions of the vas deferens which lies in the inguinal and lower abdominal region of the body cavity. After ligation of the vas deferens close to its connection with the epididymis, many spermatozoa in the vas deferens retain the potential for motility for up to 2 weeks, indicating that the viability of spermatozoa is not compromised by being restricted to core body temperature. This urethral region of the vas deferens, in which spermatozoa reside, has a highly divergent structural organization compared with that of common laboratory rodents in which there is an expanded lumen with a network of epithelial folds. Ultrastructural observations of the cells lining the duct indicate that there are not any marked differences in morphology compared with the cells lining the duct in common laboratory murids, but the infoldings of the vas deferens of the hopping mouse are highly vascular which might facilitate supply of oxygen and nutrients to the spermatozoa residing in the lumen.

Gene expression analysis of pancreatic cell lines reveals genes overexpressed in pancreatic cancer.

PubMed

Alldinger, Ingo; Dittert, Dag; Peiper, Matthias; Fusco, Alberto; Chiappetta, Gennaro; Staub, Eike; Lohr, Matthias; Jesnowski, Ralf; Baretton, Gustavo; Ockert, Detlef; Saeger, Hans-Detlev; Grützmann, Robert; Pilarsky, Christian

2005-01-01

Pancreatic cancer is one of the leading causes of cancer-related death. Using DNA gene expression analysis based on a custom made Affymetrix cancer array, we investigated the expression pattern of both primary and established pancreatic carcinoma cell lines. We analyzed the gene expression of 5 established pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-1, Capan-2 and HPAF II) and 5 primary isolates, 1 of them derived from benign pancreatic duct cells. Out of 1,540 genes which were expressed in at least 3 experiments, we found 122 genes upregulated and 18 downregulated in tumor cell lines compared to benign cells with a fold change >3. Several of the upregulated genes (like Prefoldin 5, ADAM9 and E-cadherin) have been associated with pancreatic cancer before. The other differentially regulated genes, however, play a so far unknown role in the course of human pancreatic carcinoma. By means of immunohistochemistry we could show that thymosin beta-10 (TMSB10), upregulated in tumor cell lines, is expressed in human pancreatic carcinoma, but not in non-neoplastic pancreatic tissue, suggesting a role for TMSB10 in the carcinogenesis of pancreatic carcinoma. Using gene expression profiling of pancreatic cell lines we were able to identify genes differentially expressed in pancreatic adenocarcinoma, which might contribute to pancreatic cancer development. Copyright 2005 S. Karger AG, Basel.

Mucocele of the cystic duct remnant after orthotopic liver transplant: a problem revisited.

PubMed

Chatterjee, Suvadip; Das, Debasish; Hudson, Mark; Bassendine, Margaret Fiona; Scott, John; Oppong, Kofi Ernest; Sen, Gourab; French, Jeremy J

2011-06-01

Mucocele of the cystic duct remnant is an uncommon hepatobiliary complication of a liver transplant. Current practice usually involves either excising the cystic duct, or incorporating the distal end of the transected cystic duct into the suture line of the biliary anastomosis to ensure drainage. We report a patient who developed cystic duct remnant mucocele after the latter approach was adopted. We believe that this is likely related to delayed anastomotic stricturing, which prevented draining from the remnant cystic duct. We also discuss the incidence, pathology, investigations, and treatment of this condition.

Antisense oligodeoxynucleotide to the cystic fibrosis gene inhibits anion transport in normal cultured sweat duct cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sorscher, E.J.; Kirk, K.L.; Weaver, M.L.

The authors have tested the hypothesis that the cystic fibrosis (CF) gene product, called the CF transmembrane conductance regulator (CFTR), mediates anion transport in normal human sweat duct cells. Sweat duct cells in primary culture were treated with oligodeoxynucleotides that were antisense to the CFTR gene transcript in order to block the expression of the wild-type CFTR. Anion transport in CFTR transcript antisense-treated cells was then assessed with a halide-specific dye, 6-methoxy-N-(3-sulfopropryl)quinolinium, and fluorescent digital imaging microscopy to monitor halide influx and efflux from single sweat duct cells. Antisense oligodeoxynucleotide treatment for 24 hr virtually abolished Cl{sup {minus}} transport inmore » sweat duct cells compared with untreated cells or control cells treated with sense oligodeoxynucleotides. Br{sup {minus}} uptake into sweat duct cells was also blocked after a 24-hr CFTR transcript antisense treatments, but not after treatments for only 4 hr. Lower concentrations of antisense oligodeoxynucleotides were less effective at inhibiting Cl{sup {minus}} transport. These results indicate that oligodeoxynucleotides that are antisense to CFTR transcript inhibit sweat duct Cl{sup {minus}} permeability in both a time-dependent and dose-dependent manner. This approach provides evidence that inhibition of the expression of the wild-type CFTR gene in a normal, untransfected epithelial cell results in an inhibition of Cl{sup {minus}} permeability.« less

Argon/UF6 plasma exhaust gas reconstitution experiments using preheated fluorine and on-line diagnostics. [fissioning uranium plasma core reactor design

NASA Technical Reports Server (NTRS)

Roman, W. C.

1979-01-01

The feasibility of employing a flowing, high-temperature, pure fluorine/UF6 regeneration system to efficiently convert a large fraction of the effluent plasma exhaust back to pure UF6 was demonstrated. The custom built T.O.F. mass spectrometer sampling system permitted on-line measurements of the UF6 concentration at different locations in the exhaust system. Negligible amounts ( 100 ppm) of UF6 were detected in the axial bypass exhaust duct and the exhaust ducts downstream of the cryogenic trap system used to collect the UF6, thus verifying the overall system efficiency over a range of operating conditions. Use of a porous Monel duct as part of the exhaust duct system, including provision for injection of pure fluorine, provided a viable technique to eliminate uranium compound residue on the inside surface of the exhaust ducts. Typical uranium compound mass deposition per unit area of duct was 2 micron g/sq cm. This porous duct technique is directly applicable to future uranium compound transfer exhaust systems. Throughout these experiments, additional basic data on the corrosion aspects of hot, pressurized UF6/fluorine were also accumulated.

Enhanced cytotoxic activity of effector T-cells against cholangiocarcinoma by dendritic cells pulsed with pooled mRNA.

PubMed

Junking, Mutita; Grainok, Janya; Thepmalee, Chutamas; Wongkham, Sopit; Yenchitsomanus, Pa-Thai

2017-10-01

Cholangiocarcinoma is a malignancy of bile duct epithelia with an increasing in incidence rate worldwide. Surgery is the only curative treatment, while adjuvant chemotherapy and radiotherapy render poor responses. Cell-based immunotherapy is a potential strategy for cholangiocarcinoma treatment. However, variation of tumor antigens in cholangiocarcinoma leads to the ineffectiveness of cell-based immunotherapy. In this study, we examined the activation of effector T-cells by dendritic cells pulsed with protein lysate or total RNA from cholangiocarcinoma cell lines for their cytolytic activity against cholangiocarcinoma. Broad-spectrum antigen types with respect to RNA antigen sources were obtained from combination of three cholangiocarcinoma cell lines (KKU-213, KKU-100, and KKU-055). Compared with protein lysate-pulsed dendritic cells, total RNA-pulsed dendritic cells induced anti-tumor effector T-cell response with higher killing ability to KKU-100 and KKU-213 cells compared with protein lysate-pulsed dendritic cells. Moreover, pooled messenger RNA from three cholangiocarcinoma cell lines significantly increased the specific killing capacity of activated lymphocytes against KKU-213 cells. These results suggest that activation of anti-tumor effector T-cells against cholangiocarcinoma by RNA-pulsed dendritic cells is more effective than that by protein lysate-pulsed dendritic cells. In addition, pulsing dendritic cells with pooled messenger RNA from multiple cell lines enhanced the efficacy of a cellular immune response against cholangiocarcinoma.

Flat Epithelial Atypia of the Breast.

PubMed

Collins, Laura C

2009-06-01

Lesions of the breast characterized by enlarged terminal duct lobular units lined by columnar epithelial cells are being encountered increasingly in breast biopsy specimens. Some of these lesions feature cuboidal to columnar epithelial cells in which the lining cells exhibit cytologic atypia. The role of these lesions (recently designated "flat epithelial atypia" [FEA]) in breast tumor progression is still emerging. FEA commonly coexists with well-developed examples of atypical ductal hyperplasia, low-grade ductal carcinoma in situ, lobular neoplasia, and tubular carcinoma. These findings and those of recent genetic studies suggest that FEA is a neoplastic lesion that may represent a precursor to or the earliest morphologic manifestation of ductal carcinoma in situ. Additional studies are needed to better understand the biologic nature and clinical significance of these lesions. Copyright © 2009 Elsevier Inc. All rights reserved.

Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells.

PubMed

Zhou, Junnian; Zhao, Lei; Qin, Lipeng; Wang, Jing; Jia, Yali; Yao, Hailei; Sang, Chen; Hu, Qinghua; Shi, Shuangshuang; Nan, Xue; Yue, Wen; Zhuang, Fengyuan; Yang, Chun; Wang, Yunfang; Pei, Xuetao

2010-03-17

Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bile duct formation (DF) from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bile duct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bile ducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3alpha and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, beta1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bile duct formation, during which determination of MO plays a crucial role.

Cell-specific Expression of CYP2A5 in the Mouse Respiratory Tract: Effects of Olfactory Toxicants

PubMed Central

Piras, Elena; Franzén, Anna; Fernández, Estíbaliz L.; Bergström, Ulrika; Raffalli-Mathieu, Françoise; Lang, Matti; Brittebo, Eva B.

2003-01-01

We performed a detailed analysis of mouse cytochrome P450 2A5 (CYP2A5) expression by in situ hybridization (ISH) and immunohistochemistry (IHC) in the respiratory tissues of mice. The CYP2A5 mRNA and the corresponding protein co-localized at most sites and were predominantly detected in the olfactory region, with an expression in sustentacular cells, Bowman's gland, and duct cells. In the respiratory and transitional epithelium there was no or only weak expression. The nasolacrimal duct and the excretory ducts of nasal and salivary glands displayed expression, whereas no expression occurred in the acini. There was decreasing expression along the epithelial linings of the trachea and lower respiratory tract, whereas no expression occurred in the alveoli. The hepatic CYP2A5 inducers pyrazole and phenobarbital neither changed the CYP2A5 expression pattern nor damaged the olfactory mucosa. In contrast, the olfactory toxicants dichlobenil and methimazole induced characteristic changes. The damaged Bowman's glands displayed no expression, whereas the damaged epithelium expressed the enzyme. The CYP2A5 expression pattern is in accordance with previously reported localization of protein and DNA adducts and the toxicity of some CYP2A5 substrates. This suggests that CYP2A5 is an important determinant for the susceptibility of the nasal and respiratory epithelia to protoxicants and procarcinogens. PMID:14566026

Duct modes damping through an adjustable electroacoustic liner under grazing incidence

NASA Astrophysics Data System (ADS)

Boulandet, R.; Lissek, H.; Karkar, S.; Collet, M.; Matten, G.; Ouisse, M.; Versaevel, M.

2018-07-01

This paper deals with active sound attenuation in lined ducts with flow and its application to duct modes damping in aircraft engine nacelles. It presents an active lining concept based on an arrangement of electroacoustic absorbers flush mounted in the duct wall. Such feedback-controlled loudspeaker membranes are used to achieve locally reacting impedances with adjustable resistance and reactance. A broadband impedance model is formulated from the loudspeaker parameters and a design procedure is proposed to achieve specified acoustic resistances and reactances. The performance is studied for multimodal excitation by simulation using the finite element method and the results are compared to measurements made in a flow duct facility. This electroacoustic liner has an attenuation potential comparable to that of a conventional passive liner, but also offers greater flexibility to achieve the target acoustic impedance in the low frequencies. In addition, it is adaptive in real time to track variable engine speeds. It is shown with the liner prototype that the duct modes can be attenuated over a bandwidth of two octaves around the resonance frequency of the loudspeakers.

Scribble Modulates the MAPK/Fra1 Pathway to Disrupt Luminal and Ductal Integrity and Suppress Tumour Formation in the Mammary Gland

PubMed Central

Godde, Nathan J.; Sheridan, Julie M.; Smith, Lorey K.; Pearson, Helen B.; Britt, Kara L.; Galea, Ryan C.; Yates, Laura L.; Visvader, Jane E.; Humbert, Patrick O.

2014-01-01

Polarity coordinates cell movement, differentiation, proliferation and apoptosis to build and maintain complex epithelial tissues such as the mammary gland. Loss of polarity and the deregulation of these processes are critical events in malignant progression but precisely how and at which stage polarity loss impacts on mammary development and tumourigenesis is unclear. Scrib is a core polarity regulator and tumour suppressor gene however to date our understanding of Scrib function in the mammary gland has been limited to cell culture and transplantation studies of cell lines. Utilizing a conditional mouse model of Scrib loss we report for the first time that Scrib is essential for mammary duct morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a critical and specific role for Scribble in the control of the early steps of breast cancer progression. In particular, Scrib-deficiency significantly induced Fra1 expression and basal progenitor clonogenicity, which resulted in fully penetrant ductal hyperplasia characterized by high cell turnover, MAPK hyperactivity, frank polarity loss with mixing of apical and basolateral membrane constituents and expansion of atypical luminal cells. We also show for the first time a role for Scribble in mammalian spindle orientation with the onset of mammary hyperplasia being associated with aberrant luminal cell spindle orientation and a failure to apoptose during the final stage of duct tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib-hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and increased the incidence, onset and grade of mammary tumours. These findings, based on a definitive genetic mouse model provide fundamental insights into mammary duct maturation and homeostasis and reveal that Scrib loss activates a MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy and accelerate tumour progression. PMID:24852022

A Minireview on Vasopressin-regulated Aquaporin-2 in Kidney Collecting Duct Cells.

PubMed

Park, Eui-Jung; Kwon, Tae-Hwan

2015-06-01

The kidney collecting duct is an important renal tubular segment for the regulation of body water and salt homeostasis. Water reabsorption in the collecting duct cells is regulated by arginine vasopressin (AVP) via the vasopressin V2-receptor (V2R). AVP increases the osmotic water permeability of the collecting duct cells through aquaporin-2 (AQP2) and aquaporin-3 (AQP3). AVP induces the apical targeting of AQP2 and transcription of AQP2 gene in the kidney collecting duct principal cells. The signaling transduction pathways resulting in the AQP2 trafficking to the apical plasma membrane of the collecting duct principal cells, include AQP2 phosphorylation, RhoA phosphorylation, actin depolymerization and calcium mobilization, and the changes of AQP2 protein abundance in water balance disorders have been extensively studied. These studies elucidate the underlying cellular and molecular mechanisms of body water homeostasis and provide the basis for the treatment of body water balance disorders.

An improved multimodal method for sound propagation in nonuniform lined ducts.

PubMed

Bi, WenPing; Pagneux, Vincent; Lafarge, Denis; Aurégan, Yves

2007-07-01

An efficient method is proposed for modeling time harmonic acoustic propagation in a nonuniform lined duct without flow. The lining impedance is axially segmented uniform, but varies circumferentially. The sound pressure is expanded in term of rigid duct modes and an additional function that carries the information about the impedance boundary. The rigid duct modes and the additional function are known a priori so that calculations of the true liner modes, which are difficult, are avoided. By matching the pressure and axial velocity at the interface between different uniform segments, scattering matrices are obtained for each individual segment; these are then combined to construct a global scattering matrix for multiple segments. The present method is an improvement of the multimodal propagation method, developed in a previous paper [Bi et al., J. Sound Vib. 289, 1091-1111 (2006)]. The radial rate of convergence is improved from O(n(-2)), where n is the radial mode indices, to O(n(-4)). It is numerically shown that using the present method, acoustic propagation in the nonuniform lined intake of an aeroengine can be calculated by a personal computer for dimensionless frequency K up to 80, approaching the third blade passing frequency of turbofan noise.

Functional characterization of the vertebrate primary ureter: Structure and ion transport mechanisms of the pronephric duct in axolotl larvae (Amphibia)

PubMed Central

2010-01-01

Background Three kidney systems appear during vertebrate development: the pronephroi, mesonephroi and metanephroi. The pronephric duct is the first or primary ureter of these kidney systems. Its role as a key player in the induction of nephrogenic mesenchyme is well established. Here we investigate whether the duct is involved in urine modification using larvae of the freshwater amphibian Ambystoma mexicanum (axolotl) as model. Results We investigated structural as well as physiological properties of the pronephric duct. The key elements of our methodology were: using histology, light and transmission electron microscopy as well as confocal laser scanning microscopy on fixed tissue and applying the microperfusion technique on isolated pronephric ducts in combination with single cell microelectrode impalements. Our data show that the fully differentiated pronephric duct is composed of a single layered epithelium consisting of one cell type comparable to the principal cell of the renal collecting duct system. The cells are characterized by a prominent basolateral labyrinth and a relatively smooth apical surface with one central cilium. Cellular impalements demonstrate the presence of apical Na+ and K+ conductances, as well as a large K+ conductance in the basolateral cell membrane. Immunolabeling experiments indicate heavy expression of Na+/K+-ATPase in the basolateral labyrinth. Conclusions We propose that the pronephric duct is important for the subsequent modification of urine produced by the pronephros. Our results indicate that it reabsorbs sodium and secretes potassium via channels present in the apical cell membrane with the driving force for ion movement provided by the Na+/K+ pump. This is to our knowledge the first characterization of the pronephric duct, the precursor of the collecting duct system, which provides a model of cell structure and basic mechanisms for ion transport. Such information may be important in understanding the evolution of vertebrate kidney systems and human diseases associated with congenital malformations. PMID:20507566

Plaster core washout tool

NASA Technical Reports Server (NTRS)

Heisman, R. M.; Keir, A. R.; Teramura, K.

1977-01-01

Tool powered by pressurized water or air removes water soluble plaster lining from Kevlar/epoxy duct. Rotating plastic cutterhead with sealed end fitting connects flexible shaft that allows tool to be used with curved ducts.

Generation and characterization of p53 null transformed hepatic progenitor cells: oval cells give rise to hepatocellular carcinoma.

PubMed

Dumble, Melissa L; Croager, Emma J; Yeoh, George C T; Quail, Elizabeth A

2002-03-01

Oval cells are bipotential liver stem cells able to differentiate into hepatocytes and bile duct epithelia. In normal adult liver oval cells are quiescent, existing in low numbers around the periportal region, and proliferate following severe, prolonged liver trauma. There is evidence implicating oval cells in the development of hepatocellular carcinoma, and hence the availability of an immortalized oval cell line would be invaluable for the study of liver cell lineage differentiation and carcinogenesis. A novel approach in the generation of cell lines is the use of the p53 knockout mouse. Absence of p53 allows a cell to cycle past the normal Hayflick limit, rendering it immortalized, although subsequent genetic alterations are thought necessary for transformation. p53 knockout mice were fed a choline-deficient, ethionine-supplemented diet, previously shown to increase oval cell numbers in wild-type mice. The oval cells were isolated by centrifugal elutriation and maintained in culture. Colonies of hepatic cells were isolated and characterized with respect to phenotype, growth characteristics and tumorigenicity. Analysis of gene expression by Northern blotting and immunocytochemistry suggests they are oval-like cells by virtue of albumin and transferrin expression, as well as the oval cell markers alpha fetoprotein, M(2)-pyruvate kinase and A6. Injection into athymic nude mice shows the cell lines are capable of forming tumors which phenotypically resemble hepatocellular carcinoma. Thus, the use of p53 null hepatic cells successfully generated immortalized and tumorigenic hepatic stem cell lines. The results presented support the idea that deleting p53 allows immortalization and contributes to the transformation of the oval-like cell lines. Further, the tumorigenic status of the cell lines is direct evidence for the participation of oval cells in the formation of hepatocellular carcinoma.

Extracellular Ca2+ Sensing in Salivary Ductal Cells*

PubMed Central

Bandyopadhyay, Bidhan C.; Swaim, William D.; Sarkar, Ankana; Liu, Xibao; Ambudkar, Indu S.

2012-01-01

Ca2+ is secreted from the salivary acinar cells as an ionic constituent of primary saliva. Ions such as Na+ and Cl− get reabsorbed whereas primary saliva flows through the salivary ductal system. Although earlier studies have shown that salivary [Ca2+] decreases as it flows down the ductal tree into the oral cavity, ductal reabsorption of Ca2+ remains enigmatic. Here we report a potential role for the G protein-coupled receptor, calcium-sensing receptor (CSR), in the regulation of Ca2+ reabsorption by salivary gland ducts. Our data show that CSR is present in the apical region of ductal cells where it is co-localized with transient receptor potential canonical 3 (TRPC3). CSR is activated in isolated salivary gland ducts as well as a ductal cell line (SMIE) by altering extracellular [Ca2+] or by aromatic amino acid, l-phenylalanine (l-Phe, endogenous component of saliva), as well as neomycin. CSR activation leads to Ca2+ influx that, in polarized cells grown on a filter support, is initiated in the luminal region. We show that TRPC3 contributes to Ca2+ entry triggered by CSR activation. Further, stimulation of CSR in SMIE cells enhances the CSR-TRPC3 association as well as surface expression of TRPC3. Together our findings suggest that CSR could serve as a Ca2+ sensor in the luminal membrane of salivary gland ducts and regulate reabsorption of [Ca2+] from the saliva via TRPC3, thus contributing to maintenance of salivary [Ca2+]. CSR could therefore be a potentially important protective mechanism against formation of salivary gland stones (sialolithiasis) and infection (sialoadenitis). PMID:22778254

Molecular characteristics and alterations during early development of the human vagina

PubMed Central

Fritsch, Helga; Richter, Elisabeth; Adam, Nadia

2012-01-01

Unresolved questions remain concerning the derivation of the vagina with respect to the relative contributions from the Müllerian ducts, the urogenital sinus, and the Wolffian ducts. Recent molecular and cellular studies in rodents have opened up a large gap between the level of understanding of vaginal development in mice and understanding of human vaginal development, which is based on histology. To compare the findings in mice with human vaginal development and to address this gap, we analysed molecular characteristics of the urogenital sinus, Wolffian ducts, and Müllerian ducts in 8–14-week-old human specimens using immunohistochemical methods. The monoclonal antibodies used were directed against cytokeratin (CK) 14, CK19, vimentin, laminin, p63, E-cadherin, caspase-3, Ki67, HOX A13, and BMP-4. The immunohistochemical analysis revealed that, during weeks 8–9, the epithelium of the Müllerian ducts became positive for p63 as p63-positive cells that originated from the sinus epithelium reached the caudal tip of the fused Müllerian ducts via the Wolffian ducts. The lumen of the fused Müllerian ducts was closed by an epithelial plug that contained both vimentin-positive and vimentin-negative cells. Subsequently, the resulting epithelial tube enlarged by proliferation of basal p63-positive cells. The first signs of squamous differentiation were detected during week 14, with the appearance of CK14-positive cells. According to our results, all three components, namely, the urogenital sinus, Wolffian ducts, and Müllerian ducts, interacted during the formation of the human vagina. The sinus epithelium provided p63-positive cells, the Wollfian ducts acted as a ‘transporter’, and the Müllerian ducts contributed the guiding structure for the vaginal anlagen. Epithelial differentiation began at the end of the period studied and extended in a caudo-cranial direction. The present study is one of the first to provide up-to-date molecular correlates for human vaginal development that can be compared with the results of cell biological studies in rodents. PMID:22256858

Methods for the calculation of axial wave numbers in lined ducts with mean flow

NASA Technical Reports Server (NTRS)

Eversman, W.

1981-01-01

A survey is made of the methods available for the calculation of axial wave numbers in lined ducts. Rectangular and circular ducts with both uniform and non-uniform flow are considered as are ducts with peripherally varying liners. A historical perspective is provided by a discussion of the classical methods for computing attenuation when no mean flow is present. When flow is present these techniques become either impractical or impossible. A number of direct eigenvalue determination schemes which have been used when flow is present are discussed. Methods described are extensions of the classical no-flow technique, perturbation methods based on the no-flow technique, direct integration methods for solution of the eigenvalue equation, an integration-iteration method based on the governing differential equation for acoustic transmission, Galerkin methods, finite difference methods, and finite element methods.

Mechanosensation and the Primary Cilium

NASA Astrophysics Data System (ADS)

Glaser, Joseph; Resnick, Andrew

2010-10-01

The primary cilium has come under increased scrutiny as a site for mechano- and chemosensation by cells. We have undertaken a program of study using mouse renal cell lines from the cortical collecting duct to quantify how mechanical forces arising from fluid shear are transduced into cellular responses. Fluid flow through a model nephron has been analyzed to determine the in vivo forces. A novel tissue culture flow chamber permitting accurate reproduction of physiologically relevant conditions has been calibrated. We have determined that in vivo conditions can be accurately modeled in our flow chamber.

Subnormothermic ex vivo liver perfusion reduces endothelial cell and bile duct injury after donation after cardiac death pig liver transplantation.

PubMed

Knaak, Jan M; Spetzler, Vinzent N; Goldaracena, Nicolas; Boehnert, Markus U; Bazerbachi, Fateh; Louis, Kristine S; Adeyi, Oyedele A; Minkovich, Leonid; Yip, Paul M; Keshavjee, Shaf; Levy, Gary A; Grant, David R; Selzner, Nazia; Selzner, Markus

2014-11-01

An ischemic-type biliary stricture (ITBS) is a common feature after liver transplantation using donation after cardiac death (DCD) grafts. We compared sequential subnormothermic ex vivo liver perfusion (SNEVLP; 33°C) with cold storage (CS) for the prevention of ITBS in DCD liver grafts in pig liver transplantation (n = 5 for each group). Liver grafts were stored for 10 hours at 4°C (CS) or preserved with combined 7-hour CS and 3-hour SNEVLP. Parameters of hepatocyte [aspartate aminotransferase (AST), international normalized ratio (INR), factor V, and caspase 3 immunohistochemistry], endothelial cell (EC; CD31 immunohistochemistry and hyaluronic acid), and biliary injury and function [alkaline phosphatase (ALP), total bilirubin, and bile lactate dehydrogenase (LDH)] were determined. Long-term survival (7 days) after transplantation was similar between the SNEVLP and CS groups (60% versus 40%, P = 0.13). No difference was observed between SNEVLP- and CS-treated animals with respect to the peak of serum INR, factor V, or AST levels within 24 hours. CD31 staining 8 hours after transplantation demonstrated intact EC lining in SNEVLP-treated livers (7.3 × 10(-4) ± 2.6 × 10(-4) cells/μm(2)) but not in CS-treated livers (3.7 × 10(-4) ± 1.3 × 10(-4) cells/μm(2) , P = 0.03). Posttransplant SNEVLP animals had decreased serum ALP and serum bilirubin levels in comparison with CS animals. In addition, LDH in bile fluid was lower in SNEVLP pigs versus CS pigs (14 ± 10 versus 60 ± 18 μmol/L, P = 0.02). Bile duct histology revealed severe bile duct necrosis in 3 of 5 animals in the CS group but none in the SNEVLP group (P = 0.03). Sequential SNEVLP preservation of DCD grafts reduces bile duct and EC injury after liver transplantation. © 2014 American Association for the Study of Liver Diseases.

Flow duct for nuclear reactors

DOEpatents

Straalsund, Jerry L.

1978-01-01

Improved liquid sodium flow ducts for nuclear reactors are described wherein the improvement comprises varying the wall thickness of each of the walls of a polygonal tubular duct structure so that each of the walls is of reduced cross-section along the longitudinal center line and of a greater cross-section along wall junctions with the other walls to form the polygonal tubular configuration.

Prediction of Breast Cancer Risk by Aberrant Methylation in Mammary Duct Lavage

DTIC Science & Technology

2006-07-01

Assessment of breast epithelial cells obtained by nipple duct lavage (NDL) may have value for breast cancer risk stratification. NDL was performed in 150...contribute to risk stratification. 15. SUBJECT TERMS breast cancer, DNA methylation, Methylation Specific PCR, Nipple Duct Lavage, Risk assessment 16...carcinogenesis. Nipple duct lavage (NDL) is a minimally invasive approach for obtaining breast epithelial cells. Cytological atypia identified in nipple

Localization and in-Vivo Characterization of Thapsia garganica CYP76AE2 Indicates a Role in Thapsigargin Biosynthesis1

PubMed Central

Andersen, Trine Bundgaard; Martinez-Swatson, Karen Agatha; Rasmussen, Silas Anselm; Boughton, Berin Alain; Jørgensen, Kirsten; Andersen-Ranberg, Johan; Nyberg, Nils; Christensen, Søren Brøgger; Simonsen, Henrik Toft

2017-01-01

The Mediterranean plant Thapsia garganica (dicot, Apiaceae), also known as deadly carrot, produces the highly toxic compound thapsigargin. This compound is a potent inhibitor of the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase calcium pump in mammals and is of industrial importance as the active moiety of the anticancer drug mipsagargin, currently in clinical trials. Knowledge of thapsigargin in planta storage and biosynthesis has been limited. Here, we present the putative second step in thapsigargin biosynthesis, by showing that the cytochrome P450 TgCYP76AE2, transiently expressed in Nicotiana benthamiana, converts epikunzeaol into epidihydrocostunolide. Furthermore, we show that thapsigargin is likely to be stored in secretory ducts in the roots. Transcripts from TgTPS2 (epikunzeaol synthase) and TgCYP76AE2 in roots were found only in the epithelial cells lining these secretory ducts. This emphasizes the involvement of these cells in the biosynthesis of thapsigargin. This study paves the way for further studies of thapsigargin biosynthesis. PMID:28275147

Alkaline pH induces IRR-mediated phosphorylation of IRS-1 and actin cytoskeleton remodeling in a pancreatic beta cell line.

PubMed

Deyev, Igor E; Popova, Nadezhda V; Serova, Oxana V; Zhenilo, Svetlana V; Regoli, Marì; Bertelli, Eugenio; Petrenko, Alexander G

2017-07-01

Secretion of mildly alkaline (pH 8.0-8.5) juice to intestines is one of the key functions of the pancreas. Recent reports indicate that the pancreatic duct system containing the alkaline juice may adjoin the endocrine cells of pancreatic islets. We have previously identified the insulin receptor-related receptor (IRR) that is expressed in islets as a sensor of mildly alkaline extracellular media. In this study, we show that those islet cells that are in contact with the excretory ducts are also IRR-expressing cells. We further analyzed the effects of alkaline media on pancreatic beta cell line MIN6. Activation of endogenous IRR but not of the insulin receptor was detected that could be inhibited with linsitinib. The IRR autophosphorylation correlated with pH-dependent linsitinib-sensitive activation of insulin receptor substrate 1 (IRS-1), the primary adaptor in the insulin signaling pathway. However, in contrast with insulin stimulation, no protein kinase B (Akt/PKB) phosphorylation was detected as a result of alkali treatment. We observed overexpression of several early response genes (EGR2, IER2, FOSB, EGR1 and NPAS4) upon alkali treatment of MIN6 cells but those were IRR-independent. The alkaline medium but not insulin also triggered actin cytoskeleton remodeling that was blocked by pre-incubation with linsitinib. We propose that the activation of IRR by alkali might be part of a local loop of signaling between the exocrine and endocrine parts of the pancreas where alkalinization of the juice facilitate insulin release that increases the volume of secreted juice to control its pH and bicabonate content. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Effects of partial portal vein arterialization on the hilar bile duct in a rat model.

PubMed

Guo, Shao-Hua; Li, Chong-Hui; Chen, Yong-Liang; Song, Jian-Ning; Zhang, Ai-Qun; Zhou, Cheng

2011-10-01

Liver revascularization is frequently required during the enlarged radical operation for hilar cholangiocarcinoma involving the hepatic artery. Researchers have carried out a number of experiments applying partial portal vein arterialization (PVA) in clinical practice. In this study we aimed to establish a theoretical basis for clinical application of partial PVA and to investigate the effects of partial PVA on rat hilar bile duct and hepatic functions. Thirty rats were randomly and equally assigned into 3 groups: control (group A), hepatic artery ligation+bile duct recanalization (group B), and partial PVA+bile duct recanalization (group C). Proliferation and apoptosis of rat hilar bile duct epithelial cells, arteriolar counts of the peribiliary plexus (PBP) of the bile duct wall, changes in serum biochemistry, and pathologic changes in the bile duct were assessed 1 month after operation. The proliferation of hilar bile duct epithelial cells in group B was greater than in groups A and C (P<0.01). No apoptotic hilar bile duct epithelial cells were detected in any of the groups. The PBP arteriolar counts of the hilar bile duct wall were similar in groups A and C (P>0.05), but the count was lower in group B than in group A (P<0.01). No statistically significant differences in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin were found in the 3 groups. The gamma-glutamyltransferase value was higher in group B than in groups A and C (P<0.01). The hepatic tissues of groups A and C showed no significant abnormality. Chronic inflammatory changes in the hilar bile duct walls were observed only in group B. Partial PVA can restore the arterial blood supply of the hilar bile duct and significantly extenuate the injury to hilar bile duct epithelial cells resulting from hepatic artery ligation.

HDAC gene expression in pancreatic tumor cell lines following treatment with the HDAC inhibitors panobinostat (LBH589) and trichostatine (TSA).

PubMed

Mehdi, Ouaïssi; Françoise, Silvy; Sofia, Costa Lima; Urs, Giger; Kevin, Zemmour; Bernard, Sastre; Igor, Sielezneff; Anabela, Cordeiro-da-Silva; Dominique, Lombardo; Eric, Mas; Ali, Ouaïssi

2012-01-01

In this study, the effect of LBH589 and trichostatin (TSA), a standard histone deacetylase inhibitor (HDACi) toward the growth of pancreatic cancer cell lines was studied. Thus, we examined for the first time, the HDAC family gene expression levels before and after drug treatment. Several human pancreatic cancer cell lines (Panc-1, BxPC-3, SOJ-6) and a normal human pancreatic duct immortalized epithelial cell line (HPDE/E6E7) were used as target cells. The cell growth was measured by MTT assay, cell cycle alteration, membrane phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane potential loss, RT-PCR and Western blots were done using standard methods. The effect of drugs on tumor growth in vivo was studied using subcutaneous xenograft model. Except in the case of certain HDAC gene/tumor cell line couples: (SIRT1/HPDE-SOJ6/TSA- or LBH589-treated cells; LBH589-treated Panc-1 Cells; HDAC2/BxPC-3/LBH589-treated cells or TSA-treated SOJ-6-1 cells), there were no major significant changes of HDACs genes transcription in cells upon drug treatment. However, significant variation in HDACs and SIRTs protein expression levels could be seen among individual cell samples. The in vivo results showed that LBH589 formulation exhibited similar tumor reduction efficacy as the commercial drug gemcitabine. Our data demonstrate that LBH589 induced the death of pancreatic tumor cell by apoptosis. In line with its in vitro activity, LBH589 achieved a significant reduction in tumor growth in BxPC-3 pancreatic tumor cell line subcutaneous xenograft mouse model. Furthermore, exploring the impact of LBH589 on HDACs encoding genes expression revealed for the first time that some of them, depending on the cell line considered, seem to be regulated during translation. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Fumigation of a laboratory-scale HVAC system with hydrogen peroxide for decontamination following a biological contamination incident.

PubMed

Meyer, K M; Calfee, M W; Wood, J P; Mickelsen, L; Attwood, B; Clayton, M; Touati, A; Delafield, R

2014-03-01

To evaluate hydrogen peroxide vapour (H2 O2 ) for its ability to inactivate Bacillus spores within a laboratory-scale heating, ventilation and air-conditioning (HVAC) duct system. Experiments were conducted in a closed-loop duct system, constructed of either internally lined or unlined galvanized metal. Bacterial spores were aerosol-deposited onto 18-mm-diameter test material coupons and strategically placed at several locations within the duct environment. Various concentrations of H2 O2 and exposure times were evaluated to determine the sporicidal efficacy and minimum exposure needed for decontamination. For the unlined duct, high variability was observed in the recovery of spores between sample locations, likely due to complex, unpredictable flow patterns within the ducts. In comparison, the lined duct exhibited a significant desorption of the H2 O2 following the fumigant dwell period and thus resulted in complete decontamination at all sampling locations. These findings suggest that decontamination of Bacillus spore-contaminated unlined HVAC ducts by hydrogen peroxide fumigation may require more stringent conditions (higher concentrations, longer dwell duration) than internally insulated ductwork. These data may help emergency responders when developing remediation plans during building decontamination. © 2013 The Society for Applied Microbiology This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Amphiregulin mediates self-renewal in an immortal mammary epithelial cell line with stem cell characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Booth, Brian W., E-mail: brbooth@clemson.edu; Institute for Biological Interfaces of Engineering, Clemson University, Clemson, SC 29634; Boulanger, Corinne A.

2010-02-01

Amphiregulin (AREG), a ligand for epidermal growth factor receptor, is required for mammary gland ductal morphogenesis and mediates estrogen actions in vivo, emerging as an essential growth factor during mammary gland growth and differentiation. The COMMA-D {beta}-geo (CD{beta}geo) mouse mammary cell line displays characteristics of normal mammary progenitor cells including the ability to regenerate a mammary gland when transplanted into the cleared fat pad of a juvenile mouse, nuclear label retention, and the capacity to form anchorage-independent mammospheres. We demonstrate that AREG is essential for formation of floating mammospheres by CD{beta}geo cells and that the mitogen activated protein kinase signalingmore » pathway is involved in AREG-mediated mammosphere formation. Addition of exogenous AREG promotes mammosphere formation in cells where AREG expression is knocked down by siRNA and mammosphere formation by AREG{sup -/-} mammary epithelial cells. AREG knockdown inhibits mammosphere formation by duct-limited mammary progenitor cells but not lobule-limited mammary progenitor cells. These data demonstrate AREG mediates the function of a subset of mammary progenitor cells in vitro.« less

Amphiregulin mediates self-renewal in an immortal mammary epithelial cell line with stem cell characteristics.

PubMed

Booth, Brian W; Boulanger, Corinne A; Anderson, Lisa H; Jimenez-Rojo, Lucia; Brisken, Cathrin; Smith, Gilbert H

2010-02-01

Amphiregulin (AREG), a ligand for epidermal growth factor receptor, is required for mammary gland ductal morphogenesis and mediates estrogen actions in vivo, emerging as an essential growth factor during mammary gland growth and differentiation. The COMMA-D beta-geo (CDbetageo) mouse mammary cell line displays characteristics of normal mammary progenitor cells including the ability to regenerate a mammary gland when transplanted into the cleared fat pad of a juvenile mouse, nuclear label retention, and the capacity to form anchorage-independent mammospheres. We demonstrate that AREG is essential for formation of floating mammospheres by CDbetageo cells and that the mitogen activated protein kinase signaling pathway is involved in AREG-mediated mammosphere formation. Addition of exogenous AREG promotes mammosphere formation in cells where AREG expression is knocked down by siRNA and mammosphere formation by AREG(-/-) mammary epithelial cells. AREG knockdown inhibits mammosphere formation by duct-limited mammary progenitor cells but not lobule-limited mammary progenitor cells. These data demonstrate AREG mediates the function of a subset of mammary progenitor cells in vitro. Copyright 2009 Elsevier Inc. All rights reserved.

Fuel cell stack arrangements

DOEpatents

Kothmann, Richard E.; Somers, Edward V.

1982-01-01

Arrangements of stacks of fuel cells and ducts, for fuel cells operating with separate fuel, oxidant and coolant streams. An even number of stacks are arranged generally end-to-end in a loop. Ducts located at the juncture of consecutive stacks of the loop feed oxidant or fuel to or from the two consecutive stacks, each individual duct communicating with two stacks. A coolant fluid flows from outside the loop, into and through cooling channels of the stack, and is discharged into an enclosure duct formed within the loop by the stacks and seals at the junctures at the stacks.

A new species of myxosporean (Sphaeromyxidae), a parasite of lined seahorses, Hippocampus erectus, from the Gulf of Mexico.

PubMed

Sears, B F; Anderson, P; Greiner, E C

2011-08-01

Sphaeromyxa cannolii sp. n. is described from the bile ducts of aquaria-maintained lined seahorses (Hippocampus erectus) from the Gulf of Mexico. Spores of the new species are linear, 17-18 µm long and 5-6 µm wide, with flattened tips; polar capsules measure 4 × 3 µm. Routine necropsies of H. erectus following planned death revealed liver inflammation, bile duct obstruction, bile accumulation, and myxozoan parasites in the bile ducts of 11 of 40 animals sampled (27.5%). The presence of S. cannolii in an aquaculture setting should prompt keepers to carefully quarantine new animals and exclude annelid fauna, a potential intermediate host of myxozoans.

An experimental investigation of sound radiation from a duct with a circumferentially varying liner

NASA Technical Reports Server (NTRS)

Fuller, C. R.; Silcox, R. J.

1983-01-01

The radiation of sound from an asymmetrically lined duct is experimentally studied for various hard-walled standing mode sources. Measurements were made of the directivity of the radiated field and amplitude reflection coefficients in the hard-walled source section. These measurements are compared with baseline hardwall and uniformly lined duct data. The dependence of these characteristics on mode number and angular location of the source is investigated. A comparison between previous theoretical calculations and the experimentally measured results is made and in general good agreement is obtained. For the several cases presented an asymmetry in the liner impedance distribution was found to produce related asymmetries in the radiated acoustic field.

Dact2 is expressed in the developing ureteric bud/collecting duct system of the kidney and controls morphogenetic behavior of collecting duct cells.

PubMed

Lee, Wen-Chin; Hough, Melinda T; Liu, Weijia; Ekiert, Robert; Lindström, Nils O; Hohenstein, Peter; Davies, Jamie A

2010-10-01

The overall pattern of the developing kidney is set in large part by the developing ureteric bud/collecting duct system, and dysgenesis of this system accounts for a variety of clinically significant renal diseases. Understanding how the behavior of cells in the developing ureteric bud/collecting duct is controlled is therefore important to understanding the normal and abnormal kidney. Dact proteins have recently been identified as cytoplasmic regulators of intracellular signaling. Dact1 inhibits Wnt signaling, and Dact2 inhibits transforming growth factor (TGF)-β signaling. Here, we report that Dact2 is expressed in developing and adult mouse kidneys, specifically in the ureteric bud/collecting duct epithelium, a structure whose morphogenesis is controlled partially by TGF-β. When small interfering RNA is used to knock down Dact2 expression in collecting duct cells, they show some constitutive phospho-Smad2, undetectable in controls, and elevated phospho-Smad2 in response to TGF-β. They also show defective migration and, in a monolayer wound-healing assay, they fail to assemble a leading edge "cable" of actomyosin and advance instead as a disorganized mass of lamellipodium-bearing cells. This effect is seriously exacerbated by exogenous TGF-β, although control cells tolerate it well. In three-dimensional culture, Dact2 knockdown cells form cysts and branching tubules, but the outlines of the cysts made by knockdown cells are ragged rather than smooth and the branching tubules are decorated with many fine spikes not seen in controls. These data suggest Dact2 plays a role in regulating morphogenesis by renal collecting duct cells, probably by protecting cells from overly strong TGF-β pathway activation.

Venom and Dufour's glands of the emerald cockroach wasp Ampulex compressa (Insecta, Hymenoptera, Sphecidae): structural and biochemical aspects.

PubMed

Gnatzy, Werner; Michels, Jan; Volknandt, Walter; Goller, Stephan; Schulz, Stefan

2015-09-01

The digger wasp species Ampulex compressa produces its venom in two branched gland tubules. They terminate in a short common duct, which is bifurcated at its proximal end. One leg is linked with the venom reservoir, the other one extends to the ductus venatus. Each venom gland tubule possesses, over its entire length, a cuticle-lined central duct. Around this duct densely packed class 3 gland units each composed of a secretory cell and a canal cell are arranged. The position of their nuclei was demonstrated by DAPI staining. The brush border of the secretory cells surrounds the coiled end-apparatus. Venom is stored in a bladder like reservoir, which is surrounded by a thin reticulated layer of muscle fibres. The reservoir as a whole is lined with class 3 gland units. The tubiform Dufour's gland has a length of about 350 μm (∅ 125 μm) only and is surrounded by a network of pronounced striated muscle fibres. The glandular epithelium is mono-layered belonging to the class 1 type of insect epidermal glands. The gland cells are characterized by conspicuous lipid vesicles. Secretion of material via the gland cuticle into the gland lumen is apparent. Analysis of the polypeptide composition demonstrated that the free gland tubules and the venom reservoir contain numerous proteins ranging from 3.4 to 200 kDa. The polypeptide composition of the Dufour's gland is completely different and contains no lectin-binding glycoproteins, whereas a dominant component of the venom droplets is a glycoprotein of about 80 kDa. Comparison of the venom reservoir contents with the polypeptide pattern of venom droplets revealed that all of the major proteinaceous constituents are secreted. The secreted venom contains exclusively proteins present in the soluble contents of the venom gland. The most abundant compound class in the Dufour's gland consisted of n-alkanes followed by monomethyl-branched alkanes and alkadienes. Heptacosane was the most abundant n-alkane. Furthermore, a single volatile compound, 2-methylpentan-3-one, was identified in various concentrations in the lipid extract of the Dufour's gland. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sound propagation in a duct of periodic wall structure. [numerical analysis

NASA Technical Reports Server (NTRS)

Kurze, U.

1978-01-01

A boundary condition, which accounts for the coupling in the sections behind the duct boundary, is given for the sound-absorbing duct with a periodic structure of the wall lining and using regular partition walls. The soundfield in the duct is suitably described by the method of differences. For locally active walls this renders an explicit approximate solution for the propagation constant. Coupling may be accounted for by the method of differences in a clear manner. Numerical results agree with measurements and yield information which has technical applications.

A histochemical study of rat salivary gland acid phosphatase.

PubMed

Isacsson, G

1986-01-01

Male Sprague-Dawley rats received 4 mg pilocarpine/100 g body wt intraperitoneally or physiological saline as control and were killed at various intervals. Acid phosphatase was reacted on frozen sections from soft palate, parotid and submandibular glands using sodium-alpha-naphthyl acid phosphate as substrate. Various inhibitors were added to the incubation medium. The strongest acid phosphatase activity was in the parotid gland acinar and proximal secretory duct cells; the mucous minor glands of the palate were completely negative. Activity was found in the acinar cells, proximal secretory duct cells, granular and striated duct and excretory duct cells. Pilocarpine injection slightly reduced the activity up to 6 h after injection. Cupric chloride added to the incubation medium lowered the overall activity. Fluoride and molybdate inhibited the acid phosphatase reaction in all structures. Tartrate inhibited the reaction in all structures except the submandibular striated duct cells. The tartrate-resistant activity may be a Na+K+-dependent ATPase involved in re-absorbing water and electrolytes from the primary saliva.

Tuft Cell Regulation of miRNAs in Pancreatic Cancer

DTIC Science & Technology

2013-10-01

are involved in chemosensensing of the microenvironment. With the successful deletion of Dclk1 throughout the pancreatic ducts , we can begin...characterization, which extends our understanding of the role tuft cells play within ducts and their broader effects on the overall pancreatic...characterization of Pdx-1-Cre;Dclk1flox/flox was completed which demonstrated the loss of Dclk1 expression within tuft cells in all pancreatic ducts

Detection of human T lymphotropic virus type-I bZIP factor and tax in the salivary glands of Sjögren's syndrome patients.

PubMed

Nakamura, Hideki; Hasegawa, Hiroo; Sasaki, Daisuke; Takatani, Ayuko; Shimizu, Toshimasa; Kurushima, Shota; Horai, Yoshiro; Nakashima, Yoshikazu; Nakamura, Tatsufumi; Fukuoka, Junya; Kawakami, Atsushi

2018-03-20

To detect HTLV-I bZIP factor (HBZ), tax and relevant molecules in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS). The expressions of HBZ and tax in T cell lines and LSGs were analysed by in situ hybridization (ISH) or real time PCR. The expressions of forkhead box P3 (Foxp3) and p65 in immunohistochemistry were quantified. After specificity of ISH probes was determined in 5 T cell lines, in LSGs from an adult T-cell leukemia (ATL) patient and 3 HTLV-I-associated myelopathy (HAM)-SS patients, both HBZ and tax signals were detected in infiltrating mononuclear cells (MNCs) and ducts, and HBZ and tax were dominantly expressed in MNCs of ATL and HAM-SS, respectively. HBZ was dominantly observed in LSGs from 8 HTLV-I asymptomatic carrier (AC)-SS patients; faint expression of HBZ was observed in LSGs from 5 HTLV-I-seronegative SS patients. No cell adhesion molecule 1(CADM1) expressed in LSGs from the ATL patient. Although Foxp3 expression was observed in LSG MNCs of all of the SS patients, the ATL patient's expression was significantly greater than that of the AC-SS (p<0.01) and HTLV-I-seronegative SS (p<0.01) patients. The Foxp3 expression was similar in ATL and HAMSS, but significantly higher in HAM-SS than AC-SS (p<0.05). p65 was expressed in LSG MNC nuclei from all SS patients and co-expressed with Foxp3. The expressions of Foxp3 in ducts differed according to HTLV-I infection. These results suggest that HBZ-mediated Foxp3 expression is partly associated with the pathogenesis of HTLV-I-seropositive SS.

[Effect of thyroid hormones on the histotopography of lectin receptors in the rat salivary gland].

PubMed

Lutsik, A D; Iashchenko, A M; Detiuk, E S

1987-04-01

Using lectin-peroxidase technique, the influence of hypo- and hyperthyroidism on histotopography of glycoconjugates has been investigated in rat submandibular gland. The following lectins were used: peanut agglutinin (PNA), wheat germ agglutinin (WGA), Laburnum anagyroides lectin (LAL) and concanavalin A (con A). It has been demonstrated that hyperthyroidism is accompanied by the loss of con A, WGA and LAL receptor sites. Hypothyrodism enhanced con A binding to granular duct cells with a parallel reduction in WGA and LAL binding to these or other duct cells. Hypothyroidism as well as hyperthyroidism markedly enhanced PNA binding to duct epitheliocytes with redistribution of these lectin binding sites from the luminal surface of salivary ducts into the cytoplasm of duct cells. Possible interpretations of the observed phenomena are discussed.

Cholangiocarcinoma…Or Not?

PubMed Central

Kenny, Patrick; Kerns, Tamie

2013-01-01

Introduction Cholangiocarcinoma includes all tumors originating in the epithelium of the bile duct and is the ninth most common gastrointestinal tract cancer. Metastatic disease may also rarely be present in the common bile duct. We present a case of metastatic malignant melanoma presenting as obstructive hepatitis and initially was thought to be and was almost treated as cholangiocarcinoma prior to adequate tissue sampling. Case Report A 76-year-old man presented with nausea, vomiting, and painless jaundice. He had a mixed hepatocellular pattern with transaminases and alkaline phosphatase greater than 1000 and total bilirubin of 12. A three-phase liver CT showed an enhancing mass within a dilated common bile duct and extension of the mass into the right and left intrahepatic bile ducts. He subsequently underwent ERCP with bile duct brushings and stent placement. Bile duct brushings showed benign reactive ductal epithelial cells. An endoscopic ultrasound with fine needle aspiration of the bile duct mass was performed. Pathology was negative for CK7, CK20, and positive for S100, Pan-melanoma, and negative for BRAF. No suspicious skin lesions were seen on close inspection by a dermatologist. However, two years prior the patient was diagnosed with cutaneous malignant melanoma in situ that was surgically resected. Thus, it was felt that this case represented metastatic melanoma to the bile duct. Due to significant comorbidities the patient was determined to be a poor surgical candidate. He has completed first line therapy for unresectable multiple melanoma with four rounds of ipilimumab. Discussion Pathologic diagnosis of cholangiocarcinoma is often difficult to obtain from ERCP secondary to paucicellularity of these tumors and with no imaging modality that is specific for cholangiocarcinma. The hepatobiliary tract is a possible, though relatively rare, location for metastatic focus of malignant melanoma and should be considered in a patient with a history of melanoma and no tissue diagnosis after ERCP. There are multiple case reports of metastatic melanoma to the ampula of Vater causing obstructive hepatitis, but only 10 reports of disease found in the common bile duct. This case highlights the importance of obtaining tissue from suspected malignant lesions using various forms of endoscopy to ensure proper treatment and prolonged survival.

Submucosal glands in the columnar-lined oesophagus: evidence of an association with metaplasia and neosquamous epithelium.

PubMed

Lörinc, Ester; Öberg, Stefan

2012-07-01

A multipotential stem cell, possibly located in the submucosal gland ducts, has been suggested as the origin of metaplastic mucosa in the oesophagus. The topographic distribution of these glands and their excretory ducts (SMG) within the columnar lined oesophagus (CLO) is largely unknown. The aim of this study was to examine the distribution of SMG in relation to the type of overlying epithelium in patients with CLO. Seven oesophageal resection specimens were examined histologically in toto. The median frequency of SMG was similar in the metaplastic segments (0.12 SMG/mm) and the normal squamous segments (0.10 SMG/mm). Within the metaplastic segments, the median frequency of SMG beneath the squamous islands was significantly higher than that observed under the columnar lined parts (0.22 versus 0.08 SMG/mm, P = 0.046), There was a strong accumulation of SMG at the squamo-columnar transition zones (0.53 SMG/mm), which was significantly greater than that found in the columnar and squamous parts (P = 0.001 and 0.002, respectively). The relative accumulation of SMG beneath squamous islands and the squamo-columnar junctions within the metaplastic segment supports the hypothesis that both metaplastic columnar mucosa and neosquamous epithelium originate from a progenitor in the SMG. © 2012 Blackwell Publishing Ltd.

[Water regulation in the cochlea : Do molecular water channels facilitate potassium-dependent sound transduction?].

PubMed

Eckhard, A; Löwenheim, H

2014-06-01

Sound transduction in the cochlea critically depends on the circulation of potassium ions (K(+)) along so-called "K(+) recycling routes" between the endolymph and perilymph. These K(+) currents generate high ionic and osmotic gradients, which potentially impair the excitability of sensory hair cells and threaten cell survival in the entire cochlear duct. Molecular water channels-aquaporins (AQP)-are expressed in all cochlear supporting cells along the K(+) recycling routes; however, their significance for osmotic equilibration in cochlear duct cells is unknown. The diffusive and osmotic water permeabilies of Reissner's membrane, the organ of Corti and the entire cochlear duct epithelium were determined. Expression of the potassium channel Kir4.1 and the water channel AQP4 in the cochlear duct was investigated by immunohistochemistry. The calculated water permeability values indicate the extent of AQP-facilitated water flux across the cochlear duct epithelium. Immunohistochemically, Kir4.1 and AQP4 were found to colocalize in distinct membrane domains of supporting cells along the K(+)-recycling routes. These observations suggest the presence of a rapid AQP-mediated water exchange between the endolymph, the cells of the cochlear duct and the perilymph. The subcellular colocalization of Kir4.1 and AQP4 in epithelial supporting cells indicates functional coupling of potassium and water flow in the cochlea. Finally, this offers an explanation for the hearing impairment observed in individuals with mutations in the AQP4 gene.

Light microscopic detection of sugar residues in glycoconjugates of salivary glands and the pancreas with lectin-horseradish peroxidase conjugates. I. Mouse.

PubMed

Schulte, B A; Spicer, S S

1983-12-01

Mouse salivary glands and pancreases were stained with a battery of ten horseradish peroxidase-conjugated lectins. Lectin staining revealed striking differences in the structure of oligosaccharides of stored intracellular secretory glycoproteins and glycoconjugates associated with the surface of epithelial cells lining excretory ducts. The percentage of acinar cells containing terminal alpha-N-acetylgalactosamine residues varied greatly in submandibular glands of 30 male mice, but all submandibular acinar cells contained oligosaccharides with terminal sialic acid and penultimate beta-galactose residues. The last named dimer was abundant in secretory glycoprotein of all mucous acinar cells in murine sublingual glands and an additional 20-50% of these cells in all glands contained terminal N-acetylglucosamine residues. In contrast, terminal alpha-N-acetylgalactosamine was abundant in sublingual serous demilune secretions. Serous acinar cells in the exorbital lacrimal gland, posterior lingual gland, parotid gland and pancreas exhibited a staining pattern unique to each organ. In contrast, the apical cytoplasm and surface of striated duct epithelial cells in the submandibular, sublingual, parotid and exorbital lacrimal gland stained similarly. A comparison of staining with conjugated lectins reported biochemically to have very similar carbohydrate binding specificity has revealed some remarkable differences in their reactivity, suggesting different binding specificity for the same terminal sugars having different glycosidic linkages or with different penultimate sugar residues.

Computer analysis of three-dimensional morphological characteristics of the bile duct

NASA Astrophysics Data System (ADS)

Ma, Jinyuan; Chen, Houjin; Peng, Yahui; Shang, Hua

2017-01-01

In this paper, a computer image-processing algorithm for analyzing the morphological characteristics of bile ducts in Magnetic Resonance Cholangiopancreatography (MRCP) images was proposed. The algorithm consisted of mathematical morphology methods including erosion, closing and skeletonization, and a spline curve fitting method to obtain the length and curvature of the center line of the bile duct. Of 10 cases, the average length of the bile duct was 14.56 cm. The maximum curvature was in the range of 0.111 2.339. These experimental results show that using the computer image-processing algorithm to assess the morphological characteristics of the bile duct is feasible and further research is needed to evaluate its potential clinical values.

Constructing kidney-like tissues from cells based on programs for organ development: toward a method of in vitro tissue engineering of the kidney.

PubMed

Rosines, Eran; Johkura, Kohei; Zhang, Xing; Schmidt, Heidi J; Decambre, Marvalyn; Bush, Kevin T; Nigam, Sanjay K

2010-08-01

The plausibility of constructing vascularized three-dimensional (3D) kidney tissue from cells was investigated. The kidney develops from mutual inductive interactions between cells of the ureteric bud (UB), derived from the Wolffian duct (WD), and the metanephric mesenchyme (MM). We found that isolated MMs were capable of inducing branching morphogenesis of the WD (an epithelial tube) in recombination cultures; suggesting that the isolated MM retains inductive capacity for WD-derived epithelial tubule cells other than those from the UB. Hanging drop aggregates of embryonic and adult renal epithelial cells from UB and mouse inner medullary collecting duct cell (IMCD) lines, which are ultimately of WD origin, were capable of inducing MM epithelialization and tubulogenesis with apparent connections (UB cells) and collecting duct-like tubules with lumens (IMCD). This supports the view that the collecting system can be constructed from certain epithelial cells (those ultimately of WD origin) when stimulated by MM. Although the functions of the MM could not be replaced by cultured mesenchymal cells, primary MM cells and one MM-derived cell line (BSN) produced factors that stimulate UB branching morphogenesis, whereas another, rat inducible metanephric mesenchyme (RIMM-18), supported WD budding as a feeder layer. This indicates that some MM functions can be recapitulated by cells. Although engineering of a kidney-like tissue from cultured cells alone remains to be achieved, these results suggest the feasibility of such an approach following the normal developmental progression of the UB and MM. Consistent with this notion, implants of kidney-like tissues constructed in vitro from recombinations of the UB and MM survived for over 5 weeks and achieved an apparently host-derived glomerular vasculature. Lastly, we addressed the issue of optimal macro- and micro-patterning of kidney-like tissue, which might be necessary for function of an organ assembled using a tissue engineering approach. To identify suitable conditions, 3D reconstructions of HoxB7-green fluorescent protein mouse rudiments (E12) cultured on a filter or suspended in a collagen gel (type I or type IV) revealed that type IV collagen 3D culture supports the deepest tissue growth (600 +/- 8 microm) and the largest kidney volume (0.22 +/- 0.02 mm(3)), and enabled the development of an umbrella-shaped collecting system such as occurs in vivo. Taken together with prior work (Rosines et al., 2007; Steer et al., 2002), these results support the plausibility of a developmental strategy for constructing and propagating vascularized 3D kidney-like tissues from recombinations of cultured renal progenitor cells and/or primordial tissue.

Combined Hepatocellular-Cholangiocarcinoma in a Yellow-Headed Amazon (Amazona oratrix)

PubMed Central

TENNAKOON, Anusha Hemamali; IZAWA, Takeshi; FUJITA, Daisuke; DENDA, Yuki; SETO, Eiko; SASAI, Hiroshi; KUWAMURA, Mitsuru; YAMATE, Jyoji

2013-01-01

ABSTRACT A 9-year-old male Yellow-headed Amazon (Amazona oratrix) with a history of anorexia and vomiting died of a liver tumor. The tumor consisted of neoplastic cells with hepatocellular and cholangiocellular differentiations and their intermingled areas. Neoplastic hepatocytes showed islands or trabecular growth with vacuolated eosinophilic cytoplasm. Cells showing biliary differentiation formed ducts or tubules lined by cytokeratin AE1/AE3-positive epithelia, accompanied by desmoplasia consisting of myofibroblasts reacting to α-smooth muscle actin and desmin. The tumor was diagnosed as a combined hepatocellular-cholangiocarcinoma, which is very rare in the avian. PMID:23800973

Combined hepatocellular-cholangiocarcinoma in a Yellow-headed Amazon (Amazona oratrix).

PubMed

Tennakoon, Anusha Hemamali; Izawa, Takeshi; Fujita, Daisuke; Denda, Yuki; Seto, Eiko; Sasai, Hiroshi; Kuwamura, Mitsuru; Yamate, Jyoji

2013-11-01

A 9-year-old male Yellow-headed Amazon (Amazona oratrix) with a history of anorexia and vomiting died of a liver tumor. The tumor consisted of neoplastic cells with hepatocellular and cholangiocellular differentiations and their intermingled areas. Neoplastic hepatocytes showed islands or trabecular growth with vacuolated eosinophilic cytoplasm. Cells showing biliary differentiation formed ducts or tubules lined by cytokeratin AE1/AE3-positive epithelia, accompanied by desmoplasia consisting of myofibroblasts reacting to α-smooth muscle actin and desmin. The tumor was diagnosed as a combined hepatocellular-cholangiocarcinoma, which is very rare in the avian.

β-Cell regeneration through the transdifferentiation of pancreatic cells: Pancreatic progenitor cells in the pancreas.

PubMed

Kim, Hyo-Sup; Lee, Moon-Kyu

2016-05-01

Pancreatic progenitor cell research has been in the spotlight, as these cells have the potential to replace pancreatic β-cells for the treatment of type 1 and 2 diabetic patients with the absence or reduction of pancreatic β-cells. During the past few decades, the successful treatment of diabetes through transplantation of the whole pancreas or isolated islets has nearly been achieved. However, novel sources of pancreatic islets or insulin-producing cells are required to provide sufficient amounts of donor tissues. To overcome this limitation, the use of pancreatic progenitor cells is gaining more attention. In particular, pancreatic exocrine cells, such as duct epithelial cells and acinar cells, are attractive candidates for β-cell regeneration because of their differentiation potential and pancreatic lineage characteristics. It has been assumed that β-cell neogenesis from pancreatic progenitor cells could occur in pancreatic ducts in the postnatal stage. Several studies have shown that insulin-producing cells can arise in the duct tissue of the adult pancreas. Acinar cells also might have the potential to differentiate into insulin-producing cells. The present review summarizes recent progress in research on the transdifferentiation of pancreatic exocrine cells into insulin-producing cells, especially duct and acinar cells.

Toxicologic Characterization of a Novel Explosive, Triaminoguanidinium-1-methyl-5-nitriminotetrazolate (TAG-MNT), in Female Rats and in vitro Assays

DTIC Science & Technology

2011-03-01

inflammation, hepatocyte degeneration, centrilobular hepatocyte hyper- trophy, increased mitoses, megakaryocytic hepatocytes, and bile duct ...of 2 g/L. However, TAG-MNT was cytotoxic to bacteria and a human liver cell line at 250 mg/L and greater. Unlike RDX, TAG-MNT did not have an...food intake, weight loss, increased kidney weight, leucopenia, and elevated blood urea nitrogen and creatinine levels. Leucopenia, increased liver mass

A quantitative analysis of electrolyte exchange in the salivary duct

PubMed Central

Catalán, Marcelo A.; Melvin, James E.; Yule, David I.; Crampin, Edmund J.; Sneyd, James

2012-01-01

A healthy salivary gland secretes saliva in two stages. First, acinar cells generate primary saliva, a plasma-like, isotonic fluid high in Na+ and Cl−. In the second stage, the ducts exchange Na+ and Cl− for K+ and HCO3−, producing a hypotonic final saliva with no apparent loss in volume. We have developed a tool that aims to understand how the ducts achieve this electrolyte exchange while maintaining the same volume. This tool is part of a larger multiscale model of the salivary gland and can be used at the duct or gland level to investigate the effects of genetic and chemical alterations. In this study, we construct a radially symmetric mathematical model of the mouse salivary gland duct, representing the lumen, the cell, and the interstitium. For a given flow and primary saliva composition, we predict the potential differences and the luminal and cytosolic concentrations along a duct. Our model accounts well for experimental data obtained in wild-type animals as well as knockouts and chemical inhibitors. Additionally, the luminal membrane potential of the duct cells is predicted to be very depolarized compared with acinar cells. We investigate the effects of an electrogenic vs. electroneutral anion exchanger in the luminal membrane on concentration and the potential difference across the luminal membrane as well as how impairing the cystic fibrosis transmembrane conductance regulator channel affects other ion transporting mechanisms. Our model suggests the electrogenicity of the anion exchanger has little effect in the submandibular duct. PMID:22899825

Comparative morphology and ultrastructure of the prosomal salivary glands in the unfed larvae Leptotrombidium orientale (Acariformes, Trombiculidae), a possible vector of tsutsugamushi disease agent.

PubMed

Shatrov, Andrew B

2015-07-01

The prosomal salivary glands of the unfed larvae Leptotrombidium orientale (Schluger) were investigated using transmission electron microscopy. In total, four pairs of the prosomal glands were identified--three pairs, the lateral, the medial and the anterior, belong to the podocephalic system, and one pair, the posterior, is separate having an own excretory duct. All glands are simple alveolar/acinous with prismatic cells arranged around a relatively small intra-alveolar lumen with the duct base. The cells of all glands besides the lateral ones contain practically mature electron-dense secretory granules ready to be discharged from the cells. The secretory granules in the lateral glands undergo formation and maturation due to the Golgi body activity. The cells of all gland types contain a large basally located nucleus and variously expressed rough endoplasmic reticulum. Specialized duct-forming cells filled with numerous freely scattered microtubules are situated in the middle zone of each gland's acinus and form the intra-alveolar lumen and the duct base. Both the acinar (secretory) and the duct-forming cells contact each other via gap junctions and septate desmosomes. Axons of nerve cells come close to the basal extensions of the duct-forming cells where they form the bulb-shaped synaptic terminations. The process of secretion is under the control of the nerve system that provides contraction of the duct-forming cells and discharge of secretion from the secretory cells into the intra-alveolar lumen and further to the exterior. Unfed larvae of L. orientale, the potential vector of tsutsugamushi disease agents, contain the most simply organized salivary secretory granules among known trombiculid larvae, and this secretion, besides the lateral glands, does not undergo significant additional maturation. Thus, the larvae are apparently ready to feed on the appropriate host just nearly after hatching.

Intensification and refraction of acoustical signals in partially choked converging ducts

NASA Technical Reports Server (NTRS)

Nayfeh, A. H.

1980-01-01

A computer code based on the wave-envelope technique is used to perform detailed numerical calculations for the intensification and refraction of sound in converging hard walled and lined circular ducts carrying high mean Mach number flows. The results show that converging ducts produce substantial refractions toward the duct center for waves propagating against near choked flows. As expected, the magnitude of the refraction decreases as the real part of the admittance increases. The pressure wave pattern is that of interference among the different modes, and hence the variation of the magnitude of pressure refraction with frequency is not monotonic.

Specific down-regulation of XIAP with RNA interference enhances the sensitivity of canine tumor cell-lines to TRAIL and doxorubicin

PubMed Central

Spee, Bart; Jonkers, Martijn DB; Arends, Brigitte; Rutteman, Gerard R; Rothuizen, Jan; Penning, Louis C

2006-01-01

Background Apoptosis resistance occurs in various tumors. The anti-apoptotic XIAP protein is responsible for inhibiting apoptosis by reducing caspase-3 activation. Our aim is to evaluate whether RNA inhibition against XIAP increases the sensitivity of canine cell-lines for chemotherapeutics such as TRAIL and doxorubicin. We used small interfering RNA's (siRNA) directed against XIAP in three cell-lines derived from bile-duct epithelia (BDE), mammary carcinoma (P114), and osteosarcoma (D17). These cell-lines represent frequently occurring canine cancers and are highly comparable to their human counterparts. XIAP down-regulation was measured by means of quantitative PCR (Q-PCR) and Western blotting. The XIAP depleted cells were treated with a serial dilution of TRAIL or doxorubicin and compared to mock- and nonsense-treated controls. Viability was measured with a MTT assay. Results All XIAP siRNA treated cell-lines showed a mRNA down-regulation over 80 percent. Western blot analysis confirmed mRNA measurements. No compensatory effect of IAP family members was seen in XIAP depleted cells. The sensitivity of XIAP depleted cells for TRAIL was highest in BDE cells with an increase in the ED50 of 14-fold, compared to mock- and nonsense-treated controls. The sensitivity of P114 and D17 cell-lines increased six- and five-fold, respectively. Doxorubicin treatment in XIAP depleted cells increased sensitivity in BDE cells more than eight-fold, whereas P114 and D17 cell-lines showed an increase in sensitivity of three- and five-fold, respectively. Conclusion XIAP directed siRNA's have a strong sensitizing effect on TRAIL-reduced cell-viability and a smaller but significant effect with the DNA damaging drug doxorubicin. The increase in efficacy of chemotherapeutics with XIAP depletion provides the rationale for the use of XIAP siRNA's in insensitive canine tumors. PMID:16953886

Establishment of cholangiocarcinoma cell lines from patients in the endemic area of liver fluke infection in Thailand.

PubMed

Saensa-Ard, Sunitta; Leuangwattanawanit, Saman; Senggunprai, Laddawan; Namwat, Nisana; Kongpetch, Sarinya; Chamgramol, Yaovalux; Loilome, Watcharin; Khansaard, Walaiporn; Jusakul, Apinya; Prawan, Auemduan; Pairojkul, Chawalit; Khantikeo, Narong; Yongvanit, Puangrat; Kukongviriyapan, Veerapol

2017-11-01

Cholangiocarcinoma is a rare type of cancer which is an increasingly discernible health threat. The disease is usually very difficult in diagnosis and various treatment modalities are typically not effective. Cholangiocarcinoma is a complex and very heterogeneous malignancy characterized by tumor location, different risk factors, molecular profiling, and prognosis. Cancer cell lines represent an important tool for investigation in various aspects of tumor biology and molecular therapeutics. We established two cell lines, KKU-452 and KKU-023, which were derived from patients residing in the endemic area of liver fluke infection in Thailand. Both of tumor tissues have gross pathology of perihilar and intrahepatic mass-forming cholangiocarcinoma. Two cell lines were characterized for their biological, molecular and genetic properties. KKU-452 and KKU-023 cells are both adherent cells with epithelium morphology, but have some differences in their growth pattern (a doubling time of 17.9 vs 34.8 h, respectively) and the expression of epithelial bile duct markers, CK7 and CK19. Cytogenetic analysis of KKU-452 and KKU-023 cells revealed their highly complex karyotypes; hypertriploid and hypotetraploid, respectively, with multiple chromosomal aberrations. Both cell lines showed mutations in p53 but not in KRAS. KKU-452 showed a very rapid migration and invasion properties in concert with low expression of E-cadherin and high expression of N-cadherin, whereas KKU-023 showed opposite characters. KKU-023, but not KKU-452, showed in vivo tumorigenicity in xenografted nude mice. Those two established cholangiocarcinoma cell lines with unique characters may be valuable for better understanding the process of carcinogenesis and developing new therapeutics for the patients.

Mucoepidermoid carcinoma in a salivary duct cyst of the parotid gland. Contribution to the development of tumours in salivary gland cysts.

PubMed

Seifert, G

1996-12-01

Concerning the hypothesis that distinct types of salivary gland cysts may be the starting point of a salivary gland tumour, a histological examination of 1,661 salivary gland cysts was performed in order to analyse the cell types and their proliferative activity. Epithelial alterations were found especially in salivary duct cysts of parotid gland and in mucous retention cysts of minor salivary glands. Characteristic cellular changes were epithelial metaplasias (goblet cells, clear cells, squamous cells) and focal epithelial proliferations with plump or papillary plaques projecting into the cyst lumen. Only in one case had a mucoepidermoid carcinoma developed in the wall of a parotid duct cyst. The epithelial metaplasia and focal proliferative activity in salivary duct cysts is comparable to similar alterations in odontogenic cysts as possible early manifestation of a tumour, especially of an ameloblastoma or mucoepidermoid carcinoma. The differential diagnosis of salivary duct cysts must take primarily cystadenomas and cystic mucoepidermoid carcinomas of well-differentiated type into account.

The morphology and ultrastructure of salivary glands of Zoraptera (Insecta).

PubMed

Dallai, R; Mercati, D; Mashimo, Y; Machida, R; Beutel, R G

2017-07-01

The salivary glands of two species of Zoraptera, Zorotypus caudelli and Zorotypus hubbardi, were examined and documented mainly using transmission electron microscopy (TEM). The results obtained for males and females of the two species are compared and functional aspects related to ultrastructural features are discussed. The salivary glands are divided into two regions: the secretory cell region and the long efferent duct, the latter with its distal end opening in the salivarium below the hypopharyngeal base. The secretory region consists of a complex of secretory cells provided with microvillated cavities connected by short ectodermal ducts to large ones, which are connected with the long efferent duct. The secretory cell cytoplasm contains a large system of rough endoplasmic reticulum and Golgi apparatus producing numerous dense secretions. The cells of the efferent duct, characterized by reduced cytoplasm and the presence of long membrane infoldings associated with mitochondria, are possibly involved in fluid uptaking from the duct lumen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heterogeneity of SOX9 and HNF1β in Pancreatic Ducts Is Dynamic.

PubMed

Rezanejad, Habib; Ouziel-Yahalom, Limor; Keyzer, Charlotte A; Sullivan, Brooke A; Hollister-Lock, Jennifer; Li, Wan-Chun; Guo, Lili; Deng, Shaopeng; Lei, Ji; Markmann, James; Bonner-Weir, Susan

2018-03-13

Pancreatic duct epithelial cells have been suggested as a source of progenitors for pancreatic growth and regeneration. However, genetic lineage-tracing experiments with pancreatic duct-specific Cre expression have given conflicting results. Using immunofluorescence and flow cytometry, we show heterogeneous expression of both HNF1β and SOX9 in adult human and murine ductal epithelium. Their expression was dynamic and diminished significantly after induced replication. Purified pancreatic duct cells formed organoid structures in 3D culture, and heterogeneity of expression of Hnf1β and Sox9 was maintained even after passaging. Using antibodies against a second cell surface molecule CD51 (human) or CD24 (mouse), we could isolate living subpopulations of duct cells enriched for high or low expression of HNF1β and SOX9. Only the CD24 high (Hnfβ high /Sox9 high ) subpopulation was able to form organoids. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis

PubMed Central

Huch, Meritxell; Bonfanti, Paola; Boj, Sylvia F; Sato, Toshiro; Loomans, Cindy J M; van de Wetering, Marc; Sojoodi, Mozhdeh; Li, Vivian S W; Schuijers, Jurian; Gracanin, Ana; Ringnalda, Femke; Begthel, Harry; Hamer, Karien; Mulder, Joyce; van Es, Johan H; de Koning, Eelco; Vries, Robert G J; Heimberg, Harry; Clevers, Hans

2013-01-01

Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5+ stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) that expand five-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality. PMID:24045232

Isocitrate dehydrogenase mutations confer dasatinib hypersensitivity and SRC-dependence in intrahepatic cholangiocarcinoma

PubMed Central

Saha, Supriya K.; Gordan, John D.; Kleinstiver, Benjamin P.; Vu, Phuong; Najem, Mortada S.; Yeo, Jia-Chi; Shi, Lei; Kato, Yasutaka; Levin, Rebecca S.; Webber, James T.; Damon, Leah J.; Egan, Regina K.; Greninger, Patricia; McDermott, Ultan; Garnett, Mathew J.; Jenkins, Roger L.; Rieger-Christ, Kimberly M.; Sullivan, Travis B.; Hezel, Aram F.; Liss, Andrew S.; Mizukami, Yusuke; Goyal, Lipika; Ferrone, Cristina R.; Zhu, Andrew X.; Joung, J. Keith; Shokat, Kevan M.; Benes, Cyril H.; Bardeesy, Nabeel

2017-01-01

Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver bile duct malignancy exhibiting frequent isocitrate dehydrogenase (IDH1/IDH2) mutations. Through a high-throughput drug screen of a large panel of cancer cell lines including 17 biliary tract cancers, we found that IDH mutant (IDHm) ICC cells demonstrate a striking response to the multi-kinase inhibitor dasatinib, with the highest sensitivity among 682 solid tumor cell lines. Using unbiased proteomics to capture the activated kinome and CRISPR/Cas9-based genome editing to introduce dasatinib-resistant ‘gatekeeper’ mutant kinases, we identified SRC as a critical dasatinib target in IDHm ICC. Importantly, dasatinib-treated IDHm xenografts exhibited pronounced apoptosis and tumor regression. Our results show that IDHm ICC cells have a unique dependency on SRC and suggest that dasatinib may have therapeutic benefit against IDHm ICC. Moreover, these proteomic and genome-editing strategies provide a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness. PMID:27231123

Expression and clinical significance of PIWIL2 in hilar cholangiocarcinoma tissues and cell lines.

PubMed

Chen, Y J; Xiong, X F; Wen, S Q; Tian, L; Cheng, W L; Qi, Y Q

2015-06-26

The objective of this study was to explore the relationship between PIWI-like protein 2 (PIWIL2) and clinicopathological charac-teristics and prognosis after radical resection. To accomplish this, we analyzed PIWIL2 expression in hilar cholangiocarcinoma tissues and cell lines. PIWIL2 expression was detected by immunohistochemistry in 41 hilar cholangiocarcinoma samples and 10 control tissues. Western blotting and immunocytofluorescence were used to investigate PIWIL2 expression in the cholangiocarcinoma cell line QBC939 and the bile duct epithelial cell line HIBEpic. Univariate and multivariate surviv-al analyses were performed using the Kaplan-Meier method for hilar cholangiocarcinoma patients who underwent radical resection. PIWIL2 expression was significantly higher in the hilar cholangiocarcinoma tissues and QBC939 cells than in control tissues and HIBEpic cells, respectively (P < 0.05). Poorly and moderately differentiated cholan-giocarcinoma tissues had significantly higher PIWIL2 expression than well-differentiated tissues (P < 0.05). Univariate analysis demonstrated that high PIWIL2 expression was associated with shorter survival time after radical resection (P < 0.05). Multivariate analysis showed that PI-WIL2 expression was an independent prognostic factor after radical re-section of hilar cholangiocarcinoma (P < 0.05). PIWIL2 expression was also associated with tumor-node-metastasis stage and differentiation. PIWIL2 was an independent prognostic factor after radical resection of hilar cholangiocarcinoma.

miR-34a-dependent overexpression of Per1 decreases cholangiocarcinoma growth.

PubMed

Han, Yuyan; Meng, Fanyin; Venter, Julie; Wu, Nan; Wan, Ying; Standeford, Holly; Francis, Heather; Meininger, Cynthia; Greene, John; Trzeciakowski, Jerome P; Ehrlich, Laurent; Glaser, Shannon; Alpini, Gianfranco

2016-06-01

Disruption of circadian rhythm is associated with cancer development and progression. MicroRNAs (miRNAs) are a class of small non-coding RNAs that trigger mRNA translation inhibition. We aimed to evaluate the role of Per1 and related miRNAs in cholangiocarcinoma growth. The expression of clock genes was evaluated in human cholangiocarcinoma tissue arrays and cholangiocarcinoma lines. The rhythmic expression of clock genes was evaluated in cholangiocarcinoma cells and H69 (non-malignant cholangiocytes) by qPCR. We measured cell proliferation, cell cycle and apoptosis in Mz-ChA-1 cells after Per1 overexpression. We examined tumor growth in vivo after injection of Per1 overexpressing cells. We verified miRNAs that targets Per1. The circadian rhythm of miR-34a was evaluated in cholangiocarcinoma and H69 cells. We evaluated cell proliferation, apoptosis and invasion after inhibition of miR-34a in vitro, and the potential molecular mechanisms by mRNA profiling after overexpression of Per1. Expression of Per1 was decreased in cholangiocarcinoma. The circadian rhythm of Per1 expression was lost in cholangiocarcinoma cells. Decreased cell proliferation, lower G2/M arrest, and enhanced apoptosis were shown in Per1 overexpressing cells. An in vivo study revealed decreased tumor growth, decreased proliferation, angiogenesis and metastasis after overexpressing Per1. Per1 was verified as a target of miR-34a. miR-34a was rhythmically expressed in cholangiocarcinoma cells and H69. The inhibition of miR-34a decreased proliferation, migration and invasion in cholangiocarcinoma cells. mRNA profiling has shown that overexpression of Per1 inhibits cell growth through regulation of multiple cancer-related pathways, such as cell cycle, cell growth and apoptosis pathways. Disruption of circadian rhythms of clock genes contribute to the malignant phenotypes of human cholangiocarcinoma. The current study is about how biological clock and its regulators affect the bile duct tumor growth. The disruption of biological clock has a negative impact in different cancers. Per1 is a gene that is involved in maintaining the biological clock and show 24h oscillation. Reduced levels of Per1 and disruption of 24h circadian rhythm was found in bile duct cancer cells. Therefore, a genetic modified bile duct cancer cells was created. It has a higher level of Per1 expression and partially recovered circadian rhythm. Those genetic modified cells also displayed slower cell growth or higher rate of cell death. We also used mice model that lack of immune system to show that our genetic modified bile duct cells form smaller tumor. In addition, we tried to see how Per1 is communicating with other genes in regarding of controlling the tumor growth. We found Per1 is regulated by microRNA-34a, a small non-coding RNA that directly binds to genes and inhibit gene expression. Decreased level of miR-34a has also significantly reduced tumor growth through controlling the cell growth and cell death balance. Therefore bile duct cancer patients may be treated with miR-34a inhibitor or Per1 stimulator in the future. Published by Elsevier B.V.

EMP-1 is a junctional protein in a liver stem cell line and in the liver.

PubMed

Lee, Hsuan-Shu; Sherley, James L; Chen, Jeremy J W; Chiu, Chien-Chang; Chiou, Ling-Ling; Liang, Ja-Der; Yang, Pan-Chyr; Huang, Guan-Tarn; Sheu, Jin-Chuan

2005-09-09

In an attempt to discover cell markers for liver stem cells, a cDNA microarray analysis was carried out to compare the gene expression profiles between an adult liver stem cell line, Lig-8, and mature hepatocytes. Several genes in the categories of extracellular matrix, cell membrane, cell adhesion, transcription factor, signal molecule, transporter, and metabolic enzyme were shown to be differentially expressed in Lig-8 cells. Among them, epithelial membrane protein (EMP)-1 has been previously implicated with stem cell phenotypes. Antiserum to EMP-1 was produced to localize its expression. On monolayers of Lig-8 cells, EMP-1 was expressed along the intercellular border. In the liver harboring proliferating oval cells, the liver progenitors, EMP-1 was localized as ribbon bands, a staining pattern for epithelial junctions, all the way through bile duct epithelia, oval cell ductules, and into peri-hepatocytic regions. These peri-hepatocytic regions were proved to be bile canaliculi by co-localization of EMP-1 and dipeptidyl peptidase IV, an enzyme located on bile canaliculi. This report is the first to indicate EMP-1 to be a junctional protein in the liver.

Bile duct adenoma and von Meyenburg complex-like duct arising in hepatitis and cirrhosis: pathogenesis and histological characteristics.

PubMed

Aishima, Shinichi; Tanaka, Yuki; Kubo, Yuichiro; Shirabe, Ken; Maehara, Yoshihiko; Oda, Yoshinao

2014-11-01

Morphologic features and neoplastic potentials of bile duct adenoma (BDA) and von Meyenburg complex (VMC)-like duct arising in chronic liver disease were unknown. Thirty-five BDAs and 12 VMC-like duct lesions were observed in 39 cases with chronic liver disease. BDAs were divided into the EMA-cytoplasmic type (n = 14) and EMA-luminal type (n = 21). EMA-cytoplasmic BDA composed of a proliferation of cuboidal to low-columnar cells forming an open lumen with NCAM(+)/MUC6(-), resembling an interlobular bile duct. EMA-luminal BDA showed uniform cuboidal cells with narrow lumen, and NCAM(++)/MUC6(++), resembling a ductular reaction. VMC-like duct showed positive MUC1 expression and negative MUC6. The expression of S100P, glucose transporter-1 (GLUT-1) and insulin-like growth factor II mRNA-binding protein 3 (IMP-3) were not detected in three lesions. p16 expression was higher than those of the ductular reaction, and the Ki67 and p53 indexes were very low (<1.0%). Large-sized EMA-luminal BDA shows sclerotic stroma. We classified small nodular lesions of ductal or ductular cells in chronic hepatitis and cirrhosis into the following groups: BDA, interlobular bile duct type; BDA, ductular/peribiliary gland type; and VMC-like duct. They may be reactive proliferation rather than neoplastic lesions. © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Silencing of CXCR4 inhibits tumor cell proliferation and neural invasion in human hilar cholangiocarcinoma.

PubMed

Tan, Xin-Yu; Chang, Shi; Liu, Wei; Tang, Hui-Huan

2014-03-01

To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.

Microgravity

NASA Image and Video Library

1998-10-10

Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue; A: Duct element recovered from breast tissue digest. B: Outgrowth of cells from duct element in upper right corner cultured in a standard dish; most cells spontaneousely die during early cell divisions, but a few will establish long-term growth. C: Isolate of long-term frowth HMEC from outgrowth of duct element; cells shown soon after isolation and in early full-cell contact growth in culture in a dish. D: same long-term growth HMEC, but after 3 weeks in late full-cell contact growth in a continuous culture in a dish. Note attempts to reform duct elements but this in two demensions in a dish rather than in three dimensions in tissue. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Richmond, NASA/Marshall Space Flight Center (MSFC).

Analytical and experimental studies of an optimum multisegment phased liner noise suppression concept

NASA Technical Reports Server (NTRS)

Sawdy, D. T.; Beckemeyer, R. J.; Patterson, J. D.

1976-01-01

Results are presented from detailed analytical studies made to define methods for obtaining improved multisegment lining performance by taking advantage of relative placement of each lining segment. Properly phased liner segments reflect and spatially redistribute the incident acoustic energy and thus provide additional attenuation. A mathematical model was developed for rectangular ducts with uniform mean flow. Segmented acoustic fields were represented by duct eigenfunction expansions, and mode-matching was used to ensure continuity of the total field. Parametric studies were performed to identify attenuation mechanisms and define preliminary liner configurations. An optimization procedure was used to determine optimum liner impedance values for a given total lining length, Mach number, and incident modal distribution. Optimal segmented liners are presented and it is shown that, provided the sound source is well-defined and flow environment is known, conventional infinite duct optimum attenuation rates can be improved. To confirm these results, an experimental program was conducted in a laboratory test facility. The measured data are presented in the form of analytical-experimental correlations. Excellent agreement between theory and experiment verifies and substantiates the analytical prediction techniques. The results indicate that phased liners may be of immediate benefit in the development of improved aircraft exhaust duct noise suppressors.

Single-cell heterogeneity in ductal carcinoma in situ of breast.

PubMed

Gerdes, Michael J; Gökmen-Polar, Yesim; Sui, Yunxia; Pang, Alberto Santamaria; LaPlante, Nicole; Harris, Adrian L; Tan, Puay-Hoon; Ginty, Fiona; Badve, Sunil S

2018-03-01

Heterogeneous patterns of mutations and RNA expression have been well documented in invasive cancers. However, technological challenges have limited the ability to study heterogeneity of protein expression. This is particularly true for pre-invasive lesions such as ductal carcinoma in situ of the breast. Cell-level heterogeneity in ductal carcinoma in situ was analyzed in a single 5 μm tissue section using a multiplexed immunofluorescence analysis of 11 disease-related markers (EGFR, HER2, HER4, S6, pmTOR, CD44v6, SLC7A5 and CD10, CD4, CD8 and CD20, plus pan-cytokeratin, pan-cadherin, DAPI, and Na+K+ATPase for cell segmentation). Expression was quantified at cell level using a single-cell segmentation algorithm. K-means clustering was used to determine co-expression patterns of epithelial cell markers and immune markers. We document for the first time the presence of epithelial cell heterogeneity within ducts, between ducts and between patients with ductal carcinoma in situ. There was moderate heterogeneity in a distribution of eight clusters within each duct (average Shannon index 0.76; range 0-1.61). Furthermore, within each patient, the average Shannon index across all ducts ranged from 0.33 to 1.02 (s.d. 0.09-0.38). As the distribution of clusters within ducts was uneven, the analysis of eight ducts might be sufficient to represent all the clusters ie within- and between-duct heterogeneity. The pattern of epithelial cell clustering was associated with the presence and type of immune infiltrates, indicating a complex interaction between the epithelial tumor and immune system for each patient. This analysis also provides the first evidence that simultaneous analysis of both the epithelial and immune/stromal components might be necessary to understand the complex milieu in ductal carcinoma in situ lesions.

Leaf blade structure of Verbesina macrophylla (Cass.) F. S. Blake (Asteraceae): ontogeny, duct secretion mechanism and essential oil composition.

PubMed

Bezerra, L D A; Mangabeira, P A O; de Oliveira, R A; Costa, L C D B; Da Cunha, M

2018-05-01

Secretory structures are common in Asteraceae, where they exhibit a high degree of morphological diversity. The species Verbesina macrophylla, popularly known as assa-peixe, is native to Brazil where it is widely used for medicinal purposes. Despite its potential medical importance, there have been no studies of the anatomy of this species, especially its secretory structures and secreted compounds. This study examined leaves of V. macrophylla with emphasis on secretory structures and secreted secondary metabolites. Development of secretory ducts and the mechanism of secretion production are described for V. macrophylla using ultrastructure, yield and chemical composition of its essential oils. Verbesina macrophylla has a hypostomatic leaf blade with dorsiventral mesophyll and secretory ducts associated with vascular bundles of schizogenous origin. Histochemistry identified the presence of lipids, terpenes, alkaloids and mucopolysaccharides. Ultrastructure suggests that the secretion released into the duct lumen is produced in plastids of transfer cells, parenchymal sheath cells and stored in vacuoles in these cells and duct epithelial cells. The essential oil content was 0.8%, and its major components were germacrene D, germacrene D-4-ol, β-caryophyllene, bicyclogermacrene and α-cadinol. Secretory ducts of V. macrophylla are squizogenous. Substances identified in tissues suggest that both secretions stored in the ducts and in adjacent parenchyma cells are involved in chemical defence. The essential oil is rich in sesquiterpenes, with germacrene D and its derivatives being notable components. © 2018 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

Histopathologic findings in Unna's nevus suggest it is a tardive congenital nevus.

PubMed

Sowa, Junko; Kobayashi, Hiromi; Ishii, Masamitsu; Kimura, Tetsunori

2008-12-01

According to A. Bernard Ackerman's clinical histopathologic classification of nevi, the essential histopathologic finding of an Unna's nevus is localization of melanocytic nevus cells to a markedly thickened papillary dermis of an exophytic lesion. In this study, we examined 94 completely resected Unna's nevi in which several sections of the same lesion could be examined. We examined that melanocytic nevus cells were not just localized to the exophytic portion but were also commonly distributed below it (81 lesions, 86.2%). Melanocytic nevus cells were found in a periadnexal distribution in most of the lesions in which they extended below the exophytic part and were most frequently noted around hair follicles (60 lesions, 63.8%), then around eccrine ducts (43 lesions, 45.7%), and least frequently around sebaceous glands or ducts (36 lesions, 38.3%). Nests of melanocytic nevus cells were present in follicular epithelium in 7 lesions, sebaceous ducts in 1 lesion, and eccrine ducts in 1 lesion. Moreover, type A nevus cells containing melanin granules were observed in 16 lesions (17.0%) when they were distributed around hair follicles, in 8 lesions (8.5%) when distributed around sebaceous glands or ducts, and in 1 lesion (1.1%) when distributed around eccrine ducts. Although Unna's nevus is clinically an acquired nevus, it has many histopathologic characteristics of a congenital melanocytic nevus and is therefore likely a tardive congenital lesion.

A non-local computational boundary condition for duct acoustics

NASA Technical Reports Server (NTRS)

Zorumski, William E.; Watson, Willie R.; Hodge, Steve L.

1994-01-01

A non-local boundary condition is formulated for acoustic waves in ducts without flow. The ducts are two dimensional with constant area, but with variable impedance wall lining. Extension of the formulation to three dimensional and variable area ducts is straightforward in principle, but requires significantly more computation. The boundary condition simulates a nonreflecting wave field in an infinite duct. It is implemented by a constant matrix operator which is applied at the boundary of the computational domain. An efficient computational solution scheme is developed which allows calculations for high frequencies and long duct lengths. This computational solution utilizes the boundary condition to limit the computational space while preserving the radiation boundary condition. The boundary condition is tested for several sources. It is demonstrated that the boundary condition can be applied close to the sound sources, rendering the computational domain small. Computational solutions with the new non-local boundary condition are shown to be consistent with the known solutions for nonreflecting wavefields in an infinite uniform duct.

On-line ultrasonic gas entrainment monitor

DOEpatents

Day, Clifford K.; Pedersen, Herbert N.

1978-01-01

Apparatus employing ultrasonic energy for detecting and measuring the quantity of gas bubbles present in liquids being transported through pipes. An ultrasonic transducer is positioned along the longitudinal axis of a fluid duct, oriented to transmit acoustic energy radially of the duct around the circumference of the enclosure walls. The back-reflected energy is received centrally of the duct and interpreted as a measure of gas entrainment. One specific embodiment employs a conical reflector to direct the transmitted acoustic energy radially of the duct and redirect the reflected energy back to the transducer for reception. A modified embodiment employs a cylindrical ultrasonic transducer for this purpose.

Cross-talk between insulin and IGF-1 receptors in the cortical collecting duct principal cells: implication for ENaC-mediated Na+ reabsorption

PubMed Central

Ilatovskaya, Daria V.; Levchenko, Vladislav; Brands, Michael W.; Pavlov, Tengis S.

2015-01-01

Insulin and IGF-1 are recognized as powerful regulators of the epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron. As previously described, these hormones both acutely increase ENaC activity in freshly isolated split open tubules and cultured principal cortical collecting duct cells. The present study was aimed at differentiating the effects of insulin and IGF-1 on Na+ transport in immortalized mpkCCDcl4 cells and defining their interrelations. We have shown that both insulin and IGF-1 applied basolaterally, but not apically, enhanced transepithelial Na+ transport in the mpkCCDcl4 cell line with EC50 values of 8.8 and 14.5 nM, respectively. Insulin treatment evoked phosphorylation of both insulin and IGF-1 receptors, whereas the effects of IGF-1 were more profound on its own receptor rather than the insulin receptor. AG-1024 and PPP, inhibitors of IGF-1 and insulin receptor tyrosine kinase activity, diminished insulin- and IGF-1-stimulated Na+ transport in mpkCCDcl4 cells. The effects of insulin and IGF-1 on ENaC-mediated currents were found to be additive, with insulin likely stimulating both IGF-1 and insulin receptors. We hypothesize that insulin activates IGF-1 receptors in addition to its own receptors, making the effects of these hormones interconnected. PMID:25651558

Effects of double ligation of Stensen's duct on the rabbit parotid gland.

PubMed

Maria, O M; Maria, S M; Redman, R S; Maria, A M; Saad El-Din, T A; Soussa, E F; Tran, S D

2014-04-01

Salivary gland duct ligation is an alternative to gland excision for treating sialorrhea or reducing salivary gland size prior to tumor excision. Duct ligation also is used as an approach to study salivary gland aging, regeneration, radiotherapy, sialolithiasis and sialadenitis. Reports conflict about the contribution of each salivary cell population to gland size reduction after ductal ligation. Certain cell populations, especially acini, reportedly undergo atrophy, apoptosis and proliferation during reduction of gland size. Acini also have been reported to de-differentiate into ducts. These contradictory results have been attributed to different animal or salivary gland models, or to methods of ligation. We report here a bilateral double ligature technique for rabbit parotid glands with histologic observations at 1, 7, 14, 30, 60 days after ligation. A large battery of special stains and immunohistochemical procedures was employed to define the cell populations. Four stages with overlapping features were observed that led to progressive shutdown of gland activities: 1) marked atrophy of the acinar cells occurred by 14 days, 2) response to and removal of the secretory material trapped in the acinar and ductal lumens mainly between 30 and 60 days, 3) reduction in the number of parenchymal (mostly acinar) cells by apoptosis that occurred mainly between 14-30 days, and 4) maintenance of steady-state at 60 days with a low rate of fluid, protein, and glycoprotein secretion, which greatly decreased the number of leukocytes engaged in the removal of the luminal contents. The main post- ligation characteristics were dilation of ductal and acinar lumens, massive transient infiltration of mostly heterophils (rabbit polymorphonuclear leukocytes), acinar atrophy, and apoptosis of both acinar and ductal cells. Proliferation was uncommon except in the larger ducts. By 30 days, the distribution of myoepithelial cells had spread from exclusively investing the intercalated ducts pre-ligation to surrounding a majority of the residual duct-like structures, many of which clearly were atrophic acini. Thus, both atrophy and apoptosis made major contributions to the post-ligation reduction in gland size. Structures also occurred with both ductal and acinar markers that suggested acini differentiating into ducts. Overall, the reaction to duct ligation proceeded at a considerably slower pace in the rabbit parotid glands than has been reported for the salivary glands of the rat.

Locating and Quantifying Broadband Fan Sources Using In-Duct Microphones

NASA Technical Reports Server (NTRS)

Dougherty, Robert P.; Walker, Bruce E.; Sutliff, Daniel L.

2010-01-01

In-duct beamforming techniques have been developed for locating broadband noise sources on a low-speed fan and quantifying the acoustic power in the inlet and aft fan ducts. The NASA Glenn Research Center's Advanced Noise Control Fan was used as a test bed. Several of the blades were modified to provide a broadband source to evaluate the efficacy of the in-duct beamforming technique. Phased arrays consisting of rings and line arrays of microphones were employed. For the imaging, the data were mathematically resampled in the frame of reference of the rotating fan. For both the imaging and power measurement steps, array steering vectors were computed using annular duct modal expansions, selected subsets of the cross spectral matrix elements were used, and the DAMAS and CLEAN-SC deconvolution algorithms were applied.

Humanization of the mouse mammary gland by replacement of the luminal layer with genetically engineered preneoplastic human cells.

PubMed

Verbeke, Stephanie; Richard, Elodie; Monceau, Elodie; Schmidt, Xenia; Rousseau, Benoit; Velasco, Valerie; Bernard, David; Bonnefoi, Herve; MacGrogan, Gaetan; Iggo, Richard D

2014-12-20

The cell of origin for estrogen receptor α-positive (ERα+) breast cancer is probably a luminal stem cell in the terminal duct lobular units. To model these cells, we have used the murine myoepithelial layer in the mouse mammary ducts as a scaffold upon which to build a human luminal layer. To prevent squamous metaplasia, a common artifact in genetically-engineered breast cancer models, we sought to limit activation of the epidermal growth factor receptor (EGFR) during in vitro cell culture before grafting the cells. Human reduction mammoplasty cells were grown in vitro in WIT medium. Epidermal growth factor in the medium was replaced with amphiregulin and neuregulin to decrease activation of EGFR and increase activation of EGFR homologs 3 and 4 (ERBB3 and ERBB4). Lentiviral vectors were used to express oncogenic transgenes and fluorescent proteins. Human mammary epithelial cells were mixed with irradiated mouse fibroblasts and Matrigel, then injected through the nipple into the mammary ducts of immunodeficient mice. Engrafted cells were visualized by stereomicroscopy for fluorescent proteins and characterized by histology and immunohistochemistry. Growth of normal mammary epithelial cells in conditions favoring ERBB3/4 signaling prevented squamous metaplasia in vitro. Normal human cells were quickly lost after intraductal injection, but cells infected with lentiviruses expressing CCND1, MYC, TERT, BMI1 and a short-hairpin RNA targeting TP53 were able to engraft and progressively replace the luminal layer in the mouse mammary ducts, resulting in the formation of an extensive network of humanized ducts. Despite expressing multiple oncogenes, the human cells formed a morphologically normal luminal layer. Expression of a single additional oncogene, PIK3CA-H1047R, converted the cells into invasive cancer cells. The resulting tumors were ERα+, Ki67+ luminal B adenocarcinomas that were resistant to treatment with fulvestrant. Injection of preneoplastic human mammary epithelial cells into the mammary ducts of immunodeficient mice leads to replacement of the murine luminal layer with morphologically normal human cells. Genetic manipulation of the injected cells makes it possible to study defined steps in the transformation of human mammary epithelial cells in a more physiological environment than has hitherto been possible.

Chimeric analysis of EGFP and DsRed2 transgenic mice demonstrates polyclonal maintenance of pancreatic acini.

PubMed

Ryu, Je-Young; Siswanto, Antoni; Harimoto, Kenichi; Tagawa, Yoh-ichi

2013-06-01

The pancreatic islet is an assembly of specific endocrine cells. There are many conflicting reports regarding whether the acinus develops from single or multiple progenitor cells. This study investigated the development and maintenance clonality of the pancreatic acinus and duct using a chimeric analysis with EGFP and DsRed2 transgenic mice. Chimeric mice (G-R mice) were obtained by the aggregation method, using 8-cell stage embryos from EGFP and DsRed2 transgenic mice. The islets from the G-R mice were chimeric and mosaic, consisting of either EGFP- or DsRed2-positive populations, as in previous reports. On the other hand, most acini developed from either EGFP or DsRed2 origin, but some were chimeric. Interestingly, these chimeric acini were clearly separated into two-color regions and were not mosaic. Some large intralobular pancreatic ducts consisting of more than 10 cells were found to be chimeric, but no small ducts made up of less than 9 cells were chimeric. Our histological observations suggest that the pancreatic acinus polyclonally and directionally is maintained by multiple progenitor cells. Pancreatic large ducts also seem to develop polyclonally and might result from the assembly of small ducts that develop from a single origin. These findings provide useful information for further understanding pancreatic maintenance.

Granular Cell Tumor of the Common Hepatic Duct as an Unusual Cause of Jaundice in a Hepatitis C Patient.

PubMed

Chopade, Tripti R; Smith, Colin L; Maley, Warren R; Siddiqui, Ali A; Sass, David A

2016-01-01

A 33-year-old woman with a history of intravenous cocaine abuse presented with fatigue, nausea, and jaundice. Serologic testing revealed a positive hepatitis C virus (HCV) antibody and HCV RNA. Ultrasound and magnetic resonance imaging/magnetic resonance cholangiopancreatography showed a partially obstructing lesion in the common hepatic duct, which was confirmed by endoscopic retrograde cholangiopancreatography. Surgical excision revealed a granular cell tumor of the common hepatic duct, with immunohistochemical staining of tumor cells positive for S-100.

Cadherin-17 is required to maintain pronephric duct integrity during zebrafish development.

PubMed

Horsfield, Julia; Ramachandran, Anassuya; Reuter, Katja; LaVallie, Edward; Collins-Racie, Lisa; Crosier, Kathryn; Crosier, Philip

2002-07-01

We have isolated a zebrafish cadherin that is orthologous to human LI-cadherin (CDH17). Zebrafish cdh17 is expressed exclusively in the pronephric ducts during embryogenesis, and in the mesonephros during larval development and adulthood. Like its mammalian ortholog, cdh17 is also expressed in liver and intestine in adult zebrafish. We show that cdh17-positive mesodermal cells do not contribute to the hematopoietic system. Consistent with a cell adhesion role for Cdh17, depletion of Cdh17 function using antisense morpholino oligonucleotides compromised cell cohesion during pronephric duct formation. Our results indicate that Cdh17 is necessary for maintaining the integrity of the pronephric ducts during zebrafish embryogenesis. This finding contrasts with the role of mammalian CDH17, which does not appear to be involved in nephric development.

Design curves for circular and annular duct silencers

NASA Technical Reports Server (NTRS)

Watson, Willie R.; Ramakrishnan, R.

1989-01-01

Conventional models of sound propagation between porous walls (Scott, 1946) are adapted in order to calculate design curves for the lined circular and annular-duct silencers used in HVAC systems. The derivation of the governing equations is outlined, and results for two typical cases are presented graphically. Good agreement with published experimental data is demonstrated.

A displacement-pressure finite element formulation for analyzing the sound transmission in ducted shear flows with finite poroelastic lining.

PubMed

Nennig, Benoit; Tahar, Mabrouk Ben; Perrey-Debain, Emmanuel

2011-07-01

In the present work, the propagation of sound in a lined duct containing sheared mean flow is studied. Walls of the duct are acoustically treated with absorbent poroelastic foams. The propagation of elasto-acoustic waves in the liner is described by Biot's model. In the fluid domain, the propagation of sound in a sheared mean flow is governed by the Galbrun's equation. The problem is solved using a mixed displacement-pressure finite element formulation in both domains. A 3D implementation of the model has been performed and is illustrated on axisymmetric examples. Convergence and accuracy of the numerical model are shown for the particular case of the modal propagation in a infinite duct containing a uniform flow. Practical examples concerning the sound attenuation through dissipative silencers are discussed. In particular, effects of the refraction effects in the shear layer as well as the mounting conditions of the foam on the transmission loss are shown. The presence of a perforate screen at the air-porous interface is also considered and included in the model. © 2011 Acoustical Society of America

Breast Cancer Research at NASA

NASA Technical Reports Server (NTRS)

1998-01-01

Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue; A: Duct element recovered from breast tissue digest. B: Outgrowth of cells from duct element in upper right corner cultured in a standard dish; most cells spontaneousely die during early cell divisions, but a few will establish long-term growth. C: Isolate of long-term frowth HMEC from outgrowth of duct element; cells shown soon after isolation and in early full-cell contact growth in culture in a dish. D: same long-term growth HMEC, but after 3 weeks in late full-cell contact growth in a continuous culture in a dish. Note attempts to reform duct elements but this in two demensions in a dish rather than in three dimensions in tissue. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Richmond, NASA/Marshall Space Flight Center (MSFC).

Proximal location of mouse prostate epithelial stem cells

PubMed Central

Tsujimura, Akira; Koikawa, Yasuhiro; Salm, Sarah; Takao, Tetsuya; Coetzee, Sandra; Moscatelli, David; Shapiro, Ellen; Lepor, Herbert; Sun, Tung-Tien; Wilson, E. Lynette

2002-01-01

Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propose a model of prostatic homeostasis in which mouse prostatic epithelial stem cells are concentrated in the proximal region of prostatic ducts while the transit-amplifying cells occupy the distal region of the ducts. This model can account for many biological differences between cells of the proximal and distal regions, and has implications for prostatic disease formation. PMID:12082083

β-Cell dedifferentiation, reduced duct cell plasticity, and impaired β-cell mass regeneration in middle-aged rats.

PubMed

Téllez, Noèlia; Vilaseca, Marina; Martí, Yasmina; Pla, Arturo; Montanya, Eduard

2016-09-01

Limitations in β-cell regeneration potential in middle-aged animals could contribute to the increased risk to develop diabetes associated with aging. We investigated β-cell regeneration of middle-aged Wistar rats in response to two different regenerative stimuli: partial pancreatectomy (Px + V) and gastrin administration (Px + G). Pancreatic remnants were analyzed 3 and 14 days after surgery. β-Cell mass increased in young animals after Px and was further increased after gastrin treatment. In contrast, β-cell mass did not change after Px or after gastrin treatment in middle-aged rats. β-Cell replication and individual β-cell size were similarly increased after Px in young and middle-aged animals, and β-cell apoptosis was not modified. Nuclear immunolocalization of neurog3 or nkx6.1 in regenerative duct cells, markers of duct cell plasticity, was increased in young but not in middle-aged Px rats. The pancreatic progenitor-associated transcription factors neurog3 and sox9 were upregulated in islet β-cells of middle-aged rats and further increased after Px. The percentage of chromogranin A+/hormone islet cells was significantly increased in the pancreases of middle-aged Px rats. In summary, the potential for compensatory β-cell hyperplasia and hypertrophy was retained in middle-aged rats, but β-cell dedifferentiation and impaired duct cell plasticity limited β-cell regeneration. Copyright © 2016 the American Physiological Society.

Developmental biology of the pancreas: a comprehensive review.

PubMed

Gittes, George K

2009-02-01

Pancreatic development represents a fascinating process in which two morphologically distinct tissue types must derive from one simple epithelium. These two tissue types, exocrine (including acinar cells, centro-acinar cells, and ducts) and endocrine cells serve disparate functions, and have entirely different morphology. In addition, the endocrine tissue must become disconnected from the epithelial lining during its development. The pancreatic development field has exploded in recent years, and numerous published reviews have dealt specifically with only recent findings, or specifically with certain aspects of pancreatic development. Here I wish to present a more comprehensive review of all aspects of pancreatic development, though still there is not a room for discussion of stem cell differentiation to pancreas, nor for discussion of post-natal regeneration phenomena, two important fields closely related to pancreatic development.

Epithelial proliferation in small ducts of salivary cystadenoma resembling atypical ductal hyperplasia of breast.

PubMed

Fahim, Lisa; Weinreb, Ilan; Alexander, Cherupushpam; Perez Ordoñez, Bayardo

2008-09-01

Salivary gland cystadenomas are cystic neoplasms with diverse architecture and cytology. Cystadenomas may have a considerable intracystic epithelial component, but an epithelial proliferation in small ducts and cysts resembling atypical ductal hyperplasia of breast has not been documented. The patient was a 68-year-old man with a slow growing right submandibular mass. He has no recurrence 13 months after resection. The tumor was polycystic and measured 3.0 x 2.5 x 2.5 cm. The epithelium of the larger cysts was composed of flat, cuboidal, columnar, and apocrine-like cells. Many of the larger cysts showed "Roman bridges", epithelial tufting, and papillae. The smaller cysts and ducts had apocrine-like cells forming secondary glandular lumens. The ductal cells were surrounded by clear myoepithelial cells. Nuclear pleomorphism and hyperchromasia was seen in the apocrine-like cells. Adjacent to the larger cysts, there was an adenomatoid proliferation of small ducts surrounded by myoepithelial cells. No mitotic activity, necrosis, or stromal invasion was identified. The ductal cells were diffusely positive for keratin 7 and androgen receptors with focal expression of keratin 19 and high-molecular weight keratin. S-100, estrogen and progesterone receptors, and BRST-2 were negative in the ductal cells. Recognition of a prominent intraductal epithelial component in cystadenomas is important to avoid a misdiagnosis of cystadenocarcinoma or low-grade salivary duct carcinoma. Cystadenomas join the list of salivary gland lesions with microscopic similarities to primary lesions of the breast.

Distribution of serotonergic and dopaminergic nerve fibers in the salivary gland complex of the cockroach Periplaneta americana

PubMed Central

Baumann, Otto; Dames, Petra; Kühnel, Dana; Walz, Bernd

2002-01-01

Background The cockroach salivary gland consists of secretory acini with peripheral ion-transporting cells and central protein-producing cells, an extensive duct system, and a pair of reservoirs. Salivation is controled by serotonergic and dopaminergic innervation. Serotonin stimulates the secretion of a protein-rich saliva, dopamine causes the production of a saliva without proteins. These findings suggest a model in which serotonin acts on the central cells and possibly other cell types, and dopamine acts selectively on the ion-transporting cells. To examine this model, we have analyzed the spatial relationship of dopaminergic and serotonergic nerve fibers to the various cell types. Results The acinar tissue is entangled in a meshwork of serotonergic and dopaminergic varicose fibers. Dopaminergic fibers reside only at the surface of the acini next to the peripheral cells. Serotonergic fibers invade the acini and form a dense network between central cells. Salivary duct segments close to the acini are locally associated with dopaminergic and serotonergic fibers, whereas duct segments further downstream have only dopaminergic fibers on their surface and within the epithelium. In addition, the reservoirs have both a dopaminergic and a serotonergic innervation. Conclusion Our results suggest that dopamine is released on the acinar surface, close to peripheral cells, and along the entire duct system. Serotonin is probably released close to peripheral and central cells, and at initial segments of the duct system. Moreover, the presence of serotonergic and dopaminergic fiber terminals on the reservoir indicates that the functions of this structure are also regulated by dopamine and serotonin. PMID:12095424

Distribution of serotonergic and dopaminergic nerve fibers in the salivary gland complex of the cockroach Periplaneta americana.

PubMed

Baumann, Otto; Dames, Petra; Kühnel, Dana; Walz, Bernd

2002-06-24

The cockroach salivary gland consists of secretory acini with peripheral ion-transporting cells and central protein-producing cells, an extensive duct system, and a pair of reservoirs. Salivation is controlled by serotonergic and dopaminergic innervation. Serotonin stimulates the secretion of a protein-rich saliva, dopamine causes the production of a saliva without proteins. These findings suggest a model in which serotonin acts on the central cells and possibly other cell types, and dopamine acts selectively on the ion-transporting cells. To examine this model, we have analyzed the spatial relationship of dopaminergic and serotonergic nerve fibers to the various cell types. The acinar tissue is entangled in a meshwork of serotonergic and dopaminergic varicose fibers. Dopaminergic fibers reside only at the surface of the acini next to the peripheral cells. Serotonergic fibers invade the acini and form a dense network between central cells. Salivary duct segments close to the acini are locally associated with dopaminergic and serotonergic fibers, whereas duct segments further downstream have only dopaminergic fibers on their surface and within the epithelium. In addition, the reservoirs have both a dopaminergic and a serotonergic innervation. Our results suggest that dopamine is released on the acinar surface, close to peripheral cells, and along the entire duct system. Serotonin is probably released close to peripheral and central cells, and at initial segments of the duct system. Moreover, the presence of serotonergic and dopaminergic fiber terminals on the reservoir indicates that the functions of this structure are also regulated by dopamine and serotonin.

Duct wall impedance control as an advanced concept for acoustic impression

NASA Technical Reports Server (NTRS)

Dean, P. D.; Tester, B. J.

1975-01-01

Models and tests on an acoustic duct liner system which has the property of controlled-variable acoustic impedance are described. This is achieved by a novel concept which uses the effect of steady air flow through a multi-layer, locally reacting, resonant-cavity absorber. The scope of this work was limited to a 'proof of concept.' The test of the concept was implemented by means of a small-scale, square-section flow duct facility designed specifically for acoustic measurements, with one side of the duct acoustically lined. The test liners were designed with the aid of previously established duct acoustic theory and a semi-empirical impedance model of the liner system. Over the limited range tested, the liner behaved primarily as predicted, exhibiting significant changes in resistance and reactance, thus providing the necessary concept validation.

Basolateral cholesterol depletion alters Aquaporin-2 post-translational modifications and disrupts apical plasma membrane targeting.

PubMed

Moeller, Hanne B; Fuglsang, Cecilia Hvitfeldt; Pedersen, Cecilie Nøhr; Fenton, Robert A

2018-01-01

Apical plasma membrane accumulation of the water channel Aquaporin-2 (AQP2) in kidney collecting duct principal cells is critical for body water homeostasis. Posttranslational modification (PTM) of AQP2 is important for regulating AQP2 trafficking. The aim of this study was to determine the role of cholesterol in regulation of AQP2 PTM and in apical plasma membrane targeting of AQP2. Cholesterol depletion from the basolateral plasma membrane of a collecting duct cell line (mpkCCD14) using methyl-beta-cyclodextrin (MBCD) increased AQP2 ubiquitylation. Forskolin, cAMP or dDAVP-mediated AQP2 phosphorylation at Ser269 (pS269-AQP2) was prevented by cholesterol depletion from the basolateral membrane. None of these effects on pS269-AQP2 were observed when cholesterol was depleted from the apical side of cells, or when MBCD was applied subsequent to dDAVP stimulation. Basolateral, but not apical, MBCD application prevented cAMP-induced apical plasma membrane accumulation of AQP2. These studies indicate that manipulation of the cholesterol content of the basolateral plasma membrane interferes with AQP2 PTM and subsequently regulated apical plasma membrane targeting of AQP2. Copyright © 2017 Elsevier Inc. All rights reserved.

Resin duct characteristics in the wood of fire-scarred North American conifers

Treesearch

Estelle Arbellay; Markus Stoffel; Elaine K. Sutherland; Kevin T. Smith; Donald A. Falk

2013-01-01

Traumatic resin ducts form in xylem and phloem tissue of conifers in response to abiotic wounding, fungal invasion, and insect attack. Little is known about resin duct characteristics in the wood of fire-scarred trees. The aim of this study is to quantify changes in traits of both axial and radial resin ducts, along with those of associated epithelial cells and...

Silencing of CXCR4 Inhibits Tumor Cell Proliferation and Neural Invasion in Human Hilar Cholangiocarcinoma

PubMed Central

Tan, Xin-Yu; Chang, Shi; Liu, Wei

2014-01-01

Background/Aims To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. Methods An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. Results The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. Conclusions CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA. PMID:24672662

Cirrhosis induces apoptosis in renal tissue through intracellular oxidative stress.

PubMed

Silveira, Keli Cristina Simões da; Viau, Cassiana Macagnan; Colares, Josiane Raskopf; Saffi, Jenifer; Marroni, Norma Possa; Porawski, Marilene

2015-01-01

Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. We aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation. There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis.

Conceptual design study of advanced acoustic-composite nacelles

NASA Technical Reports Server (NTRS)

Nordstrom, K. E.; Marsh, A. H.; Sargisson, D. F.

1975-01-01

Conceptual studies were conducted to assess the impact of incorporating advanced technologies in the nacelles of a current wide-bodied transport and an advanced technology transport. The improvement possible in the areas of fuel consumption, flyover noise levels, airplane weight, manufacturing costs, and airplane operating cost were evaluated for short and long-duct nacelles. Use of composite structures for acoustic duct linings in the fan inlet and exhaust ducts was considered as well as for other nacelle components. For the wide-bodied transport, the use of a long-duct nacelle with an internal mixer nozzle in the primary exhaust showed significant improvement in installed specific fuel consumption and airplane direct operating costs compared to the current short-duct nacelle. The long-duct mixed-flow nacelle is expected to achieve significant reductions in jet noise during takeoff and in turbo-machinery noise during landing approach. Recommendations were made of the technology development needed to achieve the potential fuel conservation and noise reduction benefits.

Effect of flow on the acoustic performance of extended reaction lined ducts

NASA Technical Reports Server (NTRS)

Hersh, A. S.; Walker, B.

1983-01-01

A model is developed for the effects of uniform and boundary-layer mean flow on the attenuation and propagation of harmonically excited sound waves in an extended reaction lined cylindrical duct. A duct geometry consisting of an annular outer region of bulk material surrounding an inner cylinder of air is utilized. A numerical solution is obtained for the coupled wave equations governing the motion of the sound in both the inner and annular regions. It is found that the numerically predicted attenuation and propagations constants are in excellent agreement with measured values using Kevlar as the liner material for plane-wave mode (O,O) excitation over a wide range of mean flows and sound frequency. The boundary-layer effects are determined to be unimportant, at least for plane-wave sound. In addition, numerical studies indicate small differences between the use of either the radial velocity or the radial displacement boundary conditions.

The acoustic and instability waves of jets confined inside an acoustically lined rectangular duct

NASA Technical Reports Server (NTRS)

Hu, Fang Q.

1993-01-01

An analysis of linear wave modes associated with supersonic jets confined inside an acoustically lined rectangular duct is presented. Mathematical formulations are given for the vortex-sheet model and continuous mean flow model of the jet flow profiles. Detailed dispersion relations of these waves in a two-dimensional confined jet as well as an unconfined free jet are computed. Effects of the confining duct and the liners on the jet instability and acoustic waves are studied numerically. It is found that the effect of the liners is to attenuate waves that have supersonic phase velocities relative to the ambient flow. Numerical results also show that the growth rates of the instability waves could be reduced significantly by the use of liners. In addition, it is found that the upstream propagating neutral waves of an unconfined jet could become attenuated when the jet is confined.

The Nkx5/HMX homeodomain protein MLS-2 is required for proper tube cell shape in the C.elegans excretory system

PubMed Central

Abdus-Saboor, Ishmail; Stone, Craig E.; Murray, John I.; Sundaram, Meera V.

2012-01-01

Cells perform wide varieties of functions that are facilitated, in part, by adopting unique shapes. Many of the genes and pathways that promote cell fate specification have been elucidated. However, relatively few transcription factors have been identified that promote shape acquisition after fate specification. Here we show that the Nkx5/HMX homeodomain protein MLS-2 is required for cellular elongation and shape maintenance of two tubular epithelial cells in the C.elegans excretory system, the duct and pore cells. The Nkx5/HMX family is highly conserved from sea urchins to humans, with known roles in neuronal and glial development. MLS-2 is expressed in the duct and pore, and defects in mls-2 mutants first arise when the duct and pore normally adopt unique shapes. MLS-2 cooperates with the EGF-Ras-ERK pathway to turn on the LIN-48/Ovo transcription factor in the duct cell during morphogenesis. These results reveal a novel interaction between the Nkx5/HMX family and the EGF-Ras pathway and implicate a transcription factor, MLS-2, as a regulator of cell shape. PMID:22537498

The Nkx5/HMX homeodomain protein MLS-2 is required for proper tube cell shape in the C. elegans excretory system.

PubMed

Abdus-Saboor, Ishmail; Stone, Craig E; Murray, John I; Sundaram, Meera V

2012-06-15

Cells perform wide varieties of functions that are facilitated, in part, by adopting unique shapes. Many of the genes and pathways that promote cell fate specification have been elucidated. However, relatively few transcription factors have been identified that promote shape acquisition after fate specification. Here we show that the Nkx5/HMX homeodomain protein MLS-2 is required for cellular elongation and shape maintenance of two tubular epithelial cells in the C. elegans excretory system, the duct and pore cells. The Nkx5/HMX family is highly conserved from sea urchins to humans, with known roles in neuronal and glial development. MLS-2 is expressed in the duct and pore, and defects in mls-2 mutants first arise when the duct and pore normally adopt unique shapes. MLS-2 cooperates with the EGF-Ras-ERK pathway to turn on the LIN-48/Ovo transcription factor in the duct cell during morphogenesis. These results reveal a novel interaction between the Nkx5/HMX family and the EGF-Ras pathway and implicate a transcription factor, MLS-2, as a regulator of cell shape. Copyright © 2012 Elsevier Inc. All rights reserved.

Modeling of field-aligned guided echoes in the plasmasphere

NASA Astrophysics Data System (ADS)

Fung, Shing F.; Green, James L.

2005-01-01

Ray tracing modeling is used to investigate the plasma conditions under which high-frequency (f ≫ fuh) extraordinary mode waves can be guided along geomagnetic field lines. These guided signals have often been observed as long-range discrete echoes in the plasmasphere by the Radio Plasma Imager (RPI) onboard the Imager for Magnetopause-to-Aurora Global Exploration satellite. Field-aligned discrete echoes are most commonly observed by RPI in the plasmasphere, although they are also observed over the polar cap region. The plasmasphere field-aligned echoes appearing as multiple echo traces at different virtual ranges are attributed to signals reflected successively between conjugate hemispheres that propagate along or nearly along closed geomagnetic field lines. The ray tracing simulations show that field-aligned ducts with as little as 1% density perturbations (depletions) and <10 wavelengths wide can guide nearly field-aligned propagating high-frequency X mode waves. Effective guidance of a wave at a given frequency and wave normal angle (Ψ) depends on the cross-field density scale of the duct, such that ducts with stronger density depletions need to be wider in order to maintain the same gradient of refractive index across the magnetic field. While signal guidance by field aligned density gradient without ducting is possible only over the polar region, conjugate field-aligned echoes that have traversed through the equatorial region are most likely guided by ducting.

Deregulated Methionine Adenosyltransferase α1, c-Myc and Maf Proteins Interplay Promotes Cholangiocarcinoma Growth in Mice and Humans

PubMed Central

Yang, Heping; Liu, Ting; Wang, Jiaohong; Li, Tony W.H.; Fan, Wei; Peng, Hui; Krishnan, Anuradha; Gores, Gregory J.; Mato, Jose M.; Lu, Shelly C.

2016-01-01

We reported c-Myc induction drives cholestatic liver injury and cholangiocarcinoma (CCA) in mice. We also showed induction of Maf proteins (MafG and c-Maf) contributed to cholestatic liver injury, whereas S-adenosylmethionine (SAMe) administration was protective. Here we determined whether there is interplay between c-Myc, Maf proteins and methionine adenosyltransferase α1 (MATα1), which is responsible for SAMe biosynthesis in liver. We used bile duct ligation (BDL) and lithocholic acid (LCA) treatment in mice as chronic cholestasis models, a murine CCA model, human CCA cell lines KMCH and Huh-28, human liver cancer HepG2, and human CCA specimens to study gene and protein expression, protein-protein interactions, molecular mechanisms and functional outcomes. We found c-Myc, MATα1 (encoded by MAT1A), MafG and c-Maf interact with each other directly. MAT1A expression fell in hepatocytes and bile duct epithelial cells during chronic cholestasis and in murine and human CCA. The opposite occurred with c-Myc, MafG and c-Maf expression. MATα1 interacts mainly with Mnt in normal liver but this switches to c-Maf, MafG and c-Myc in cholestatic livers and CCA. Promoter regions of these genes have E-boxes that are bound by MATα1 and Mnt in normal liver and benign bile duct epithelial cells that switched to c-Myc, c-Maf and MafG in cholestasis and CCA cells. E-box positively regulates c-Myc, MafG and c-Maf, but it negatively regulates MAT1A. MATα1 represses whereas c-Myc, MafG and c-Maf enhance E-box-driven promoter activity. Knocking down MAT1A or overexpressing MafG or c-Maf enhanced CCA growth and invasion in vivo. Conclusion We have uncovered a novel interplay between MATα1, c-Myc and Maf proteins and their deregulation during chronic cholestasis may facilitate CCA oncogenesis. PMID:26969892

Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches

PubMed Central

Michelotti, Gregory A; Tucker, Anikia; Swiderska-Syn, Marzena; Machado, Mariana Verdelho; Choi, Steve S; Kruger, Leandi; Soderblom, Erik; Thompson, J Will; Mayer-Salman, Meredith; Himburg, Heather A; Moylan, Cynthia A; Guy, Cynthia D; Garman, Katherine S; Premont, Richard T; Chute, John P; Diehl, Anna Mae

2016-01-01

Objective The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell niches produce pleiotrophin (PTN) to inactivate the PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby augmenting phosphoprotein-dependent signalling. We hypothesised that the DR is regulated by PTN/PTPRZ1 signalling. Design PTN-GFP, PTN-knockout (KO), PTPRZ1-KO, and wild type (WT) mice were examined before and after bile duct ligation (BDL) for PTN, PTPRZ1 and the DR. RDC and HSC from WT, PTN-KO, and PTPRZ1-KO mice were also treated with PTN to determine effects on downstream signaling phosphoproteins, gene expression, growth, and migration. Liver biopsies from patients with DRs were also interrogated. Results Although quiescent HSC and RDC lines expressed PTN and PTPRZ1 mRNAs, neither PTN nor PTPRZ1 protein was demonstrated in healthy liver. BDL induced PTN in MF-HSC and increased PTPRZ1 in MF-HSC and RDC. In WT mice, BDL triggered a DR characterised by periportal accumulation of collagen, RDC and MF-HSC. All aspects of this DR were increased in PTN-KO mice and suppressed in PTPRZ1-KO mice. In vitro studies revealed PTN-dependent accumulation of phosphoproteins that control cell-cell adhesion and migration, with resultant inhibition of cell migration. PTPRZ1-positive cells were prominent in the DRs of patients with ductal plate defects and adult cholestatic diseases. Conclusions PTN, and its receptor, PTPRZ1, regulate the DR to liver injury by controlling the migration of resident cells in adult liver progenitor niches. PMID:25596181

The Primary Duct of Bothrops jararaca Glandular Apparatus Secretes Toxins

PubMed Central

Sakai, Fernanda; Portes-Junior, José Antonio; Godoy Viana, Luciana; Mendes Carneiro, Sylvia; Perales, Jonas; Yamanouye, Norma

2018-01-01

Despite numerous studies concerning morphology and venom production and secretion in the main venom gland (and some data on the accessory gland) of the venom glandular apparatus of Viperidae snakes, the primary duct has been overlooked. We characterized the primary duct of the Bothrops jararaca snake by morphological analysis, immunohistochemistry and proteomics. The duct has a pseudostratified epithelium with secretory columnar cells with vesicles of various electrondensities, as well as mitochondria-rich, dark, basal, and horizontal cells. Morphological analysis, at different periods after venom extraction, showed that the primary duct has a long cycle of synthesis and secretion, as do the main venom and accessory glands; however, the duct has a mixed mode venom storage, both in the lumen and in secretory vesicles. Mouse anti-B. jararaca venom serum strongly stained the primary duct’s epithelium. Subsequent proteomic analysis revealed the synthesis of venom toxins—mainly C-type lectin/C-type lectin-like proteins. We propose that the primary duct’s toxin synthesis products complement the final venom bolus. Finally, we hypothesize that the primary duct and the accessory gland (components of the venom glandular apparatus) are part of the evolutionary path from a salivary gland towards the main venom gland. PMID:29533989

New experimental method to study acid/base transporters and their regulation in lacrimal gland ductal epithelia.

PubMed

Tóth-Molnár, Edit; Venglovecz, Viktória; Ozsvári, Béla; Rakonczay, Zoltán; Varró, András; Papp, Julius G; Tóth, András; Lonovics, János; Takács, Tamás; Ignáth, Imre; Iványi, Béla; Hegyi, Péter

2007-08-01

The main function of the lacrimal gland is to produce the most aqueous component of the tear film covering the surfaces of the cornea and the conjunctiva. Studies have been conducted that characterize the mixed fluid and protein secretion of isolated acini, but no methods have been developed to characterize lacrimal gland ductal cell (LGDC) secretion. Secretory mechanisms of ductal epithelia may play physiological roles in the maintenance of the standard environments for the cornea and the conjunctiva. In this study, the authors developed a rapid method to isolate large quantities of intact lacrimal ducts. The preparation of isolated intact lacrimal gland ducts for the first time enabled the performance of real-time functional experiments on cleaned ducts. Electron microscopy and fluorescence measurements were used to evaluate the viability of lacrimal ducts. Fluorescence measurements showed that LGDCs express functionally active Na(+)/H(+) exchanger (NHE) and Cl(-)/HCO(3)(-) exchanger (AE). Parasympathomimetic stimulation by carbachol stimulated NHE and AE through the elevation of intracellular calcium concentration. This mechanism can play a role in the regulation of ion and water secretion by LGDCs. The authors have described a lacrimal gland duct isolation technique in which the intact ducts remain viable and the role of duct cells in tear film secretion can be characterized. These data combined with the novel isolation facilitated understanding of the regulation mechanisms of ductal cell secretion at cellular and molecular levels under normal and pathologic conditions.

A mathematical model of the pancreatic duct cell generating high bicarbonate concentrations in pancreatic juice.

PubMed

Whitcomb, David C; Ermentrout, G Bard

2004-08-01

To develop a simple, physiologically based mathematical model of pancreatic duct cell secretion using experimentally derived parameters that generates pancreatic fluid bicarbonate concentrations of >140 mM after CFTR activation. A new mathematical model was developed simulating a duct cell within a proximal pancreatic duct and included a sodium-2-bicarbonate cotransporter (NBC) and sodium-potassium pump (NaK pump) on a chloride-impermeable basolateral membrane, CFTR on the luminal membrane with 0.2 to 1 bicarbonate to chloride permeability ratio. Chloride-bicarbonate antiporters (Cl/HCO3 AP) were added or subtracted from the basolateral (APb) and luminal (APl) membranes. The model was integrated over time using XPPAUT. This model predicts robust, NaK pump-dependent bicarbonate secretion with opening of the CFTR, generates and maintains pancreatic fluid secretion with bicarbonate concentrations >140 mM, and returns to basal levels with CFTR closure. Limiting CFTR permeability to bicarbonate, as seen in some CFTR mutations, markedly inhibited pancreatic bicarbonate and fluid secretion. A simple CFTR-dependent duct cell model can explain active, high-volume, high-concentration bicarbonate secretion in pancreatic juice that reproduces the experimental findings. This model may also provide insight into why CFTR mutations that predominantly affect bicarbonate permeability predispose to pancreatic dysfunction in humans.

Meibomian gland studies: histologic and ultrastructural investigations.

PubMed

Jester, J V; Nicolaides, N; Smith, R E

1981-04-01

Heightened interest in meibomian gland dysfunction has prompted us to evaluate the normal morphological and ultrastructural characteristics of the meibomian gland. Histologic analysis of human, primate, steer, and rabbit glands revealed evidence of keratinized epithelium extending throughout the meibomian gland duct. Characteristic ultrastructural features of keratinized epithelium identified in primate and rabbit glands included tonofilaments, keratohyaline granules, lamellar bodies, and keratinized squamous cells. Comparison of the meibomian gland duct to the pilosebaceous canal and the sebaceous duct brought out certain dissimilarities such as (1) the lack of a well-developed stratum granulosum and (2) the absence of lipid inclusions within transitional cells from duct to acini. We postulate that abnormalities of the keratinizing process may be responsible for meibomian gland dysfunction states.

Liver stem/progenitor cells in the canals of Hering: cellular origin of hepatocellular carcinoma with bile duct tumor thrombi?

PubMed

Peng, Ningfu; Li, Lequn; Cai, Xiang; Tan, Shaozao; Wu, Ting

2010-12-01

It is generally believed that the invasion of hepatocellular carcinoma (HCC) into the biliary tree ultimately leads to the formation of bile duct tumor thrombi (BDTT). However, recent studies revealed that primary tumor might be small, even undetectable, and there was no histopathologic evidence of direct tumor invasion into bile duct wall in some patients. During the last decade, efforts on stem cell biology may shed light on the pathogenesis of BDTT. Presently, accumulating evidence supports the following notions: (1) the canals of Hering (CoH) are the most likely origin of liver stem/progenitor cells (LSPCs) in adult livers; (2) similar signalling pathways may regulate self-renewal in LSPCs and liver cancer cells, and a substantial proportion of liver tumors may often originate from the transformation of LSPCs; and (3) liver cancer contains rare cells with stem cell-like properties, which could derive from malignant transformation of LSPCs. Herein, we propose that HCC with BDTT, especially with small or undetectable primary lesion and/or no histopathologic evidence for bile duct invasion, might arise from LSPCs residing in the CoH and, possibly, some primary lesions are formed firstly within the intrahepatic biliary tree. When "tumor thrombi" extends mainly along bile duct, there might be "BDTT" alone; when it invades into surrounding parenchyma, there might often be small "primary tumor" with "BDTT". If this holds true, the putative type may be a particular subset of HCC, and most importantly it would facilitate our understanding of stem-cell origin of HCC.

Immunolocalization of aquaporin CHIP in the guinea pig inner ear.

PubMed

Stanković, K M; Adams, J C; Brown, D

1995-12-01

Aquaporin CHIP (AQP-CHIP) is a water channel protein previously identified in red blood cells and water transporting epithelia. The inner ear is an organ of hearing and balance whose normal function depends critically on maintenance of fluid homeostasis. In this study, AQP-CHIP, or a close homologue, was found in specific cells of the inner ear, as assessed by immunocytochemistry with the use of affinity-purified polyclonal antibodies against AQP-CHIP.AQP-CHIP was predominantly found in fibrocytes in close association with bone, including most of the cells lining the bony labyrinth and in fibrocytes lining the endolymphatic duct and sac. AQP-CHIP-positive cells not directly apposing bone include cells under the basilar membrane, some type III fibrocytes of the spiral ligament, fibrocytes of the spiral limbus, and the trabecular perilymphatic tissue extending from the membranous to the bony labyrinth. AQP-CHIP was also found in the periosteum of the middle ear and cranial bones, as well as in chondrocytes of the oval window and stapes. The distribution of AQP-CHIP in the inner ear suggests that AQP-CHIP may have special significance for maintenance of bone and the basilar membrane, and for function of the spiral ligament.

[Notch signaling pathway participates in the differentiation of hepatic progenitor cells into bile duct epithelial cells and progression of hepatic fibrosis in cholestatic liver fibrosis rat].

PubMed

Mu, Y P; Zhang, X; Xu, Y; Fan, W W; Li, X W; Chen, J M; Chen, G F; Liu, P

2017-06-08

Objective: To investigate differentiation direction of hepatic progenitor cells (HPCs) in cholestatic liver fibrosis (CLF), and the role of Notch signaling pathway in the differentiation of HPCs. Methods: A CLF rat model was established by bile duct ligation (BDL) followed by monitoring changes of Notch signal pathway and the cellular origin of proliferating cholangiocytes. After intraperitoneal injection of DAPT (a Notch signaling inhibitor) after bile duct ligation, the progress of liver fibrosis and the proliferation of cholangiocytes after inhibition of the Notch pathway were analyzed. Results: Data showed that bile duct proliferation gradually increased along with inflammatory cell infiltration and proliferating bile duct cells surrounded by abundant collagen in the BDL group. Immunostaining confirmed markedly increased expression of CK19, OV6, Sox9 and EpCAM. In addition, RT-PCR results showed that Notch signaling pathway was activated significantly. Once the Notch signaling pathway was inhibited by DAPT, bile duct proliferation markedly suppressed along with significantly decreased the mRNA expression of CK19, OV6, Sox9 and EpCAM, compared with BDL group [(10.2±0.7) vs . (22.3±0.8), (7.6±1.5) vs . (18.1±3.7), (1.4±0.4) vs . (4.1±1.1), (1.3±0.3) vs . (5.0±1.4), respectively, P <0.01]. Moreover, liver fibrosis was also reduced significantly. Conclusion: Notch signaling activation is required for HPCs differentiation into cholangiocytes in CLF and inhibition of the Notch signaling pathway may offer a therapeutic option for treating CLF.

Chronic granulomatous mastitis: review of 26 cases with special reference to chronic lobular mastitis.

PubMed

Bhaskaran, C S; Prasad, K R; Rao, G; Kameshwari, R; Saheb, D A; Aruna, C A

1992-01-01

Twenty six cases of chronic granulomatous mastitis are reported in a 5 year period and the slides are reviewed. They are sub-classified into Chronic lobular mastitis (CLM), Plasma cell mastitis and subareolar granuloma. There are 10 cases each of CLM and plasma cell mastitis and one of subareolar granuloma. All the three conditions are associated with duct ectasia. Fat necrosis and infective granulomas were 2 each and one of foreign body granuloma. These lesions can be easily differentiated by histology. While most of the CLM occurred in younger age group, plasma cell mastitis is seen in older women. Histologically, there is a florid inflammatory cell reaction of the stroma with dilatation and destruction of some ducts, with microabscess formation. In plasma cell mastitis, the lesion is more chronic with predominance of plasma cells and involutionary changes of the ducts are seen.

Computational modeling of epithelial fluid and ion transport in the parotid duct after transfection of human aquaporin-1

PubMed Central

Chiorini, John A; Sneyd, James; Suresh, Vinod

2017-01-01

Previous studies have shown that localized delivery of the aquaporin-1 (AQP1) gene to the parotid duct can restore saliva flow in minipigs following irradiation-induced salivary hypofunction. The resulting flow rate and electrochemistry of secreted saliva contradicts current understanding of ductal fluid transport. We hypothesized that changes in expression of ion transport proteins have occurred following AQP1 transfection. We use a mathematical model of ion and fluid transport across the parotid duct epithelial cells to predict the expression profile of ion transporters that are consistent with the experimental measurements of saliva composition and secretion rates. Using a baseline set of parameters, the model reproduces the data for the irradiated, non-AQP1-transfected case. We propose three scenarios which may have occurred after transfection, which differ in the location of the AQP1 gene. The first scenario places AQP1 within nonsecretory cells, and requires that epithelial sodium channel (ENaC) expression is greatly reduced (1.3% of baseline), and ductal bicarbonate concentration is increased from 40.6 to 137.0 mM, to drive water secretion into the duct. The second scenario introduces the AQP1 gene into all ductal cells. The final scenario has AQP1 primarily in the proximal duct cells which secrete water under baseline conditions. We find the change in the remaining cells includes a 95.8% reduction in ENaC expression, enabling us to reproduce all experimental ionic concentrations within 9 mM. These findings provide a mechanistic basis for the observations and will guide the further development of gene transfer therapy for salivary hypofunction. NEW & NOTEWORTHY Following transfection of aquaporin into the parotid ducts of minipigs with salivary hypofunction, the resulting increase in salivary flow rates contradicts current understanding of ductal fluid transport. We show that the change in saliva electrochemistry and flow rate can be explained by changes in expression of ion transporters in the ductal cell membranes, using a mathematical model replicating a single parotid duct. PMID:27932503

Computational modeling of epithelial fluid and ion transport in the parotid duct after transfection of human aquaporin-1.

PubMed

Fong, Shelley; Chiorini, John A; Sneyd, James; Suresh, Vinod

2017-02-01

Previous studies have shown that localized delivery of the aquaporin-1 (AQP1) gene to the parotid duct can restore saliva flow in minipigs following irradiation-induced salivary hypofunction. The resulting flow rate and electrochemistry of secreted saliva contradicts current understanding of ductal fluid transport. We hypothesized that changes in expression of ion transport proteins have occurred following AQP1 transfection. We use a mathematical model of ion and fluid transport across the parotid duct epithelial cells to predict the expression profile of ion transporters that are consistent with the experimental measurements of saliva composition and secretion rates. Using a baseline set of parameters, the model reproduces the data for the irradiated, non-AQP1-transfected case. We propose three scenarios which may have occurred after transfection, which differ in the location of the AQP1 gene. The first scenario places AQP1 within nonsecretory cells, and requires that epithelial sodium channel (ENaC) expression is greatly reduced (1.3% of baseline), and ductal bicarbonate concentration is increased from 40.6 to 137.0 mM, to drive water secretion into the duct. The second scenario introduces the AQP1 gene into all ductal cells. The final scenario has AQP1 primarily in the proximal duct cells which secrete water under baseline conditions. We find the change in the remaining cells includes a 95.8% reduction in ENaC expression, enabling us to reproduce all experimental ionic concentrations within 9 mM. These findings provide a mechanistic basis for the observations and will guide the further development of gene transfer therapy for salivary hypofunction. Following transfection of aquaporin into the parotid ducts of minipigs with salivary hypofunction, the resulting increase in salivary flow rates contradicts current understanding of ductal fluid transport. We show that the change in saliva electrochemistry and flow rate can be explained by changes in expression of ion transporters in the ductal cell membranes, using a mathematical model replicating a single parotid duct. Copyright © 2017 the American Physiological Society.

Induction of pancreatic duct cells of neonatal rats into insulin-producing cells with fetal bovine serum: A natural protocol and its use for patch clamp experiments

PubMed Central

Leng, San-Hua; Lu, Fu-Er

2005-01-01

AIM: To induce the pancreatic duct cells into endocrine cells with a new natural protocol for electrophysiological study. METHODS: The pancreatic duct cells of neonatal rats were isolated, cultured and induced into endocrine cells with 15% fetal bovine serum for a period of 20 d. During this period, insulin secretion, MTT value, and morphological change of neonatal and adult pancreatic islet cells were comparatively investigated. Pancreatic β-cells were identified by morphological and electrophysiological characteristics, while ATP sensitive potassium channels (KATP), voltage-dependent potassium channels (KV), and voltage-dependent calcium channels (KCA) in β-cells were identified by patch clamp technique. RESULTS: After incubation with fetal bovine serum, the neonatal duct cells budded out, changed from duct-like cells into islet clusters. In the first 4 d, MTT value and insulin secretion increased slowly (MTT value from 0.024±0.003 to 0.028±0.003, insulin secretion from 2.6±0.6 to 3.1±0.8 mIU/L). Then MTT value and insulin secretion increased quickly from d 5 to d 10 (MTT value from 0.028±0.003 to 0.052±0.008, insulin secretion from 3.1±0.8 to 18.3±2.6 mIU/L), then reached high plateau (MTT value >0.052±0.008, insulin secretion >18.3±2.6 mIU/L). In contrast, for the isolated adult pancreatic islet cells, both insulin release and MTT value were stable in the first 4 d (MTT value from 0.029±0.01 to 0.031±0.011, insulin secretion from 13.9±3.1 to 14.3±3.3 mIU/L), but afterwards they reduced gradually (MTT value <0.031±0.011, insulin secretion <8.2±1.5 mIU/L), and the pancreatic islet cells became dispersed, broken or atrophied correspondingly. The differentiated neonatal cells were identified as pancreatic islet cells by dithizone staining method, and pancreatic β-cells were further identified by both morphological features and electrophysiological characteristics, i.e. the existence of recording currents from KATP, KV, and KCA. CONCLUSION: Islet cells differentiated from neonatal pancreatic duct cells with the new natural protocol are more advantageous in performing patch clamp study over the isolated adult pancreatic islet cells. PMID:16437601

cAMP-dependent chloride secretion mediates tubule enlargement and cyst formation by cultured mammalian collecting duct cells.

PubMed

Montesano, Roberto; Ghzili, Hafida; Carrozzino, Fabio; Rossier, Bernard C; Féraille, Eric

2009-02-01

Polycystic kidney diseases result from disruption of the genetically defined program that controls the size and geometry of renal tubules. Cysts which frequently arise from the collecting duct (CD) result from cell proliferation and fluid secretion. From mCCD(cl1) cells, a differentiated mouse CD cell line, we isolated a clonal subpopulation (mCCD-N21) that retains morphogenetic capacity. When grown in three-dimensional gels, mCCD-N21 cells formed highly organized tubular structures consisting of a palisade of polarized epithelial cells surrounding a cylindrical lumen. Subsequent addition of cAMP-elevating agents (forskolin or cholera toxin) or of membrane-permeable cAMP analogs (CPT-cAMP) resulted in rapid and progressive dilatation of existing tubules, leading to the formation of cystlike structures. When grown on filters, mCCD-N21 cells exhibited a high transepithelial resistance as well as aldosterone- and/or vasopressin-induced amiloride-sensitive and -insensitive current. The latter was in part inhibited by Na(+)-K(+)-2Cl(-) cotransporter (bumetanide) and chloride channel (NPPB) inhibitors. Real-time PCR analysis confirmed the expression of NKCC1, the ubiquitous Na(+)-K(+)-2Cl(-) cotransporter and cystic fibrosis transmembrane regulator (CFTR) in mCCD-N21 cells. Tubule enlargement and cyst formation were prevented by inhibitors of Na(+)-K(+)-2Cl(-) cotransporters (bumetanide or ethacrynic acid) or CFTR (NPPB or CFTR inhibitor-172). These results further support the notion that cAMP signaling plays a key role in renal cyst formation, at least in part by promoting chloride-driven fluid secretion. This new in vitro model of tubule-to-cyst conversion affords a unique opportunity for investigating the molecular mechanisms that govern the architecture of epithelial tubes, as well as for dissecting the pathophysiological processes underlying cystic kidney diseases.

Cystogenesis in ARPKD results from increased apoptosis in collecting duct epithelial cells of Pkhd1 mutant kidneys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Bo; Department of Medicine, Vanderbilt University, Nashville, TN 37232; He, Xiusheng

2011-01-15

Mutations in the PKHD1 gene result in autosomal recessive polycystic kidney disease (ARPKD) in humans. To determine the molecular mechanism of the cystogenesis in ARPKD, we recently generated a mouse model for ARPKD that carries a targeted mutation in the mouse orthologue of human PKHD1. The homozygous mutant mice display hepatorenal cysts whose phenotypes are similar to those of human ARPKD patients. By littermates of this mouse, we developed two immortalized renal collecting duct cell lines with Pkhd1 and two without. Under nonpermissive culture conditions, the Pkhd1{sup -/-} renal cells displayed aberrant cell-cell contacts and tubulomorphogenesis. The Pkhd1{sup -/-} cellsmore » also showed significantly reduced cell proliferation and elevated apoptosis. To validate this finding in vivo, we examined proliferation and apoptosis in the kidneys of Pkhd1{sup -/-} mice and their wildtype littermates. Using proliferation (PCNA and Histone-3) and apoptosis (TUNEL and caspase-3) markers, similar results were obtained in the Pkhd1{sup -/-} kidney tissues as in the cells. To identify the molecular basis of these findings, we analyzed the effect of Pkhd1 loss on multiple putative signaling regulators. We demonstrated that the loss of Pkhd1 disrupts multiple major phosphorylations of focal adhesion kinase (FAK), and these disruptions either inhibit the Ras/C-Raf pathways to suppress MEK/ERK activity and ultimately reduce cell proliferation, or suppress PDK1/AKT to upregulate Bax/caspase-9/caspase-3 and promote apoptosis. Our findings indicate that apoptosis may be a major player in the cyst formation in ARPKD, which may lead to new therapeutic strategies for human ARPKD.« less

Phospholipase D Is Involved in the Formation of Golgi Associated Clathrin Coated Vesicles in Human Parotid Duct Cells

PubMed Central

Brito de Souza, Lorena; Pinto da Silva, Luis Lamberti; Jamur, Maria Célia; Oliver, Constance

2014-01-01

Phospholipase D (PLD) has been implicated in many cellular functions, such as vesicle trafficking, exocytosis, differentiation, and proliferation. The aim of this study was to characterize the role of PLD in HSY cells, a human cell line originating from the intercalated duct of the parotid gland. As the function and intracellular localization of PLD varies according to cell type, initially, the intracellular localization of PLD1 and PLD2 was determined. By immunofluorescence, PLD1 and PLD2 both showed a punctate cytoplasmic distribution with extensive co-localization with TGN-46. PLD1 was also found in the nucleus, while PLD2 was associated with the plasma membrane. Treatment of cells with the primary alcohol 1-butanol inhibits the hydrolysis of phosphatidylcoline by PLD thereby suppressing phosphatidic acid (PA) production. In untreated HSY cells, there was only a slight co-localization of PLD with the clathrin coated vesicles. When HSY cells were incubated with 1-butanol the total number of clathrin coated vesicles increased, especially in the juxtanuclear region and the co-localization of PLD with the clathrin coated vesicles was augmented. Transmission electron microscopy confirmed that the number of Golgi-associated coated vesicles was greater. Treatment with 1-butanol also affected the Golgi apparatus, increasing the volume of the Golgi saccules. The decrease in PA levels after treatment with 1-butanol likewise resulted in an accumulation of enlarged lysosomes in the perinuclear region. Therefore, in HSY cells PLD appears to be involved in the formation of Golgi associated clathrin coated vesicles as well as in the structural maintenance of the Golgi apparatus. PMID:24618697

Rapamycin inhibition of mTORC1 reverses lithium-induced proliferation of renal collecting duct cells

PubMed Central

Gao, Yang; Romero-Aleshire, Melissa J.; Cai, Qi; Price, Theodore J.

2013-01-01

Nephrogenic diabetes insipidus (NDI) is the most common renal side effect in patients undergoing lithium therapy for bipolar affective disorders. Approximately 2 million US patients take lithium of whom ∼50% will have altered renal function and develop NDI (2, 37). Lithium-induced NDI is a defect in the urinary concentrating mechanism. Lithium therapy also leads to proliferation and abundant renal cysts (microcysts), commonly in the collecting ducts of the cortico-medullary region. The mTOR pathway integrates nutrient and mitogen signals to control cell proliferation and cell growth (size) via the mTOR Complex 1 (mTORC1). To address our hypothesis that mTOR activation may be responsible for lithium-induced proliferation of collecting ducts, we fed mice lithium chronically and assessed mTORC1 signaling in the renal medulla. We demonstrate that mTOR signaling is activated in the renal collecting ducts of lithium-treated mice; lithium increased the phosphorylation of rS6 (Ser240/Ser244), p-TSC2 (Thr1462), and p-mTOR (Ser2448). Consistent with our hypothesis, treatment with rapamycin, an allosteric inhibitor of mTOR, reversed lithium-induced proliferation of medullary collecting duct cells and reduced levels of p-rS6 and p-mTOR. Medullary levels of p-GSK3β were increased in the renal medullas of lithium-treated mice and remained elevated following rapamycin treatment. However, mTOR inhibition did not improve lithium-induced NDI and did not restore the expression of collecting duct proteins aquaporin-2 or UT-A1. PMID:23884148

Salivary duct carcinoma with rhabdoid features: Report of 2 cases with immunohistochemical and ultrastructural analyses

PubMed Central

Kusafuka, Kimihide; Onitsuka, Tetsuro; Muramatsu, Koji; Miki, Tomoko; Murai, Chika; Suda, Toshihito; Fuke, Tomohito; Kamijo, Tomoyuki; Iida, Yoshiyuki; Nakajima, Takashi

2014-01-01

Background Salivary duct carcinoma with rhabdoid features is extremely rare. Methods We report 2 cases of salivary duct carcinoma with rhabdoid features treated at our institution. Results Case 1 was a 44-year-old Japanese man who had swelling in the left parotid region. This tumor consisted of residual pleomorphic adenoma and widely invasive carcinoma, which showed a diffuse growth pattern by atypical rhabdoid cells. Case 2 was a 66-year-old Japanese man who had swelling of the right cervical region. This submandibular tumor was also composed of both residual pleomorphic adenoma region and invasive adenocarcinoma components, whereas some metastatic lesions were purely composed of rhabdoid cells. Such cells were strongly and diffusely positive for cytokeratins (CKs), gross cystic disease fluid protein-15 (GCDFP), and androgen receptor (AR). Case 1 was also positive for Her-2 and p53. Conclusion Both patients were diagnosed with carcinoma ex pleomorphic adenoma and their carcinomatous components were composed of salivary duct carcinoma with rhabdoid features, which is a highly aggressive tumor, similar to salivary duct carcinoma. © 2013 The Authors. Head & Neck published by Wiley Periodicals, Inc. Head Neck 36: E28–E35, 2014 PMID:24038506

Molecular basis of potassium channels in pancreatic duct epithelial cells

PubMed Central

Hayashi, Mikio; Novak, Ivana

2013-01-01

Potassium channels regulate excitability, epithelial ion transport, proliferation, and apoptosis. In pancreatic ducts, K+ channels hyperpolarize the membrane potential and provide the driving force for anion secretion. This review focuses on the molecular candidates of functional K+ channels in pancreatic duct cells, including KCNN4 (KCa3.1), KCNMA1 (KCa1.1), KCNQ1 (Kv7.1), KCNH2 (Kv11.1), KCNH5 (Kv10.2), KCNT1 (KCa4.1), KCNT2 (KCa4.2), and KCNK5 (K2P5.1). We will give an overview of K+ channels with respect to their electrophysiological and pharmacological characteristics and regulation, which we know from other cell types, preferably in epithelia, and, where known, their identification and functions in pancreatic ducts and in adenocarcinoma cells. We conclude by pointing out some outstanding questions and future directions in pancreatic K+ channel research with respect to the physiology of secretion and pancreatic pathologies, including pancreatitis, cystic fibrosis, and cancer, in which the dysregulation or altered expression of K+ channels may be of importance. PMID:23962792

Observations on the anterior testicular ducts in snakes with emphasis on sea snakes and ultrastructure in the yellow-bellied sea snake, Pelamis platurus.

PubMed

Sever, David M; Freeborn, Layla R

2012-03-01

The anterior testicular ducts of squamates transport sperm from the seminiferous tubules to the ductus deferens. These ducts consist of the rete testis, ductuli efferentes, and ductus epididymis. Many histological and a few ultrastructural studies of the squamate reproductive tract exist, but none concern the Hydrophiidae, the sea snakes and sea kraits. In this study, we describe the anterior testicular ducts of six species of hydrophiid snakes as well as representatives from the Elapidae, Homolapsidae, Leptotyphlopidae, and Uropeltidae. In addition, we examine the ultrastructure of these ducts in the yellow-bellied Sea Snake, Pelamis platurus, only the third such study on snakes. The anterior testicular ducts are similar in histology in all species examined. The rete testis is simple squamous or cuboidal epithelium and transports sperm from the seminiferous tubules to the ductuli efferentes in the extratesticular epididymal sheath. The ductuli efferentes are branched, convoluted tubules composed of simple cuboidal, ciliated epithelium, and many species possess periodic acid-Schiff+ granules in the cytoplasm. The ductus epididymis at the light microscopy level appears composed of pseudostratified columnar epithelium. At the ultrastructural level, the rete testis and ductuli efferentes of P. platurus possess numerous small coated vesicles and lack secretory vacuoles. Apocrine blebs in the ductuli efferentes, however, indicate secretory activity, possibly by a constitutive pathway. Ultrastructure reveals three types of cells in the ductus epididymis of P. platurus: columnar principal cells, squamous basal cells, and mitochondria-rich apical cells. This is the first report of apical cells in a snake. In addition, occasional principal cells possess a single cilium, which has not been reported in reptiles previously but is known in some birds. Finally, the ductus epididymis of P. platurus differs from other snakes that have been studied in possession of apical, biphasic secretory vacuoles. All of the proximal ducts are characterized by widening of adjacent plasma membranes into wide intercellular spaces, especially between the principal cells of the ductus epididymis. Our results contribute to a larger, collaborative study of the evolution of the squamate reproductive tract and to the potential for utilizing cellular characters in future phylogenetic inferences. Copyright © 2011 Wiley Periodicals, Inc.

Characterization of human pancreatic progenitor cells.

PubMed

Noguchi, Hirofumi; Naziruddin, Bashoo; Jackson, Andrew; Shimoda, Masayuki; Ikemoto, Tetsuya; Fujita, Yasutaka; Chujo, Daisuke; Takita, Morihito; Kobayashi, Naoya; Onaca, Nicholas; Hayashi, Shuji; Levy, Marlon F; Matsumoto, Shinichi

2010-01-01

β-Cell replacement therapy via islet transplantation is an effective treatment for diabetes mellitus, but its widespread use is severely limited by the shortage of donor organs. Because pancreatic stem/progenitor cells are abundantly available in the pancreas of these patients and in donor organs, the cells could become a useful target for β-cell replacement therapy. We previously established a mouse pancreatic stem cell line without genetic manipulation. In this study, we used the techniques to identify and isolate human pancreatic stem/progenitor cells. The cells from a duct-rich population were cultured in 23 kinds of culture media, based on media for mouse pancreatic stem cells or for human embryonic stem cells. The cells in serum-free media formed "cobblestone" morphologies, similar to a mouse pancreatic stem cell line. On the other hand, the cells in serum-containing medium and the medium for human embryonic stem cells formed "fibroblast-like" morphologies. The cells divided actively until day 30, and the population doubling level (PDL) was 6-10. However, the cells stopped dividing after 30 days in any culture conditions. During the cultures, the nucleus/cytoplasm (N/C) ratio decreased, suggesting that the cells entered senescence. Exendin-4 treatment and transduction of PDX-1 and NeuroD proteins by protein transduction technology into the cells induced insulin and pancreas-related gene expression. Although the duplications of these cells were limited, this approach could provide a potential new source of insulin-producing cells for transplantation.

Plectin controls biliary tree architecture and stability in cholestasis.

PubMed

Jirouskova, Marketa; Nepomucka, Katerina; Oyman-Eyrilmez, Gizem; Kalendova, Alzbeta; Havelkova, Helena; Sarnova, Lenka; Chalupsky, Karel; Schuster, Bjoern; Benada, Oldrich; Miksatkova, Petra; Kuchar, Martin; Fabian, Ondrej; Sedlacek, Radislav; Wiche, Gerhard; Gregor, Martin

2018-05-01

Plectin, a highly versatile cytolinker protein, controls intermediate filament cytoarchitecture and cellular stress response. In the present study, we investigate the role of plectin in the liver under basal conditions and in experimental cholestasis. We generated liver-specific plectin knockout (Ple Δalb ) mice and analyzed them using two cholestatic liver injury models: bile duct ligation (BDL) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding. Primary hepatocytes and a cholangiocyte cell line were used to address the impact of plectin on keratin filament organization and stability in vitro. Plectin deficiency in hepatocytes and biliary epithelial cells led to aberrant keratin filament network organization, biliary tree malformations, and collapse of bile ducts and ductules. Further, plectin ablation significantly aggravated biliary damage upon cholestatic challenge. Coincidently, we observed a significant expansion of A6-positive progenitor cells in Ple Δalb livers. After BDL, plectin-deficient bile ducts were prominently dilated with more frequent ruptures corresponding to an increased number of bile infarcts. In addition, more abundant keratin aggregates indicated less stable keratin filaments in Ple Δalb hepatocytes. A transmission electron microscopy analysis revealed a compromised tight junction formation in plectin-deficient biliary epithelial cells. In addition, protein profiling showed increased expression of the adherens junction protein E-Cadherin, and inefficient upregulation of the desmosomal protein desmoplakin in response to BDL. In vitro analyses revealed a higher susceptibility of plectin-deficient keratin networks to stress-induced collapse, paralleled by elevated activation of p38 MAP kinase. Our study shows that by maintaining proper keratin network cytoarchitecture and biliary epithelial stability, plectin plays a critical role in protecting the liver from stress elicited by cholestasis. Plectin is a cytolinker protein capable of interconnecting all three cytoskeletal filament systems and linking them to plasma membrane-bound junctional complexes. In liver, the plectin-controlled cytoskeleton mechanically stabilizes epithelial cells and provides them with the capacity to adapt to increased bile pressure under cholestasis. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

TBIEM3D: A Computer Program for Predicting Ducted Fan Engine Noise. Version 1.1

NASA Technical Reports Server (NTRS)

Dunn, M. H.

1997-01-01

This document describes the usage of the ducted fan noise prediction program TBIEM3D (Thin duct - Boundary Integral Equation Method - 3 Dimensional). A scattering approach is adopted in which the acoustic pressure field is split into known incident and unknown scattered parts. The scattering of fan-generated noise by a finite length circular cylinder in a uniform flow field is considered. The fan noise is modeled by a collection of spinning point thrust dipoles. The program, based on a Boundary Integral Equation Method (BIEM), calculates circumferential modal coefficients of the acoustic pressure at user-specified field locations. The duct interior can be of the hard wall type or lined. The duct liner is axisymmetric, locally reactive, and can be uniform or axially segmented. TBIEM3D is written in the FORTRAN programming language. Input to TBIEM3D is minimal and consists of geometric and kinematic parameters. Discretization and numerical parameters are determined automatically by the code. Several examples are presented to demonstrate TBIEM3D capabilities.

Turbofan Acoustic Propagation and Radiation

NASA Technical Reports Server (NTRS)

Eversman, Walter

2000-01-01

This document describes progress in the development of finite element codes for the prediction of near and far field acoustic radiation from the inlet and aft fan ducts of turbofan engines. The report consists of nine papers which have appeared in archival journals and conference proceedings, or are presently in review for publication. Topics included are: 1. Aft Fan Duct Acoustic Radiation; 2. Mapped Infinite Wave Envelope Elements for Acoustic Radiation in a Uniformly Moving Medium; 3. A Reflection Free Boundary Condition for Propagation in Uniform Flow Using Mapped Infinite Wave Envelope Elements; 4. A Numerical Comparison Between Multiple-Scales and FEM Solution for Sound Propagation in Lined Flow Ducts; 5. Acoustic Propagation at High Frequencies in Ducts; 6. The Boundary Condition at an Impedance Wall in a Nonuniform Duct with Potential Flow; 7. A Reverse Flow Theorem and Acoustic Reciprocity in Compressible Potential Flows; 8. Reciprocity and Acoustics Power in One Dimensional Compressible Potential Flows; and 9. Numerical Experiments on Acoustic Reciprocity in Compressible Potential Flows.

Morphology of the kidney of adult bowfin, Amia calva, with emphasis on "renal chloride cells" in the tubule.

PubMed

Youson, J H; Butler, D G

1988-05-01

The nephron of adult bowfin, Amia calva, was described using light and electron microscopic techniques. The kidney of the bowfin possesses an abundant supply of renal corpuscles with each consisting of a glomerulus and a Bowman's capsule of visceral (podocyte) and parietal layers. No juxtaglomerular apparatus is present. The epithelium of the tubule is continuous with the parietal epithelium and is divisible in descending order into neck, first proximal, second proximal, first distal, second distal, and collecting segments. The tubules drain into a complex system of collecting ducts that ultimately unite with the main excretory duct, the archinephric duct. Mucous cells are the dominant cell throughout the entire ductular system. Nephrostomes are dispersed along the kidney capsule. The neck segment has a ciliated epithelium, and while both proximal segments possess a prominent brush border, the fine structure of the first implies involvement in protein absorption and the second in the transport and reabsorption of solutes. The cells of the first distal segment are characterized by deep infolding of the plasma membrane and a rich supply of mitochondria suggesting the presence of a mechanism for ion transport. The second distal segment is composed of cells resembling the chloride cells of fishes and these cells are present in progressively decreasing numbers in the collecting segment and duct system so that only a few are present in the epithelium of the archinephric duct. The "renal chloride cells" possess an abundant network of smooth tubules and numerous mitochondria with a rich supply of cristae. Glycogen is also a conspicuous component of these cells. The presence of "renal chloride cells" in this freshwater holostean, in other relatively primitive freshwater teleosts, and in larval and adult lampreys is discussed with reference to both phylogeny and the need for a special mechanism for renal ion conservation through absorption.

The potent activation of Ca(2+)-activated K(+) current by NVP-AUY922 in the human pancreatic duct cell line (PANC-1) possibly independent of heat shock protein 90 inhibition.

PubMed

Chiang, Nai-Jung; Wu, Sheng-Nan; Chen, Li-Tzong

2015-04-01

NVP-AUY922 (AUY) is a potent inhibitor of heat shock protein 90 (HSP90). Whether this compound can exert additional effects on membrane ion channels remains elusive. We investigated the effect of AUY on ion currents in human pancreatic duct epithelial cells (PDECs), including PANC-1 and MIA PaCa-2. AUY increased the amplitude of the K(+) current (IK) in PANC-1 cells shown by whole-cell configuration. Single-channel recordings revealed a large-conductance Ca(2+)-activated K(+) (BKCa) channel in PANC-1, but not in MIA PaCa-2. In cell-attached mode, AUY increased the probability of BKCa channel opening and also potentiated the activity of stretch-induced channels. However, other HSP inhibitors, 17-AAG or BIIB021 only slightly increased the activity of BKCa channels. In inside-out recordings, sodium hydrosulphide or caffeic acid phenethyl ester increased the activity of BKCa channels, but AUY did not. We further evaluated whether conductance of Ca(2+)-activated K(+) channels (IK(Ca)) influenced secretion of HCO3(-) and fluid in PDECs by using a modified Whitcomb-Ermentrout model. Simulation studies showed that an increase in IK(Ca) resulted in additional secretion of HCO3(-) and fluid by mimicking the effect of AUY in PDECs. Collectively, AUY can interact with the BKCa channel to largely increase IK(Ca) in PDECs. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Da Vinci robot-assisted anatomic left hemihepatectomy and biliary reconstruction.

PubMed

Wang, Zhifei; Liu, Quanda; Chen, Junzhou; Duan, Weihong; Zhou, Ningxin

2013-06-01

Since the introduction of Da Vinci robotic surgery, more and more complicated surgeries can now be performed robotically, yet there have been very few on robotic hepatectomy, especially when billiary reconstruction is involved. The video shows our initial experience with an anatomic hepatectomy using Da Vinci surgical robot. In this case, we also conducted billiary reconstruction due to the anatomic abnormality of bile duct, while applying the choledochoscopy. The preoperative diagnosis is primary liver carcinoma, tumor thrombi in bile duct, and hepatitis B. First, the gallbladder was resected, and cystic artery and duct were identified. After opening of the common bile duct above the junction, the choledochoscopy was performed. Tumor thrombi were found in common bile duct and left hepatic duct, and they were all removed. Left branches hepatic artery and portal vein were dissected, ligated, and divided. Thrombi in the left hepatic duct were removed also. After marking the cutting line along the ischemic boarder, liver parenchyma was transected using robotic harmonic scalpel. Branches of ducts were encountered and managed by either direct coagulating or dividing after clipping. The left hepatic vein was visualized, exposed, and divided during hepatectomy. Two T tubes were placed into common hepatic duct and the proximal cutting end of right anterior bile duct which was found to join the left hepatic duct, respectively. The operation went on successfully. The operation time was 410 minutes, the blood loss was 200 mL. The pathologic diagnosis was introductal papillary adenocarcinoma of left hepatic duct. The patient went on well postoperatively and was followed up for 22 months till now. Postoperative computed tomography examination showed no recurrence. Da Vinci-assisted robotic hepatectomy can be performed safely in the hands of experienced hepatobilliary surgeons, and choledochoscopy can be combined for bile duct exploration. With the advantages of Da Vinci robot system, complicated billiary reconstruction can be performed (http://links.lww.com/SLE/A74).

Development of the genital ducts and external genitalia in the early human embryo.

PubMed

Sajjad, Yasmin

2010-10-01

The course of development of the human genital tract is undifferentiated to the 9th week of development. At this time two symmetrical paired ducts known as the mesonephric (MD) and paramesonephric ducts (PMD) are present, which together with the urogenital sinus provide the tissue sources for internal and external genital development. Normal differentiation of the bipotential external genitalia and reproductive ducts are dependent upon the presence or absence of certain hormones. Masculinization of the internal and external genitalia during fetal development depends on the existence of two discrete testicular hormones. Testosterone secreted from Leydig cells induces the differentiation of the mesonephric ducts into the epididymis, vasa deferentia and seminal vesicles, whereas anti-Müllerian hormone (AMH) produced by Sertoli cells induces the regression of the paramesonephric ducts. The absence of AMH action in early fetal life results in the formation of the fallopian tubes, uterus and upper third of the vagina. In some target tissues, testosterone is converted to dihydrotestosterone, which is responsible for the masculinization of the urogenital sinus and external genitalia. © 2010 The Author. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

A Non-linear Lifting Line Model for Design and Analysis of Trochoidal Propulsors

NASA Astrophysics Data System (ADS)

Roesler, Bernard; Epps, Brenden

2014-11-01

Flapping wing propulsors may increase the propulsive efficiency of large shipping vessels. A comparison of the design of a notional propulsor for a large shipping vessel with (a) a conventional ducted propeller versus (b) a flapping wing propulsor is presented. Calculations for flapping wing propulsors are performed using an open-source MATLAB software suite developed by the authors, CyROD, implementing an unsteady lifting-line model with free vortex wake roll-up to study the non-linear effects of foil-wake, and foil-foil interactions. Improvements to the traditional lifting line theory are made using further discretization of the wake vortex ring spacing near the trailing edge. Considerations of packaging options for a flapping wing propulsor on a large shipping vessel are presented, and compared with those for a conventional ducted propeller.

Immunohistochemical localization of D-aspartate oxidase in porcine peripheral tissues.

PubMed

Yamamoto, Atsushi; Tanaka, Hiroyuki; Ishida, Tetsuo; Horiike, Kihachiro

2011-07-01

D-Aspartate (D-Asp) is an endogenous substance in mammals. Degradation of D-Asp is carried out only by D-aspartate oxidase (DDO). We measured DDO activity in porcine tissues, and produced an anti-porcine DDO antibody to examine the cellular localization of DDO. All the tissues examined showed DDO activities, whereas the substrate D-Asp was not detected in kidney cortex, liver, heart, and gastric mucosa. In the kidney, intensive immunohistochemical staining for DDO was found in the epithelial cells of the proximal tubules. In the liver, the epithelial cells of interlobular bile ducts, liver sinusoid-lining cells with cytoplasmic processes, and the smooth muscle cells of arterioles were strongly stained for DDO. In the heart, cardiomyocytes and the smooth muscle cells of arterioles showed DDO-immunoreactivity. In the gastric mucosa, only the chief cells were DDO-positive. These newly identified DDO-positive cells seem to actively degrade D-Asp to prevent an excess of D-Asp from exerting harmful effects on the respective functions of porcine tissues.

Development and characterization of a hydrogen peroxide-resistant cholangiocyte cell line: A novel model of oxidative stress-related cholangiocarcinoma genesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanan, Raynoo; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002; Techasen, Anchalee

Oxidative stress is a cause of inflammation–related diseases, including cancers. Cholangiocarcinoma is a liver cancer with bile duct epithelial cell phenotypes. Our previous studies in animal and human models indicated that oxidative stress is a major cause of cholangiocarcinoma development. Hydrogen peroxide (H{sub 2}O{sub 2}) can generate hydroxyl radicals, which damage lipids, proteins, and nucleic acids, leading to cell death. However, some cells can survive by adapting to oxidative stress conditions, and selective clonal expansion of these resistant cells would be involved in oxidative stress-related carcinogenesis. The present study aimed to establish H{sub 2}O{sub 2}-resistant cell line from an immortal cholangiocytemore » cell line (MMNK1) by chronic treatment with low-concentration H{sub 2}O{sub 2} (25 μM). After 72 days of induction, H{sub 2}O{sub 2}-resistant cell lines (ox-MMNK1-L) were obtained. The ox-MMNK1-L cell line showed H{sub 2}O{sub 2}-resistant properties, increasing the expression of the anti-oxidant genes catalase (CAT), superoxide dismutase-1 (SOD1), superoxide dismutase-2 (SOD2), and superoxide dismutase-3 (SOD3) and the enzyme activities of CAT and intracellular SODs. Furthermore, the resistant cells showed increased expression levels of an epigenetics-related gene, DNA methyltransferase-1 (DNMT1), when compared to the parental cells. Interestingly, the ox-MMNK1-L cell line had a significantly higher cell proliferation rate than the MMNK1 normal cell line. Moreover, ox-MMNK1-L cells showed pseudopodia formation and the loss of cell-to-cell adhesion (multi-layers) under additional oxidative stress (100 μM H{sub 2}O{sub 2}). These findings suggest that H{sub 2}O{sub 2}-resistant cells can be used as a model of oxidative stress-related cholangiocarcinoma genesis through molecular changes such as alteration of gene expression and epigenetic changes. - Highlights: • An H{sub 2}O{sub 2}-resistant ox-MMNK1-L cells was established from immortalized cholangiocytes. • The resistance was acquired by daily treatment of low H{sub 2}O{sub 2} (25 μM) for 15 passages. • The cells highly expressed catalase, SODs and DNMT1 with rapid cell proliferation. • Pseudopodia and the loss of cell-to-cell adhesion appeared by 100 μM H{sub 2}O{sub 2} treatment. • The resistant cells can be used as a model of oxidative stress-related carcinogenesis.« less

Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues.

PubMed

Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

2008-10-01

Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and breast cancer tissue. Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed Western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Applying the four IDE-directed antibodies, we demonstrated IDE expression at the protein level, by means of immunoblotting and immunocytochemistry, in each of the tumor cell lines analyzed. Insulin-degrading enzyme protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in each of the cell lines and tissues assessed. In conclusion, we performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells thus extending our knowledge on the cellular and tissue distribution of IDE, an enzyme which to date has mainly been studied in connection with Alzheimer's disease and diabetes but not in cancer.

[Clinicopathologic features of drug-induced vanishing bile duct syndrome].

PubMed

Ye, L H; Wang, C K; Zhang, H C; Liu, Z Q; Zheng, H W

2017-04-20

Vanishing bile duct syndrome (VBDS) manifests as progressive destruction and disappearance of the intrahepatic bile duct caused by various factors and cholestasis. VBDS associated with drug-induced liver injury (D-VBDS) is an important etiology of VBDS, and immune disorder or immune imbalance may be the main pathogenesis. According to its clinical symptoms, serological markers, and course of the disease, D-VBDS is classified into major form and minor form, and its clinical features are based on various pathomorphological findings. Its prognosis is associated various factors including regeneration of bile duct cells, number of bile duct injuries, level and range of bile duct injury, bile duct proliferation, and compensatory shunt of bile duct branches. This disease has various clinical outcomes; most patients have good prognosis after drug withdrawal, and some patients may experience cholestatic cirrhosis, liver failure, and even death. Due to the clinical manifestation and biochemical changes are similar to the primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), it need to identify by clinical physician.

α7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile-Duct Ligated Mice.

PubMed

Ehrlich, Laurent; O'Brien, April; Hall, Chad; White, Tori; Chen, Lixian; Wu, Nan; Venter, Julie; Scrushy, Marinda; Mubarak, Muhammad; Meng, Fanyin; Dostal, David; Wu, Chaodong; Lairmore, Terry C; Alpini, Gianfranco; Glaser, Shannon

2018-03-26

α7-nAChR is a nicotinic acetylcholine receptor (specifically expressed on hepatic stellate cells, Kupffer cells, and cholangiocytes) that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. Bile-duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile-duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition. Immunofluorescence was performed to assess co-localization of α7-nAChR with bile ducts (co-stained with CK-19) and hepatic stellate cells (HSCs) (co-stained with desmin). The mRNA expression of α7-nAChR, Ki67/PCNA (proliferation), fibrosis genes (TGF-β1, Fibronectin-1, Col1α1, and α-SMA), and inflammatory markers (IL-6, IL-1β, and TNFα) was measured by real-time PCR. Biliary TGF-β1 and hepatic CD68 (Kupffer cell marker) expression was assessed using IHC. α7-nAChR immunoreactivity was observed in both bile ducts and HSCs and increased following BDL. α7-nAChR-/- BDL mice exhibited decreased: (i) bile duct mass, liver fibrosis, and inflammation; and (ii) immunoreactivity of TGF-1 as well as expression of fibrosis genes compared to WT BDL mice. α7-nAChR activation triggers biliary proliferation and liver fibrosis and may be a therapeutic target in managing extra-hepatic biliary obstruction.

Positive predictive value of cholescintigraphy in common bile duct obstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lecklitner, M.L.; Austin, A.R.; Benedetto, A.R.

1986-09-01

Technetium-99m DISIDA imaging was employed in 400 patients to differentiate obstruction of the common bile duct from medical and other surgical causes of hyperbilirubinemia. Sequential anterior images demonstrated variable degrees of liver uptake, yet there was no evidence of intrabiliary or extrabiliary radioactivity for at least 4 hr after injection in 25 patients. Twenty-three patients were surgically documented to have complete obstruction of the common bile duct. One patient had hepatitis, and another had sickle cell crisis without bile duct obstruction. The remaining patients had either partial or no obstruction of the common bile duct. We conclude that the presencemore » of liver uptake without evident biliary excretion by 4 hr on cholescintigraphy is highly sensitive and predictive of total obstruction of the common bile duct.« less

Prostaglandin E2 induces chloride secretion through crosstalk between cAMP and calcium signaling in mouse inner medullary collecting duct cells

PubMed Central

Rajagopal, Madhumitha; Thomas, Sheela V.; Kathpalia, Paru P.; Chen, Yu

2013-01-01

Under conditions of high dietary salt intake, prostaglandin E2 (PGE2) production is increased in the collecting duct and promotes urinary sodium chloride (NaCl) excretion; however, the molecular mechanisms by which PGE2 increases NaCl excretion in this context have not been clearly defined. We used the mouse inner medullary collecting duct (mIMCD)-K2 cell line to characterize mechanisms underlying PGE2-regulated NaCl transport. When epithelial Na+ channels were inhibited, PGE2 exclusively stimulated basolateral EP4 receptors to increase short-circuit current (IscPGE2). We found that IscPGE2 was sensitive to inhibition by H-89 and CFTR-172, indicating that EP4 receptors signal through protein kinase A to induce Cl− secretion via cystic fibrosis transmembrane conductance regulator (CFTR). Unexpectedly, we also found that IscPGE2 was sensitive to inhibition by BAPTA-AM (Ca2+ chelator), 2-aminoethoxydiphenyl borate (2-APB) (inositol triphosphate receptor blocker), and flufenamic acid (FFA) [Ca2+-activated Cl− channel (CACC) inhibitor], suggesting that EP4 receptors also signal through Ca2+ to induce Cl− secretion via CACC. Additionally, we observed that PGE2 stimulated an increase in Isc through crosstalk between cAMP and Ca2+ signaling; BAPTA-AM or 2-APB inhibited a component of IscPGE2 that was sensitive to CFTR-172 inhibition; H-89 inhibited a component of IscPGE2 that was sensitive to FFA inhibition. Together, our findings indicate that PGE2 activates basolateral EP4 receptors and signals through both cAMP and Ca2+ to stimulate Cl− secretion in IMCD-K2 cells. We propose that these signaling pathways, and the crosstalk between them, may provide a concerted mechanism for enhancing urinary NaCl excretion under conditions of high dietary NaCl intake. PMID:24284792

Expression of a Diverse Array of Ca2+-Activated K+ Channels (SK1/3, IK1, BK) that Functionally Couple to the Mechanosensitive TRPV4 Channel in the Collecting Duct System of Kidney.

PubMed

Li, Yue; Hu, Hongxiang; Butterworth, Michael B; Tian, Jin-Bin; Zhu, Michael X; O'Neil, Roger G

2016-01-01

The voltage- and Ca2+-activated, large conductance K+ channel (BK, maxi-K) is expressed in the collecting duct system of kidney where it underlies flow- and Ca2+-dependent K+ excretion. To determine if other Ca2+-activated K+ channels (KCa) may participate in this process, mouse kidney and the K+-secreting mouse cortical collecting duct (CCD) cell line, mCCDcl1, were assessed for TRPV4 and KCa channel expression and cross-talk. qPCR mRNA analysis and immunocytochemical staining demonstrated TRPV4 and KCa expression in mCCDcl1 cells and kidney connecting tubule (CNT) and CCD. Three subfamilies of KCa channels were revealed: the high Ca2+-binding affinity small-conductance SK channels, SK1and SK3, the intermediate conductance channel, IK1, and the low Ca2+-binding affinity, BK channel (BKα subunit). Apparent expression levels varied in CNT/CCD where analysis of CCD principal cells (PC) and intercalated cells (IC) demonstrated differential staining: SK1:PCIC, IK1:PC>IC, BKα:PC = IC, and TRPV4:PC>IC. Patch clamp analysis and fluorescence Ca2+ imaging of mCCDcl1 cells demonstrated potent TRPV4-mediated Ca2+ entry and strong functional cross-talk between TRPV4 and KCa channels. TRPV4-mediated Ca2+ influx activated each KCa channel, as evidenced by selective inhibition of KCa channels, with each active KCa channel enhancing Ca2+ entry (due to membrane hyperpolarization). Transepithelial electrical resistance (TEER) analysis of confluent mCCDcl1 cells grown on permeable supports further demonstrated this cross-talk where TRPV4 activation induce a decrease in TEER which was partially restored upon selective inhibition of each KCa channel. It is concluded that SK1/SK3 and IK1 are highly expressed along with BKα in CNT and CCD and are closely coupled to TRPV4 activation as observed in mCCDcl1 cells. The data support a model in CNT/CCD segments where strong cross talk between TRPV4-mediated Ca2+ influx and each KCa channel leads to enhance Ca2+ entry which will support activation of the low Ca2+-binding affinity BK channel to promote BK-mediated K+ secretion.

Modulation of Sodium/Iodide Symporter Expression in the Salivary Gland

PubMed Central

La Perle, Krista M.D.; Kim, Dong Chul; Hall, Nathan C.; Bobbey, Adam; Shen, Daniel H.; Nagy, Rebecca S.; Wakely, Paul E.; Lehman, Amy; Jarjoura, David

2013-01-01

Background Physiologic iodide-uptake, mediated by the sodium/iodide symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine–induced damage following 131I treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland. Methods NIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative 123I radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after 123I administration in 50 thyroid cancer patients. Results NIS is highly expressed in the basolateral membranes of the majority of striated ducts, yet weakly expressed in few intercalated and excretory duct cells. The ratio of 123I accumulation between parotid and submandibular glands is 2.38±0.19. However, the corresponding ratio of 123I accumulation normalized by volume of interest is 1.19±0.06. The percentage of NIS-positive striated duct cells in submandibular salivary glands was statistically greater than in parotid salivary glands, suggesting a higher clearance rate of saliva secretion in submandibular salivary glands. NIS expression in striated ducts was heterogeneously decreased or absent in sialoadenitis. Most ductal salivary gland tumors did not express NIS. However, Warthin's tumors of striated duct origin exhibited consistent and intense NIS staining, corresponding with radioactive iodine uptake. Conclusions NIS expression is tightly modulated during the transition of intercalated to striated ducts and striated to excretory ducts in salivary ductal cells. NIS expression in salivary glands is decreased during inflammation and tumor formation. Further investigation may identify molecular targets and/or pharmacologic agents that allow selective inhibition of NIS expression/activity in salivary glands during radioactive iodine treatment. PMID:23441638

A case of annular pancreas with Wirsung's duct encircling the duodenum: embryological hypothesis based on cholangiopancreatographic and immunohistochemical findings.

PubMed

Fukai, Manami; Kamisawa, Terumi; Horiguchi, Shin-Ichirou; Hishima, Tsunekazu; Kuruma, Sawako; Chiba, Kazuro; Koizumi, Satomi; Tabata, Taku; Nagao, Sayaka; Kikuyama, Masataka; Honda, Goro; Kurata, Masanao

2017-06-01

We present a resected case of annular pancreas in which Wirsung's duct encircled the duodenum and continued directly to the main pancreatic duct in the body and tail. Furthermore, Wirsung's duct coursed along the right side of the lower bile duct near the major duodenal papilla. Histologically, the islets of Langerhans in the annular pancreas were irregular in shape and were characterized by a striking abundance of pancreatic polypeptide (PP)-positive cells. The PP-rich area that encircled the duodenum was fused with the PP-poor area in the head of the pancreas. The following embryological hypothesis is proposed. The tip of the ventral pancreatic anlage adhered to the duodenal wall and stretched to form a ring during clockwise rotation. The rotation was incomplete, and the pancreatic duct did not cross over the lower bile duct. Since there was adequate ventral anlage in the lower part of the head of the pancreas, fusion between the ducts of the ventral and dorsal anlagen did not occur. The tip of the ventral anlage overgrew and adhered to the dorsal anlage, and the annular duct fused with the main duct of the dorsal anlage.

The acoustics of ducted propellers

NASA Astrophysics Data System (ADS)

Ali, Sherif F.

The return of the propeller to the long haul commercial service may be rapidly approaching in the form of advanced "prop fans". It is believed that the advanced turboprop will considerably reduce the operational cost. However, such aircraft will come into general use only if their noise levels meet the standards of community acceptability currently applied to existing aircraft. In this work a time-marching boundary-element technique is developed, and used to study the acoustics of ducted propeller. The numerical technique is developed in this work eliminated the inherent instability suffered by conventional approaches. The methodology is validated against other numerical and analytical results. The results show excellent agreement with the analytical solution and show no indication of unstable behavior. For the ducted propeller problem, the propeller is modeled by a rotating source-sink pairs, and the duct is modeled by rigid annular body of elliptical cross-section. Using the model and the developed technique, the effect of different parameters on the acoustic field is predicted and analyzed. This includes the effect of duct length, propeller axial location, and source Mach number. The results of this study show that installing a short duct around the propeller can reduce the noise that reaches an observer on a side line.

Expression of nestin and chromogranin in regeneration zones of rat pancreas.

PubMed

Ege, Bahadir; Dinc, Tolga; Kayilioglu, Selami Ilgaz; Tezel, Ekmel; Ersoy, Emin

2017-01-01

The particular signals that start and orchestrate the regeneration process in pancreas are not well understood yet. We aimed to investigate the expression of nestin and chromogranin A in pancreatic regeneration zones and a secondary objective, we assessed the efficiency of pancreatic duct ligation method in creation of a pancreatic regeneration model in rats. Partial (90%) pancreatectomy and pancreatic duct ligation were performed in Wistar rats, in order to create pancreatic regeneration models. Pancreatic tissues were examined histologically. Expression profiles were investigated by immunohistochemistry for nestin and chromogranin A. Nestin and chromogranin A expressions were observed in regeneration zones. Pancreatic regenerations zones were seen in pancreatic duct ligation group samples as well as partial pancreatectomy group. Nestin was expressed prominently in acinoductular metaplasia cells in regeneration zones. This was best demonstrated in the samples of pancreatic duct ligation group. In the subsequent sections of nestin positive sites, cytoplasmic positivity with chromogranin A was observed. This study confirms that nestin and chromogranin A can be detected in neogenesis-evoked pancreatic tissue, particularly in the acinoductular epithelium. Nestin and chromogranin A may be important markers to identify pancreatic stem cells. Pancreatic duct ligation can be used for creating pancreatic regeneration model in rats. Chromogranin A, Nestin, Pancreas, Regeneration, Stem cells.

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

PubMed Central

Shubin, Andrew D.; Felong, Timothy J.; Graunke, Dean; Ovitt, Catherine E.

2015-01-01

More than 40,000 patients are diagnosed with head and neck cancers annually in the United States with the vast majority receiving radiation therapy. Salivary glands are irreparably damaged by radiation therapy resulting in xerostomia, which severely affects patient quality of life. Cell-based therapies have shown some promise in mouse models of radiation-induced xerostomia, but they suffer from insufficient and inconsistent gland regeneration and accompanying secretory function. To aid in the development of regenerative therapies, poly(ethylene glycol) hydrogels were investigated for the encapsulation of primary submandibular gland (SMG) cells for tissue engineering applications. Different methods of hydrogel formation and cell preparation were examined to identify cytocompatible encapsulation conditions for SMG cells. Cell viability was much higher after thiol-ene polymerizations compared with conventional methacrylate polymerizations due to reduced membrane peroxidation and intracellular reactive oxygen species formation. In addition, the formation of multicellular microspheres before encapsulation maximized cell–cell contacts and increased viability of SMG cells over 14-day culture periods. Thiol-ene hydrogel-encapsulated microspheres also promoted SMG proliferation. Lineage tracing was employed to determine the cellular composition of hydrogel-encapsulated microspheres using markers for acinar (Mist1) and duct (Keratin5) cells. Our findings indicate that both acinar and duct cell phenotypes are present throughout the 14 day culture period. However, the acinar:duct cell ratios are reduced over time, likely due to duct cell proliferation. Altogether, permissive encapsulation methods for primary SMG cells have been identified that promote cell viability, proliferation, and maintenance of differentiated salivary gland cell phenotypes, which allows for translation of this approach for salivary gland tissue engineering applications. PMID:25762214

Breeding and Genetics Symposium: a systems biology definition for chicken semen quality.

PubMed

Froman, D P; Rhoads, D D

2013-02-01

Rooster semen is an effluent from paired reproductive tracts. Each tract includes a testis, epididymis, and deferent duct. Upon ejaculation, efficacy of sperm propulsion varies among roosters. This phenotype is sperm mobility, that is, the movement of sperm against resistance at body temperature. The present work 1) compares reproductive tract throughput between lines of chickens selected for low and high sperm mobility, 2) demonstrates how semen quality can be defined in terms of an interaction between reproductive tract throughput and the proportion of mobile sperm ejaculated, 3) confirms that phenotype can be linked to genomewide differences in SNPlotype, and 4) shows how breeding can affect semen quality. Sperm mobility phenotype distributions were based on the average of duplicate observations per male (n = 241 and 262 roosters for low and high lines, respectively). Distributions were skewed and normal for low and high lines, respectively. Subsequent analyses used these base populations as sources for test subjects. In the first analysis, 10 males were selected from the mode of each distribution, and sperm mobility data were evaluated by nested ANOVA. Variation was observed between lines (P < 0.0001) but not among males within lines (P = 0.980). Sperm mobility data along with data from paired reproductive tracts were used to estimate combined reproductive tract throughput. Whereas testicular output was 1.2-fold greater in the low line (P = 0.037), the output of mobile sperm per day was 10.5-fold greater in the high line (P < 0.0001). Deferent duct transit differed between tails of the low line (P < 0.0001) but not between the tails of the high line (P = 0.514). Males from the mode and upper tail of the low line were SNPlotyped using a 60k chip by DNA Landmarks. These test subjects were used to associate phenotype with SNPlotype because founder effects and genetic drift could be discounted. Loci of interest were found on multiple chromosomes. Loci on chromosome Z were of particular interest because roosters are homozygous for this sex chromosome and a pronounced maternal effect was observed in a prior heritability study. Midrange phenotypes were produced by crossing low and high sperm mobility lines. Our experimental outcomes demonstrate that genes affect reproductive tract function as well as sperm cell attributes and thereby make semen quality subject to genetic selection.

Unique cellular structures in the parotid gland of an Old world fruit bat, Pteropus lylei (Lyle's flying fox).

PubMed

Lanlua, Passara; Sricharoenvej, Sirinush; Niyomchan, Apichaya; Chico, Diane E

2007-01-01

Pteropus lylei (Lyle's flying fox), an Old World fruit bat, consumes only ripe fruit, which contains low protein and sodium. The carpophagous diet of P. lylei presents an adaptive challenge for salivary glands to conserve sufficient nutrition for living. Therefore, the parotid glands in both sexes were investigated by using light microscopy and transmission electron microscopy. No structural difference was observed in the parotid glands between sexes. The acinar cell contained dense serous secretory granules, prominent luminal microvilli and intercellular canaliculi. The intercalated duct exhibited simple cuboidal epithelium with no secretory granule. Striated duct consisted of simple columnar epithelium with basal striation, numerous elongated mitochondria, and apical vesicles. In the interlobular duct, simple tall columnar epithelium and apocrine secretion were found. The interlobar and excretory ducts surprisingly contained continuous capillaries that intervened in stratified cuboidal epithelium. In addition, there were several blood vessels around the interlobular, interlobar and excretory ducts. The morphological adaptation of the parotid gland observed in P. lylei enables this species to obtain sufficient nutrients from the preferred consumption of ripe fruit. Serous secretory granule was suitable for digestion of ripe fruit. A well-developed striated duct, continuous capillaries among the epithelial cells of interlobar and excretory ducts, and numerous blood vessels around these ducts enhanced the reabsorption of amino acids and ions. Structural variations in the parotid gland can indicate not only a correlation to diet and survival but also a close relationship of the Old World fruit bat to other kinds of bats.

Expression of membrane-associated mucins MUC1 and MUC4 in major human salivary glands.

PubMed

Liu, Bing; Lague, Jessica R; Nunes, David P; Toselli, Paul; Oppenheim, Frank G; Soares, Rodrigo V; Troxler, Robert F; Offner, Gwynneth D

2002-06-01

Mucins are high molecular weight glycoproteins secreted by salivary glands and epithelial cells lining the digestive, respiratory, and reproductive tracts. These glycoproteins, encoded in at least 13 distinct human genes, can be subdivided into gel-forming and membrane-associated forms. The gel-forming mucin MUC5B is secreted by mucous acinar cells in major and minor salivary glands, but little is known about the expression pattern of membrane-associated mucins. In this study, RT-PCR and Northern blotting demonstrated the presence of transcripts for MUC1 and MUC4 in both parotid and submandibular glands, and in situ hybridization localized these transcripts to epithelial cells lining striated and excretory ducts and in some serous acinar cells. The same cellular distribution was observed by immunohistochemistry. Soluble forms of both mucins were detected in parotid secretion after immunoprecipitation with mucin-specific antibodies. These studies have shown that membrane-associated mucins are produced in both parotid and submandibular glands and that they are expressed in different cell types than gel-forming mucins. Although the function of these mucins in the oral cavity remains to be elucidated, it is possible that they both contribute to the epithelial protective mucin layer and act as receptors initiating one or more intracellular signal transduction pathways.

Right Müllerian duct in the domestic fowl during postnatal ontogenesis.

PubMed

Hlozánková, E; Zelenka, J

1978-01-01

In this study the postembryonal changes of the right Müllerian duct are investigated. This structure was found in all female broilers of the hybrid combination Ross 1 as well as in hens of the female line of parent stock for the production of this hybrid. A thready structure of the length of several millimeters observed in one-day-old females develops in chicks into a long, thin-walled ampula filled up with clear liquid. In mature hens this rudiment is markedly long and its shape is rather different. In some cases the Müllerian duct was divided into several parts which might be compared with individual parts of the left oviduct.

Initial values for the integration scheme to compute the eigenvalues for propagation in ducts

NASA Technical Reports Server (NTRS)

Eversman, W.

1977-01-01

A scheme for the calculation of eigenvalues in the problem of acoustic propagation in a two-dimensional duct is described. The computation method involves changing the coupled transcendental nonlinear algebraic equations into an initial value problem involving a nonlinear ordinary differential equation. The simplest approach is to use as initial values the hardwall eigenvalues and to integrate away from these values as the admittance varies from zero to its actual value with a linear variation. The approach leads to a powerful root finding routine capable of computing the transverse and axial wave numbers for two-dimensional ducts for any frequency, lining, admittance and Mach number without requiring initial guesses or starting points.

Designing insulation for cryogenic ducts

NASA Astrophysics Data System (ADS)

Love, C. C.

1984-03-01

It is pointed out that the great temperature difference between the outside of a cryogenic duct and the liquified gas it carries can cause a high heat input unless blocked by a high thermal resistance. High thermal resistance for lines needing maximum insulation is provided by metal vacuum jackets. Low-density foam is satisfactory in cases in which higher heat input can be tolerated. Attention is given to the heat transfer through a duct vacuum jacket, the calculation of heat input and the exterior surface's steady-state temperature for various thicknesses of insulation, the calculation of the heat transfer through gimbal jackets, and design specifications regarding the allowable pressure rise in the jacket's annular space.

Coexistent Ampullary Squamous Cell Carcinoma with Adenocarcinoma of the Pancreatic Duct

PubMed Central

Pathak, Gayatri S.; Deshmukh, Sanjay D.; Yavalkar, Prasanna A.; Ashturkar, Amrut V.

2011-01-01

Primary squamous cell carcinoma (SCC) of ampulla has seldom been reported. However, metastatic SCC to ampulla of Vater is well known. We report a case of primary SCC of ampulla of Vater coexistent with well-differentiated adenocarcinoma of the distal pancreatic duct. A 50-year-old female presented with evidence of obstructive jaundice. Endoscopic retrograde cholangio-pancreatography revealed bulging papilla with ulcero-infiltrative growth at the ampulla of Vater. An initial endoscopic biopsy of the ampullary mass showed a well-differentiated SCC. The patient underwent Whipple's operation. Thorough sampling of the dilated portion of the pancreatic duct showed presence of well-differentiated adenocarcinoma of the distal pancreatic duct. Immunohistochemical study with synaptophysin and chromogranin was done with negative result, ruling out neuroendocrine differentiation. Also, a detailed clinical, endoscopic and radiological examination was carried out, that excluded the presence of primary SCC elsewhere. PMID:22064341

Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1beta.

PubMed

Coffinier, Catherine; Gresh, Lionel; Fiette, Laurence; Tronche, François; Schütz, Günther; Babinet, Charles; Pontoglio, Marco; Yaniv, Moshe; Barra, Jacqueline

2002-04-01

The inactivation of the Hnf1beta gene identified an essential role in epithelial differentiation of the visceral endoderm and resulted in early embryonic death. In the present study, we have specifically inactivated this gene in hepatocytes and bile duct cells using the Cre/loxP system. Mutant animals exhibited severe jaundice caused by abnormalities of the gallbladder and intrahepatic bile ducts (IHBD). The paucity of small IHBD was linked to a failure in the organization of duct structures during liver organogenesis, suggesting an essential function of Hnf1b in bile duct morphogenesis. Mutant mice also lacked interlobular arteries. As HNF1beta is not expressed in these cells, it further emphasizes the link between arterial and biliary formation. Hepatocyte metabolism was also affected and we identified hepatocyte-specific HNF1beta target genes involved in bile acids sensing and in fatty acid oxidation.

Detection of Hepatitis B Virus DNA in Hepatocytes, Bile Duct Epithelium, and Vascular Elements by in situ Hybridization

NASA Astrophysics Data System (ADS)

Blum, Hubert E.; Stowring, Linda; Figus, Annalena; Montgomery, Carolyn K.; Haase, Ashley T.; Vyas, Girish N.

1983-11-01

A radiolabeled probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue from three patients with chronic hepatitis B. The HBV genome was detected not only in infected hepatocytes but also in bile duct epithelial cells, endothelial cells, and smooth muscle cells. These findings extend the known host cell range for HBV, suggest new mechanisms of viral dissemination, and illustrate the usefulness of in situ hybridization in the study of pathogenesis of HBV infection.

Characterization of synthesis and storage of TGF-alpha in rat parotid acinar and intercalated duct cells.

PubMed

Login, G R; Yang, J; Bryan, K P; Digenis, E C; McBride, J; Elovic, A; Quissell, D O; Dvorak, A M; Wong, D T

1997-03-01

Although the expression and biological role of transforming growth factor-alpha (TGF-alpha) have been explored in a variety of normal cells in mammalian species, little is known about the storage of TGF-alpha in secretory cells of exocrine organs. Parotid glands from four rats were homogenized for RNA isolation followed by reverse transcription-polymerase chain reaction to determine the presence of TGF-alpha message. In situ hybridization using a hamster-specific TGF-alpha riboprobe was done on paraffin sections. Parotid gland and isolated acinar cells were processed for transmission electron microscopy (TEM) and postembedding immunogold labeled for TGF-alpha. Gold particles were counted on approximately 200 granules in 10 acinar cells and in 10 intercalated duct cells. Labeling density was calculated as the number of gold particles per square micrometer +/- SD. Statistical significance was calculated using one-way analysis of variance. Using multiple technologies, we have established that rat parotid acinar and intercalated duct cells synthesize TGF-alpha and store the precursor form of this cytokine in their secretory granules.

Building America Case Study: Compact Buried Ducts in a Hot-Humid Climate House, Lady's Island, South Carolina

DOE Office of Scientific and Technical Information (OSTI.GOV)

2016-02-01

A system of compact, buried ducts provides a high-performance and cost-effective solution for delivering conditioned air throughout the building. This report outlines research activities that are expected to facilitate adoption of compact buried duct systems by builders. The results of this research would be scalable to many new house designs in most climates and markets, leading to wider industry acceptance and building code and energy program approval. The primary research question with buried ducts is potential condensation at the outer jacket of the duct insulation in humid climates during the cooling season. Current best practices for buried ducts rely onmore » encapsulating the insulated ducts with closed-cell spray polyurethane foam insulation to control condensation and improve air sealing. The encapsulated buried duct concept has been analyzed and shown to be effective in hot-humid climates. The purpose of this project is to develop an alternative buried duct system that performs effectively as ducts in conditioned space - durable, energy efficient, and cost-effective - in a hot-humid climate (IECC warm-humid climate zone 3A) with three goals that distinguish this project: 1) Evaluation of design criteria for buried ducts that use common materials and do not rely on encapsulation using spray foam or disrupt traditional work sequences, 2) Establishing design criteria for compact ducts and incorporate those with the buried duct criteria to further reduce energy losses and control installed costs, and 3) Developing HVAC design guidance for performing accurate heating and cooling load calculations for compact buried ducts.« less

Compact Buried Ducts in a Hot-Humid Climate House

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mallay, Dave

2016-01-07

"9A system of compact, buried ducts provides a high-performance and cost-effective solution for delivering conditioned air throughout the building. This report outlines research activities that are expected to facilitate adoption of compact buried duct systems by builders. The results of this research would be scalable to many new house designs in most climates and markets, leading to wider industry acceptance and building code and energy program approval. The primary research question with buried ducts is potential condensation at the outer jacket of the duct insulation in humid climates during the cooling season. Current best practices for buried ducts rely onmore » encapsulating the insulated ducts with closed-cell spray polyurethane foam insulation to control condensation and improve air sealing. The encapsulated buried duct concept has been analyzed and shown to be effective in hot-humid climates. The purpose of this project is to develop an alternative buried duct system that performs effectively as ducts in conditioned space - durable, energy efficient, and cost-effective - in a hot-humid climate (IECC warm-humid climate zone 3A) with three goals that distinguish this project: 1) Evaluation of design criteria for buried ducts that use common materials and do not rely on encapsulation using spray foam or disrupt traditional work sequences; 2) Establishing design criteria for compact ducts and incorporate those with the buried duct criteria to further reduce energy losses and control installed costs; 3) Developing HVAC design guidance for performing accurate heating and cooling load calculations for compact buried ducts.« less

Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing.

PubMed

Casasent, Anna K; Schalck, Aislyn; Gao, Ruli; Sei, Emi; Long, Annalyssa; Pangburn, William; Casasent, Tod; Meric-Bernstam, Funda; Edgerton, Mary E; Navin, Nicholas E

2018-01-11

Ductal carcinoma in situ (DCIS) is an early-stage breast cancer that infrequently progresses to invasive ductal carcinoma (IDC). Genomic evolution has been difficult to delineate during invasion due to intratumor heterogeneity and the low number of tumor cells in the ducts. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells while preserving their spatial context in tissue sections. We applied TSCS to 1,293 single cells from 10 synchronous patients with both DCIS and IDC regions in addition to exome sequencing. Our data reveal a direct genomic lineage between in situ and invasive tumor subpopulations and further show that most mutations and copy number aberrations evolved within the ducts prior to invasion. These results support a multiclonal invasion model, in which one or more clones escape the ducts and migrate into the adjacent tissues to establish the invasive carcinomas. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of the synthesis and expression of the GTA-kinase from transformed and normal rodent cells.

PubMed

Kerr, M; Fischer, J E; Purushotham, K R; Gao, D; Nakagawa, Y; Maeda, N; Ghanta, V; Hiramoto, R; Chegini, N; Humphreys-Beher, M G

1994-08-02

The murine transformed cell line YC-8 and beta-adrenergic receptor agonist (isoproternol) treated rat and mouse parotid gland acinar cells ectopically express cell surface beta 1-4 galactosyltransferase during active proliferation. This activity is dependent upon the expression of the GTA-kinase (p58) in these cells. Using total RNA, cDNA clones for the protein coding region of the kinase were isolated by reverse transcriptase-PCR cloning. DNA sequence analysis failed to show sequence differences with the normal homolog from mouse cells although Southern blot analysis of YC-8, and a second cell line KI81, indicated changes in the restriction enzyme digestion profile relative to murine cell lines which do not express cell surface galactosyltransferase. The rat cDNA clone from isoproterenol-treated salivary glands showed a high degree of protein and nucleic acid sequence homology to the GTA-kinase from both murine and human sources. Northern blot analysis of YC-8 and a control cell line LSTRA revealed the synthesis of a major 3.0 kb mRNA from both cell lines plus the unique expression of a 4.5 kb mRNA in the YC-8 cells. Reverse transcriptase-PCR of LSTRA and YC-8 confirmed the increased steady state levels of the GTA-kinase mRNA in YC-8. In the mouse, induction of cell proliferation by isoproterenol resulted in a 50-fold increase in steady state mRNA levels for the kinase over the low level of expression in quiescent cells. Expression of the rat 3' untranslated region in rat parotid cells in vitro led to an increased rate of DNA synthesis, cell number an ectopic expression of cell surface galactosyltransferase in the sense orientation. Antisense expression or vector alone did not alter growth characteristics of acinar cells. A polyclonal antibody monospecific to a murine amino terminal peptide sequence revealed a uniform distribution of GTA-kinase over the cytoplasm of acinar and duct cells of control mouse parotid glands. However, upon growth stimulation, kinase was detected primarily in a perinuclear and nuclear immunostaining pattern. Western blot analysis confirmed a translocation from a cytoplasmic localization in both LSTRA and quiescent salivary cells to a membrane-associated localization in YC-8 and proliferating salivary cells.

Flow Duct Data for Validation of Acoustic Liner Codes for Impedance Eduction

NASA Technical Reports Server (NTRS)

Ahuja, K. K.; Munro, Scott; Gaeta, R. J., Jr.

2000-01-01

The objective of the study reported here was to acquire acoustic and flow data with hard and lined duct wall duct sections for validation of a liner prediction code being developed at NASA LaRC. Both the mean flowfield and acoustic flowfields were determined in a cross-plane of the rectangular duct. A flow duct facility with acoustic drivers connected to a rectangular (4.7 x 2.0 inch) source section and a linear acoustic liner mounted downstream of the source section was used in this study. The liner section was designed to allow liner materials to be placed on all 4 walls of the duct. The test liner was of the locally-reacting type and was made from a ceramic material. The material, consisting of a tubular structure, was provided by NASA LaRC. The liner was approximately 8.89 cm (3.5 inches) thick. For the current study, only the two "short" sides of the duct were lined with liner material. The other two sides were hard walls. Two especially built instrumentation sections were attached on either sides of the liner section to allow acoustic and flow measurements to be made upstream and downstream of the liner. The two instrumentation duct sections were built to allow measurement of acoustic and flow properties at planes perpendicular to flow upstream and downstream of the liner section. The instrumentation section was also designed to provide a streamwise gradient in acoustic (complex) pressure from which the acoustic particle velocity, needed for the model validation, can be computed. Flow measurements included pressure, temperature, and velocity profiles upstream of the liner section. The in-flow sound pressure levels and phases were obtained with a microphone probe equipped with a nose cone in two cross planes upstream of the liner and two cross plane downstream of the liner. In addition to the acoustic measurements at the cross planes. axial centerline acoustic data was acquired using an axially traversing microphone probe which was traversed from a location upstream of the liner to some distance downstream of the liner. All probes used here had to be calibrated with respect to a standard microphone equipped with a nose cone to allow for the effects of flow.

Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches.

PubMed

Michelotti, Gregory A; Tucker, Anikia; Swiderska-Syn, Marzena; Machado, Mariana Verdelho; Choi, Steve S; Kruger, Leandi; Soderblom, Erik; Thompson, J Will; Mayer-Salman, Meredith; Himburg, Heather A; Moylan, Cynthia A; Guy, Cynthia D; Garman, Katherine S; Premont, Richard T; Chute, John P; Diehl, Anna Mae

2016-04-01

The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell niches produce pleiotrophin (PTN) to inactivate the PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby augmenting phosphoprotein-dependent signalling. We hypothesised that the DR is regulated by PTN/PTPRZ1 signalling. PTN-GFP, PTN-knockout (KO), PTPRZ1-KO, and wild type (WT) mice were examined before and after bile duct ligation (BDL) for PTN, PTPRZ1 and the DR. RDC and HSC from WT, PTN-KO, and PTPRZ1-KO mice were also treated with PTN to determine effects on downstream signaling phosphoproteins, gene expression, growth, and migration. Liver biopsies from patients with DRs were also interrogated. Although quiescent HSC and RDC lines expressed PTN and PTPRZ1 mRNAs, neither PTN nor PTPRZ1 protein was demonstrated in healthy liver. BDL induced PTN in MF-HSC and increased PTPRZ1 in MF-HSC and RDC. In WT mice, BDL triggered a DR characterised by periportal accumulation of collagen, RDC and MF-HSC. All aspects of this DR were increased in PTN-KO mice and suppressed in PTPRZ1-KO mice. In vitro studies revealed PTN-dependent accumulation of phosphoproteins that control cell-cell adhesion and migration, with resultant inhibition of cell migration. PTPRZ1-positive cells were prominent in the DRs of patients with ductal plate defects and adult cholestatic diseases. PTN, and its receptor, PTPRZ1, regulate the DR to liver injury by controlling the migration of resident cells in adult liver progenitor niches. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Evaluation of discrete frequency sound in closed-test-section wind tunnels

NASA Technical Reports Server (NTRS)

Mosher, Marianne

1990-01-01

The principal objective of this study is to assess the adequacy of linear acoustic theory with an impedance wall boundary condition for modeling the detailed sound field of an acoustic source in a duct. This study compares measurements and calculations of a simple acoustic source in a rectangular concrete duct lined with foam on the walls and anechoic end terminations. Measuring acoustic pressure for 12 wave numbers provides variation in frequency and absorption characteristics of the duct walls. The cases in this study contain low frequencies and low wall absorptions corresponding to measurements of low-frequency helicopter noise in a lined wind tunnel. This regime is particularly difficult to measure in wind tunnels due to high levels of the reverberant field relatively close to the source. Close to the source, where the interference of wall reflections is minimal, correlation is very good. Away from the source, correlation degrades, especially for the lower frequencies. Sensitivity studies show little effect on the predicted results for changes in impedance boundary condition values, source location, measurement location, temperature, and source model for variations spanning the expected measurement error.

Monograph on propagation of sound waves in curved ducts

NASA Technical Reports Server (NTRS)

Rostafinski, Wojciech

1991-01-01

After reviewing and evaluating the existing material on sound propagation in curved ducts without flow, it seems strange that, except for Lord Rayleigh in 1878, no book on acoustics has treated the case of wave motion in bends. This monograph reviews the available analytical and experimental material, nearly 30 papers published on this subject so far, and concisely summarizes what has been learned about the motion of sound in hard-wall and acoustically lined cylindrical bends.

The testicular sperm ducts and genital kidney of male Ambystoma maculatum (Amphibia, Urodela, Ambystomatidae).

PubMed

Siegel, Dustin S; Aldridge, Robert D; Rheubert, Justin L; Gribbins, Kevin M; Sever, David M; Trauth, Stanley E

2013-03-01

The ducts associated with sperm transport from the testicular lobules to the Wolffian ducts in Ambystoma maculatum were examined with transmission electron microscopy. Based on the ultrastructure and historical precedence, new terminology for this network of ducts is proposed that better represents primary hypotheses of homology. Furthermore, the terminology proposed better characterizes the distinct regions of the sperm transport ducts in salamanders based on anatomy and should, therefore, lead to more accurate comparisons in the future. While developing the above ontology, we also tested the hypothesis that nephrons from the genital kidney are modified from those of the pelvic kidney due to the fact that the former nephrons function in sperm transport. Our ultrastructural analysis of the genital kidney supports this hypothesis, as the basal plasma membrane of distinct functional regions of the nephron (proximal convoluted tubule, distal convoluted tubule, and collecting tubule) appear less folded (indicating decreased surface area and reduced reabsorption efficiency) and the proximal convoluted tubule possesses ciliated epithelial cells along its entire length. Furthermore, visible luminal filtrate is absent from the nephrons of the genital kidney throughout their entire length. Thus, it appears that the nephrons of the genital kidney have reduced reabsorptive capacity and ciliated cells of the proximal convoluted tubule may increase the movement of immature sperm through the sperm transport ducts or aid in the mixing of seminal fluids within the ducts. Copyright © 2012 Wiley Periodicals, Inc.

Molecular Mechanism of Pancreatic and Salivary Glands Fluid and HCO3− Secretion

PubMed Central

Lee, Min Goo; Ohana, Ehud; Park, Hyun Woo; Yang, Dongki; Muallem, Shmuel

2013-01-01

Fluid and HCO3− secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO3− secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren’s syndrome and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO3− secretion, in particular by secretory glands. Fluid and HCO3− secretion by secretory glands is a two step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl− and secrete HCO3−. The relative volume secreted by acinar and duct cells and modification of electrolyte composition of the secreted fluids varies among secretory glands to meet their physiological functions. In the pancreas, acinar cells secrete small amount of NaCl-rich fluid, while the duct absorbs the Cl− and secretes HCO3− and the bulk of the fluid in the pancreatic juice. Fluid secretion appears to be driven by active HCO3− secretion. In the salivary glands, acinar cells secrete the bulk of the fluid in the saliva that contains high concentrations of Na+ and Cl− and fluid secretion is mediated by active Cl− secretion. The salivary glands duct absorbs both the Na+ and Cl− and secretes K+ and HCO3−. In this review, we focus on the molecular mechanism of fluid and HCO3− secretion by the pancreas and salivary glands, to highlight the similarities of the fundamental mechanisms of acinar and duct cell functions, and point the differences to meet glands specific secretions. PMID:22298651

Increased Na+/H+ exchanger activity on the apical surface of a cilium-deficient cortical collecting duct principal cell model of polycystic kidney disease

PubMed Central

Olteanu, Dragos; Liu, Xiaofen; Liu, Wen; Roper, Venus C.; Sharma, Neeraj; Yoder, Bradley K.; Satlin, Lisa M.; Schwiebert, Erik M.

2012-01-01

Pathophysiological anomalies in autosomal dominant and recessive forms of polycystic kidney disease (PKD) may derive from impaired function/formation of the apical central monocilium of ductal epithelia such as that seen in the Oak Ridge polycystic kidney or orpk (Ift88Tg737Rpw) mouse and its immortalized cell models for the renal collecting duct. According to a previous study, Na/H exchanger (NHE) activity may contribute to hyperabsorptive Na+ movement in cilium-deficient (“mutant”) cortical collecting duct principal cell monolayers derived from the orpk mice compared with cilium-competent (“rescued”) monolayers. To examine NHE activity, we measured intracellular pH (pHi) by fluorescence imaging with the pH-sensitive dye BCECF, and used a custom-designed perfusion chamber to control the apical and basolateral solutions independently. Both mutant and rescued monolayers exhibited basolateral Na+-dependent acid-base transporter activity in the nominal absence of CO2/HCO3−. However, only the mutant cells displayed appreciable apical Na+-induced pHi recoveries from NH4+ prepulse-induced acid loads. Similar results were obtained with isolated, perfused collecting ducts from orpk vs. wild-type mice. The pHi dependence of basolateral cariporide/HOE-694-sensitive NHE activity under our experimental conditions was similar in both mutant and rescued cells, and 3.5- to 4.5-fold greater than apical HOE-sensitive NHE activity in the mutant cells (pHi 6.23–6.68). Increased apical NHE activity correlated with increased apical NHE1 expression in the mutant cells, and increased apical localization in collecting ducts of kidney sections from orpk vs. control mice. A kidney-specific conditional cilium-knockout mouse produced a more acidic urine compared with wild-type littermates and became alkalotic by 28 days of age. This study provides the first description of altered NHE activity, and an associated acid-base anomaly in any form of PKD. PMID:22301060

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagino, Ko; Yokozawa, Junji; Sasaki, Yu

Highlights: Black-Right-Pointing-Pointer Insulin secretion was increased during the OGTT or IVGTT in mesenteric lymph duct-ligated rats. Black-Right-Pointing-Pointer Proliferation of islet {beta}-cells was upregulated in lymph duct-ligated rats. Black-Right-Pointing-Pointer Mesenteric lymph duct flow has a role in glucose metabolism. -- Abstract: Background and aims: It has been suggested that intestinal lymph flow plays an important role in insulin secretion and glucose metabolism after meals. In this study, we investigated the influence of ligation of the mesenteric lymph duct on glucose metabolism and islet {beta}-cells in rats. Methods: Male Sprague-Dawley rats (10 weeks old) were divided into two groups: one underwent ligationmore » of the mesenteric lymph duct above the cistern (ligation group), and the other underwent a sham operation (sham group). After 1 and 2 weeks, fasting plasma concentrations of glucose, insulin, triglyceride, glucose-dependent insulinotropic polypeptide (GIP), and the active form of glucagon-like peptide-1 (GLP-1) were measured. At 2 weeks after the operation, the oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT) were performed. After the rats had been sacrificed, the insulin content of the pancreas was measured and the proliferation of {beta}-cells was assessed immunohistochemically using antibodies against insulin and Ki-67. Results: During the OGTT, the ligation group showed a significant decrease in the plasma glucose concentration at 120 min (p < 0.05) and a significant increase in the plasma insulin concentration by more than 2-fold at 15 min (p < 0.01). On the other hand, the plasma GIP concentration was significantly decreased at 60 min (p < 0.01) in the ligated group, while the active form of GLP-1 showed a significantly higher level at 90 min (1.7-fold; p < 0.05) and 120 min (2.5-fold; p < 0.01). During the IVGTT, the plasma insulin concentration in the ligation group was significantly higher at 2 min (more than 1.4-fold; p < 0.05). Immunohistochemistry showed that the ratios of {beta}-cell area/acinar cell area and {beta}-cell area/islet area, and also {beta}-cell proliferation, were significantly higher in the ligation group than in the sham group (p < 0.05, p < 0.01 and p < 0.01, respectively). The insulin content per unit wet weight of pancreas was also significantly increased in the ligation group (p < 0.05). Conclusions: In rats with ligation of the mesenteric lymph duct, insulin secretion during the OGTT or IVGTT was higher, and the insulin content and {beta}-cell proliferation in the pancreas were also increased. Our data show that mesenteric lymph duct flow has a role in glucose metabolism.« less

Stensen's duct injuries: the role of sialendoscopy and adjuvant botulinum toxin injection

PubMed Central

Wierzbicka, Małgorzata; Szyfter, Witold

2013-01-01

Introduction Stensen's duct injuries are uncommon but troublesome sequelae of facial surgery or other external traumas. Aim To investigate the feasibility of sialendoscopic control of Stensen's duct in iatrogenic injuries and the efficiency of botulinum toxin adjuvant therapy. Material and methods In 2008 and 2010, 5 patients with parotid sialoceles or fistulas, infrequent complications after plastic surgery or trauma, were treated in a single institution, Poznan University of Medical Sciences ENT Department. The group consisted of 5 patients with diagnosed Stensen's duct injuries, which were post-surgery and post-traumatic sequelae. All were treated by means of open surgery. Botulinum toxin injection was administered during the procedure to decrease the saliva secretion and to improve the healing process. A sialendoscopy was performed to control the lumen of the junction after the duct injury was repaired. Results Complete healing of the fistulas and sialoceles after the reparative surgery followed by a single botulinum toxin application was observed in all patients within 10-14 days. No side effects were noticed. Conclusions Our findings suggest that sialendoscopy is a valuable tool and an important step of control in the surgery of parotid duct injuries and the injection of botulinum toxin is an effective and safe second-line treatment. PMID:23837095

Pseudocyst in the pancreatic tail associated with chronic pancreatitis successfully treated by transpapillary cyst drainage.

PubMed

Naitoh, Itaru; Ohara, Hirotaka; Okayama, Yasutaka; Nakazawa, Takahiro; Ando, Tomoaki; Hayashi, Kazuki; Okumura, Fumihiro; Kitajima, Yasuhiro; Ban, Tessin; Miyabe, Katsuyuki; Ueno, Koichiro; Joh, Takashi; Sano, Hitoshi

2008-09-01

We report a 50-year-old male with pseudocysts in the pancreatic tail associated with chronic pancreatitis successfully treated by transpapillary cyst drainage. He had previously undergone ultrasonography-guided percutaneous cyst drainage for a pancreatic pseudocyst in our hospital. He was readmitted due to abdominal pain and fever. Computed tomography showed recurrence of a pseudocyst in the pancreatic tail measuring 5 cm in diameter. Since conservative treatment failed, endoscopic retrograde pancreatography was performed. There was communication between the pseudocyst and the main pancreatic duct, and pancreatic duct stenosis proximal to the pseudocyst. First, transpapillary pancreatic duct drainage was performed using a plastic stent, but the pseudocyst did not decrease in size and became infected. After removal of the stent, a pigtail type nasocystic catheter was placed in the pseudocyst via the pancreatic duct. The pseudocyst infection immediately disappeared, and the pseudocyst gradually decreased and disappeared. After removal of the nasocystic catheter, no recurrence was observed. As transpapillary drainage of pancreatic pseudocyst, cyst drainage and pancreatic duct drainage have been reported. In our patient with pseudocyst in the pancreatic tail, duct drainage was ineffective and the pseudocyst was infected, whereas cyst drainage was very effective. We considered that cyst drainage by a nasocystic catheter was the first-line therapy as the transpapillary drainage of the pancreatic pseudocyst.

Sexual dimorphic expression of DMRT1 and Sox9a during gonadal differentiation and hormone-induced sex reversal in the teleost fish Nile tilapia (Oreochromis niloticus).

PubMed

Kobayashi, Tohru; Kajiura-Kobayashi, Hiroko; Guan, Guijun; Nagahama, Yoshitaka

2008-01-01

We examined the expression profiles of tDMRT1 and Sox9a during gonadal sex differentiation and hormone-induced sex reversal. tDMRT1 was detected in the gonial germ-cell-surrounding cells in XY fry specifically before the appearance of any signs of morphological sex differentiation, that is, sex differences in germ cell number and histogenesis, such as differentiation into intratesticular efferent duct or ovarian cavity. The signals became localized in the Sertoli and epithelial cells comprising the efferent duct during gonadal differentiation. After the induction of XY sex reversal with estrogen, tDMRT1 decreased and then disappeared completely. In contrast, tDMRT1 was expressed in the germ-cell-surrounding cells in XX sex reversal with androgen. On the other hand, Sox9a did not show sexual dimorphism before the appearance of sex differences in histogenesis and was not expressed in the efferent duct in the testis. These results suggest that tDMRT1 is a superior testicular differentiation marker in tilapia.

Does Cimicifuga racemosa have the effects like estrogen on the sublingual gland in ovariectomized rats?

PubMed

Da, Yun-Meng; Niu, Kai-Yu; Liu, Shu-Ya; Wang, Ke; Wang, Wen-Juan; Jia, Jing; Qin, Li-Hua; Bai, Wen-Pei

2017-03-14

Cimicifuga racemosa is one of the herbs used for the treatment of climacteric syndrome, and it has been cited as an alternative therapy to estrogen. Apart from hectic fevers, dyspareunia and so on, dry mouth also increase significantly after menopause. It has not yet been reported whether C. racemosa has any impact on the sublingual gland, which may relate to dry mouth. In an attempt to determine this, we have compared the effects of estrogen and C. racemosa on the sublingual gland of ovariectomized rats. HE staining showed that the acinar cell area had contracted and that the intercellular spaces were broadened in the OVX (ovariectomized rats) group, while treatment with estradiol (E2) and iCR (isopropanolic extract of C. racemosa) improved these lesions. Transmission electron microscopy showed that rough endoplasmic reticulum expansion in mucous and serous acinar epithelial cells and apoptotic cells was more commonly seen in the OVX group than in the SHAM (sham-operated rats) group. Mitochondria and plasma membrane infolding lesions in the striated ducts were also observed. These lesions were alleviated by both treatments. It is of note that, in the OVX + iCR group, the volume of mitochondria in the striated duct was larger than in other groups. Immunohistochemical staining showed that the ratio of caspase-3 positive cells was significantly increased in the acinar cells of the OVX group compared with the SHAM group (p < 0.05); and the MA (mean absorbance) of caspase-3 in the striated ducts also increased (p < 0.05). Estradiol decreased the ratio of caspase-3 positive cells and the MA of caspase-3 in striated ducts significantly (p < 0.05). ICR also reduced the ratio of caspase-3 positive cells and the MA in the striated ducts (p < 0.05), but the reduction of the MA in striated ducts was inferior to that of the OVX + E2 group (p < 0.05). Both estradiol and iCR can inhibit subcellular structural damage, and down-regulate the expression of caspase-3 caused by ovariectomy, but their effects were not identical, suggesting that both drugs confer a protective effect on the sublingual gland of ovariectomized rats, but that the specific location and mechanism of action producing these effects were different.

Expression of metalloprotease insulin-degrading enzyme (insulysin) in normal and malignant human tissues

PubMed Central

Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

2013-01-01

Background Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and in breast cancer tissue (Radulescu et al., Int J Oncol 30:73; 2007). Materials and Methods Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Results Applying the four IDE-directed antibodies, we demonstrate IDE expression at the protein level, both by means of immunoblotting and immunocytochemistry, in all of the tumor cell lines analyzed. Besides, IDE protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in all of the cell lines and tissues assessed. Conclusions We performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells and thus extend knowledge about cellular and tissue distribution of IDE, an enzyme which so far has mainly been studied in connection with Alzheimer’s disease and diabetes but not in cancer. PMID:18813847

Measure Guideline: Buried and/or Encapsulated Ducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shapiro, C.; Zoeller, W.; Mantha, P.

2013-08-01

Buried and/or encapsulated ducts (BEDs) are a class of advanced, energy-efficiency strategies intended to address the significant ductwork thermal losses associated with ducts installed in unconditioned attics. BEDs are ducts installed in unconditioned attics that are covered in loose-fill insulation and/or encapsulated in closed cell polyurethane spray foam insulation. This Measure Guideline covers the technical aspects of BEDs as well as the advantages, disadvantages, and risks of BEDs compared to other alternative strategies. This guideline also provides detailed guidance on installation of BEDs strategies in new and existing homes through step-by-step installation procedures. Some of the procedures presented here, however,more » require specialized equipment or expertise. In addition, some alterations to duct systems may require a specialized license.« less

S-Adenosylmethionine attenuates bile duct early warm ischemia reperfusion injury after rat liver transplantation.

PubMed

Tang, Yong; Chu, Hongpeng; Cao, Guojun; Du, Xiaolong; Min, Xiaobo; Wan, Chidan

2018-03-01

Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 μmol/kg body weight) after orthotopic autologous liver transplantation. The histopathological observations showed that bile duct injury in the IRI group was more serious than in the SAM group. The alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DBIL) levels in the serum of the IRI group were significantly increased compared to the SAM group (P < .05). Simultaneously, SAM effectively improved the survival of the transplant recipients. Furthermore, the H 2 O 2 and malondialdehyde (MDA) of the IRI group were much higher compared to the SAM group (P < .05). The GSH/GSSG ratio in the SAM group was significantly increased by SAM treatment compared to the IRI group (P < .05). SAM administration significantly inhibited macrophage infiltration in liver and bile duct tissues, down-regulated TNF-α levels and up-regulated IL-10 expression in bile duct tissues compared to the IRI group (P < .05). The number of apoptotic biliary epithelial cells and caspase-3-positive cells in IRI rat livers were much higher compared to those in SAM-treated rats at 24 h after liver transplantation (P < .05). These data suggested that SAM protected bile ducts against warm IRI by suppressing oxidative stress, inflammatory reactions and apoptosis of biliary epithelial cells after liver transplantation.α. Copyright © 2018 Elsevier Ltd. All rights reserved.

Survival of mouse mammary gland transplants of normal, hyperplastic, and tumor tissues exposed to X-rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faulkin, L.J.; Mitchell, D.J.; Cardiff, R.D.

1982-04-01

Mouse mammary tissues, including ducts, prelactating lobules, hyperplastic outgrowth lines, and tumors, were exposed to varying doses of X-rays and then transplanted to fat pads of nonirradiated BALB/c mice for study. Estimates of the dose of radiation that would allow survival of 50% of the transplants (SD50) were made with the use of probit analysis. Nearly all duct and lobule transplants survived doses of X-rays from 0 to 800 rad. The survival rate declined rapidly following doses above 800 rad, and the calculated SD50 was 1,020 and 1,260 rad for mammary ducts and lobules, respectively. The three hyperplastic outgrowth linesmore » tested gave very different results. Hyperplastic line Z5C1 transplants had better than 90% survival at doses up to 1,200 rad and an SD50 between 1,200 and 1,600 rad. Hyperplastic line Z5D transplants had an SD50 of between 800 and 1,200 rad. Hyperplastic line D1 transplants had a better than 90% survival following doses of 0-600 rad and an SD50 between 600 and 800 rad. The survival of tumor transplants was 100% following doses of X-rays up to 1,200 rad; the SD50 was in excess of 1,600 rad. The mouse mammary transplantation system can be used to study the direct effect of X-rays on normal, premalignant, and malignant mammary tissues and provides a basis for the study of the radiobiology of mammary tissues.« less

SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

PubMed

Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

2016-10-01

Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory. Copyright © 2016 Elsevier Inc. All rights reserved.

Bile duct epithelial tight junctions and barrier function

PubMed Central

Rao, R.K.; Samak, G.

2013-01-01

Bile ducts play a crucial role in the formation and secretion of bile as well as excretion of circulating xenobiotic substances. In addition to its secretory and excretory functions, bile duct epithelium plays an important role in the formation of a barrier to the diffusion of toxic substances from bile into the hepatic interstitial tissue. Disruption of barrier function and toxic injury to liver cells appear to be involved in the pathogenesis of a variety of liver diseases such as primary sclerosing cholangitis, primary biliary cirrhosis and cholangiocarcinoma. Although the investigations into understanding the structure and regulation of tight junctions in gut, renal and endothelial tissues have expanded rapidly, very little is known about the structure and regulation of tight junctions in the bile duct epithelium. In this article we summarize the current understanding of physiology and pathophysiology of bile duct epithelium, the structure and regulation of tight junctions in canaliculi and bile duct epithelia and different mechanisms involved in the regulation of disruption and protection of bile duct epithelial tight junctions. This article will make a case for the need of future investigations toward our understanding of molecular organization and regulation of canalicular and bile duct epithelial tight junctions. PMID:24665411

Ultrasound imaging of the mouse pancreatic duct using lipid microbubbles

NASA Astrophysics Data System (ADS)

Banerjee, B.; McKeown, K. R.; Skovan, B.; Ogram, E.; Ingram, P.; Ignatenko, N.; Paine-Murrieta, G.; Witte, R.; Matsunaga, T. O.

2012-03-01

Research requiring the murine pancreatic duct to be imaged is often challenging due to the difficulty in selectively cannulating the pancreatic duct. We have successfully catheterized the pancreatic duct through the common bile duct in severe combined immune deficient (SCID) mice and imaged the pancreatic duct with gas filled lipid microbubbles that increase ultrasound imaging sensitivity due to exquisite scattering at the gas/liquid interface. A SCID mouse was euthanized by CO2, a midline abdominal incision made, the common bile duct cut at its midpoint, a 2 cm, 32 gauge tip catheter was inserted about 1 mm into the duct and tied with suture. The duodenum and pancreas were excised, removed in toto, embedded in agar and an infusion pump was used to instill normal saline or lipid-coated microbubbles (10 million / ml) into the duct. B-mode images before and after infusion of the duct with microbubbles imaged the entire pancreatic duct (~ 1 cm) with high contrast. The microbubbles were cavitated by high mechanical index (HMI) ultrasound for imaging to be repeated. Our technique of catheterization and using lipid microbubbles as a contrast agent may provide an effective, affordable technique of imaging the murine pancreatic duct; cavitation with HMI ultrasound would enable repeated imaging to be performed and clustering of targeted microbubbles to receptors on ductal cells would allow pathology to be localized accurately. This research was supported by the Experimental Mouse Shared Service of the AZ Cancer Center (Grant Number P30CA023074, NIH/NCI and the GI SPORE (NIH/NCI P50 CA95060).

Glycogen synthase kinase-3 regulation of urinary concentrating ability.

PubMed

Rao, Reena

2012-09-01

Glycogen synthase kinase-3 (GSK3) is an enzyme that is gaining prominence as a critical signaling molecule in the epithelial cells of renal tubules. This review will focus on recent findings exploring the role of GSK3 in renal collecting ducts, especially its role in urine concentration involving vasopressin signaling. Recent studies using inhibition or tissue-specific gene deletion of GSK3 revealed the mechanism by which GSK3 regulates aquaporin 2 water channels via adenylate cyclase or the prostaglandin-E2 pathway. In other studies, postnatal treatment with lithium, an inhibitor of GSK3, increased cell proliferation and led to microcyst formation in rat kidneys. These studies suggest that loss of GSK3 activity could interfere with renal water transport at two levels. In the short term, it could disrupt vasopressin signaling in collecting duct cells and in the long term it could alter the structure of the collecting ducts, making them less responsive to the hydro-osmotic effects of vasopressin. Ongoing studies reveal the crucial role played by GSK3 in the regulation of vasopressin action in the renal collecting ducts and suggest a possible use of GSK3 inhibitors in disease conditions associated with disrupted vasopressin signaling.

Acute cholecystitis

MedlinePlus

... that forms in the wall of the gallbladder) Pancreatitis (inflamed pancreas) Persistent bile duct blockage Inflammation of ... draining the liver (may occur after gallbladder surgery) Pancreatitis Perforation Peritonitis (inflammation of the lining of the ...

Ultrastructure of the genital organs in interstitial polychaetes. III. Penes and ejaculatory ducts in Hesionides arenaria (Hesionidae)

NASA Astrophysics Data System (ADS)

Westheide, W.

1982-12-01

The ejaculatory ducts of the two paired copulatory organs in the interstitial polychaete Hesionides arenaria are ciliated tubes, which open into simple, partly groove-like, non-stiffened penis papillae. The larger part of the ducts within the dorsal body wall is surrounded by circular muscle cells. Voluminous gland cell bodies lie between the pharynx-gut system and the body wall in the anterior part of the body; they extend anteriorly like long, thin necks, of which severl are always united in prominent strands. Their distal ends are expanded and penetrate the ducts. Six different types of glands can be distinguished according to the ultrastructure of their secretory granules. They produce the sheath of the double spermatophore or probably contain lytic enzymes that provide for the penetration of sperm into the body of the female. Differences in ultrastructure of the male organs in the interstitial genera Hesionides and Microphthalmus do not support the recent erection of the subfamily “Microphthalminae”.

Effect of turbulent eddy viscosity on the unstable surface mode above an acoustic liner

NASA Astrophysics Data System (ADS)

Marx, David; Aurégan, Yves

2013-07-01

Lined ducts are used to reduce noise radiation from ducts in turbofan engines. In certain conditions they may sustain hydrodynamic instabilities. A local linear stability analysis of the flow in a 2D lined channel is performed using a numerical integration of the governing equations. Several model equations are used, one of them taking into account turbulent eddy viscosity, and a realistic turbulent mean flow profile is used that vanishes at the wall. The stability analysis results are compared to published experimental results. Both the model and the experiments show the existence of an unstable mode, and the importance of taking into account eddy viscosity in the model is shown. When this is done, quantities such as the growth rate and the velocity eigenfunctions are shown to agree correctly.

In-line quincke tube muffler

NASA Astrophysics Data System (ADS)

Patrick, William P.; Bryant, Rebecca S.; Greenwald, Larry E.

2002-05-01

A unique low-pressure-drop muffler is described which has been designed to attenuate low frequency tonal noise in ducts. Flow through the muffler is divided into two noncommunicating paths in the cylindrical configuration which was designed, built, and tested. Half of the flow is ducted through a straight central annulus and the other half is ducted through a partitioned outer annulus which directs the flow in a spiral flow pattern around the inner annulus. Thus the outer flow has a longer path length and the sound within the outer annulus is phase-delayed relative to the inner flow causing destructive interference between the inner and outer waves with resulting strong attenuation at the tuned frequencies. A procedure will be described for designing a muffler (with flow) to produce high attenuation at the fundamental noise tone and all harmonics (up to the first cross mode). Results will be presented which show that the muffler achieved over 20 dB attenuation for the first five harmonics of the incident noise in a flowing duct.

An analytical and experimental study of sound propagation and attenuation in variable-area ducts. [reducing aircraft engine noise

NASA Technical Reports Server (NTRS)

Nayfeh, A. H.; Kaiser, J. E.; Marshall, R. L.; Hurst, L. J.

1978-01-01

The performance of sound suppression techniques in ducts that produce refraction effects due to axial velocity gradients was evaluated. A computer code based on the method of multiple scales was used to calculate the influence of axial variations due to slow changes in the cross-sectional area as well as transverse gradients due to the wall boundary layers. An attempt was made to verify the analytical model through direct comparison of experimental and computational results and the analytical determination of the influence of axial gradients on optimum liner properties. However, the analytical studies were unable to examine the influence of non-parallel ducts on the optimum linear conditions. For liner properties not close to optimum, the analytical predictions and the experimental measurements were compared. The circumferential variations of pressure amplitudes and phases at several axial positions were examined in straight and variable-area ducts, hard-wall and lined sections with and without a mean flow. Reasonable agreement between the theoretical and experimental results was obtained.

Biliary intraductal papillary neoplasm with metachronous multiple tumors - true multicentric tumors or intrabiliary dissemination: A case report and review of the literature.

PubMed

Yokode, Masataka; Yamashita, Yukimasa; Zen, Yoh

2017-03-01

Intraductal papillary neoplasms of the bile duct (IPNBs) are recognized as a distinct type of biliary tumor. We herein discuss the possible mechanisms underlying the development of multiple tumors in patients with IPNBs through a case presentation and literature review. A 64-year-old woman initially underwent extended right hepatectomy for IPNB in the right hepatic duct. Although the surgical margin of the common bile duct was tumor-free, recurrence was detected in the intrapancreatic bile duct 26 months later. Both tumors had similar histopathological characteristics (intestinal-type IPNB with high-grade dysplasia, but no invasive cancer). A literature review identified 9 additional cases of multiple IPNBs. Unlike conventional IPNBs, which typically affect the intrahepatic or hilar bile duct, 80% of recurrent multiple tumors developed in the extrahepatic bile duct. Although multicentric tumors have been suggested in such cases, the intrabiliary dissemination of tumor cells appears to be more likely, as the majority of recurrent tumors develop in more distal parts of the bile duct compared with the primary tumor.

Ovarian teratoma displaying a wide variety of tissue components in a broiler chicken (Gallus Domesticus): morphological heterogeneity of pluripotential germ cell during tumorigenesis.

PubMed

Ohfuji, S

2016-01-01

Spontaneous ovarian teratoma was found in a seven-week-old female Chunky broiler chicken that was slaughtered for food. On post-mortem inspection, a spherical tumor mass attaching to a juvenile ovary was found in the abdominal cavity. Histopathologically, the tumor was comprised of immature mesenchymal stroma and a variety of mature tissue elements of mesodermal and ectodermal origin. In addition, there were multiple indistinguishable tissue elements, which showed no malignant cytological features but were unidentifiable as to corresponding embryological layer of origin. These heterogeneous teratoma tissues consisted of a variety of glandular, cystic, duct-like, and tubular structures, some of which exhibited a lining by a mixture of both keratinizing/non-keratinizing stratified squamous epithelial cells and cuboidal/columnar epithelial cells. The ovarian tetatoma was considered a benign and congenital one. The highly diverse differentiation of the teratoma might have manifested a morphological aspect of intrinsic character of the pluripotential germ cells during tumorigenesis.

Regulation of Epithelial Injury and Bile Duct Obstruction by NLRP3 and IL-1R1 in Experimental Biliary Atresia.

PubMed

Yang, Li; Mizuochi, Tatsuki; Shivakumar, Pranavkumar; Mourya, Reena; Luo, Zhenhua; Gutta, Sridevi; Bezerra, Jorge A

2018-06-07

Biliary atresia (BA) results from a neonatal inflammatory and fibrosing obstruction of bile ducts of unknown etiology. Although the innate immune system has been linked to virus-induced mechanism of disease, the role of the inflammasome-mediated epithelial injury remains largely undefined. Here, we hypothesized that disruption of the inflammasome suppresses the neonatal proinflammatory response and prevents experimental BA. We determined the expression of key inflammasome-related genes in livers from infants at diagnosis of BA and in extrahepatic bile ducts (EHBDs) of neonatal mice after infection with rotavirus (RRV) immediately after birth. Then, we determined the impact of the wholesale inactivation of the genes encoding IL-1R1 (Il1r1 -/- ), NLRP3 (Nlrp3 -/- ) or Caspase-1 (Casp1 -/- ) on epithelial injury and bile duct obstruction. IL1R1, NLRP3 and CASP1 mRNA increased significantly in human livers at the time of diagnosis, and in extrahepatic bile ducts of RRV-infected mice. In Il1r1 -/- mice, the epithelial injury of EHBDs induced by RRV was suppressed, with an inability of dendritic cells (DCs) to activate natural killer (NK) cells. A similar protection was observed in Nlrp3 -/- mice, with decreased injury and inflammation of livers and EHBDs. Long-term survival was also improved. In contrast, the inactivation of the Casp1 gene had no impact on tissue injury, and all mice died. Tissue analyses in Il1r1 -/- and Nlrp3 -/- mice showed decreased population of DC and NK cells and suppressed the expression of type-1 cytokines and chemokines. Inflammasome genes are overexpressed at diagnosis of BA in humans and in the BA mouse model. In the experimental model, the targeted loss of IL-1R1 or NLRP3, but not of Capase-1, protected neonatal mice against RRV-induced bile duct obstruction. Biliary atresia is a severe inflammatory and obstructive disease of bile ducts of infancy. Although the cause is unknown, an activation of the innate and adaptive immune systems injure the bile duct epithelium. In this study we found that patients' livers had increased expression of inflammasome genes. Using mice engineered to inactivate individual inflammasome genes, the epithelial injury and bile duct obstruction were prevented by the loss of Il1r1 or Nlrp3, with a decreased activation of NK cells and expression of cytokines and chemokines. In contrast, the loss of Casp1 did not change the disease phenotype. Combined, the findings point to a differential role of inflammasome gene products in the pathogenic mechanisms of biliary atresia. Copyright © 2018. Published by Elsevier B.V.

Sound attenuation of fiberglass lined ventilation ducts

NASA Astrophysics Data System (ADS)

Albright, Jacob

Sound attenuation is a crucial part of designing any HVAC system. Most ventilation systems are designed to be in areas occupied by one or more persons. If these systems do not adequately attenuate the sound of the supply fan, compressor, or any other source of sound, the affected area could be subject to an array of problems ranging from an annoying hum to a deafening howl. The goals of this project are to quantify the sound attenuation properties of fiberglass duct liner and to perform a regression analysis to develop equations to predict insertion loss values for both rectangular and round duct liners. The first goal was accomplished via insertion loss testing. The tests performed conformed to the ASTM E477 standard. Using the insertion loss test data, regression equations were developed to predict insertion loss values for rectangular ducts ranging in size from 12-in x 18-in to 48-in x 48-in in lengths ranging from 3ft to 30ft. Regression equations were also developed to predict insertion loss values for round ducts ranging in diameters from 12-in to 48-in in lengths ranging from 3ft to 30ft.

Collecting Duct Intercalated Cell Function and Regulation

PubMed Central

Roy, Ankita; Al-bataineh, Mohammad M.

2015-01-01

Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the function of the intercalated cell has become greatly enhanced and has shaped a new model for how the distal segments of the kidney tubule integrate salt and water reabsorption, potassium homeostasis, and acid-base status. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on the species. They are most abundant in the collecting duct, where they can be detected all the way from the cortex to the initial part of the inner medulla. Intercalated cells are interspersed among the more numerous segment-specific principal cells. There are three types of intercalated cells, each having distinct structures and expressing different ensembles of transport proteins that translate into very different functions in the processing of the urine. This review includes recent findings on how intercalated cells regulate their intracellular milieu and contribute to acid-base regulation and sodium, chloride, and potassium homeostasis, thus highlighting their potential role as targets for the treatment of hypertension. Their novel regulation by paracrine signals in the collecting duct is also discussed. Finally, this article addresses their role as part of the innate immune system of the kidney tubule. PMID:25632105

[Bushen Huoxue Fang promotes the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia].

PubMed

Sun, Jie; Li, Qiu-Fen; Tian, Dai-Zhi; Jiang, Shao-Bo; Wu, Xian-De; Qiu, Shun-An; Ren, Xiao-Gang; Li, Yu-Bing

2014-09-01

To investigate the effects of Bushen Huoxue Fang (BSHX) on the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia (BPH) and its possible action mechanism. One hundred 3- month-old male Wistar rats were randomly divided into four groups of equal number (control, castrated, BPH model, and BSHX). BPH models were made by subcutaneous injection of testosterone following castration; the rats in the BSHX group were treated intragastrically with BSHX at 2.34 g/ml after modeling, while those in the other two groups with equal volume of saline, all for 37 days. On the 38th day, all the rats were sacrificed and their prostates harvested for detection of the distribution of TGF-beta1 and alpha-actin and the count of positive cells in the prostatic ductal system by immunohistochemical staining. The apoptosis rate of epithelial cells in the prostatic ductal system was determined by TUNEL assay. The expression of TGF-beta1 was significantly increased in the rats of the BSHX group as compared with the BPH models in both the proximal prostatic duct ([15.28 +/- 4.30]% vs [36.42 +/- 8.10]%, P < 0.01) and the distal prostatic duct ([4.42 +/- 2.07]% vs [8.71 +/- 2.28 ]%, P < 0.05), while the expression of alpha-actin in the proximal duct was remarkably higher in the BSHX-treated rats than in the models ([28.14 +/- 7.43]% vs [18.28 +/- 4.07]%, P < 0.01), but lower than in the control animals ([33.57 +/- 6.85]%, P < 0.05). Compared with the control group, the BPH models and BSHX-treated rats both exhibited markedly decreased apoptosis of epithelial cells in the proximal prostatic duct ([39.42 +/- 9.20]% vs [3.86 +/- 1.34]%, P < 0.01, and [31.14 +/- 5.64]%, P < 0.01) and distal prostatic duct ([17.60 +/- 4.86]% vs [3.07 +/- 1.14]%, P < 0.01, and [12.37 +/- 2.25]%, P < 0.05). The apoptosis rate of epithelial cells in the prostatic ductal system was significantly higher in the BSHX-treated rats than in the BPH models (P < 0.01). By upregulating the expression of TGF-beta, BSHX can suppress the reduction of smooth muscle cells in the proximal prostatic duct, promote the apoptosis of prostatic epithelial cells, and thus effectively inhibit benign prostatic hyperplasia.

Expression of ion transport-associated proteins in human efferent and epididymal ducts.

PubMed

Kujala, Minna; Hihnala, Satu; Tienari, Jukka; Kaunisto, Kari; Hästbacka, Johanna; Holmberg, Christer; Kere, Juha; Höglund, Pia

2007-04-01

Appropriate intraluminal microenvironment in the epididymis is essential for maturation of sperm. To clarify whether the anion transporters SLC26A2, SLC26A6, SLC26A7, and SLC26A8 might participate in generating this proper intraluminal milieu, we studied the localization of these proteins in the human efferent and the epididymal ducts by immunohistochemistry. In addition, immunohistochemistry of several SLC26-interacting proteins was performed: the Na(+)/H(+) exchanger 3 (NHE3), the Cl(-) channel cystic fibrosis transmembrane conductance regulator (CFTR), the proton pump V-ATPase, their regulator Na(+)/H(+) exchanger regulating factor 1 (NHERF-1), and carbonic anhydrase II (CAII). Our results show that SLC26A6, CFTR, NHE3, and NHERF-1 are co-expressed on the apical side of the nonciliated cells, and SLC26A2 appears in the cilia of the ciliated cells in the human efferent ducts. In the epididymal ducts, SLC26A6, CFTR, NHERF-1, CAII, and V-ATPase (B and E subunits) were co-localized to the apical mitochondria rich cells, while SLC26A7 was expressed in a subgroup of basal cells. SLC26A8 was not found in the structures studied. This is the first study describing the localization of SLC26A2, A6 and A7, and NHERF-1 in the efferent and the epididymal ducts. Immunolocalization of human CFTR, NHE3, CAII, and V-ATPase in these structures differs partly from previous reports from rodents. Our findings suggest roles for these proteins in male fertility, either independently or through interaction and reciprocal regulation with co-localized proteins shown to affect fertility, when disrupted.

Acid-base interactions during exocrine pancreatic secretion. Primary role for ductal bicarbonate in acinar lumen function.

PubMed

Freedman, S D; Scheele, G A

1994-03-23

The role of acid-base interactions during coordinated acinar and duct cell secretion in the exocrine pancreas is described. The sequence of acid-base events may be summarized as follows: (1) Sorting of secretory proteins and membrane components into the regulated secretory pathway of pancreatic acinar cells is triggered by acid- and calcium-induced aggregation and association mechanisms located in the trans-Golgi network. (2) Cholecystokinin-stimulated exocytosis in acinar cells releases the acidic contents of secretory granules into the acinar lumen. (3) Secretin-stimulated bicarbonate secretion from duct and duct-like cells neutralizes the acidic pH of exocytic contents, which leads to dissociation of protein aggregates and solubilization of (pro)enzymes within the acinar lumen. (4) Stimulated fluid secretion transports solubilized enzymes through the ductal system. (5) Further alkalinization of acinar lumen pH accelerates the enzymatic cleavage of the glycosyl phosphatidyl-inositol anchor associated with GP2 and thus releases the GP2/proteoglycan matrix from lumenal membranes, a process that appears to be required for vesicular retrieval of granule membranes from the apical plasma membrane and their reuse in the secretory process. We conclude that the central function of bicarbonate secretion by centroacinar and duct cells in the pancreas is to neutralize and then alkalinize the pH of the acinar lumen, sequential process that are required for (a) solubilization of secreted proteins and (b) cellular retrieval of granule membranes, respectively.

Expression patterns of epiplakin1 in pancreas, pancreatic cancer and regenerating pancreas.

PubMed

Yoshida, Tetsu; Shiraki, Nobuaki; Baba, Hideo; Goto, Mizuki; Fujiwara, Sakuhei; Kume, Kazuhiko; Kume, Shoen

2008-07-01

Epiplakin1 (Eppk1) is a plakin family gene with its function remains largely unknown, although the plakin genes are known to function in interconnecting cytoskeletal filaments and anchoring them at plasma membrane-associated adhesive junction. Here we analyzed the expression patterns of Eppk1 in the developing and adult pancreas in the mice. In the embryonic pancreas, Eppk1+/Pdx1+ and Eppk1+/Sox9+ pancreatic progenitor cells were observed in early pancreatic epithelium. Since Pdx1 expression overlapped with that of Sox9 at this stage, these multipotent progenitor cells are Eppk1+/Pdx1+/Sox9+ cells. Then Eppk1 expression becomes confined to Ngn3+ or Sox9+ endocrine progenitor cells, and p48+ exocrine progenitor cells, and then restricted to the duct cells and a cells at birth. In the adult pancreas, Eppk1 is expressed in centroacinar cells (CACs) and in duct cells. Eppk1 is observed in pancreatic intraepithelial neoplasia (PanIN), previously identified as pancreatic ductal adenocarcinoma (PDAC) precursor lesions. In addition, the expansion of Eppk1-positive cells occurs in a caerulein-induced acute pancreatitis, an acinar cell regeneration model. Furthermore, in the partial pancreatectomy (Px) regeneration model using mice, Eppk1 is expressed in "ducts in foci", a tubular structure transiently induced. These results suggest that Eppk1 serves as a useful marker for detecting pancreatic progenitor cells in developing and regenerating pancreas.

Early nongenomic events in aldosterone action in renal collecting duct cells: PKCalpha activation, mineralocorticoid receptor phosphorylation, and cross-talk with the genomic response.

PubMed

Le Moëllic, Cathy; Ouvrard-Pascaud, Antoine; Capurro, Claudia; Cluzeaud, Francoise; Fay, Michel; Jaisser, Frederic; Farman, Nicolette; Blot-Chabaud, Marcel

2004-05-01

Effects of aldosterone on its target cells have long been considered to be mediated exclusively through the genomic pathway; however, evidence has been provided for rapid effects of the hormone that may involve nongenomic mechanisms. Whether an interaction exists between these two signaling pathways is not yet established. In this study, the authors show that aldosterone triggers both early nongenomic and late genomic increase in sodium transport in the RCCD(2) rat cortical collecting duct cell line. In these cells, the early (up to 2.5 h) aldosterone-induced increase in short-circuit current (Isc) is not blocked by the mineralocorticoid receptor (MR) antagonist RU26752, it does not require mRNA or protein synthesis, and it involves the PKCalpha signaling pathway. In addition, this early response is reproduced by aldosterone-BSA, which acts at the cell surface and presumably does not enter the cells (aldo-BSA is unable to trigger the late response). The authors also show that MR is rapidly phosphorylated on serine and threonine residues by aldosterone or aldosterone-BSA. In contrast, the late (4 to 24 h) aldosterone-induced increase in ion transport occurs through activation of the MR and requires mRNA and protein synthesis. Interestingly, nongenomic and genomic aldosterone actions appear to be interdependent. Blocking the PKCalpha pathway results in the inhibition of the late genomic response to aldosterone, as demonstrated by the suppression of aldosterone-induced increase in MR transactivation activity, alpha1 Na(+)/K(+)/ATPase mRNA, and Isc. These data suggest cross-talk between the nongenomic and genomic responses to aldosterone in renal cells and suggest that the aldosterone-MR mediated increase in mRNA/protein synthesis and ion transport depends, at least in part, upon PKCalpha activation. E-mail: marcel.blot-chabaud@pharmacie.univ-mrs.fr

A comparison of experiment and theory for sound propagation in variable area ducts

NASA Technical Reports Server (NTRS)

Nayfeh, A. H.; Kaiser, J. E.; Marshall, R. L.; Hurst, C. J.

1980-01-01

An experimental and analytical program has been carried out to evaluate sound suppression techniques in ducts that produce refraction effects due to axial velocity gradients. The analytical program employs a computer code based on the method of multiple scales to calculate the influence of axial variations due to slow changes in the cross-sectional area as well as transverse gradients due to the wall boundary layers. Detailed comparisons between the analytical predictions and the experimental measurements have been made. The circumferential variations of pressure amplitudes and phases at several axial positions have been examined in straight and variable area ducts, with hard walls and lined sections, and with and without a mean flow. Reasonable agreement between the theoretical and experimental results has been found.

Pseudocyst in the Pancreatic Tail Associated with Chronic Pancreatitis Successfully Treated by Transpapillary Cyst Drainage

PubMed Central

Naitoh, Itaru; Ohara, Hirotaka; Okayama, Yasutaka; Nakazawa, Takahiro; Ando, Tomoaki; Hayashi, Kazuki; Okumura, Fumihiro; Kitajima, Yasuhiro; Ban, Tessin; Miyabe, Katsuyuki; Ueno, Koichiro; Joh, Takashi; Sano, Hitoshi

2008-01-01

We report a 50-year-old male with pseudocysts in the pancreatic tail associated with chronic pancreatitis successfully treated by transpapillary cyst drainage. He had previously undergone ultrasonography-guided percutaneous cyst drainage for a pancreatic pseudocyst in our hospital. He was readmitted due to abdominal pain and fever. Computed tomography showed recurrence of a pseudocyst in the pancreatic tail measuring 5 cm in diameter. Since conservative treatment failed, endoscopic retrograde pancreatography was performed. There was communication between the pseudocyst and the main pancreatic duct, and pancreatic duct stenosis proximal to the pseudocyst. First, transpapillary pancreatic duct drainage was performed using a plastic stent, but the pseudocyst did not decrease in size and became infected. After removal of the stent, a pigtail type nasocystic catheter was placed in the pseudocyst via the pancreatic duct. The pseudocyst infection immediately disappeared, and the pseudocyst gradually decreased and disappeared. After removal of the nasocystic catheter, no recurrence was observed. As transpapillary drainage of pancreatic pseudocyst, cyst drainage and pancreatic duct drainage have been reported. In our patient with pseudocyst in the pancreatic tail, duct drainage was ineffective and the pseudocyst was infected, whereas cyst drainage was very effective. We considered that cyst drainage by a nasocystic catheter was the first-line therapy as the transpapillary drainage of the pancreatic pseudocyst. PMID:21897788

Association of a renal papillary carcinoma with a low grade tumour of the collecting ducts

PubMed Central

Daniel, L; Zattara-Cannoni, H; Lechevallier, E; Pellissier, J

2001-01-01

This case report describes a 75 year old man who had a renal papillary carcinoma associated with a low grade tumour of the collecting ducts. These tumours showed different immunohistochemical patterns for epithelial membrane antigen, cytokeratin 19, and Ulex europaeus lectin expression. In addition, cytogenetic findings were 47, XY, +7 <7> and 45, XY, -8, add(12)(q–ter)<10> for the papillary renal carcinoma and the low grade tumour of the collecting ducts, respectively. This is the first report where these two types of tumour are associated and cytogenetically distinguished. Key Words: renal cell carcinoma • low grade tumour of the collecting ducts PMID:11477121

Histopathology of a benign bile duct lesion in the liver: Morphologic mimicker or precursor of intrahepatic cholangiocarcinoma.

PubMed

Lee, Kyoung-Bun

2016-09-01

A bile duct lesion originating from intrahepatic bile ducts is generally regarded as an incidental pathologic finding in liver specimens. However, a recent study on the molecular classification of intrahepatic cholangiocarcinoma has focused on the heterogeneity of this carcinoma and has suggested that the cells of different origins present in the biliary tree may have a major role in the mechanism of oncogenesis. In this review, benign intrahepatic bile duct lesions-regarded in the past as reactive changes or remnant developmental anomalies and now noted to have potential for developing precursor lesions of intrahepatic cholangiocarcinoma-are discussed by focusing on the histopathologic features and its implications in clinical practice.

The Vagal Nerve Stimulates Activation of the Hepatic Progenitor Cell Compartment via Muscarinic Acetylcholine Receptor Type 3

PubMed Central

Cassiman, David; Libbrecht, Louis; Sinelli, Nicoletta; Desmet, Valeer; Denef, Carl; Roskams, Tania

2002-01-01

In the rat the hepatic branch of the nervus vagus stimulates proliferation of hepatocytes after partial hepatectomy and growth of bile duct epithelial cells after bile duct ligation. We studied the effect of hepatic vagotomy on the activation of the hepatic progenitor cell compartment in human and rat liver. The number of hepatic progenitor cells and atypical reactive ductular cells in transplanted (denervated) human livers with hepatitis was significantly lower than in innervated matched control livers and the number of oval cells in vagotomized rat livers with galactosamine hepatitis was significantly lower than in livers of sham-operated rats with galactosamine hepatitis. The expression of muscarinic acetylcholine receptors (M1-M5 receptor) was studied by immunohistochemistry and reverse transcriptase-polymerase chain reaction. In human liver, immunoreactivity for M3 receptor was observed in hepatic progenitor cells, atypical reactive ductules, intermediate hepatocyte-like cells, and bile duct epithelial cells. mRNA for the M1-M3 and the M5 receptor, but not the M4 receptor, was detected in human liver homogenates. In conclusion, the hepatic vagus branch stimulates activation of the hepatic progenitor cell compartment in diseased liver, most likely through binding of acetylcholine to the M3 receptor expressed on these cells. These findings may be of clinical importance for patients with a transplant liver. PMID:12163377

Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney

PubMed Central

Guo, Qiusha; Wang, Yinqiu; Tripathi, Piyush; Manda, Kalyan R.; Mukherjee, Malini; Chaklader, Malay; Austin, Paul F.

2015-01-01

A disintegrin and metalloproteinase domain 10 (Adam10), a member of the ADAM family of cell membrane–anchored proteins, has been linked to the regulation of the Notch, EGF, E-cadherin, and other signaling pathways. However, it is unclear what role Adam10 has in the kidney in vivo. In this study, we showed that Adam10 deficiency in ureteric bud (UB) derivatives leads to a decrease in urinary concentrating ability, polyuria, and hydronephrosis in mice. Furthermore, Adam10 deficiency led to a reduction in the percentage of aquaporin 2 (Aqp2)+ principal cells (PCs) in the collecting ducts that was accompanied by a proportional increase in the percentage of intercalated cells (ICs). This increase was more prominent in type A ICs than in type B ICs. Foxi1, a transcription factor important for the differentiation of ICs, was upregulated in the Adam10 mutants. The observed reduction of Notch activity in Adam10 mutant collecting duct epithelium and the similar reduction of PC/IC ratios in the collecting ducts in mice deficient for mindbomb E3 ubiquitin protein ligase 1, a key regulator of the Notch and Wnt/receptor-like tyrosine kinase signaling pathways, suggest that Adam10 regulates cell fate determination through the activation of Notch signaling, probably through the regulation of Foxi1 expression. However, phenotypic differences between the Adam10 mutants, the Mib1 mutants, and the Foxi1 mutants suggest that the functions of Adam10 in determining the fate of collecting duct cells are more complex than those of a simple upstream factor in a linear pathway involving Notch and Foxi1. PMID:24904084

Expression and localization of receptor protein tyrosine phosphatase β and its ligand pleiotrophin in the submandibular gland of mice.

PubMed

Adthapanyawanich, Kannika; Yamamoto, Miyuki; Wakayama, Tomohiko; Nakata, Hiroki; Keattikunpairoj, Sunisa; Iseki, Shoichi

2013-02-01

The family of receptor protein tyrosine phosphatase β (RPTPβ) is composed of 4 splice variants and thought to play roles in the neural migration and outgrowth. Several ligands including the growth factor pleiotrophin (PTN) bind to RPTPβ and inhibit its phosphatase activity, thereby activating cellular signalling pathways. We examined the expression and localization of RPTPβ and its ligands in the submandibular gland (SMG) of mice, which is known for a prominent sexual dimorphism in the duct system. The homogenates and tissue sections of male and female mouse SMG were analysed with RT-PCR, Western blotting, and immunohistochemistry. The short receptor type of RPTPβ (RPTPβ-S) was dominantly expressed in the SMG, and the male gland had significantly higher levels of RPTPβ-S expression than the female gland. In the male, RPTPβ-S was localized predominantly in intercalated duct (ID) cells, but was not found in granular convoluted tubule (GCT) cells or acinar cells. In the female, weaker reactivity was demonstrated in both ID and striated duct (SD) cells. Of the known ligands for RPTPβ, PTN was expressed in the SMG, without sexual difference in levels. In the male, PTN was localized in ID cells as well as in cells located in the distal ends of GCT that are in close vicinity to the ID, whereas in the female PTN was colocalized with RPTPβ-S throughout ID and SD cells. These results indicated that the distribution of RPTPβ-S and its ligand PTN has a close relation to the sexual dimorphism in the duct system of mouse SMG. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mammary fibroadenoma in a lamb

PubMed Central

Guvenc, Tolga; Yarim, Murat; Kabak, Yonca B.; Sozgen, Yuksel

2007-01-01

A fibroadenoma was diagnosed in the left udder of a 3-month-old female Chios lamb. No recurrence was observed after surgery. Grossly, the tumor had a whitish-gray lobular appearance, and the lobules were interlaced with thin septa. Microscopically, the tumor was composed of proliferating fibroepithelial tissue, including differentiated ducts lined by whorls and interlacing bundles of abundant loose fibrovascular stroma. Immunohistochemistry revealed the ductal epithelium to be positive for pancytokeratin (AE1/AE3) and loose fibrovascular stroma was positive for vimentin and basal cells covering the ductal epithelium of alpha-smooth-muscle actin. Immunostaining for the estrogen and progesterone receptors was negative. A diagnosis of mammary fibroadenoma was made based on the histological and immunohistochemical findings. PMID:17993758

Novel function of LHFPL2 in female and male distal reproductive tract development.

PubMed

Zhao, Fei; Zhou, Jun; Li, Rong; Dudley, Elizabeth A; Ye, Xiaoqin

2016-03-11

Congenital reproductive tract anomalies could impair fertility. Female and male reproductive tracts are developed from Müllerian ducts and Wolffian ducts, respectively, involving initiation, elongation and differentiation. Genetic basis solely for distal reproductive tract development is largely unknown. Lhfpl2 (lipoma HMGIC fusion partner-like 2) encodes a tetra-transmembrane protein with unknown functions. It is expressed in follicle cells of ovary and epithelial cells of reproductive tracts. A spontaneous point mutation of Lhfpl2 (LHFPL2(G102E)) leads to infertility in 100% female mice, which have normal ovarian development, ovulation, uterine development, and uterine response to exogenous estrogen stimulation, but abnormal upper longitudinal vaginal septum and lower vaginal agenesis. Infertility is also observed in ~70% mutant males, which have normal mating behavior and sperm counts, but abnormal distal vas deferens convolution resulting in complete and incomplete blockage of reproductive tract in infertile and fertile males, respectively. On embryonic day 15.5, mutant Müllerian ducts and Wolffian ducts have elongated but their duct tips are enlarged and fail to merge with the urogenital sinus. These findings provide a novel function of LHFPL2 and a novel genetic basis for distal reproductive tract development; they also emphasize the importance of an additional merging phase for proper reproductive tract development.

Lymphoepithelial Carcinoma of the Nasolacrimal Duct: Clinical, Radiologic, and Immunopathologic Features.

PubMed

Jakobiec, Frederick A; Stagner, Anna M; Rubin, Peter A D

Undifferentiated lymphoepithelial carcinoma (exhibiting both begin lymphoid and malignant epithelial components) most commonly arises in the head and neck, especially in the nasopharynx. It may also be encountered in various ocular adnexal sites, including the nasolacrimal duct. A 63-year-old woman developed a swelling in the region of the right lacrimal sac accompanied by epiphora. CT scanning revealed an enlargement of the nasolacrimal duct from the lacrimal sac to the inferior nasal meatus. A biopsy during dacryocystorhinostomy for symptomatic epiphora revealed hypercellular sheets of small lymphocytes which were interpreted as evidence for a chronic dacryocystitis. Two years later the subtotally excised lesion had substantially grown in size. Repeat CT scans demonstrated an inferonasal anterior orbital mass with further enlargement of the nasolacrimal duct with a solid mass in its lumen, and bone erosion. The biopsy combined a rich background of lymphocytes within which were clusters of undifferentiated carcinoma cells that were cytokeratin and p63 positive. Critical review of the earlier biopsy led to the detection of the same cells, but in smaller numbers, that had been overlooked. An awareness of the possibility of lymphoepithelial carcinoma of the lacrimal sac/duct should improve diagnostic accuracy with the aid of immunohistochemistry. Radiation therapy is often successful in managing this highly sensitive malignant tumor.

SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization

PubMed Central

Stewart, Andrew K.; Shmukler, Boris E.; Vandorpe, David H.; Reimold, Fabian; Heneghan, John F.; Nakakuki, M.; Akhavein, Arash; Ko, Shigeru; Ishiguro, Hiroshi

2011-01-01

The secretin-stimulated human pancreatic duct secretes HCO3−-rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO3− secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl−/HCO3− exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete ∼140 mM HCO3− or more, mouse and rat ducts secrete ∼40–70 mM HCO3−. Moreover, the axial distribution and physiological roles of SLC26 anion exchangers in pancreatic duct secretory processes remain controversial and may vary among mammalian species. Thus the property of high HCO3− secretion shared by human and guinea pig pancreatic ducts prompted us to clone from guinea pig pancreatic duct cDNAs encoding Slc26a3, Slc26a6, and Slc26a11 polypeptides. We then functionally characterized these anion transporters in Xenopus oocytes and human embryonic kidney (HEK) 293 cells. In Xenopus oocytes, gpSlc26a3 mediated only Cl−/Cl− exchange and electroneutral Cl−/HCO3− exchange. gpSlc26a6 in Xenopus oocytes mediated Cl−/Cl− exchange and bidirectional exchange of Cl− for oxalate and sulfate, but Cl−/HCO3− exchange was detected only in HEK 293 cells. gpSlc26a11 in Xenopus oocytes exhibited pH-dependent Cl−, oxalate, and sulfate transport but no detectable Cl−/HCO3− exchange. The three gpSlc26 anion transporters exhibited distinct pharmacological profiles of 36Cl− influx, including partial sensitivity to CFTR inhibitors Inh-172 and GlyH101, but only Slc26a11 was inhibited by PPQ-102. This first molecular and functional assessment of recombinant SLC26 anion transporters from guinea pig pancreatic duct enhances our understanding of pancreatic HCO3− secretion in species that share a high HCO3− secretory output. PMID:21593449

Extent of fungal growth on fiberglass duct liners with and without biocides under challenging environmental conditions.

PubMed

Samimi, Behzad S; Ross, Kristen

2003-03-01

Eight brands of fiberglass duct liners, including three that contained biocides, were exposed to challenging environmental conditions that would promote fungal growth. Twenty-four rectangular sheet metal ducts in three groups of eight ducts per group were lined with the eight selected liners. Each group of ducts was exposed to one of the three test conditions within an environmental chamber for a period of 15 days. These conditions were a) 75 percent RH, b) 75 percent RH plus water spray, c) 75 percent RH plus dry nutrient, and d) 75 percent RH plus water plus nutrient. Viable spores of Aspergillus niger were aerosolized into each duct as seed. On the 16th day, air and surface samples for fungal spores were collected from inside ducts. The results of air sampling using N6 sampler and visual inspection indicated that two out of three biocide-containing liners, Permacote and Toughgard, inhibited fungal growth but only under condition A. The third biocide-containing liner, Aeroflex Plus, was effective even when it was wet (conditions A and B). All three biocide-containing liners failed to inhibit fungal growth under conditions C and D. Among the five other types of liners that did not contain biocides, ATCO Flex with a smooth Mylar coating was more preferable, exhibiting lower fungal activity during conditions A, B, and C. All liners failed under condition D when nutrient and water were added together. Surface sampling using adhesive tape failed to produce representative results, apparently due to rough/porous surface of duct liners. It was concluded that duct liners with biocide treatment could be less promoting to microbial growth under high humidity as long as their surfaces remain clean and water-free. A liner with an impermeable and smooth surface seems to be less subject to microbial growth under most conditions than biocide-containing liners having porous and/or rough surfaces.

Effect of neck geometry of resonance cells on noise reduction efficiency in sound-absorbing structures

NASA Astrophysics Data System (ADS)

Pisarev, P. V.; Anoshkin, A. N.; Pan'kov, A. A.

2016-10-01

The present work formulates the physical and mathematical models capable to forecast acoustic properties of resonance cells in sound absorbing structures. Distribution of acoustic pressure inside the duct and on sidewall cell was found, loss factor of output acoustic pressure wave was calculated for variety of geometric forms of cell's chamber and neck for monochromatic wave in 100-600Hz frequency range. Analysis of the acoustic pressure fields revealed that cell neck geometry strongly influences on cell resonant frequency and on outlet acoustic pressure loss factor. The effectiveness of the proposed by the authors biconical design of the resonant cell was proved, which increased acoustic radiation at the resonance frequency resulting significant increase of loss ratio of wave acoustic pressure at duct outlet.

Glycogen synthase kinase-3 regulation of urinary concentrating ability

PubMed Central

Rao, Reena

2013-01-01

Purpose of review Glycogen synthase kinase-3 (GSK3) is an enzyme that is gaining prominence as a critical signaling molecule in the epithelial cells of renal tubules. This review will focus on recent findings exploring the role of GSK3 in renal collecting ducts, especially its role in urine concentration involving vasopressin signaling. Recent findings Recent studies using inhibition or tissue-specific gene deletion of GSK3 revealed the mechanism by which GSK3 regulates aquaporin 2 water channels via adenylate cyclase or the prostaglandin-E2 pathway. In other studies, postnatal treatment with lithium, an inhibitor of GSK3, increased cell proliferation and led to microcyst formation in rat kidneys. These studies suggest that loss of GSK3 activity could interfere with renal water transport at two levels. In the short term, it could disrupt vasopressin signaling in collecting duct cells and in the long term it could alter the structure of the collecting ducts, making them less responsive to the hydro-osmotic effects of vasopressin. Summary Ongoing studies reveal the crucial role played by GSK3 in the regulation of vasopressin action in the renal collecting ducts and suggest a possible use of GSK3 inhibitors in disease conditions associated with disrupted vasopressin signaling. PMID:22691876

Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.

PubMed

Xia, Yin; Babitt, Jodie L; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Samad, Tarek A; Brenner, Gary J; Anderson, Jennifer L; Hong, Charles C; Schneyer, Alan L; Brown, Dennis; Lin, Herbert Y

2010-04-01

The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.

Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract.

PubMed

Schütz, Burkhard; Jurastow, Innokentij; Bader, Sandra; Ringer, Cornelia; von Engelhardt, Jakob; Chubanov, Vladimir; Gudermann, Thomas; Diener, Martin; Kummer, Wolfgang; Krasteva-Christ, Gabriela; Weihe, Eberhard

2015-01-01

The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline acetyltransferase (ChAT)-positive brush cells with taste cell-like traits. With the aid of two transgenic mouse lines that express green fluorescent protein (EGFP) under the control of the ChAT promoter (EGFP (ChAT) ) and by using in situ hybridization and immunohistochemistry we found that EGFP (ChAT) cells were clustered in the epithelium lining the gastric groove. EGFP (ChAT) cells were numerous in the gall bladder and bile duct, and found scattered as solitary cells along the small and large intestine. While all EGFP (ChAT) cells were also ChAT-positive, expression of the high-affinity choline transporter (ChT1) was never detected. Except for the proximal colon, EGFP (ChAT) cells also lacked detectable expression of the vesicular acetylcholine transporter (VAChT). EGFP (ChAT) cells were found to be separate from enteroendocrine cells, however they were all immunoreactive for cytokeratin 18 (CK18), transient receptor potential melastatin-like subtype 5 channel (TRPM5), and for cyclooxygenases 1 (COX1) and 2 (COX2). The ex vivo stimulation of colonic EGFP (ChAT) cells with the bitter substance denatonium resulted in a strong increase in intracellular calcium, while in other epithelial cells such an increase was significantly weaker and also timely delayed. Subsequent stimulation with cycloheximide was ineffective in both cell populations. Given their chemical coding and chemosensory properties, EGFP (ChAT) brush cells thus may have integrative functions and participate in induction of protective reflexes and inflammatory events by utilizing ACh and prostaglandins for paracrine signaling.

Isolation of mouse pancreatic alpha, beta, duct and acinar populations with cell surface markers.

PubMed

Dorrell, Craig; Grompe, Maria T; Pan, Fong Cheng; Zhong, Yongping; Canaday, Pamela S; Shultz, Leonard D; Greiner, Dale L; Wright, Chris V; Streeter, Philip R; Grompe, Markus

2011-06-06

Tools permitting the isolation of live pancreatic cell subsets for culture and/or molecular analysis are limited. To address this, we developed a collection of monoclonal antibodies with selective surface labeling of endocrine and exocrine pancreatic cell types. Cell type labeling specificity and cell surface reactivity were validated on mouse pancreatic sections and by gene expression analysis of cells isolated using FACS. Five antibodies which marked populations of particular interest were used to isolate and study viable populations of purified pancreatic ducts, acinar cells, and subsets of acinar cells from whole pancreatic tissue or of alpha or beta cells from isolated mouse islets. Gene expression analysis showed the presence of known endocrine markers in alpha and beta cell populations and revealed that TTR and DPPIV are primarily expressed in alpha cells whereas DGKB and GPM6A have a beta cell specific expression profile. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

ClinicalTrials.gov

2018-03-08

Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

HAARP-Induced Ionospheric Ducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milikh, Gennady; Vartanyan, Aram

2011-01-04

It is well known that strong electron heating by a powerful HF-facility can lead to the formation of electron and ion density perturbations that stretch along the magnetic field line. Those density perturbations can serve as ducts for ELF waves, both of natural and artificial origin. This paper presents observations of the plasma density perturbations caused by the HF-heating of the ionosphere by the HAARP facility. The low orbit satellite DEMETER was used as a diagnostic tool to measure the electron and ion temperature and density along the satellite orbit overflying close to the magnetic zenith of the HF-heater. Thosemore » observations will be then checked against the theoretical model of duct formation due to HF-heating of the ionosphere. The model is based on the modified SAMI2 code, and is validated by comparison with well documented experiments.« less

Lightweight Exhaust Manifold and Exhaust Pipe Ducting for Internal Combustion Engines

NASA Technical Reports Server (NTRS)

Northam, G. Burton (Inventor); Ransone, Philip O. (Inventor); Rivers, H. Kevin (Inventor)

1999-01-01

An improved exhaust system for an internal combustion gasoline-and/or diesel-fueled engine includes an engine exhaust manifold which has been fabricated from carbon- carbon composite materials in operative association with an exhaust pipe ducting which has been fabricated from carbon-carbon composite materials. When compared to conventional steel. cast iron. or ceramic-lined iron paris. the use of carbon-carbon composite exhaust-gas manifolds and exhaust pipe ducting reduces the overall weight of the engine. which allows for improved acceleration and fuel efficiency: permits operation at higher temperatures without a loss of strength: reduces the "through-the wall" heat loss, which increases engine cycle and turbocharger efficiency and ensures faster "light-off" of catalytic converters: and, with an optional thermal reactor, reduces emission of major pollutants, i.e. hydrocarbons and carbon monoxide.

Experimental validation study of an analytical model of discrete frequency sound propagation in closed-test-section wind tunnels

NASA Technical Reports Server (NTRS)

Mosher, Marianne

1990-01-01

The principal objective is to assess the adequacy of linear acoustic theory with an impedence wall boundary condition to model the detailed sound field of an acoustic source in a duct. Measurements and calculations are compared of a simple acoustic source in a rectangular concrete duct lined with foam on the walls and anechoic end terminations. Measurement of acoustic pressure for twelve wave numbers provides variation in frequency and absorption characteristics of the duct walls. Close to the source, where the interference of wall reflections is minimal, correlation is very good. Away from the source, correlation degrades, especially for the lower frequencies. Sensitivity studies show little effect on the predicted results for changes in impedance boundary condition values, source location, measurement location, temperature, and source model for variations spanning the expected measurement error.

Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma

PubMed Central

Halaoui, Ruba; Rejon, Carlis; Chatterjee, Sudipa June; Szymborski, Joseph; Meterissian, Sarkis; Muller, William J.; Omeroglu, Atilla; McCaffrey, Luke

2017-01-01

Epithelial cancers (carcinoma) account for 80%–90% of all cancers. The development of carcinoma is associated with disrupted epithelial organization and solid ductal structures. The mechanisms underlying the morphological development of carcinoma are poorly understood, but it is thought that loss of cell polarity is an early event. Here we report the characterization of the development of human breast lesions leading to carcinoma. We identified a unique mechanism that generates solid ducts in carcinoma through progressive loss of polarity and collapse of the luminal architecture. This program initiates with asymmetric divisions of polarized cells that generate a stratified epithelium containing both polarized and depolarized cells. Stratified regions form cords that penetrate into the lumen, subdividing it into polarized secondary lumina. The secondary lumina then collapse with a concomitant decrease in RhoA and myosin II activity at the apical membrane and ultimately lose apical–basal polarity. By restoring RhoA activity in mice, ducts maintained lumen and cell polarity. Notably, disrupted tissue architecture through luminal collapse was reversible, and ducts with a lumen were re-established after oncogene suppression in vivo. This reveals a novel and common mechanism that contributes to carcinoma development by progressively disrupting cell and tissue organization. PMID:28887414

Pancreatic acinar cell carcinoma extending into the common bile and main pancreatic ducts.

PubMed

Yamaguchi, Rin; Okabe, Yoshinobu; Jimi, Atsuo; Shiota, Koji; Kodama, Takahito; Naito, Yoshiki; Yasunaga, Masafumi; Kinoshita, Hisafumi; Kojiro, Masamichi

2006-10-01

Acinar cell carcinoma (ACC) of the pancreas is relatively rare, accounting for only approximately 1% of all exocrine pancreatic tumors. A 69-year-old man was found to have a mass lesion measuring approximately 4 cm in diameter in the pancreatic head on ultrasound, abdominal dynamic CT, and percutaneous transhepatic cholangiography. Magnetic resonance cholangiopancreatography showed defect of the lower common bile duct (CBD) due to obstruction by the tumor cast. Histopathologically, the pancreatic head tumor invaded the main pancreatic duct (MPD) and CBD with extension into the CBD in a form of tumor cast. The tumor cells consisted of a solid proliferation with abundant eosinophilic cytoplasm and round nuclei in an acinar and trabecular fashion. A 55-year-old man with upper abdominal pain and nausea, had a cystic lesion approximately 3 cm in size in the pancreatic tail on CT. Histopathologically, the tumor was encapsulated by fibrous capsule and had extensive central necrosis with solid areas in the tumor periphery, and invaded with extension into the MPD in a form of tumor cast. The tumor cells resembled acinar cells in solid growths. Two resected cases of ACC with unusual tumor extension into the CBD and the MPD, respectively, are reported.

Histological convergent evolution of the accessory submandibular glands in four species of frog-eating bats.

PubMed

Tandler, B; Phillips, C J; Nagato, T

1996-08-01

The accessory submandibular glands in four species of bats were examined by electron microscopy. These four species represent two independently evolved lineages. The fringe-lipped bat, Trachops cirrhosis, is a Neotropical phyllostomid species, whereas the false vampire bats of southeast Asia, Megaderma lyra and M. spasma, and the heart-nosed bat, Cardioderma cor, of East Africa are megadermatid species. These glands show extreme deviation from typical salivary gland histology: their secretory endpieces are in the form of follicles and their ducts lack the cytological details that permit identification of diverse duct segments. Despite their unusual histology, the secretory endpieces in M. lyra, M. spasma, and C. cor consist of secretory cells that conform to typical secretory cell morphology. In contrast, secretion by follicular cells in T. cirrhosis involves unusual cytoplasmic bodies, and their mitochondria frequently have intracristal crystalloids. Ducts in all four species consist of simple cuboidal to columnar epithelium without basal striations. Follicles and ducts in all four bats are surrounded by numerous myoepithelial cells and are heavily innervated by hypolemmal nerve terminals. Despite their widely separated geographical ranges, all four bat species consume frogs and other vertebrates. Frogs and toads often possess toxic cutaneous glands that provide a chemical defense against predation. It is postulated that the unusual accessory glands in the four frog-eating species secrete toxin-neutralizing salivary factors. The follicular form of the endpieces permits storage of preformed saliva and their coterie of myoepithelial cells and hypolemmal nerve terminals facilitates the sudden and rapid expulsion of saliva into the oral cavity during the consumption of noxious amphibians.

The Inactivation of Arx in Pancreatic α-Cells Triggers Their Neogenesis and Conversion into Functional β-Like Cells

PubMed Central

Courtney, Monica; Gjernes, Elisabet; Druelle, Noémie; Ravaud, Christophe; Vieira, Andhira; Ben-Othman, Nouha; Pfeifer, Anja; Avolio, Fabio; Leuckx, Gunter; Lacas-Gervais, Sandra; Burel-Vandenbos, Fanny; Ambrosetti, Damien; Hecksher-Sorensen, Jacob; Ravassard, Philippe; Heimberg, Harry; Mansouri, Ahmed; Collombat, Patrick

2013-01-01

Recently, it was demonstrated that pancreatic new-born glucagon-producing cells can regenerate and convert into insulin-producing β-like cells through the ectopic expression of a single gene, Pax4. Here, combining conditional loss-of-function and lineage tracing approaches, we show that the selective inhibition of the Arx gene in α-cells is sufficient to promote the conversion of adult α-cells into β-like cells at any age. Interestingly, this conversion induces the continuous mobilization of duct-lining precursor cells to adopt an endocrine cell fate, the glucagon+ cells thereby generated being subsequently converted into β-like cells upon Arx inhibition. Of interest, through the generation and analysis of Arx and Pax4 conditional double-mutants, we provide evidence that Pax4 is dispensable for these regeneration processes, indicating that Arx represents the main trigger of α-cell-mediated β-like cell neogenesis. Importantly, the loss of Arx in α-cells is sufficient to regenerate a functional β-cell mass and thereby reverse diabetes following toxin-induced β-cell depletion. Our data therefore suggest that strategies aiming at inhibiting the expression of Arx, or its molecular targets/co-factors, may pave new avenues for the treatment of diabetes. PMID:24204325

Inner ear development: building a spiral ganglion and an organ of Corti out of unspecified ectoderm.

PubMed

Fritzsch, Bernd; Pan, Ning; Jahan, Israt; Elliott, Karen L

2015-07-01

The mammalian inner ear develops from a placodal thickening into a complex labyrinth of ducts with five sensory organs specialized to detect position and movement in space. The mammalian ear also develops a spiraled cochlear duct containing the auditory organ, the organ of Corti (OC), specialized to translate sound into hearing. Development of the OC from a uniform sheet of ectoderm requires unparalleled precision in the topological developmental engineering of four different general cell types, namely sensory neurons, hair cells, supporting cells, and general otic epithelium, into a mosaic of ten distinctly recognizable cell types in and around the OC, each with a unique distribution. Moreover, the OC receives unique innervation by ear-derived spiral ganglion afferents and brainstem-derived motor neurons as efferents and requires neural-crest-derived Schwann cells to form myelin and neural-crest-derived cells to induce the stria vascularis. This transformation of a sheet of cells into a complicated interdigitating set of cells necessitates the orchestrated expression of multiple transcription factors that enable the cellular transformation from ectoderm into neurosensory cells forming the spiral ganglion neurons (SGNs), while simultaneously transforming the flat epithelium into a tube, the cochlear duct, housing the OC. In addition to the cellular and conformational changes forming the cochlear duct with the OC, changes in the surrounding periotic mesenchyme form passageways for sound to stimulate the OC. We review molecular developmental data, generated predominantly in mice, in order to integrate the well-described expression changes of transcription factors and their actions, as revealed in mutants, in the formation of SGNs and OC in the correct position and orientation with suitable innervation. Understanding the molecular basis of these developmental changes leading to the formation of the mammalian OC and highlighting the gaps in our knowledge might guide in vivo attempts to regenerate this most complicated cellular mosaic of the mammalian body for the reconstitution of hearing in a rapidly growing population of aging people suffering from hearing loss.

Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation

PubMed Central

De Groef, Sofie; Leuckx, Gunter; Van Gassen, Naomi; Staels, Willem; Cai, Ying; Yuchi, Yixing; Coppens, Violette; De Leu, Nico; Heremans, Yves; Baeyens, Luc; Van de Casteele, Mark; Heimberg, Harry

2015-01-01

Expansion of pancreatic beta cells in vivo or ex vivo, or generation of beta cells by differentiation from an embryonic or adult stem cell, can provide new expandable sources of beta cells to alleviate the donor scarcity in human islet transplantation as therapy for diabetes. Although recent advances have been made towards this aim, mechanisms that regulate beta cell expansion and differentiation from a stem/progenitor cell remain to be characterized. Here, we describe a protocol for an injury model in the adult mouse pancreas that can function as a tool to study mechanisms of tissue remodeling and beta cell proliferation and differentiation. Partial duct ligation (PDL) is an experimentally induced injury of the rodent pancreas involving surgical ligation of the main pancreatic duct resulting in an obstruction of drainage of exocrine products out of the tail region of the pancreas. The inflicted damage induces acinar atrophy, immune cell infiltration and severe tissue remodeling. We have previously reported the activation of Neurogenin (Ngn) 3 expressing endogenous progenitor-like cells and an increase in beta cell proliferation after PDL. Therefore, PDL provides a basis to study signals involved in beta cell dynamics and the properties of an endocrine progenitor in adult pancreas. Since, it still remains largely unclear, which factors and pathways contribute to beta cell neogenesis and proliferation in PDL, a standardized protocol for PDL will allow for comparison across laboratories. PMID:26273954

Kupffer cells induce Notch-mediated hepatocyte conversion in a common mouse model of intrahepatic cholangiocarcinoma

PubMed Central

Terada, Maiko; Horisawa, Kenichi; Miura, Shizuka; Takashima, Yasuo; Ohkawa, Yasuyuki; Sekiya, Sayaka; Matsuda-Ito, Kanae; Suzuki, Atsushi

2016-01-01

Intrahepatic cholangiocarcinoma (ICC) is a malignant epithelial neoplasm composed of cells resembling cholangiocytes that line the intrahepatic bile ducts in portal areas of the hepatic lobule. Although ICC has been defined as a tumor arising from cholangiocyte transformation, recent evidence from genetic lineage-tracing experiments has indicated that hepatocytes can be a cellular origin of ICC by directly changing their fate to that of biliary lineage cells. Notch signaling has been identified as an essential factor for hepatocyte conversion into biliary lineage cells at the onset of ICC. However, the mechanisms underlying Notch signal activation in hepatocytes remain unclear. Here, using a mouse model of ICC, we found that hepatic macrophages called Kupffer cells transiently congregate around the central veins in the liver and express the Notch ligand Jagged-1 coincident with Notch activation in pericentral hepatocytes. Depletion of Kupffer cells prevents the Notch-mediated cell-fate conversion of hepatocytes to biliary lineage cells, inducing hepatocyte apoptosis and increasing mortality in mice. These findings will be useful for uncovering the pathogenic mechanism of ICC and developing prevenient and therapeutic strategies for this refractory disease. PMID:27698452

Annexin A1: A new immunohistological marker of cholangiocarcinoma

PubMed Central

Hongsrichan, Nuttanan; Rucksaken, Rucksak; Chamgramol, Yaovalux; Pinlaor, Porntip; Techasen, Anchalee; Yongvanit, Puangrat; Khuntikeo, Narong; Pairojkul, Chawalit; Pinlaor, Somchai

2013-01-01

AIM: To evaluate a new immunohistological marker, annexin A1 (ANXA1), in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC). METHODS: Expression of ANXA1 protein was investigated in liver tissues from patients with CCA and HCC by immunohistochemistry. Its expression on differences stages of tumor development was investigated in hamster CCA tissues induced by Opisthorchis viverrini and N-nitrosodimethylamine. Moreover, mRNA expression of ANXA1 was assessed in CCA cell lines by quantitative real-time polymerase chain reaction and silencing of ANXA1 gene expression using small interfering RNA. RESULTS: In human CCA tissue arrays, immunohistochemical analysis revealed that the positive expression of ANXA1 was 94.1% (64/68 cases) consisting of a high expression (66.2%, 45/68 cases) and a low expression (33.8%, 23/68 cases). However, expression of ANXA1 protein was negative in all histologic patterns for HCC (46/46 cases) and healthy individuals (6/6 cases). In hamster with opisthorchiasis-associated CCA, the expression of ANXA1 was observed in the cytoplasm of inflammatory cells, bile duct epithelia and tumor cells. Grading scores of ANXA1 expression were significantly increased with tumor progression. In addition, mRNA expression of ANXA1 significantly increased in all of the various CCA cell lines tested compared to an immortalized human cholangiocyte cell line (MMNK1). Suppressing the ANXA1 gene significantly reduced the matrix metalloproteinase (MMP) 2 and MMP9, and transforming growth factor-β genes, but increased nuclear factor-κB gene expression. CONCLUSION: ANXA1 is highly expressed in CCA, but low in HCC, suggesting it may serve as a new immunohistochemical marker of CCA. ANXA1 may play a role in opisthorchiasis-associated cholangiocarcinogenesis. PMID:23674846

Maximum Evaporation Rates of Water Droplets Approaching Obstacles in the Atmosphere Under Icing Conditions

NASA Technical Reports Server (NTRS)

Lowell, H. H.

1953-01-01

When a closed body or a duct envelope moves through the atmosphere, air pressure and temperature rises occur ahead of the body or, under ram conditions, within the duct. If cloud water droplets are encountered, droplet evaporation will result because of the air-temperature rise and the relative velocity between the droplet and stagnating air. It is shown that the solution of the steady-state psychrometric equation provides evaporation rates which are the maximum possible when droplets are entrained in air moving along stagnation lines under such conditions. Calculations are made for a wide variety of water droplet diameters, ambient conditions, and flight Mach numbers. Droplet diameter, body size, and Mach number effects are found to predominate, whereas wide variation in ambient conditions are of relatively small significance in the determination of evaporation rates. The results are essentially exact for the case of movement of droplets having diameters smaller than about 30 microns along relatively long ducts (length at least several feet) or toward large obstacles (wings), since disequilibrium effects are then of little significance. Mass losses in the case of movement within ducts will often be significant fractions (one-fifth to one-half) of original droplet masses, while very small droplets within ducts will often disappear even though the entraining air is not fully stagnated. Wing-approach evaporation losses will usually be of the order of several percent of original droplet masses. Two numerical examples are given of the determination of local evaporation rates and total mass losses in cases involving cloud droplets approaching circular cylinders along stagnation lines. The cylinders chosen were of 3.95-inch (10.0+ cm) diameter and 39.5-inch 100+ cm) diameter. The smaller is representative of icing-rate measurement cylinders, while with the larger will be associated an air-flow field similar to that ahead of an airfoil having a leading-edge radius comparable with that of the cylinder. It is found that the losses are less than 5 percent. It is concluded that such losses are, in general, very small (less than 1 percent) in the case of smaller obstacles (of icing-rate measurement- cylinder size); the motional dynamics are such, however, that exceptions will occur by reason of failure of very small droplets (moving along stagnation lines) to impinge upon obstacle surfaces. In such cases, the droplets will evaporate completely.

Modeling of Field-Aligned Guided Echoes in the Plasmasphere

NASA Technical Reports Server (NTRS)

Fung, Shing F.; Green, James L.

2004-01-01

The conditions under which high frequency (f>>f(sub uh)) long-range extraordinary-mode discrete field-aligned echoes observed by the Radio Plasma Imager (RPI) on board the Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) satellite in the plasmasphere are investigated by ray tracing modeling. Field-aligned discrete echoes are most commonly observed by RPI in the plasmasphere although they are also observed over the polar cap region. The plasmasphere field-aligned echoes appearing as multiple echo traces at different virtual ranges are attributed to signals reflected successively between conjugate hemispheres that propagate along or nearly along closed geomagnetic field lines. The ray tracing simulations show that field-aligned ducts with as little as 1% density perturbations (depletions) and less than 10 wavelengths wide can guide nearly field-aligned propagating high frequency X mode waves. Effective guidance of wave at a given frequency and wave normal angle (Psi) depends on the cross-field density scale of the duct, such that ducts with stronger density depletions need to be wider in order to maintain the same gradient of refractive index across the magnetic field. While signal guidance by field aligned density gradient without ducting is possible only over the polar region, conjugate field-aligned echoes that have traversed through the equatorial region are most likely guided by ducting.

A new blade element method for calculating the performance of high and intermediate solidity axial flow fans

NASA Technical Reports Server (NTRS)

Borst, H. V.

1978-01-01

A method is presented to design and predict the performance of axial flow rotors operating in a duct. The same method is suitable for the design of ducted fans and open propellers. The unified method is based on the blade element approach and the vortex theory for determining the three dimensional effects, so that two dimensional airfoil data can be used for determining the resultant force on each blade element. Resolution of this force in the thrust and torque planes and integration allows the total performance of the rotor, fan or propeller to be predicted. Three different methods of analysis, one based on a momentum flow theory; another on the vortex theory of propellers; and a third based on the theory of ducted fans, agree and reduce cascade airfoil data to single line as a function of the loading and induced angle of attack at values of constant inflow angle. The theory applies for any solidity from .01 to over 1 and any blade section camber. The effects of the duct and blade number can be determined so that the procedure applies over the entire range from two blade open propellers, to ducted helicopter tail rotors, to axial flow compressors with or without guide vanes, and to wind tunnel drive fans.

Vortex shedding flow meter performance at high flow velocities

NASA Technical Reports Server (NTRS)

Siegwarth, J. D.

1986-01-01

In some of the ducts of the Space Shuttle Main Engine (SSME), the maximum liquid oxygen flow velocities approach 10 times those at which liquid flow measurements are normally made. The hydrogen gas flow velocities in other ducts exceed the maximum for gas flow measurement by more than a factor of 3. The results presented here show from water flow tests that vortex shedding flow meters of the appropriate design can measure water flow to velocities in excess of 55 m/s, which is a Reynolds number of about 2 million. Air flow tests have shown that the same meter can measure flow to a Reynolds number of at least 22 million. Vortex shedding meters were installed in two of the SSME ducts and tested with water flow. Narrow spectrum lines were obtained and the meter output frequencies were proportional to flow to + or - 0.5% or better over the test range with no flow conditioning, even though the ducts had multiple bends preceeding the meter location. Meters with the shedding elements only partially spanning the pipe and some meters with ring shaped shedding elements were also tested.

Intraoral Salivary Duct Cyst: Clinical and Histopathologic Features of 177 Cases.

PubMed

Stojanov, Ivan J; Malik, Umer A; Woo, Sook-Bin

2017-12-01

The salivary duct cyst (SDC) is a reactive ductal ectasia most frequently seen in major salivary glands, and likely caused by obstruction. The aim of this study is to define the clinical and histopathologic spectrum of intraoral SDCs. Cases were retrieved from the archives of Harvard School of Dental Medicine/StrataDx, Inc. from January 2012 to August 2014. There were 177 cases of which 103 (58.2%) occurred in females, with a median age of 56 (range 2-95). Approximately half of cases (45.8%) presented in the area of the buccal mucosa, lower lip mucosa, or mandibular vestibule, and 23.2% presented in the floor of mouth. SDCs were lined at least focally by 1-2 layers of cuboidal/columnar epithelium in 85.3% of cases and showed varying degrees of metaplasia (oncocytic, mucous cell, squamous, ciliated, apocrine-like) in 68.4% of cases. Intraluminal mucous stasis was present in 41.8% of SDCs, incipient calcification was present within 4.5% of SDCs, and chronic obstructive sialadenitis was seen in 90.2% of cases. No cysts showed adenomatous ductal proliferations or true papillary structures with fibrovascular cores, although 41.2% exhibited reactive undulation of cyst lining. Thirty-nine 'papillary oncocytic cystadenoma-like' SDCs (22.0%) demonstrated complete oncocytic metaplasia and marked undulation. An additional seven such cysts (4.0%) had a 'Warthin tumor-like' lymphoplasmacytic infiltrate. Intraoral SDCs occur most commonly in the sixth decade of life in locations distinct from extravasation mucoceles, likely secondary to intraluminal obstruction. SDCs show diverse histopathology and certain phenotypic variants may be mistaken for papillary oncocytic cystadenoma or Warthin tumor.

Immunoexpression of intermediate filaments and morphological changes in the liver and bile duct of rats infected with Fasciola hepatica.

PubMed

Kolodziejczyk, L; Laszczyńska, M; Masiuk, M; Grabowska, M; Skrzydlewska, E

2015-01-01

We investigated the immunoexpression of the intermediate filament proteins, cytokeratin and desmin, and the morphological changes in the liver of rats during experimental fasciolosis at 4, 7 and 10 weeks post-infection. Rats were infected with 30 Fasciola hepatica metacercariae. Paraffin sections of the liver were stained using H & E, PAS and azan stains. Immunohistochemical reactions were performed using antibodies against cytokeratin and desmin. The experimental F. hepatica infection led to fibrosis and cirrhosis of the liver, and to inflammation of the common bile ducts. The expression of cytokeratin was increased in the epithelial cells of both the liver bile ductules at 4, 7 and 10 weeks post-infection and in the common bile ducts at 7 and 10 weeks post-infection compared to uninfected rats; expression in the common bile ducts was more intense. The myofibroblasts of the liver and smooth myocytes of the interlobular bile ducts and common bile ducts, showed a slight increase in desmin expression compared to the uninfected rats. The increased expression of cytokeratins in the hyperplastic rat common bile duct epithelium during the biliary phase of fasciolosis at 7 and 10 weeks post-infection may be explained by mechanical irritation by the parasite and an inflammatory reaction in the bile duct epithelium and in periductal fibrous tissue.

Nonselective inhibition of prostaglandin-endoperoxide synthase by naproxen ameliorates hepatic injury in animals with acute or chronic liver injury

PubMed Central

Bahde, Ralf; Kapoor, Sorabh; Gupta, Sanjeev

2014-01-01

The rising prevalence of hepatic injury due to toxins, metabolites, viruses, etc., necessitates development of further mechanisms for protecting the liver and for treating acute or chronic liver diseases. To examine whether inhibition of inflammation directed by cyclo-oxygenase pathways, we performed animal studies with naproxen, which inhibits prostaglandin-endoperoxide synthases 1 and 2 and is in extensive clinical use. We administered carbon tetrachloride to induce acute liver injury and ligated the common bile duct to induce chronic liver injury in adult rats. These experimental manipulations produced abnormalities in liver tests, tissue necrosis, compensatory hepatocyte or biliary proliferation, and onset of fibrosis, particularly after bile duct ligation. After carbon tetrachloride-induced acute injury, naproxen decreased liver test abnormalities, tissue necrosis and compensatory hepatocellular proliferation. After bile duct ligation-induced chronic injury, naproxen decreased liver test abnormalities, tissue injury and compensatory biliary hyperplasia. Moreover, after bile duct ligation, naproxen-treated rats showed more periductular oval liver cells, which have been classified as hepatic progenitor cells. In naproxen-treated rats, we found greater expression in hepatic stellate cells and mononuclear cells of cytoprotective factors, such as vascular endothelial growth factor. The ability of naproxen to induce expression of vascular endothelial growth factor was verified in cell culture studies with CFSC-8B clone of rat hepatic stellate cells. Whereas assays for carbon tetrachloride toxicity using cultured primary hepatocytes established that naproxen was not directly cytoprotective, we found conditioned medium containing vascular endothelial growth factor from naproxen-treated CFSC-8B cells protected hepatocytes from carbon tetrachloride toxicity. Therefore, naproxen was capable of ameliorating toxic liver injury, which involved naproxen-induced release of physiological cytoprotective factors in nonparenchymal liver cells. Such drug-induced release of endogenous cytoprotectants will advance therapeutic development for hepatic injury. PMID:24220607

PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

PubMed

Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

2013-01-01

Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats.

PubMed

Aktas, Cevat; Kanter, Mehmet; Erboga, Mustafa; Mete, Rafet; Oran, Mustafa

2014-10-01

The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress. © The Author(s) 2012.

Multiple pure tone noise prediction

NASA Astrophysics Data System (ADS)

Han, Fei; Sharma, Anupam; Paliath, Umesh; Shieh, Chingwei

2014-12-01

This paper presents a fully numerical method for predicting multiple pure tones, also known as “Buzzsaw” noise. It consists of three steps that account for noise source generation, nonlinear acoustic propagation with hard as well as lined walls inside the nacelle, and linear acoustic propagation outside the engine. Noise generation is modeled by steady, part-annulus computational fluid dynamics (CFD) simulations. A linear superposition algorithm is used to construct full-annulus shock/pressure pattern just upstream of the fan from part-annulus CFD results. Nonlinear wave propagation is carried out inside the duct using a pseudo-two-dimensional solution of Burgers' equation. Scattering from nacelle lip as well as radiation to farfield is performed using the commercial solver ACTRAN/TM. The proposed prediction process is verified by comparing against full-annulus CFD simulations as well as against static engine test data for a typical high bypass ratio aircraft engine with hardwall as well as lined inlets. Comparisons are drawn against nacelle unsteady pressure transducer measurements at two axial locations as well as against near- and far-field microphone array measurements outside the duct. This is the first fully numerical approach (no experimental or empirical input is required) to predict multiple pure tone noise generation, in-duct propagation and far-field radiation. It uses measured blade coordinates to calculate MPT noise.

Advanced Nacelle Acoustic Lining Concepts Development

NASA Technical Reports Server (NTRS)

Bielak, G.; Gallman, J.; Kunze, R.; Murray, P.; Premo, J.; Kosanchick, M.; Hersh, A.; Celano, J.; Walker, B.; Yu, J.;

Repair of a common bile duct defect with a decellularized ureteral graft

PubMed Central

Cheng, Yao; Xiong, Xian-Ze; Zhou, Rong-Xing; Deng, Yi-Lei; Jin, Yan-Wen; Lu, Jiong; Li, Fu-Yu; Cheng, Nan-Sheng

2016-01-01

AIM To evaluate the feasibility of repairing a common bile duct defect with a decellularized ureteral graft in a porcine model. METHODS Eighteen pigs were randomly divided into three groups. An approximately 1 cm segment of the common bile duct was excised from all the pigs. The defect was repaired using a 2 cm long decellularized ureteral graft over a T-tube (T-tube group, n = 6) or a silicone stent (stent group, n = 6). Six pigs underwent bile duct reconstruction with a graft alone (stentless group). The surviving animals were euthanized at 3 mo. Specimens of the common bile ducts were obtained for histological analysis. RESULTS The animals in the T-tube and stent groups survived until sacrifice. The blood test results were normal in both groups. The histology results showed a biliary epithelial layer covering the neo-bile duct. In contrast, all the animals in the stentless group died due to biliary peritonitis and cholangitis within two months post-surgery. Neither biliary epithelial cells nor accessory glands were observed at the graft sites in the stentless group. CONCLUSION Repair of a common bile duct defect with a decellularized ureteral graft appears to be feasible. A T-tube or intraluminal stent was necessary to reduce postoperative complications. PMID:28082809

The vomeronasal system of the mink, Mustela vison. I. The vomeronasal organ.

PubMed

Salazar, I; Cifuentes, J M; Quinteiro, P S; Caballero, G

1994-01-01

The vomeronasal organ (VNO) of the mink is restricted to the area of the Fissura palatina and thus always topographically related to the Ductus incisivus (DI). The VNO and DI have also a functional relation because the vomeronasal duct ends in the incisive duct. On the other hand, as the DI has its mouth in the Papilla incisiva there is a communication between the VNO and the oral cavity. The vomeronasal cartilage, approximately in 1/6 of its length, wraps completely the parenchyma of the VNO whose main structure is the vomeronasal duct, with two different epithelia: sensory receptor in the medial wall, and respiratory in the lateral one. Nevertheless the variations of epithelia belong to the segment of the duct because in its rostral and caudal parts the medial and lateral epithelia are very similar. Branches and tubular PAS positive glands stand out in three points: superior, inferior and medial areas of the vomeronasal duct in which they end. An important number of vessels, mainly veins of different diameter, are located around the duct, while the nervous fibers are close to the medial wall of the duct and very easy to identify in the caudal third of the organ. Two immunohistochemical techniques were used to identify the nerve fibers and the receptor cells.

Pyramidal lobe of the thyroid gland and the thyroglossal duct remnant: a study using human fetal sections.

PubMed

Takanashi, Yoshitaka; Honkura, Yohei; Rodriguez-Vazquez, Jose Francisco; Murakami, Gen; Kawase, Tetsuaki; Katori, Yukio

2015-01-01

To investigate developmental changes in the thyroglossal duct, we observed serial sagittal sections of eight embryos (crown-rump length (CRL) 6-12 mm; approximately 5-6 weeks of gestation) as well as serial horizontal or cross-sections of 70 embryos and fetuses (CRL 15-110 mm; 6-15 weeks). In the sagittal sections, the thyroglossal duct was identified as a small sheet or mass of relatively large cells with vacuolization anterior, superior or inferior to the fourth pharyngeal arch artery. However, we found no continuous duct-like structure that reached the thyroid gland. Thus, previous classical schemes might have overestimated the continuity of the duct. Among cross-sections of 70 specimens, we found the thyroglossal duct remnant in only two specimens (CRL 15 mm and 100 mm), in contrast to the pyramidal lobe, which was seen in one-third of the specimens. The duct remnant ran downward along the lateral edge of the hyoid body to reach the anterior aspect of the thyroid cartilage. However, the connection between the pyramidal lobe and the duct remnant was interrupted by the anterior cervical muscles. Therefore, it was unlikely that the thyroglossal duct remnant would more frequently be evident in fetuses than in adults. The highly tortuous course of the duct along the lingual aspect of the hyoid body, which has been reported previously, appeared to become established near term. Descent of the thyroid gland was not evident after the CRL 20 mm stage (6 weeks): the gland appeared to retain its position at the level of the third-sixth cervical vertebrae. Copyright © 2014 Elsevier GmbH. All rights reserved.

Pure 3D laparoscopic living donor right hemihepatectomy in a donor with separate right posterior and right anterior hepatic ducts and portal veins.

PubMed

Hong, Suk Kyun; Suh, Kyung-Suk; Kim, Hyo-Sin; Yoon, Kyung Chul; Ahn, Sung-Woo; Oh, Dongkyu; Kim, Hyeyoung; Yi, Nam-Joon; Lee, Kwang-Woong

2017-11-01

Despite increases in the performance of pure laparoscopic living donor hepatectomy, variations in the bile duct or portal vein have been regarded as relative contraindications to this technique [1-3]. This report describes a donor with separate right posterior and right anterior hepatic ducts and portal veins who underwent pure laparoscopic living donor right hemihepatectomy, integrated with 3D laparoscopy and indocyanine green (ICG) near-infrared fluorescence cholangiography [1, 4, 5]. A 50-year-old man offered to donate part of his liver to his older brother, who required a transplant for hepatitis B-associated liver cirrhosis and hepatocellular carcinoma. Donor height was 178.0 cm, body weight was 82.7 kg, and body mass index was 26.1 kg/m 2 . Preoperative computed tomography and magnetic resonance cholangiopancreatography showed that the donor had separate right posterior and right anterior hepatic ducts and portal veins. The entire procedure was performed under 3D laparoscopic view. Following intravenous injections of 0.05 mg/kg ICG, ICG near-infrared fluorescence camera was used to demarcate the exact transection line and determine the optimal bile duct division point. The total operation time was 443 min; the donor required no transfusions and experienced no intraoperative complications. The graft weighed 1146 g with a graft-to-recipient weight ratio of 1.88%. The optimal bile duct division point was identified using ICG fluorescence cholangiography, and the bile duct was divided with good patency without any stricture. The right anterior and posterior portal veins were transected with endostaplers without any torsion. The patient was discharged on postoperative day 8, with no complications. Using a 3D view and ICG fluorescence cholangiography, pure 3D laparoscopic living donor right hemihepatectomy is feasible in a donor with separate right posterior and right anterior hepatic ducts and portal veins.

Advanced Turbofan Duct Liner Concepts

NASA Technical Reports Server (NTRS)

Bielak, Gerald W.; Premo, John W.; Hersh, Alan S.

1999-01-01

The Advanced Subsonic Technology Noise Reduction Program goal is to reduce aircraft noise by 10 EPNdB by the year 2000 relative, to 1992 technology. The improvement goal for nacelle attenuation is 25% relative to 1992 technology by 1997 and 50% by 2000. The Advanced Turbofan Duct Liner Concepts Task work by Boeing presented in this document was in support of these goals. The basis for the technical approach was a Boeing study conducted in 1993-94 under NASA/FAA contract NAS1-19349, Task 6, investigating broadband acoustic liner concepts. As a result of this work, it was recommended that linear double layer, linear and perforate triple layer, parallel element, and bulk absorber liners be further investigated to improve nacelle attenuations. NASA LaRC also suggested that "adaptive" liner concepts that would allow "in-situ" acoustic impedance control also be considered. As a result, bias flow and high-temperature liner concepts were also added to the investigation. The major conclusion from the above studies is that improvements in nacelle liner average acoustic impedance characteristics alone will not result in 25% increased nacelle noise reduction relative to 1992 technology. Nacelle design advancements currently being developed by Boeing are expected to add 20-40% more acoustic lining to hardwall regions in current inlets, which is predicted to result in and additional 40-80% attenuation improvement. Similar advancements are expected to allow 10-30% more acoustic lining in current fan ducts with 10-30% more attenuation expected. In addition, Boeing is currently developing a scarf inlet concept which is expected to give an additional 40-80% attenuation improvement for equivalent lining areas.

Dendritic Cells Regulate Treg-Th17 Axis in Obstructive Phase of Bile Duct Injury in Murine Biliary Atresia

PubMed Central

Tang, Shao-tao; Wang, Xin-xing; Cao, Guo-qing; Li, Shuai; Lei, Hai-yan; Zhang, Xi

2015-01-01

Several cell types are considered to be effector cells in bile duct injury in rhesus rotavirus (RRV)-induced experimental biliary atresia (BA). Here, we identified an increased T helper 17 (Th17) cell population in a BA mode. By depleting the Th17 cells, the BA symptoms (onset of jaundice, acholic stools and retarded growth) were attenuated and the survival rate was improved. Furthermore, we found that in mice with BA, the percentage of CD4+CD25highFoxp3+ T regulatory (Treg) cells decreased along with the increased percentage of Th17 cells. However, the absolute numbers of Treg and Th17 cells were both increased in liver of RRV-injected mice compared to saline-injected mice. The proportion of Th17 cells at 7 days post-infection was decreased if Treg cells isolated from normal adult mice, but not Treg cells from the livers of mice with BA, were intraperitoneally transferred on day 5 of life. In vitro experiments also showed that Treg cells from mice with BA had a diminished suppressive effect on Th17 cell generation. To determine the mechanisms, we investigated the production of cytokines in the liver. The level of IL-6, which has been shown to be abundantly secreted by activated dendritic cells (DCs), was remarkably elevated. Importantly, in a Treg/Th17 cell suppression assay, IL-6 was demonstrated to paralyze the Treg cells’ suppressive effect on Th17 cells and eventually the unrestrained increase of Th17 cells contributed to bile duct injury. In conclusion, the DC-regulated Treg-Th17 axis, probably in conjunction with other effector T cells, aggravates progressive inflammatory injury at the time of ductal obstruction. PMID:26325187

Trefoil factors: Tumor progression markers and mitogens via EGFR/MAPK activation in cholangiocarcinoma

PubMed Central

Kosriwong, Kanuengnuch; Menheniott, Trevelyan R; Giraud, Andrew S; Jearanaikoon, Patcharee; Sripa, Banchob; Limpaiboon, Temduang

2011-01-01

AIM: To investigate trefoil factor (TFF) gene copy number, mRNA and protein expression as potential biomarkers in cholangiocarcinoma (CCA). METHODS: TFF mRNA levels, gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction (PCR), quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA, precancerous bile duct dysplasia and from disease-free controls. The functional impact of recombinant human (rh)TFF2 peptide treatment on proliferation and epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling was assessed in the CCA cell line, KMBC, by viable cell counting and immunoblotting, respectively. RESULTS: TFF1, TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls, and was unrelated to gene copy number. TFF1 immunoreactivity was strongly increased in both dysplasia and CCA, whereas TFF2 immunoreactivity was increased only in CCA compared to disease-free controls. By contrast, TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA. Kaplan-Meier analysis found no association of TFF mRNA, protein and copy number with age, gender, histological subtype, and patient survival time. Treatment of KMBC cells with rhTFF2 stimulated proliferation, triggered phosphorylation of EGFR and downstream extracellular signal related kinase (ERK), whereas co-incubation with the EGFR tyrosine kinase inhibitor, PD153035, blocked rhTFF2-dependent proliferation and EGFR/ERK responses. CONCLUSION: TFF mRNA/protein expression is indicative of CCA tumor progression, but not predictive for histological sub-type or survival time. TFF2 is mitogenic in CCA via EGFR/MAPK activation. PMID:21472131

Vitamin K1 attenuates bile duct ligation-induced liver fibrosis in rats.

PubMed

Jiao, Kun; Sun, Quan; Chen, Baian; Li, Shengli; Lu, Jing

2014-06-01

Vitamin K1 is used as a liver protection drug for cholestasis-induced liver fibrosis in China, but the mechanism of vitamin K1's action in liver fibrosis is unclear. In this study, a model of liver fibrosis was achieved via bile duct ligation in rats. The rats were then injected with vitamin K1, and the levels of serum aspartate aminotransferase, alanine transaminase, total bilirubin and the fibrotic grade score, collagen content, the expressions of α-smooth muscle actin (SMA) and cytokeratin 19 (CK19) were measured on day 28 after ligation. The levels of the biochemical parameters, fibrotic score and collagen content were significantly reduced by treatment with vitamin K1 in bile duct-ligated rats. In addition, α-SMA and CK19 expression was significantly reduced by vitamin K1 treatment in bile duct-ligated rats. These results suggested that vitamin K1 may attenuate liver fibrosis by inhibiting hepatic stellate cell activation in bile duct-ligated rats.

Juxtaglomerular cell tumor of the kidney: report of two cases with a papillary pattern.

PubMed

Têtu, B; Vaillancourt, L; Camilleri, J P; Bruneval, P; Bernier, L; Tourigny, R

1993-11-01

We report the clinicopathologic, immunohistochemical, and electron microscopic study of two cases of juxtaglomerular cell tumor of the kidney with a hitherto unreported dominant papillary pattern. Both tumors were associated with high blood pressure that did not respond to medical therapy, but that returned to normal after removal of the kidney. They were well delineated, tan, and had no necrosis. The cores of the papillary structures consisted of polygonal cells found to express renin by immunohistochemistry and to contain renin protogranules by electron microscopy. The papillary fronds were covered by one layer of cuboidal epithelial cells that did not stain for renin and had ultrastructural features reminiscent of the collecting duct epithelium. These tumors must be differentiated from malignant papillary tumors of the kidney, such as papillary clear cell carcinoma, transitional cell carcinoma, and collecting duct carcinoma.

Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes

PubMed Central

Tarlow, Branden D.; Pelz, Carl; Naugler, Willscott E.; Wakefield, Leslie; Wilson, Elizabeth M.; Finegold, Milton J.; Grompe, Markus

2014-01-01

Summary Adult liver progenitor cells are biliary-like epithelial cells that emerge only under injury conditions in the periportal region of the liver. They exhibit phenotypes of both hepatocytes and bile ducts. However, their origin and their significance to injury repair remain unclear. Here, we used a chimeric lineage tracing system to demonstrate that hepatocytes contribute to the progenitor pool. RNA-sequencing, ultrastructural analysis, and in vitro progenitor assays revealed that hepatocyte-derived progenitors were distinct from their biliary-derived counterparts. In vivo lineage tracing and serial transplantation assays showed that hepatocyte-derived proliferative ducts retained a memory of their origin and differentiated back into hepatocytes upon cessation of injury. Similarly, human hepatocytes in chimeric mice also gave rise to biliary progenitors in vivo. We conclude that human and mouse hepatocytes can undergo reversible ductal metaplasia in response to injury, expand as ducts and subsequently contribute to restoration of the hepatocyte mass. PMID:25312494

Regulators of apoptosis in cholangiocarcinoma.

PubMed

Jhala, Nirag C; Vickers, Selwyn M; Argani, Pedram; McDonald, Jay M

2005-04-01

Dysregulation of mediators of apoptosis is associated with carcinogenesis. For biliary duct cancers, p53 gene mutation is an important contributor to carcinogenesis. Mutations in the p53 gene affect transcription of the Fas gene, resulting in lack of Fas expression on cell membrane. It has been previously shown that cloned Fas-negative but not Fas-positive human cholangiocarcinoma cells are resistant to anti-Fas-mediated apoptosis and develop tumors in nude mice. In addition, interferon gamma induces Fas expression in Fas-negative cholangiocarcinoma cells and makes them susceptible to apoptosis. Therefore, it becomes important to characterize immunophenotypic expression of p53 and Fas in normal and neoplastic human tissues of the biliary tract to further understand the pathogenesis of the disease. To date, human studies to characterize differences in immunophenotypic expression of the Fas protein between intrahepatic and extrahepatic biliary duct cancers and in their precursor lesions have not been performed. To report the immunophenotypic expression of p53 and Fas expression in various stages in the development of bile duct cancers (intrahepatic and extrahepatic tumor location) and their association with tumor differentiation. Thirty bile duct cancer samples (13 intrahepatic and 17 extrahepatic) from 18 men and 12 women who ranged in age from 44 to 77 years (mean age, 65.6 years) were retrieved from the surgical pathology files. Hematoxylin-eosin-stained slides were evaluated for the type and grade of tumor and dysplastic changes in the biliary tract epithelium. Additional slides were immunohistochemically stained with p53 and anti-Fas mouse monoclonal antibody. The pattern of Fas distribution and percentage of cells positive for p53 and Fas expression were determined. The percentage of Fas-expressing cells is significantly (P = .01) more frequently noted in extrahepatic tumors compared with intrahepatic tumors. Furthermore, Fas expression decreased from dysplastic epithelium to cholangiocarcinoma (P = .01), and this decreasing trend continued from well to poorly differentiated tumors. Nuclear p53 expression was not identified in normal and dysplastic epithelium but was noted in 30% of carcinomas (P = .02). Fas expression is an early event in pathogenesis of bile duct cancers. Immunophenotypic expression of Fas is associated with well to moderately differentiated tumors but not with poor tumor differentiation.

Colocalization of insulin-like growth factor-binding protein with insulin-like growth factor I.

PubMed

Kobayashi, S; Clemmons, D R; Venkatachalam, M A

1991-07-01

We report the localization of insulin-like growth factor I (IGF-I) and a 25-kDa form of insulin-like growth factor-binding protein (IGF-BP-1) in adult rat kidney. The antigens were localized using a rabbit anti-human IGF-I antibody, and a rabbit anti-human IGF-BP-1 antibody raised against human 25-kDa IGF-BP-1 purified from amniotic fluid. Immunohistochemistry by the avidin-biotin peroxidase conjugate technique showed that both peptides are located in the same nephron segments, in the same cell types. The most intense staining was in papillary collecting ducts. There was moderate staining also in cortical collecting ducts and medullary thick ascending limbs of Henle's loop. In collecting ducts the antigens were shown to be present in principal cells but not in intercalated cells. In distal convoluted tubules, cortical thick ascending limbs, and in structures presumptively identified as thin limbs of Henle's loops there was only modest staining. The macula densa, however, lacked immunoreactivity. Colocalization of IGF-I and IGF-BP-1 in the same cells supports the notion, derived from studies on cultured cells, that the actions of IGF-I may be modified by IGF-BPs that are present in the same location.

THE EFFECT OF PILOCARPINE ON THE OUTPUT OF LYMPHOCYTES THROUGH THE THORACIC DUCT.

PubMed

Rous, F P

1908-05-01

The intravenous injection of pilocarpine nitrate causes in the dog a rapid and considerable increase in the output of lymphocytes through the thoracic duct. The corresponding lymphocytosis induced by the drug in the blood of this animal is not profound, and increased cell-output with the lymph will explain a large part if not all of it. Quickened lymph-flow and dyspnoeic breathing are accessory in the production of the large cell-output with the lymph, but it is mainly dependent on some undetermined element. The evidence points to the mechanical nature of this element. It is probably to be sought in direct pressure from contraction of smooth muscle, as suggested by Harvey, but his observation that atropine prevents the appearance of a lymphocytosis after pilocarpine cannot be quoted in proof because atropine much slows the lymph-flow, and thus decreases cell-output. These findings are in accord with the theory that makes mechanical factors responsible for rapidly appearing lymphocytosis. They show that there are more such factors than has been supposed. Especially do they indicate that the contribution of cells through the thoracic duct may be important in the production of lymphocytosis, and is not, as is often asserted, subsidiary to direct migration into the blood of cells from spleen, bone-marrow and the lymph-glands.

A histological study of the seminal vesicle of the armoured catfish Corydoras aeneus.

PubMed

Franceschini-Vicentini, I B; Papa, L P; Bombonato, M T S; Vicentini, C A; Ribeiro, K; Orsi, A M

2007-04-01

Most species of Corydoras exhibited a reproductive behaviour called 'T-position', and exhibited an accessory gland in the male genital tract, called the seminal vesicle. It appeared that both the structure and the composition of the fluid varied considerably between the species investigated. Consequently, different opinions were proposed regarding the possible role of seminal vesicle on this particular reproductive behaviour. Male adults of Corydoras aeneus were collected, anaesthetized, and samples of seminal vesicle were fixed in Bouin's solution. The sections were stained with haematoxylin-eosin and periodic acid Schiff. The seminal vesicle showed a system of anastomosed secretory tubules, forming a vesicular collective network, which gave rise to the vesicular ducts. The latter fused with the testicular efferent ducts and formed the spermatic ducts. Considering this fusion, when the sperm cells reached the spermatic ducts, the fluid produced at the seminal vesicle covered them. Histochemical studies evidenced the presence of neutral and acid glycosaminoglycans in the seminal fluid. Considering the reproductive behaviour of C. aeneus, it is believed that the protection associated with the immobilization of the sperm cells assures the sperm integrity during the passage through female's intestine until fertilization.

The renal TRPV4 channel is essential for adaptation to increased dietary potassium

PubMed Central

Mamenko, Mykola; Boukelmoune, Nabila; Tomilin, Viktor; Zaika, Oleg; Jensen, V. Behrana; O’Neil, Roger G.; Pochynyuk, Oleh

2016-01-01

To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells. This, in turn, leads to augmented TRPV4-mediated flow-dependent calcium ion responses in freshly isolated split-opened collecting ducts from mice fed the high potassium diet. Genetic TRPV4 ablation greatly diminished BK channel activity in collecting duct cells pointing to a reduced capacity to excrete potassium. Consistently, elevated potassium intake induced hyperkalemia in TRPV4 knockout mice due to deficient renal potassium excretion. Thus, regulation of TRPV4 activity in the distal nephron by dietary potassium is an indispensable component of whole body potassium balance. PMID:28187982

Characterization of pancreatic stem cells derived from adult human pancreas ducts by fluorescence activated cell sorting.

PubMed

Lin, Han-Tso; Chiou, Shih-Hwa; Kao, Chung-Lan; Shyr, Yi-Ming; Hsu, Chien-Jen; Tarng, Yih-Wen; Ho, Larry L-T; Kwok, Ching-Fai; Ku, Hung-Hai

2006-07-28

To isolate putative pancreatic stem cells (PSCs) from human adult tissues of pancreas duct using serum-free, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cytometry. The potential for pancreatic lineage and the capability of beta-cell differentiation in these PSCs were evaluated as well. By using serum-free medium supplemented with essential growth factors, we attempted to isolate the putative PSCs which has been reported to express nestin and pdx-1. The Matrigel(TM) was employed to evaluate the differential capacity of isolated cells. Dithizone staining, insulin content/secretion measurement, and immunohistochemistry staining were used to monitor the differentiation. Fluorescence activated cell sorting (FACS) was used to detect the phenotypic markers of putative PSCs. A monolayer of spindle-like cells was cultivated. The putative PSCs expressed pdx-1 and nestin. They were also able to differentiate into insulin-, glucagon-, and somatostatin-positive cells. The spectrum of phenotypic markers in PSCs was investigated; a similarity was revealed when using human bone marrow-derived stem cells as the comparative experiment, such as CD29, CD44, CD49, CD50, CD51, CD62E, PDGFR-alpha, CD73 (SH2), CD81, CD105(SH3). In this study, we successfully isolated PSCs from adult human pancreatic duct by using serum-free medium. These PSCs not only expressed nestin and pdx-1 but also exhibited markers attributable to mesenchymal stem cells. Although work is needed to elucidate the role of these cells, the application of these PSCs might be therapeutic strategies for diabetes mellitus.

Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice

PubMed Central

Uemura, Mami; Ozawa, Aisa; Nagata, Takumi; Kurasawa, Kaoruko; Tsunekawa, Naoki; Nobuhisa, Ikuo; Taga, Tetsuya; Hara, Kenshiro; Kudo, Akihiko; Kawakami, Hayato; Saijoh, Yukio; Kurohmaru, Masamichi; Kanai-Azuma, Masami; Kanai, Yoshiakira

2013-01-01

Congenital biliary atresia is an incurable disease of newborn infants, of unknown genetic causes, that results in congenital deformation of the gallbladder and biliary duct system. Here, we show that during mouse organogenesis, insufficient SOX17 expression in the gallbladder and bile duct epithelia results in congenital biliary atresia and subsequent acute ‘embryonic hepatitis’, leading to perinatal death in ~95% of the Sox17 heterozygote neonates in C57BL/6 (B6) background mice. During gallbladder and bile duct development, Sox17 was expressed at the distal edge of the gallbladder primordium. In the Sox17+/− B6 embryos, gallbladder epithelia were hypoplastic, and some were detached from the luminal wall, leading to bile duct stenosis or atresia. The shredding of the gallbladder epithelia is probably caused by cell-autonomous defects in proliferation and maintenance of the Sox17+/− gallbladder/bile duct epithelia. Our results suggest that Sox17 plays a dosage-dependent function in the morphogenesis and maturation of gallbladder and bile duct epithelia during the late-organogenic stages, highlighting a novel entry point to the understanding of the etiology and pathogenesis of human congenital biliary atresia. PMID:23293295

Caffeine Inhibits Fluid Secretion by Interlobular Ducts From Guinea Pig Pancreas.

PubMed

Mochimaru, Yuka; Yamamoto, Akiko; Nakakuki, Miyuki; Yamaguchi, Makoto; Taniguchi, Ituka; Ishiguro, Hiroshi

2017-04-01

Caffeine is contained in coffee, tea, and numerous beverages and foods. We examined the direct effects of caffeine on the physiological function of pancreatic duct cells by using interlobular duct segments isolated from guinea pig pancreas. The rate of fluid secretion was continuously measured by monitoring the luminal volume of isolated duct segments. Changes in intracellular Ca concentration ([Ca]i) were estimated by microfluorometry in ducts loaded with Fura-2. Both secretin-stimulated and acetylcholine (ACh)-stimulated fluid secretions were substantially and reversibly inhibited by relatively low concentrations of caffeine as low as 0.03 mM relevant to blood levels after ingestion of caffeine-containing beverages. Caffeine inhibited ACh-induced elevation of [Ca]i and secretin-induced fluctuation of [Ca]i. Caffeine abolished thapsigargin-induced intracellular Ca release but did not affect the entry of extracellular Ca. Caffeine (0.05 mM) abolished ethanol (1 mM)-induced fluid hypersecretion in secretin-stimulated pancreatic duct. Low concentrations of caffeine directly inhibit pancreatic ductal fluid secretion stimulated by secretin or ACh and also ethanol-induced fluid hypersecretion. The inhibition by caffeine seems to be mediated by the blockade of intracellular Ca mobilization. Daily intake of caffeine may reduce the volume of pancreatic juice secretion.

An immortal cell line to study the role of endogenous CFTR in electrolyte absorption.

PubMed

Bell, C L; Quinton, P M

1995-01-01

The intact human reabsorptive sweat duct (RD) has been a reliable model for investigations of the functional role of "endogenous" CFTR (cystic fibrosis transmembrane conductance regulator) in normal and abnormal electrolyte absorptive function. But to overcome the limitations imposed by the use of fresh, intact tissue, we transformed cultured RD cells using the chimeric virus Ad5/SV40 1613 ori-. The resultant cell line, RD2(NL), has remained differentiated forming a polarized epithelium that expressed two fundamental components of absorption, a cAMP activated Cl- conductance (GCl) and an amiloride-sensitive Na+ conductance (GNa). In the unstimulated state, there was a low level of transport activity; however, addition of forskolin (10(-5) M) significantly increased the Cl- diffusion potential (Vt) generated by a luminally directed Cl- gradient from -15.3 +/- 0.7 mV to -23.9 +/- 1.1 mV, n = 39; and decreased the transepithelial resistance (Rt) from 814.8 +/- 56.3 omega.cm2 to 750.5 +/- 47.5 omega.cm2, n = 39, (n = number of cultures). cAMP activation, anion selectivity (Cl- > I- > gluconate), and a dependence upon metabolic energy (metabolic poisoning inhibited GCl), all indicate that the GCl expressed in RD2(NL) is in fact CFTR-GCl. The presence of an apical amiloride-sensitive GNa was shown by the amiloride (10(-5) M) inhibition of GNa as indicated by a reduction of Vt and equivalent short circuit current by 78.0 +/- 3.1% and 77.9 +/- 2.6%, respectively, and an increase in Rt by 7.2 +/- 0.8%, n = 36. In conclusion, the RD2(NL) cell line presents the first model system in which CFTR-GCl is expressed in a purely absorptive tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

PubMed Central

Magenheim, Judith; Klein, Allon M.; Stanger, Ben Z.; Ashery-Padan, Ruth; Sosa-Pineda, Beatriz; Gu, Guoqiang; Dor, Yuval

2013-01-01

Summary During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3−/− mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta-cells from stem cells. PMID:21888903

3 alpha-Hydroxylated bile acid profiles in clinically normal cats, cats with severe hepatic lipidosis, and cats with complete extrahepatic bile duct occlusion.

PubMed

Center, S A; Thompson, M; Guida, L

1993-05-01

Concentrations of 3 alpha-hydroxylated bile acids were measured in serum and urine of clinically normal (healthy) cats (n = 6), cats with severe hepatic lipidosis (n = 9), and cats with complete bile duct occlusion (n = 4). Bile acid concentrations were measured by use of a gradient flow high-performance liquid chromatography procedure with an acetonitrile and ammonium phosphate mobile phase and an in-line postanalytic column containing 3 alpha-hydroxy-steroid dehydrogenase and a fluorescence detector. Specific identification of all bile acid peaks was not completed; unidentified moieties were represented in terms of their elution time (in minutes). Significant differences in serum and urine bile acid concentrations, quantitative and proportional, were determined among groups of cats. Cats with hepatic lipidosis and bile duct occlusion had significantly (P > or = 0.05) greater total serum and urine bile acids concentrations than did healthy cats. The proportion of hydrophobic bile acids in serum, those eluting at > or = 400 minutes, was 1.9% for healthy cats, 3.3% for cats with lipidosis, and 5.4% for bile duct-obstructed cats. Both groups of ill cats had a broader spectrum of unidentified late-eluting serum bile acids than did healthy cats; the largest spectrum developed in bile duct-occluded cats.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effects of Acoustic Treatment on Pressure Disturbances From a Supersonic Jet in a Circular Duct

NASA Technical Reports Server (NTRS)

Dahl, Milo D.

1996-01-01

The pressure disturbances generated by an instability wave in the shear layer of a supersonic jet are studied for an axisymmetric jet inside a lined circular duct. For the supersonic jet, locally linear stability analysis with duct wall boundary conditions is used to calculate the eigenvalues and the eigenfunctions at each axial location. These values are used to determine the growth rates and phase velocities of the instability waves and the near field pressure disturbance patterns. The study is confined to the dominant Kelvin-Helmholtz instability mode and to the region just downstream of the nozzle exit where the shear layer is growing but is still small in size compared to the radius of the duct. Numerical results are used to study the effects of changes in the outer flow, growth in the shear layer thickness, wall distance, and wall impedance, and the effects of these changes on non-axisymmetric modes. The primary results indicate that the effects of the duct wall on stability characteristics diminish as the outer flow increases and as the jet azimuthal mode number increases. Also, wall reflections are reduced when using a finite impedance boundary condition at the wall; but in addition, reflections are reduced and growth rates diminished by keeping the imaginary part of the impedance negative when using the negative exponential for the harmonic dependence.

A new concept of the pathogenesis of oral mucous cysts based on a study of 200 cases.

PubMed

Praetorius, F; Hammarstrom, L

1992-05-01

A new hypothesis regarding the pathogenesis of mucous cysts of the oral mucosa is proposed. Based upon a histological study of 188 mucous cysts without epithelial lining out of a total of 200 cysts it is claimed that some cysts may not develop in any of the hitherto described ways as intraductal "mucous retention cysts" or extraductal "mucous extravasation cysts" or from destruction of acini due to the pressure of mucous caused by duct obstruction. It is suggested that some of the cysts, that are found to have developed intraglandularly, are caused by traumatic destruction of a large amount of glandular acini ("parenchymal destruction cysts") and continuous secretion from the remaining acini. The mucus from the disintegrated cells forms a pool, which in time is surrounded by a connective tissue capsule that contains remnants of parenchyma from the affected lobule. This parenchyma degenerates, and eventually the cyst shows the same histological picture as the "mucous extravasation cyst". It is argued that the presence of a feeder duct does not necessarily indicate an extravasation cyst, but may be seen in the "parenchymal destruction cysts" as well. Of the 188 cysts examined 20 (11 per cent) were found to develop intraglandularly, and 36 (19 per cent) were considered probably to have developed intraglandularly.

A theoretical study of passive control of duct noise using panels of varying compliance.

PubMed

Huang, L

2001-06-01

It is theoretically demonstrated that, in a duct, a substantial amount of sound energy can be transferred to flexural waves on a finite wall panel when the upstream portion of the panel is made to couple strongly with sound. The flexural wave then loses its energy either through radiating reflection sound waves or by internal friction. The effectiveness of the energy transfer and damping is greatly enhanced if the panel has a gradually decreasing in vacuo wave speed, which, in this study, is achieved by using a tapered membrane under tension. A high noise attenuation rate is possible with the usual viscoelastic materials such as rubber. The transmission loss has a broadband spectrum, and it offers an alternative to conventional duct lining where a smooth air passage is desired and nonacoustical considerations, such as chemical contamination or cost of operation maintenance, are important. Another advantage of the tapered panel is that, at very low frequencies, typically 5% of the first cut-on frequency of the duct, sound reflection occurs over the entire panel length. This supplements the inevitable drop in sound absorption coefficient, and a high transmission loss may still be obtained at very low frequencies.

Inner ear development: Building a spiral ganglion and an organ of Corti out of unspecified ectoderm

PubMed Central

Fritzsch, Bernd; Pan, Ning; Jahan, Israt; Elliott, Karen L.

2014-01-01

The mammalian inner ear develops from a placodal thickening into a complex labyrinth of ducts with five sensory organs specialized to detect position and movement in space. In addition, the mammalian ear develops a spiraled cochlear duct containing the auditory organ, the organ of Corti (OC), specialized to translate sound into hearing. Developing the OC out of a uniform sheet of ectoderm requires an unparalleled precision in topological developmental engineering of four different general cell types, sensory neurons, hair cells, supporting cells, and general otic epithelium, into a mosaic of ten distinctly recognizable cell types in and around the OC, each with a unique distribution. In addition, the OC receives a unique innervation by ear-derived spiral ganglion afferents and brainstem-derived motor neurons as efferents, and requires neural crest-derived Schwann cells to form myelin and neural crest-derived cells to induce the stria vascularis. To achieve this transformation of a sheet of cells into a complicated interdigitating set of cells necessitates the orchestrated expression of multiple transcription factors that enable the cellular transformation from ectoderm into neurosensory cells forming the spiral ganglion neurons (SGN) while simultaneously transforming the flat epithelium into a tube, the cochlear duct housing the OC. In addition to the cellular and conformational changes to make the cochlear duct with the OC, additional changes in the surrounding periotic mesenchyme form passageways for sound to stimulate the OC. This article reviews molecular developmental data generated predominantly in mice. The available data are ordered into a plausible scenario that integrates the well described expression changes of transcription factors and their actions revealed in mouse mutants for formation of SGNs and OC in the right position and orientation with the right kind of innervation. Understanding the molecular basis of these developmental changes leading to the formation of the mammalian OC and highlighting the gaps in our knowledge may guide in vivo attempts to regenerate this most complicated cellular mosaic of the mammalian body to reconstitute hearing in a rapidly growing population of aging people suffering from hearing loss. PMID:25381571

Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation.

PubMed

Liu, Yang; Wang, Jiazhong; Yang, Peng; Lu, Hongwei; Lu, Le; Wang, Jinlong; Li, Hua; Duan, Yanxia; Wang, Jun; Li, Yiming

2015-03-01

Nonanastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure. Different delayed rearterialization times were compared using a porcine LT model. Morphological and functional changes in bile canaliculus were evaluated by transmission electron microscopy and real-time PCR. Immunohistochemistry and TUNEL were performed to validate intrahepatic bile duct injury. Three months after LT was performed, biliary duct stricture was determined by cholangiography; the tissue of common bile duct was detected by real-time PCR. Bile canaliculi were impaired in early postoperative stage and then exacerbated as delayed rearterialization time was prolonged. Nevertheless, damaged bile canaliculi could fully recover in subsequent months. TNF-α and TGF-β expressions and apoptosis cell ratio increased in the intrahepatic bile duct only during early postoperative period in a time-dependent manner. No abnormality was observed by cholangiography and common bile duct examination after 3 months. Delayed rearterialization caused temporary injury to bile canaliculi and intrahepatic bile duct in a time-dependent manner. Injury could be fully treated in succeeding months. Solo delayed rearterialization cannot induce NAS after LT. © 2014 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

Measure Guideline: Buried and/or Encapsulated Ducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shapiro, C.; Zoeller, W.; Mantha, P.

2013-08-01

Buried and/or encapsulated ducts (BEDs) are a class of advanced, energy-efficiency strategies intended to address the significant ductwork thermal losses associated with ducts installed in unconditioned attics. BEDs are ducts installed in unconditioned attics that are covered in loose-fill insulation and/or encapsulated in closed cell polyurethane spray foam insulation. This Measure Guideline covers the technical aspects of BEDs as well as the advantages, disadvantages, and risks of BEDs compared to other alternative strategies. This guideline also provides detailed guidance on installation of BEDs strategies in new and existing homes through step-by-step installation procedures. This Building America Measure Guideline synthesizes previouslymore » published research on BEDs and provides practical information to builders, contractors, homeowners, policy analysts, building professions, and building scientists. Some of the procedures presented here, however, require specialized equipment or expertise. In addition, some alterations to duct systems may require a specialized license. Persons implementing duct system improvements should not go beyond their expertise or qualifications. This guideline provides valuable information for a building industry that has struggled to address ductwork thermal losses in new and existing homes. As building codes strengthen requirements for duct air sealing and insulation, flexibility is needed to address energy efficiency goals. While ductwork in conditioned spaces has been promoted as the panacea for addressing ductwork thermal losses, BEDs installations approach - and sometimes exceed - the performance of ductwork in conditioned spaces.« less

Roles of basolateral solute uptake via NKCC1 and of myosin II in vasopressin-induced cell swelling in inner medullary collecting duct.

PubMed

Chou, Chung-Lin; Yu, Ming-Jiun; Kassai, Eliza M; Morris, Ryan G; Hoffert, Jason D; Wall, Susan M; Knepper, Mark A

2008-07-01

Collecting duct cells swell when exposed to arginine vasopressin (AVP) in the presence of a transepithelial osmolality gradient. We investigated the mechanisms of AVP-induced cell swelling in isolated, perfused rat inner medullary collecting ducts (IMCDs) using quantitative video microscopy and fluorescence-based measurements of transepithelial water transport. We tested the roles of transepithelial water flow, basolateral solute entry, and the cytoskeleton (actomyosin). When a transepithelial osmolality gradient was imposed by addition of NaCl to the bath, AVP significantly increased both water flux and cell height. When the osmolality gradient was imposed by addition of mannitol, AVP increased water flux but not cell height, suggesting that AVP-induced cell swelling requires a NaCl gradient and is not merely dependent on the associated water flux. Bumetanide (Na-K-2Cl cotransporter inhibitor) added to the bath markedly diminished the AVP-induced cell height increase. AVP-induced cell swelling was absent in IMCDs from NKCC1-knockout mice. In rat IMCDs, replacement of Na, K, or Cl in the peritubular bath caused significant cell shrinkage, consistent with a basolateral solute transport pathway dependent on all three ions. Immunocytochemistry using an antibody to NKCC1 confirmed basolateral expression in IMCD cells. The conventional nonmuscle myosin II inhibitor blebbistatin also diminished the AVP-induced cell height increase and cell shape change, consistent with a role for the actin cytoskeleton and myosin II. We conclude that the AVP-induced cell height increase is dependent on basolateral solute uptake via NKCC1 and changes in actin organization via myosin II, but is not dependent specifically on increased apical water entry.

Aberrant c-erbB2 expression in cell clusters overlying focally disrupted breast myoepithelial cell layers: a trigger or sign for emergence of more aggressive cell clones?

PubMed Central

Zhang, Xichen; Hashemi, Shahreyar Shar; Yousefi, Morvarid; Ni, Jinsong; Wang, Qiuyue; Gao, Ling; Gong, Pengtao; Gao, Chunling; Sheng, Joy; Mason, Jeffrey; Man, Yan-gao

2008-01-01

Our recent studies revealed that cell clusters overlying focal myoepithelial cell layer disruption (FMCLD) had a significantly higher frequency of genetic instabilities and expression of invasion-related genes than their adjacent counterparts within the same duct. Our current study attempted to assess whether these cell clusters would also have elevated c-erbB2 expression. Human breast tumors (n=50) with a high frequency of FMCLD were analyzed with double immunohistochemistry, real-time RT-PCR, and chromogenic in situ hybridization for c-erbB2 protein and gene expression. Of 448 FMCLD detected, 404 (90.2%) were associated with cell clusters that had intense c-erbB2 immunoreactivities primarily in their cytoplasm, in contrast to their adjacent counterparts within the same duct, which had no or barely detectable c-erbB2 expression. These c-erbB2 positive cells were arranged as tongue-like projections, “puncturing” into the stroma, and about 20% of them were in direct continuity with tube-like structures that resembled blood vessels. Aberrant c-erbB2 expression was also seen in clusters of architecturally normal-appearing ducts that had distinct cytological abnormalities in both ME and epithelial cells, whereas not in their clear-cut normal counterparts. Molecular assays detected markedly higher c-erbB2 mRNA and gene amplification in cell clusters associated with FMCLD than in those associated with non-disrupted ME cell layers. Our findings suggest that cell clusters overlying FMCLD may represent the precursors of pending invasive lesions, and that aberrant cerbB2 expression may trigger or signify the emergence of biologically more aggressive cell clones. PMID:18726004

Biliary Tree Stem Cells, Precursors to Pancreatic Committed Progenitors: Evidence for Possible Life-long Pancreatic Organogenesis

PubMed Central

Wang, Yunfang; Lanzoni, Giacomo; Carpino, Guido; Cui, Cai-Bin; Dominguez-Bendala, Juan; Wauthier, Eliane; Cardinale, Vincenzo; Oikawa, Tsunekazu; Pileggi, Antonello; Gerber, David; Furth, Mark E.; Alvaro, Domenico; Gaudio, Eugenio; Inverardi, Luca; Reid, Lola M.

2013-01-01

Peribiliary glands (PBGs) in bile duct walls, and pancreatic duct glands (PDGs) associated with pancreatic ducts, in humans of all ages, contain a continuous, ramifying network of cells in overlapping maturational lineages. We show that proximal (PBGs)-to-distal (PDGs) maturational lineages start near the duodenum with cells expressing markers of pluripotency (NANOG,OCT4,SOX2), proliferation (Ki67), self-replication (SALL4), and early hepato-pancreatic commitment (SOX9,SOX17,PDX1,LGR5), transitioning to PDG cells with no expression of pluripotency or self-replication markers, maintenance of pancreatic genes (PDX1), and expression of markers of pancreatic endocrine maturation (NGN3,MUC6,insulin). Radial-axis lineages start in PBGs near the ducts’ fibromuscular layers with stem cells and end at the ducts’ lumens with cells devoid of stem cell traits and positive for pancreatic endocrine genes. Biliary tree-derived cells behaved as stem cells in culture under expansion conditions, culture plastic and serum-free Kubota’s Medium, proliferating for months as undifferentiated cells, whereas pancreas-derived cells underwent only ∼8-10 divisions, then partially differentiated towards an islet fate. Biliary tree-derived cells proved precursors of pancreas’ committed progenitors. Both could be driven by 3-dimensional conditions, islet-derived matrix components and a serum-free, hormonally defined medium for an islet fate (HDM-P), to form spheroids with ultrastructural, electrophysiological and functional characteristics of neoislets, including glucose regulatability. Implantation of these neoislets into epididymal fat pads of immuno-compromised mice, chemically rendered diabetic, resulted in secretion of human C-peptide, regulatable by glucose, and able to alleviate hyperglycemia in hosts. The biliary tree-derived stem cells and their connections to pancreatic committed progenitors constitute a biological framework for life-long pancreatic organogenesis. PMID:23847135

A HISTOLOGICAL STUDY OF TYPHOID FEVER

PubMed Central

Mallory, F. B.

1898-01-01

The typhoid bacillus produces a mild diffusible toxine, partly within the intestinal tract, partly within the blood and organs of the body. This toxine produces proliferation of endothelial cells which acquire for a certain length of time malignant properties. The new-formed cells are epithelioid in character, have irregular, lightly staining, eccentrically situated nuclei, abundant, sharply defined, acidophilic protoplasm, and are characterized by marked phagocytic properties. These phagocytic cells are produced most abundantly along the line of absorption from the intestinal tract, both in the lymphatic apparatus and in the blood-vessels. They are also produced by distribution of the toxine through the general circulation, in greatest numbers where the circulation is slowest. Finally, they are produced all over the body in the lymphatic spaces and vessels by absorption of the toxine eliminated from the blood-vessels. The swelling of the intestinal lymphoid tissue of the mesenteric lymph nodes, and of the spleen is due almost entirely to the formation of phagocytic cells. The necrosis of the intestinal lymphoid tissue is accidental in nature and is caused through occlusion of the veins and capillaries by fibrinous thrombi, which owe their origin to degeneration of phagocytic cells beneath the lining endothelium of the vessels. Two varieties of focal lesions occur in the liver: one consists of the formation of phagocytic cells in the lymph spaces and vessels around the portal vessels under the action of the toxine absorbed by the lymphatics; the other is due to obstruction of liver capillaries by phagocytic cells derived in small part from the lining endothelium of the liver capillaries, but chiefly by embolism through the portal circulation of cells originating from the endothelium of the blood-vessels of the intestine and spleen. The liver cells lying between the occluded capillaries undergo necrosis and disappear. Later the foci of cells degenerate and fibrin forms between them. Invasion with polymorphonuclear leucocytes is rare. Many of the phagocytic cells pass through the liver and lungs, and get into the general circulation. A few come from the abdominal lymphatics through the thoracic duct. PMID:19866884

Fibrosis of the pancreas: the initial tissue damage and the resulting pattern.

PubMed

Klöppel, Günter; Detlefsen, Sönke; Feyerabend, Bernd

2004-07-01

Fibrosis in the pancreas is caused by such processes as necrosis/apoptosis, inflammation or duct obstruction. The initial event that induces fibrogenesis in the pancreas is an injury that may involve the interstitial mesenchymal cells, the duct cells and/or the acinar cells. Damage to any one of these tissue compartments of the pancreas is associated with cytokine-triggered transformation of resident fibroblasts/pancreatic stellate cells into myofibroblasts and the subsequent production and deposition of extracellular matrix. Depending on the site of injury in the pancreas and the involved tissue compartment, predominantly inter(peri)lobular fibrosis (as in alcoholic chronic pancreatitis), periductal fibrosis (as in hereditary pancreatitis), periductal and interlobular fibrosis (as in autoimmune pancreatitis) or diffuse inter- and intralobular fibrosis (as in obstructive chronic pancreatitis) develops.

On approaches to the functional restoration of salivary glands damaged by radiation therapy for head and neck cancer, with a review of related aspects of salivary gland morphology and development.

PubMed

Redman, R S

2008-06-01

Radiation therapy for cancer of the head and neck can devastate the salivary glands and partially devitalize the mandible and maxilla. As a result, saliva production is drastically reduced and its quality adversely altered. Without diligent home and professional care, the teeth are subject to rapid destruction by caries, necessitating extractions with attendant high risk of necrosis of the supporting bone. Innovative techniques in delivery of radiation therapy and administration of drugs that selectively protect normal tissues can reduce significantly the radiation effects on salivary glands. Nonetheless, many patients still suffer severe oral dryness. I review here the functional morphology and development of salivary glands as these relate to approaches to preventing and restoring radiation-induced loss of salivary function. The acinar cells are responsible for most of the fluid and organic material in saliva, while the larger ducts influence the inorganic content. A central theme of this review is the extent to which the several types of epithelial cells in salivary glands may be pluripotential and the circumstances that may influence their ability to replace cells that have been lost or functionally inactivated due to the effects of radiation. The evidence suggests that the highly differentiated cells of the acini and large ducts of mature glands can replace themselves except when the respective pools of available cells are greatly diminished via apoptosis or necrosis owing to severely stressful events. Under the latter circumstances, relatively undifferentiated cells in the intercalated ducts proliferate and redifferentiate as may be required to replenish the depleted pools. It is likely that some, if not many, acinar cells may de-differentiate into intercalated duct-like cells and thus add to the pool of progenitor cells in such situations. If the stress is heavy doses of radiation, however, the result is not only the death of acinar cells, but also a marked decline in functional differentiation and proliferative capacity of all of the surviving cells, including those with progenitor capability. Restoration of gland function, therefore, seems to require increasing the secretory capacity of the surviving cells, or replacing the acinar cells and their progenitors either in the existing gland remnants or with artificial glands.

Cotton rats (Sigmodon hispidus) possess pharyngeal pouch remnants originating from different primordia.

PubMed

Nakamura, Teppei; Ichii, Osamu; Irie, Takao; Mizoguchi, Tatsuya; Shinohara, Akio; Kouguchi, Hirokazu; Sunden, Yuji; Otsuka-Kanazawa, Saori; Ali Elewa, Yaser Hosny; Koshimoto, Chihiro; Nagasaki, Ken-Ichi; Kon, Yasuhiro

2018-06-01

Pharyngeal pouches in mammals develop into specific derivatives. If the differentiation of the pharyngeal pouches is anomalous, their remnants can result in cysts, sinuses, and fistulae in the differentiated organs or around the neck. In the present study, we found several pharyngeal pouch remnants, such as cystic structures in thymus and parathyroid gland and fossulae extended from the piriform fossa, in the inbred cotton rats maintained at Hokkaido Institute of Public Health (HIS/Hiph) and University of Miyazaki (HIS/Mz). In HIS/Hiph, the fossulae extended from the apex of the piriform fossa into the thyroid glands and were lined with stratified squamous and cuboidal epithelium. Calcitonin-positive C-cells were present within their epithelium in HIS/Hiph. In contrast, the fossulae of HIS/Mz ran outside the thyroid glands toward the parathyroid glands; they were lined with columnar ciliated epithelium and a few goblet cells, but had no C-cells, which was consistent with the cystic structures in the thymus and the parathyroid gland. These results indicated that the fossulae were a remnant of the ultimobranchial body in HIS/Hiph and of the thymopharyngeal duct in HIS/Mz. Thus, the fossulae of the piriform fossa resembled the piriform sinus fistula in human. In conclusion, cotton rats frequently possessed pharyngeal pouch remnants, including the piriform sinus fistula, and therefore, might serve as a novel model to elucidate the mechanisms of pharyngeal pouch development.

Development of a new dynamic gas flow-control system in the pressure range of 1 Pa-133 Pa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, S. S.; Chung, J. W.; Khan, Wakil

2011-12-15

A new flow-control system (FCS-705) has been developed at Korea Research Institute of Standards and Science. The system is intended for calibration of vacuum gauges in the pressure range of 1 Pa-133 Pa by comparison method. This paper describes some basic characteristics of the system including; (1) the design and construction of the system, (2) the generation of stable pressures in the chamber, (3) achieving high upstream pressure limit by installing a short duct in the by-pass pumping line, and (4) investigation of the gas flow regimes within the short duct.

Handbook on Special Works. Technological Lines of Industrial Enterprises. Part 1,

DTIC Science & Technology

1979-10-16

notching it perpealicalaz to longitudinal axis at the-depth not less than 0.8 D. duct ot in the- sample/specimen with a length of 20-50 mm, cut off froe the...4" kl/cma (U 3555-62). 6-40 6-01-3 1-3 50-70 8&-100 4- 258 6-a 6-7 Keys (tq.mQts Mae oil steel.. 121. carbide brand 20. (1alyGof b-C14JS/ rna #,ks. DOC...rolling irom aluminum and aluminum alloys, in form and state of material divide into: ducts circular anneidlau (4), uardened/tempered and naturally aged (T

Lipidomic and proteomic analysis of exosomes from mouse cortical collecting duct cells.

PubMed

Dang, Viet D; Jella, Kishore Kumar; Ragheb, Ragy R T; Denslow, Nancy D; Alli, Abdel A

2017-12-01

Exosomes are endosome-derived nanovesicles that are involved in cellular communication and signaling. Exosomes are produced by epithelial cells and are found in biologic fluids including blood and urine. The packaged material within exosomes includes proteins and lipids, but the molecular comparison within exosome subtypes is largely unknown. The purpose of this study was to investigate differences between exosomes derived from the apical plasma membrane and basolateral plasma membrane of polarized murine cortical collecting duct principal cells. Nanoparticle tracking analysis showed that the size and concentration of apical and basolateral exosomes remained relatively stable across 3 different temperatures (23, 37, and 42°C). Liquid chromatography-tandem mass spectrometry analysis revealed marked differences between the proteins packaged within the two types of exosomes from the same cells. Several proteins expressed at the inner leaflet of the plasma membrane, including α-actinin-1, moesin, 14-3-3 protein ζ/δ, annexin A1/A3/A4/A5/A6, clathrin heavy chain 1, glyceraldehyde-3-phosphate dehydrogenase, α-enolase, filamin-A, and heat shock protein 90, were identified in samples of apical plasma membrane-derived exosomes, but not in basolateral plasma membrane exosomes from mouse cortical collecting duct cells. In addition to differences at the protein level, mass spectrometry-based shotgun lipidomics analysis showed significant differences in the lipid classes and fatty acid composition of the two types of exosomes. We found higher levels of sphingomyelin and lower levels of cardiolipin, among other phospholipids in the apical plasma membrane compared to the basolateral plasma membrane exosomes. The molecular analyses of exosome subtypes presented herein will contribute to our understanding of exosome biogenesis, and the results may have potential implications for biomarker discovery.-Dang, V. D., Jella, K. K., Ragheb, R. R. T., Denslow, N. D., Alli, A. A. Lipidomic and proteomic analysis of exosomes from mouse cortical collecting duct cells. © FASEB.

Aquaporin-2 Regulation in Health and Disease

PubMed Central

Radin, M. Judith; Yu, Ming-Jiun; Stoedkilde, Lene; Miller, R. Lance; Hoffert, Jason D.; Frokiaer, Jorgen; Pisitkun, Trairak; Knepper, Mark A.

2012-01-01

Aquaporin-2 (AQP2), the vasopressin-regulated water channel of the renal collecting duct, is dysregulated in numerous water balance disorders in humans and animals including those associated with polyuria (e.g. urinary tract obstruction, hypokalemia, inflammation, and lithium toxicity) and dilutional hyponatremia (e.g. SIADH). Normal regulation of AQP2 by vasopressin involves two independent regulatory mechanisms: 1) short-term regulation of AQP2 trafficking to and from the apical plasma membrane, and 2) long term regulation of the total abundance of the AQP2 protein in the cells. Most water balance disorders are the result of dysregulation of processes that regulate the total abundance of AQP2 in collecting duct cells. In general, the level of AQP2 in a collecting duct cell is determined by a balance between production via translation of AQP2 mRNA and removal via degradation and/or secretion into the urine in exosomes. AQP2 abundance increases in response to vasopressin chiefly due to increased translation subsequent to increases in AQP2 mRNA. Vasopressin-mediated regulation AQP2 gene transcription is poorly understood, although several transcription factor binding elements in the 5’ flanking region of the AQP2 gene have been identified and candidate transcription factors corresponding to these element have been discovered in proteomics studies. Here we review progress in this area and discuss elements of vasopressin signaling in the collecting duct that may impinge on regulation of AQP2 in health and in the context of examples of polyuric diseases. PMID:23130944

Expression and Function of αvβ3 and αvβ5 Integrins in the Developing Pancreas

PubMed Central

Cirulli, Vincenzo; Beattie, Gillian M.; Klier, George; Ellisman, Mark; Ricordi, Camillo; Quaranta, Vito; Frasier, Francine; Ishii, Jennifer K.; Hayek, Alberto; Salomon, Daniel R.

2000-01-01

Cell–cell and cell–matrix interactions play a critical role in tissue morphogenesis and in homeostasis of adult tissues. The integrin family of adhesion receptors regulates cellular interactions with the extracellular matrix, which provides three-dimensional information for tissue organization. It is currently thought that pancreatic islet cells develop from undifferentiated progenitors residing within the ductal epithelium of the fetal pancreas. This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans. Here we report that αvβ3 and αvβ5, two integrins known to coordinate epithelial cell adhesion and movement, are expressed in pancreatic ductal cells and clusters of undifferentiated cells emerging from the ductal epithelium. We show that expression and function of αvβ3 and αvβ5 integrins are developmentally regulated during pancreatic islet ontogeny, and mediate adhesion and migration of putative endocrine progenitor cells both in vitro and in vivo in a model of pancreatic islet development. Moreover, we demonstrate the expression of fibronectin and collagen IV in the basal membrane of pancreatic ducts and of cell clusters budding from the ductal epithelium. Conversely, expression of vitronectin marks a population of epithelial cells adjacent to, or emerging from, pancreatic ducts. Thus, these data provide the first evidence for the contribution of integrins αvβ3 and αvβ5 and their ligands to morphogenetic events in the human endocrine pancreas. PMID:10995448

Hyperplasia of the submucosal glands of the columnar-lined oesophagus.

PubMed

Lörinc, Ester; Öberg, Stefan

2015-04-01

To evaluate the presence of multi-layered epithelium (ME) and to compare the distribution, size and morphology of the oesophageal submucosal glands (SMG) beneath reflux exposed metaplastic columnar mucosa with those of normal squamous epithelium in patients with columnar-lined oesophagus (CLO). In eight oesophageal resection specimens, the SMG of the metaplastic segments were significantly larger than those in the squamous segments of patients with CLO (0.81 versus 0.56 mm(2) , P = <0.001). There was an accumulation of SMG close to the neosquamocolumnar junction (NSCJ), as indicated by a higher median frequency of SMG (0.080 SMG/mm) compared with that of the squamous (0.013 SMG/mm) and metaplastic segments (0.031 SMG/mm) (P = 0.022). The frequency of ME was significantly higher in the metaplastic compared with the normal squamous segments (1/158 mm and 1/341 mm, respectively, P = 0.028) and ME was found almost exclusively (96%) in direct connection with the excretory ducts of SMG. Hyperplasia of SMG in the metaplastic segment, accumulation of SMG near the NSCJ, the presence of ME in connection with the excretory ducts of SMG and metaplasia are all reflux-induced morphological changes, possibly induced by stimulation of progenitors in the excretory ducts of the SMG. © 2014 John Wiley & Sons Ltd.

New autosomal recessive mutations in aquaporin-2 causing nephrogenic diabetes insipidus through deficient targeting display normal expression in Xenopus oocytes

PubMed Central

Leduc-Nadeau, Alexandre; Lussier, Yoann; Arthus, Marie-Françoise; Lonergan, Michèle; Martinez-Aguayo, Alejandro; Riveira-Munoz, Eva; Devuyst, Olivier; Bissonnette, Pierre; Bichet, Daniel G

2010-01-01

Aquaporin-2 (AQP2), located at the luminal side of the collecting duct principal cells, is a water channel responsible for the final concentration of urine. Lack of function, often occurring through mistargeting of mutated proteins, induces nephrogenic diabetes insipidus (NDI), a condition characterized by large urinary volumes. In the present study, two new mutations (K228E and V24A) identified in NDI-affected individuals from distinct families along with the already reported R187C were analysed in comparison to the wild-type protein (AQP2-wt) using Xenopus laevis oocytes and a mouse collecting duct cell-line (mIMCD-3). Initial data in oocytes showed that all mutations were adequately expressed at reduced levels when compared to AQP2-wt. K228E and V24A were found to be properly targeted at the plasma membrane and exhibited adequate functionality similar to AQP2-wt, as opposed to R187C which was retained in internal stores and was thus inactive. In coexpression studies using oocytes, R187C impeded the functionality of all other AQP2 variants while combinations with K228E, V24A and AQP2-wt only showed additive functionalities. When expressed in mIMCD-3 cells, forskolin treatment efficiently promoted the targeting of AQP2-wt at the plasma membrane (>90%) while K228E only weakly responded to the same treatment (∼20%) and both V24A and R187C remained completely insensitive to the treatment. We concluded that both V24A and K228E are intrinsically functional water channels that lack a proper response to vasopressin, which leads to NDI as found in both compound mutations studied (K228E + R187C and V24A + R187C). The discrepancies in plasma membrane targeting response found in both expression systems stress the need to evaluate such data using mammalian cell systems. PMID:20403973

Protective effect of Urtica dioica on liver damage induced by biliary obstruction in rats.

PubMed

Oguz, Serhat; Kanter, Mehmet; Erboga, Mustafa; Ibis, Cem

2013-10-01

The aim of this study was to evaluate the possible protective effects of Urtica dioica (UD) against liver damage in the common bile duct-ligated rats. A total of 24 male Sprague Dawley rats were divided into three groups, namely, control, bile duct ligation (BDL) and BDL + received UD groups, containing eight animals in each group. The rats in UD-treated groups were given UD oils (2 ml/kg) once a day intraperitoneally for 2 weeks starting 3 days prior to BDL operation. The change demonstrating the bile duct proliferation and fibrosis in expanded portal tracts includes the extension of proliferated bile ducts into the lobules; inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with UD attenuated alterations in liver histology. The α-smooth muscle actin, cytokeratin-positive ductular proliferation and the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in the BDL were observed to be reduced with the UD treatment. The data indicate that UD attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis.

An unusual melanocytic lesion associated with eccrine duct fibroadenomatosis and syringoid features.

PubMed

Stefanato, C M; Simkin, D A; Bhawan, J

2001-04-01

The intimate association of nevomelanocytic nevi with eccrine ducts commonly seen in congenital nevi was emphasized by Mishima, who described as eccrine-centered nevi those lesions characterized by nevomelanocytic cells predominantly proliferating around and within the eccrine sweat duct walls. However, there were no changes in the overlying epidermis, dermis, or eccrine acrosyringeal or dermal duct proliferation in these lesions. We present the case of a 16-year-old boy with a 1-year-history of a 0.6-cm diameter single tan papule on the right heel, clinically thought to be a Spitz nevus. Histopathologic examination revealed a compound nevomelanocytic nevus associated with epidermal hyperplasia, thin anastomosing cords of acrosyringeal epithelium extending within the dermis, and eccrine ductal proliferation in a syringoma-like pattern associated with a dense fibrous stroma. Features that distinguish our case from eccrine-centered nevus are that the latter lacks epidermal and eccrine duct hyperplasia and a dense fibrous stroma. The location of the lesion on the heel in our case suggests the possibility that the pathologic changes observed could result from repetitive trauma.

Submergible barge retrievable storage and permanent disposal system for radioactive waste

DOEpatents

Goldsberry, Fred L.; Cawley, William E.

1981-01-01

A submergible barge and process for submerging and storing radioactive waste material along a seabed. A submergible barge receives individual packages of radwaste within segregated cells. The cells are formed integrally within the barge, preferably surrounded by reinforced concrete. The cells are individually sealed by a concrete decking and by concrete hatch covers. Seawater may be vented into the cells for cooling, through an integral vent arrangement. The vent ducts may be attached to pumps when the barge is bouyant. The ducts are also arranged to promote passive ventilation of the cells when the barge is submerged. Packages of the radwaste are loaded into individual cells within the barge. The cells are then sealed and the barge is towed to the designated disposal-storage site. There, the individual cells are flooded and the barge will begin descent controlled by a powered submarine control device to the seabed storage site. The submerged barge will rest on the seabed permanently or until recovered by a submarine control device.

Renal Type A Intercalated Cells Contain Albumin in Organelles with Aldosterone-Regulated Abundance

PubMed Central

Jensen, Thomas Buus; Cheema, Muhammad Umar; Szymiczek, Agata; Damkier, Helle Hasager; Praetorius, Jeppe

2015-01-01

Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1), late endosomes/lysosomes (cathepsin D) or recycling endosomes (Rab11). Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells. PMID:25874770

Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct.

PubMed

Yu, Ming-Jiun; Miller, R Lance; Uawithya, Panapat; Rinschen, Markus M; Khositseth, Sookkasem; Braucht, Drew W W; Chou, Chung-Lin; Pisitkun, Trairak; Nelson, Raoul D; Knepper, Mark A

2009-02-17

We used a systems biology-based approach to investigate the basis of cell-specific expression of the water channel aquaporin-2 (AQP2) in the renal collecting duct. Computational analysis of the 5'-flanking region of the AQP2 gene (Genomatix) revealed 2 conserved clusters of putative transcriptional regulator (TR) binding elements (BEs) centered at -513 bp (corresponding to the SF1, NFAT, and FKHD TR families) and -224 bp (corresponding to the AP2, SRF, CREB, GATA, and HOX TR families). Three other conserved motifs corresponded to the ETS, EBOX, and RXR TR families. To identify TRs that potentially bind to these BEs, we carried out mRNA profiling (Affymetrix) in mouse mpkCCDc14 collecting duct cells, revealing expression of 25 TRs that are also expressed in native inner medullary collecting duct. One showed a significant positive correlation with AQP2 mRNA abundance among mpkCCD subclones (Ets1), and 2 showed a significant negative correlation (Elf1 and an orphan nuclear receptor Nr1h2). Transcriptomic profiling in native proximal tubules (PT), medullary thick ascending limbs (MTAL), and IMCDs from kidney identified 14 TRs (including Ets1 and HoxD3) expressed in the IMCD but not PT or MTAL (candidate AQP2 enhancer roles), and 5 TRs (including HoxA5, HoxA9 and HoxA10) expressed in PT and MTAL but not in IMCD (candidate AQP2 repressor roles). In luciferase reporter assays, overexpression of 3 ETS family TRs transactivated the mouse proximal AQP2 promoter. The results implicate ETS family TRs in cell-specific expression of AQP2 and point to HOX, RXR, CREB and GATA family TRs as playing likely additional roles.

Identification of AQP5 in lipid rafts and its translocation to apical membranes by activation of M3 mAChRs in interlobular ducts of rat parotid gland.

PubMed

Ishikawa, Yasuko; Yuan, Zhenfang; Inoue, Noriko; Skowronski, Mariusz T; Nakae, Yoshiko; Shono, Masayuki; Cho, Gota; Yasui, Masato; Agre, Peter; Nielsen, Søren

2005-11-01

Aquaporin-5 (AQP5), an apical plasma membrane (APM) water channel in salivary glands, lacrimal glands, and airway epithelium, has an important role in fluid secretion. M(3) muscarinic acetylcholine receptor (mAChR)-induced changes in AQP5 localization in rat parotid glands were investigated with immunofluorescence or immunoelectron microscopy, detergent solubility, and gradient density floatation assays. Confocal microscopy revealed AQP5 localization in intracellular vesicles of interlobular duct cells in rat parotid glands and AQP5 trafficking to the APM 10 min after injection of the mAChR agonist cevimeline. Conversely, 60 min after injection, there was a diffuse pattern of AQP5 staining in the cell cytoplasm. The calcium ionophore A-23187 mimicked the effects of cevimeline. Immunoelectron microscopic studies confirmed that cevimeline induced AQP5 trafficking from intracellular structures to APMs in the interlobular duct cells of rat parotid glands. Lipid raft markers flotillin-2 and GM1 colocalized with AQP5 and moved with AQP5 in response to cevimeline. Under control conditions, the majority of AQP5 localized in the Triton X-100-insoluble fraction and floated to the light-density fraction on discontinuous density gradients. After 10-min incubation of parotid tissue slices with cevimeline or A-23187, AQP5 levels decreased in the Triton X-100-insoluble fraction and increased in the Triton X-100-soluble fraction. Thus AQP5 localizes in the intracellular lipid rafts, and M(3) mAChR activation induces AQP5 trafficking to the APM with lipid rafts via intracellular Ca(2+) signaling and induces AQP5 dissociation from lipid rafts to nonrafts on the APM in the interlobular duct cells of rat parotid glands.

Contribution of Caudal Müllerian Duct Mesenchyme to Prostate Development

PubMed Central

Brechka, Hannah; McAuley, Erin M.; Lamperis, Sophia M.; Paner, Gladell P.

2016-01-01

A fundamental understanding of prostate development and tissue homeostasis has the high potential to reveal mechanisms for prostate disease initiation and identify novel therapeutic approaches for disease prevention and treatment. Our current understanding of prostate lineage specification stems from the use of developmental model systems that rely upon the embryonic preprostatic urogenital sinus mesenchyme to induce the formation of mature prostate epithelial cells. It is unclear, however, how the urogenital sinus epithelium can derive both adult urethral glands and prostate epithelia. Furthermore, the vast disparity in disease initiation between these two glands highlights key developmental factors that predispose prostate epithelia to hyperplasia and cancer. In this study we demonstrate that the caudal Müllerian duct mesenchyme (CMDM) drives prostate epithelial differentiation and is a key determinant in cell lineage specification between urethral glands and prostate epithelia. Utilizing both human embryonic stem cells and mouse embryonic tissues, we document that the CMDM is capable of inducing the specification of androgen receptor, prostate-specific antigen, NKX3.1, and Hoxb13-positive prostate epithelial cells. These results help to explain key developmental differences between prostate and urethral gland differentiation, and implicate factors secreted by the caudal Müllerian duct as novel targets for prostate disease prevention and treatment. PMID:27595922

A novel therapy strategy for bile duct repair using tissue engineering technique: PCL/PLGA bilayered scaffold with hMSCs.

PubMed

Zong, Chen; Wang, Meicong; Yang, Fuchun; Chen, Guojun; Chen, Jiarong; Tang, Zihua; Liu, Quanwen; Gao, Changyou; Ma, Lie; Wang, Jinfu

2017-04-01

The current clinical treatments for complications caused by hepatobiliary surgery still have some inevitable weakness. The aim of the study was to fabricate a tissue-engineered bile duct that utilized a novel bilayered polymer scaffold combined with human bone marrow-derived mesenchymal stem cells (hMSCs) for new treatment of biliary disease. The biocompatibility of polycaprolactone (PCL) (PCL)/poly(lactide-co-glycolide) (PLGA) scaffold with hMSCs was first examined, and the hMSC-PCL/PLGA constructs (MPPCs) prepared. The MPPCs and blank scaffolds were then transplanted into 18 pigs for evaluation its efficacy on bile duct repairing, respectively. In vitro, the PCL/PLGA scaffold was verified to support the adhesion, proliferation and matrix deposition of hMSCs. There was no sign of bile duct narrowing and cholestasis in all experimental animals. At 6 months, the MPPCs had a superior repairing effect on the bile duct injury, compared with the blank PCL/PLGA scaffolds. Therefore, the implanted scaffolds could not only support the biliary tract and allow free bile flow but also had direct or indirect positive effects on repair of injured bile duct. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Metabolic regulation of cellular plasticity in the pancreas.

PubMed

Ninov, Nikolay; Hesselson, Daniel; Gut, Philipp; Zhou, Amy; Fidelin, Kevin; Stainier, Didier Y R

2013-07-08

Obese individuals exhibit an increase in pancreatic β cell mass; conversely, scarce nutrition during pregnancy has been linked to β cell insufficiency in the offspring [reviewed in 1, 2]. These phenomena are thought to be mediated mainly through effects on β cell proliferation, given that a nutrient-sensitive β cell progenitor population in the pancreas has not been identified. Here, we employed the fluorescent ubiquitination-based cell-cycle indicator system to investigate β cell replication in real time and found that high nutrient concentrations induce rapid β cell proliferation. Importantly, we found that high nutrient concentrations also stimulate β cell differentiation from progenitors in the intrapancreatic duct (IPD). Furthermore, using a new zebrafish line where β cells are constitutively ablated, we show that β cell loss and high nutrient intake synergistically activate these progenitors. At the cellular level, this activation process causes ductal cell reorganization as it stimulates their proliferation and differentiation. Notably, we link the nutrient-dependent activation of these progenitors to a downregulation of Notch signaling specifically within the IPD. Furthermore, we show that the nutrient sensor mechanistic target of rapamycin (mTOR) is required for endocrine differentiation from the IPD under physiological conditions as well as in the diabetic state. Thus, this study reveals critical insights into how cells modulate their plasticity in response to metabolic cues and identifies nutrient-sensitive progenitors in the mature pancreas. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intra-oral Sebaceous Gland Tumours in Two Dogs.

PubMed

Go, D-M; Lee, S-H; Woo, S-H; Kim, D-Y

2017-11-01

A 12-year-old female miniature schnauzer and a 12-year-old neutered female cocker spaniel each had a grey-yellow nodular lesion arising from the gingiva. Microscopical examination showed that both nodules were composed of varied proportions of sebocytes and basal-type reserve cells with few ducts lined by stratified squamous epithelium. Based on the histopathological findings, the cases were diagnosed as sebaceous adenoma and sebaceous epithelioma, respectively. In man, the occurrence of sebaceous neoplasms in the oral cavity has been reported to some extent, but these lesions are very rare in animals. To the best of our knowledge, this is the first report of intra-oral sebaceous neoplasms in dogs. Intra-oral sebaceous epithelioma has never been reported in animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heat Recovery System

NASA Technical Reports Server (NTRS)

1984-01-01

Ball Metal's design of ducting and controls for series of roof top heat exchangers was inspired by Tech Briefs. Heat exchangers are installed on eight press and coating lines used to decorate sheet metal. The heat recovery system provides an estimated energy savings of more than $250,000 per year.

The renal TRPV4 channel is essential for adaptation to increased dietary potassium.

PubMed

Mamenko, Mykola V; Boukelmoune, Nabila; Tomilin, Viktor N; Zaika, Oleg L; Jensen, V Behrana; O'Neil, Roger G; Pochynyuk, Oleh M

2017-06-01

To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells. This, in turn, leads to augmented TRPV4-mediated flow-dependent calcium ion responses in freshly isolated split-opened collecting ducts from mice fed the high potassium diet. Genetic TRPV4 ablation greatly diminished BK channel activity in collecting duct cells pointing to a reduced capacity to excrete potassium. Consistently, elevated potassium intake induced hyperkalemia in TRPV4 knockout mice due to deficient renal potassium excretion. Thus, regulation of TRPV4 activity in the distal nephron by dietary potassium is an indispensable component of whole body potassium balance. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Expression of the extracellular matrix protein periostin in liver tumours and bile duct carcinomas.

PubMed

Riener, Marc-Oliver; Fritzsche, Florian R; Soll, Christopher; Pestalozzi, Bernhard C; Probst-Hensch, Nicole; Clavien, Pierre-Alain; Jochum, Wolfram; Soltermann, Alex; Moch, Holger; Kristiansen, Glen

2010-04-01

To study the relevance of periostin, known to be involved in epithelial-mesenchymal transition (EMT), in hepatocellular and bile duct cancer. Immunohistochemical periostin expression was semiquantitatively analysed in normal liver tissue (n = 20), hepatocellular carcinoma (HCC; n = 91), liver-cell adenoma (n = 9), focal nodular hyperplasia (n = 13) and bile duct carcinomas (BDC; n = 116) using tissue microarrays. Normal bile ducts, gallbladder epithelium and hepatocytes showed weak cytoplasmic periostin expression. In HCC, there was strong epithelial periostin expression in 19/91 (20.9%) and strong stromal periostin expression in 10/91 cases (11%). Epithelial expression in tumour cells was significantly associated with a higher tumour grade (P < 0.05) and hepatitis B virus infection (P = 0.007). Importantly, there was no strong periostin expression in benign liver tumours. Strong stromal periostin expression was detected in 78/116 (67.2%) BDC and strong epithelial expression in 39/116 (33.6%) BDC. pT stage, differentiation grade and proliferation rate in primary BDC were independent of periostin expression. Epithelial periostin expression was associated with reduced overall survival on univariate and multivariate analysis. The EMT protein periostin is expressed in the stroma and epithelium of a subset of BDC and HCC. Epithelial periostin expression is a marker for malignant transformation of hepatocytes and a novel prognostic marker in BDC.

Acoustic Prediction State of the Art Assessment

NASA Technical Reports Server (NTRS)

Dahl, Milo D.

2007-01-01

The acoustic assessment task for both the Subsonic Fixed Wing and the Supersonic projects under NASA s Fundamental Aeronautics Program was designed to assess the current state-of-the-art in noise prediction capability and to establish baselines for gauging future progress. The documentation of our current capabilities included quantifying the differences between predictions of noise from computer codes and measurements of noise from experimental tests. Quantifying the accuracy of both the computed and experimental results further enhanced the credibility of the assessment. This presentation gives sample results from codes representative of NASA s capabilities in aircraft noise prediction both for systems and components. These include semi-empirical, statistical, analytical, and numerical codes. System level results are shown for both aircraft and engines. Component level results are shown for a landing gear prototype, for fan broadband noise, for jet noise from a subsonic round nozzle, and for propulsion airframe aeroacoustic interactions. Additional results are shown for modeling of the acoustic behavior of duct acoustic lining and the attenuation of sound in lined ducts with flow.

A comparison of matrix methods for calculating eigenvalues in acoustically lined ducts

NASA Technical Reports Server (NTRS)

Watson, W.; Lansing, D. L.

1976-01-01

Three approximate methods - finite differences, weighted residuals, and finite elements - were used to solve the eigenvalue problem which arises in finding the acoustic modes and propagation constants in an absorptively lined two-dimensional duct without airflow. The matrix equations derived for each of these methods were solved for the eigenvalues corresponding to various values of wall impedance. Two matrix orders, 20 x 20 and 40 x 40, were used. The cases considered included values of wall admittance for which exact eigenvalues were known and for which several nearly equal roots were present. Ten of the lower order eigenvalues obtained from the three approximate methods were compared with solutions calculated from the exact characteristic equation in order to make an assessment of the relative accuracy and reliability of the three methods. The best results were given by the finite element method using a cubic polynomial. Excellent accuracy was consistently obtained, even for nearly equal eigenvalues, by using a 20 x 20 order matrix.

Interactions between Exosomes from Breast Cancer Cells and Primary Mammary Epithelial Cells Leads to Generation of Reactive Oxygen Species Which Induce DNA Damage Response, Stabilization of p53 and Autophagy in Epithelial Cells

PubMed Central

Dutta, Sujoy; Warshall, Case; Bandyopadhyay, Chirosree; Dutta, Dipanjan; Chandran, Bala

2014-01-01

Exosomes are nanovesicles originating from multivesicular bodies and are released by all cell types. They contain proteins, lipids, microRNAs, mRNAs and DNA fragments, which act as mediators of intercellular communications by inducing phenotypic changes in recipient cells. Tumor-derived exosomes have been shown to play critical roles in different stages of tumor development and metastasis of almost all types of cancer. One of the ways by which exosomes affect tumorigenesis is to manipulate the tumor microenvironments to create tumor permissive “niches”. Whether breast cancer cell secreted exosomes manipulate epithelial cells of the mammary duct to facilitate tumor development is not known. To address whether and how breast cancer cell secreted exosomes manipulate ductal epithelial cells we studied the interactions between exosomes isolated from conditioned media of 3 different breast cancer cell lines (MDA-MB-231, T47DA18 and MCF7), representing three different types of breast carcinomas, and normal human primary mammary epithelial cells (HMECs). Our studies show that exosomes released by breast cancer cell lines are taken up by HMECs, resulting in the induction of reactive oxygen species (ROS) and autophagy. Inhibition of ROS by N-acetyl-L-cysteine (NAC) led to abrogation of autophagy. HMEC-exosome interactions also induced the phosphorylation of ATM, H2AX and Chk1 indicating the induction of DNA damage repair (DDR) responses. Under these conditions, phosphorylation of p53 at serine 15 was also observed. Both DDR responses and phosphorylation of p53 induced by HMEC-exosome interactions were also inhibited by NAC. Furthermore, exosome induced autophagic HMECs were found to release breast cancer cell growth promoting factors. Taken together, our results suggest novel mechanisms by which breast cancer cell secreted exosomes manipulate HMECs to create a tumor permissive microenvironment. PMID:24831807

Burner Rig with an Unattached Duct for Evaluating the Erosion Resistance of Thermal Barrier Coatings

NASA Technical Reports Server (NTRS)

Miller, Robert A.; Kuczmarski, Maria A.; Zhu, Dongming

2011-01-01

Extensive computational fluid dynamics (CFD) modeling backed by experimental observation has demonstrated the feasibility of using an unattached duct to increase the velocity and spatial spread of erodent particles exiting from a burner rig. It was shown that gas velocity and temperature are mostly retained if the inner diameter of the unattached duct equaled the exit diameter of the burner rig nozzle. For particles having a mean diameter of 550 millimeters, the modeled velocity attained at a distance 2.0 in. (50.8 millimeters) beyond the exit of a 12 in. (305 millimeters) long duct was approximately twice as large as the velocity the same distance from the nozzle when the duct was not present. For finer particles, the relative enhancement was somewhat less approximately 1.5 times greater. CFD modeling was also used to guide the construction of a device for slowing down the velocity of the particles being injected into the burner rig. This device used a simple 45 degree fitting to slow the particle velocity in the feed line from 20 meters per second, which is in the range needed to convey the particles, to about 3 meters per second just as they are injected into the burner. This lower injection velocity would lessen the severity of the collision of large particles with the wall of the burner liner opposite the injection port, thereby reducing potential damage to the burner liner by high-velocity particles.

Intrahepatic cholangiocarcinoma.

PubMed

Nakano, Masayuki; Ariizumi, Shun-Ichi; Yamamoto, Masakazu

2017-03-01

Cholangiocarcinoma, also referred to as cholangiocellular carcinoma (particularly in Japan), develops along the biliary tract. The tumor may be intra- or extrahepatic and have different features with specific treatments based on the site of origin. Guidelines for diagnosis and management of cholangiorcarcinoma, such as those proposed by EASL (European Association for the Study of the Liver) 1 and the Mayo Clinic 2 classify the tumor into intrahepatic, perihilar, and distal cholangiocarcinoma. There are three main macroscopic patterns of growth of cholangiocarcinoma: mass-forming, periductal-infiltrating and intraductal. A combination of mass-forming and periductal infiltrating tumors have been shown to have a poor prognosis. 3 Intrahepatic cholangiocarcinoma (ICC) comprises two microscopic subtypes: bile duct and cholangiolar. 4 The bile duct subtype has tall columnar cells that form large glands, whereas cholangiolar tumors are composed of cuboidal and low columnar cells. Patients with cholangiolar tumors, referred to as cholangiolocellular carcinoma, reportedly have a better 5-year survival rate than those with the bile duct type. 4 . Copyright © 2017 Elsevier Inc. All rights reserved.

Cholangiocarcinoma of intrahepatic bile ducts with disseminated metastases in an African lion (Panthera leo).

PubMed

Lepri, Elvio; Sforna, Monica; Brachelente, Chiara; Chiara, Brachelente; Vitellozzi, Giovanni; Giovanni, Vitellozzi

2013-06-01

A cholangiocarcinoma is reported in an 18-yr-old, female African lion (Panthera leo). The primary tumor consisted of multifocal to coalescing, hepatic, white-yellow masses distributed throughout the liver lobes. Metastases were present in regional lymph nodes, peritoneal surface, and lungs. Histologically, the tumor was characterized by a tubular pattern with alcian- and periodic acid-Schiff-positive secretory material in cystic spaces. The neoplastic cells were positive to broad-spectrum cytokeratins. Histochemical and immunohistochemical stains were consistent with bile duct carcinoma. Biliary tumors arising from the gallbladder have been reported in lions. However, to the authors' knowledge, this is the first case of intrahepatic bile duct carcinoma reported in an African lion.

Body-force-driven multiplicity and stability of combined free and forced convection in rotating curved ducts: Coriolis force

NASA Astrophysics Data System (ADS)

Yang, T.; Wang, L.

A numerical study is made on the fully developed bifurcation structure and stability of forced convection in a rotating curved duct of square cross-section. Solution structure is determined as variation of a parameter that indicates the effect of rotation (Coriolis-force-driven multiplicity). Three solutions for the flows in a stationary curved duct obtained in the work of Yang and Wang [1] are used as initial solutions of continuation calculations to unfold the solution branches. Twenty-one solution branches are found comparing with five obtained by Selmi and Nandakumar [2]. Dynamic responses of the multiple solutions to finite random disturbances are examined by the direct transient computation. Results show that characteristics of physically realizable fully developed flows changes significantly with variation of effect of rotation. Fourteen sub-ranges are identified according to characteristics of physically realizable solutions. As rotation effect changes, possible physically realizable fully-developed flows can be stable steady 2-cell state, stable multi-cell state, temporal periodic oscillation between symmetric/asymmetric 2-cell/4-cell flows, temporal oscillation with intermittency, temporal chaotic oscillation and temporal oscillation with pseudo intermittency. Among these possible physically realizable fully developed flows, stable multi-cell state and stable steady 2-cell state exist as dual stable. And oscillation with pseudo intermittency is a new phenomenon. In addition to the temporal oscillation with intermittency, sudden shift from stationary stable solution to temporal chaotic oscillation is identified to be another way of onset of chaos.

Experiments in dilution jet mixing

NASA Technical Reports Server (NTRS)

Holdeman, J. D.; Srinivasan, R.; Berenfeld, A.

1983-01-01

Experimental results are given on the mixing of a single row of jets with an isothermal mainstream in a straight duct, to include flow and geometric variations typical of combustion chambers in gas turbine engines. The principal conclusions reached from these experiments were: at constant momentum ratio, variations in density ratio have only a second-order effect on the profiles; a first-order approximation to the mixing of jets with a variable temperature mainstream can be obtained by superimposing the jets-in-an isothermal-crossflow and mainstream profiles; flow area convergence, especially injection-wall convergence, significantly improves the mixing; for opposed rows of jets, with the orifice centerlines in-line, the optimum ratio of orifice spacing to duct height is one half of the optimum value for single side injection at the same momentum ratio; and for opposed rows of jets, with the orifice centerlines staggered, the optimum ratio of orifice spacing to duct height is twice the optimum value for single side injection at the same momentum ratio.

Experimental study of noise sources and acoustic propagation in a turbofan model

NASA Astrophysics Data System (ADS)

Lewy, S.; Canard-Caruana, S.; Julliard, J.

1990-10-01

Experimental studies of the acoustic radiation of subsonic fans mainly due to blade and vane presure fluctuations were performed in the SNECMA 5C2 compressor anechoic facility. A brief description of the test rig is presented noting that the CA5 turbojet engine model fan has a diameter of 47 cm, 48 blades, and a nominal rotation speed of 12,600 rpm. The two chief experiments discussed are the measurement of blade and vane pressure fluctuations by thin-film transducers and the spinning mode analysis of the sound field propagating in the intake duct. Several examples of applications are discussed, and it is shown that an inflow control device, as expected, reduces the aerodynamic disturbances by about 10 dB. Rotor-stator interaction tones are determined by the modal analysis, and it is found that a duct lining with a length of one duct radius could give an insertion loss up to 20 dB in flight.

Mucinous Cystic Neoplasm of the Liver or Intraductal Papillary Mucinous Neoplasm of the Bile Duct? A Case Report and a Review of Literature.

PubMed

Kunovsky, Lumir; Kala, Zdenek; Svaton, Roman; Moravcik, Petr; Mazanec, Jan; Husty, Jakub; Prochazka, Vladimir

2018-01-01

Mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are diagnoses that were classified by the World Health Organization in 2010 as mucin-producing bile duct tumors of the hepatobiliary system. The preoperative differential diagnosis between these two entities is difficult; the presence of a communication with the bile duct is usually considered as a typical sign of IPMN-B. However, the presence of an ovarian-like stroma (OLS) has been established to define the diagnosis of MCN-L. We present the case of a 33-year-old woman with a rapid progression of a cystic tumor of the liver. In 2 years, the lesion increased from 27 to 64 mm and a dilation of the left hepatic duct appeared. Percutaneous transhepatic drainage with a biopsy was performed. No malignant cells were found on biopsy. Because of the rapid progression of the cystic tumor and unclear malignant potential, left hemihepatectomy was performed. Even though tumor masses were present in the biliary duct, on the basis of the presence of OLS, histology finally confirmed MCN-L with intermediate-grade intraepithelial dysplasia to high-grade intraepithelial dysplasia. The patient is currently under oncologic follow-up with no signs of recurrence of the disease. We present a rare case where MCN-L caused a dilation of the left hepatic duct, a sign that is usually a characteristic of IPMN-B.

Retinoic acid signaling determines the fate of uterine stroma in the mouse Müllerian duct

PubMed Central

Nakajima, Tadaaki; Iguchi, Taisen; Sato, Tomomi

2016-01-01

The Müllerian duct develops into the oviduct, uterus, and vagina, all of which are quite distinct in their morphology and function. The epithelial fate of these female reproductive organs in developing mice is determined by factors secreted from the stroma; however, how stromal differentiation occurs in the female reproductive organs derived from the Müllerian duct is still unclear. In the present study, roles of retinoic acid (RA) signaling in developing female reproductive tracts were investigated. Retinol dehydrogenase 10 (RDH10) and aldehyde dehydrogenase family 1 subfamily A2 (ALDH1A2) mRNAs and proteins and transactivation activity of endogenous RA were found in the stroma of proximal Müllerian ducts and gradually decreased from the proximal to caudal regions in fetal mice. In organ-cultured Müllerian ducts, retinaldehyde or RA treatment induced uterine epithelial differentiation, defined as a layer of columnar epithelial cells negative for oviductal and vaginal epithelial markers. In contrast, inhibition of RA receptor (RAR) signaling induced vaginal epithelial differentiation, characterized as vaginal epithelial marker genes–positive stratified epithelium. Grafting experiments of the organ-cultured Müllerian duct revealed irreversible epithelial fate determination. Although RAR did not directly bind to the homeobox A10 (Hoxa10) promoter region, RA–RAR signaling stimulated Hoxa10 expression. Thus, RA–RAR signaling in the Müllerian duct determines the fate of stroma to form the future uterus and vagina. PMID:27911779

Deletion of the pH sensor GPR4 decreases renal acid excretion.

PubMed

Sun, Xuming; Yang, Li V; Tiegs, Brian C; Arend, Lois J; McGraw, Dennis W; Penn, Raymond B; Petrovic, Snezana

2010-10-01

Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.

An Approach for Treating the Hepatobiliary Disease of Cystic Fibrosis by Somatic Gene Transfer

NASA Astrophysics Data System (ADS)

Yang, Yiping; Raper, Steven E.; Cohn, Jonathan A.; Engelhardt, John F.; Wilson, James M.

1993-05-01

Cystic fibrosis (CF) is an inherited disease of epithelial cell ion transport that is associated with pathology in multiple organ systems, including lung, pancreas, and liver. As treatment of the pulmonary manifestations of CF has improved, management of CF liver disease has become increasingly important in adult patients. This report describes an approach for treating CF liver disease by somatic gene transfer. In situ hybridization and immunocytochemistry analysis of rat liver sections indicated that the endogenous CFTR (cystic fibrosis transmembrane conductance regulator) gene is primarily expressed in the intrahepatic biliary epithelial cells. To specifically target recombinant genes to the biliary epithelium in vivo, recombinant adenoviruses expressing lacZ or human CFTR were infused retrograde into the biliary tract through the common bile duct. Conditions were established for achieving recombinant gene expression in virtually all cells of the intrahepatic bile ducts in vivo. Expression persisted in the smaller bile ducts for the duration of the experiment, which was 21 days. These studies suggest that it may be feasible to prevent CF liver disease by genetically reconstituting CFTR expression in the biliary tract, using an approach that is clinically feasible.

Expression and localization of c-ros oncogene along the human excurrent duct.

PubMed

Légaré, Christine; Sullivan, Robert

2004-09-01

Compared to other animals, the anatomy of the human epididymis appears unusual. The caput epididymis is composed mostly of efferent ducts with an undefined initial segment. The present study investigates the regionalization of c-ros in human epididymis by real-time quantitative RT-PCR, in situ hybridization and immunohistochemistry studies. C-ros gene encodes a receptor-type protein tyrosine kinase that is expressed in adult mice exclusively in the epithelial cells of the initial segment of the epididymis. Transgenic mice targeted for the c-ros gene lack the initial segment of the epididymis and are infertile. Real-time PCR analysis showed that c-ros mRNA is expressed all along the human epididymis with the exception of the proximal caput epididymidis, where c-ros transcript was undetectable. In situ hydridization revealed that c-ros transcript was strongly expressed by principal cells and to a lower level by basal cells. Immunohistochemical studies showed that c-ros protein distribution was similar to the transcript. These results showed that c-ros expression in the human epididymis differs from that in mice suggesting that the unusual morphology of the human epididymis may reflect species differences in gene expression along the excurrent duct.

CARS Temperature Measurements in a Hypersonic Propulsion Test Facility

NASA Technical Reports Server (NTRS)

Jarrett, Olin, Jr.; Smith, M. W.; Antcliff, R. R.; Northam, G. Burt; Cutler, A. D.; Capriotti, D. P.; Taylor, D. J.

1990-01-01

Nonintrusive diagnostic measurements were performed in the supersonic reacting flow of the Hypersonic Propulsion Test Cell 2 at NASA-Langley. A Coherent Anti-stokes Raman Spectroscopy (CARS) system was assembled specifically for the test cell environment. System design considerations were: (1) test cell noise and vibration; (2) contamination from flow field or atmospheric borne dust; (3) unwanted laser or electrically induced combustion (inside or outside the duct); (4) efficient signal collection; (5) signal splitting to span the wide dynamic range present throughout the flow field; (6) movement of the sampling volume in the flow; and (7) modification of the scramjet model duct to permit optical access to the reacting flow with the CARS system. The flow in the duct was a nominal Mach 2 flow with static pressure near one atmosphere. A single perpendicular injector introduced hydrogen into the flow behind a rearward facing step. CARS data was obtained in three planes downstream of the injection region. At least 20 CARS data points were collected at each of the regularly spaced sampling locations in each data plane. Contour plots of scramjet combustor static temperature in a reacting flow region are presented.

Claudins and the Kidney Volume 75: Annual Review of Physiology

PubMed Central

Hou, Jianghui; Rajagopal, Madhumitha; Yu, Alan S. L.

2013-01-01

Claudins are tight junction membrane proteins that regulate paracellular permeability of renal epithelia to small ions, solutes and water. Claudins interact within the cell membrane and between neighboring cells to form tight junction strands and constitute both the paracellular barrier and pore. The first extracellular domain of claudins is thought to be the pore-lining domain and contains the determinants of charge selectivity. Multiple claudins are expressed in different nephron segments and this likely determines the permeability properties of each segment. Recent evidence has identified claudin-2 as constituting the cation-reabsorptive pathway in the proximal tubule, claudin-14, -16 and -19 as forming a complex that regulates calcium transport in the thick ascending limb of the loop of Henle, and claudin-4, -7 and -8 as determinants of collecting duct choride permeability. Mutations in claudin-16 and -19 cause familial hypercalciuric hypomagnesemia. The roles of other claudins in kidney diseases remain to be fully elucidated. PMID:23140368

The lining of the gut in the developing rat embryo. Its relation to the hypoblast (primary endoderm) and the notochord.

PubMed

Lamers, W H; Spliet, W G; Langemeyer, R A

1987-01-01

A light microscopical study of the morphogenesis of the gut in the rat embryo was undertaken to provide a careful map of temporal changes in the topographical relations of the (definitive) endoderm, the notochord and the hypoblast (primary endoderm). The borderline between the (definitive) endoderm and the hypoblast that appears upon gastrulation defines the lateral extension of the future gut epithelium. Within this initially semiglobular disk, the foregut and hindgut originate sequentially as blind, rapidly growing pouches. Upon the turning of the embryo, the hardly growing peripheral part of the disk becomes located in the vitelline duct. Within the head process, endodermal and notochordal cells could not be separately identified. However, slightly more posteriorly notochordal cells are seen to become embedded into the endoderm of the foregut during gastrulation. This process is not seen over the hindgut and may explain why the detachment of the notochord from the (fore)gut begins caudally.

Inhibition of histone deacetylase for the treatment of biliary tract cancer: A new effective pharmacological approach

PubMed Central

Bluethner, Thilo; Niederhagen, Manuel; Caca, Karel; Serr, Frederik; Witzigmann, Helmut; Moebius, Christian; Mossner, Joachim; Wiedmann, Marcus

2007-01-01

AIM: To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS: Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 7 human biliary tract cancer cell lines by MTT assay. In addition, the anti-tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral drug mechanism was assessed by immunoblotting for acH4 and p21WAF-1/CIP-1, PARP assay, cell cycle analysis, TUNEL assay, and immunhistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines [mean IC50 (3 d) 0.11 and 0.05 μmol/L, respectively], and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21WAF-1/CIP-1, induction of apoptosis (PARP cleavage), and cell cycle arrest at G2/M checkpoint. After 28 d, NVP-LBH589 significantly reduced tumor mass by 66% (bile duct cancer) and 87% (gallbladder cancer) in vivo in comparison to placebo, and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed increased apoptosis by TUNEL assay and reduced cell proliferation (MIB-1). CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended. PMID:17729398

Bradykinin-stimulated cyclooxygenase activity stimulates vas deferens epithelial anion secretion in vitro in swine and humans.

PubMed

Pierucci-Alves, Fernando; Schultz, Bruce D

2008-09-01

Epithelia lining the male reproductive duct modulate fertility by altering the luminal environment to which sperm are exposed. Although vas deferens epithelial cells reportedly express high levels of cyclooxygenases (Ptgs), and activation of bradykinin (BK) receptors can lead to upregulation of PTGS activity in epididymal epithelia, it remains unknown whether BKs and/or PTGSs have any role in modulating epithelial ion transport across vas deferens epithelia. Porcine and human vas deferens epithelial cell primary cultures and the PVD9902 cell line responded to lysylbradykinin with an increase in short circuit current (I SC; indicating net anion secretion), an effect that was 60%-93% reduced by indomethacin. The BK effect was inhibited by the B2 receptor subtype (BDKRB2) antagonist HOE140, whereas the B1 receptor subtype agonist des-Arg9-BK had no effect. BDKRB2 immunoreactivity was documented in most epithelial cells composing the native epithelium and on Western blots derived from cultured cells. Gene expression analysis revealed that the PTGS2 transcript is 20 times more abundant than its PTGS1 counterpart in cultured porcine vas deferens epithelia and that BDKRB2 mRNA is likewise highly expressed. Subsequent experiments revealed that prostaglandin E2, 1-OH prostaglandin E1 (prostaglandin E receptor 4 [PTGER4] agonist) and butaprost (PTGER2 agonist) increase I SC in a concentration-dependent manner, whereas sulprostone (mixed PTGER1 and PTGER3 agonist) produced no change in I SC. These results demonstrate that autacoids can affect epithelial cells to acutely modulate the luminal environment to which sperm are exposed in the vas deferens by enhancing PTGS activity, leading to the production of prostaglandins that act at PTGER4 and/or PTGER2 to induce or enhance anion secretion.

Bradykinin-Stimulated Cyclooxygenase Activity Stimulates Vas Deferens Epithelial Anion Secretion In Vitro in Swine and Humans1

PubMed Central

Pierucci-Alves, Fernando; Schultz, Bruce D.

2008-01-01

Epithelia lining the male reproductive duct modulate fertility by altering the luminal environment to which sperm are exposed. Although vas deferens epithelial cells reportedly express high levels of cyclooxygenases (Ptgs), and activation of bradykinin (BK) receptors can lead to upregulation of PTGS activity in epididymal epithelia, it remains unknown whether BKs and/or PTGSs have any role in modulating epithelial ion transport across vas deferens epithelia. Porcine and human vas deferens epithelial cell primary cultures and the PVD9902 cell line responded to lysylbradykinin with an increase in short circuit current (ISC; indicating net anion secretion), an effect that was 60%–93% reduced by indomethacin. The BK effect was inhibited by the B2 receptor subtype (BDKRB2) antagonist HOE140, whereas the B1 receptor subtype agonist des-Arg9-BK had no effect. BDKRB2 immunoreactivity was documented in most epithelial cells composing the native epithelium and on Western blots derived from cultured cells. Gene expression analysis revealed that the PTGS2 transcript is 20 times more abundant than its PTGS1 counterpart in cultured porcine vas deferens epithelia and that BDKRB2 mRNA is likewise highly expressed. Subsequent experiments revealed that prostaglandin E2, 1-OH prostaglandin E1 (prostaglandin E receptor 4 [PTGER4] agonist) and butaprost (PTGER2 agonist) increase ISC in a concentration-dependent manner, whereas sulprostone (mixed PTGER1 and PTGER3 agonist) produced no change in ISC. These results demonstrate that autacoids can affect epithelial cells to acutely modulate the luminal environment to which sperm are exposed in the vas deferens by enhancing PTGS activity, leading to the production of prostaglandins that act at PTGER4 and/or PTGER2 to induce or enhance anion secretion. PMID:18480467

Intermedilysin induces EGR-1 expression through calcineurin/NFAT pathway in human cholangiocellular carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Susilowati, Heni; Okamura, Hirohiko; Hirota, Katsuhiko, E-mail: hirota@dent.tokushima-u.ac.jp

2011-01-07

Research highlights: {yields} ILY leads to the accumulation of [Ca{sup 2+}]i in the nucleus in HuCCT1 cells. {yields} ILY induced activation of NFAT1 through a calcineurin-dependent pathway. {yields} Calcineuri/NFAT pathway is involved in EGR-1 expression in response to ILY treatment. -- Abstract: Intermedilysin (ILY) is a cholesterol-dependent cytolysin produced by Streptococcus intermedius, which is associated with human brain and liver abscesses. Although intrahepatic bile duct cells play a valuable role in the pathogenesis of liver abscess, the molecular mechanism of ILY-treated intrahepatic bile duct cells remains unknown. In this study, we report that ILY induced a nuclear accumulation of intracellularmore » calcium ([Ca{sup 2+}]i) in human cholangiocellular cells HuCCT1. We also demonstrate that 10 ng/ml ILY induced NFAT1 dephosphorylation and its nuclear translocation in HuCCT1 cells. In contrast to the result that ILY induced NF-{kappa}B translocation in human hepatic HepG2 cells, ILY did not affect NF-{kappa}B localization in HuCCT1 cells. Dephosphorylation and nuclear translocation of NFAT1 caused by ILY were prevented by [Ca{sup 2+}]i calcium chelator, BAPTA/AM, and calcineurin inhibitors, cyclosporine A and tacrolimus. ILY induced early growth response-1 (EGR-1) expression and it was inhibited by the pre-treatment with cyclosporine A, indicating that the calcineurin/NFAT pathway was involved in EGR-1 expression in response to ILY. ILY-induced calcineurin/NFAT1 activation and sequential EGR-1 expression might be related to the pathogenesis of S. intermedius in human bile duct cells.« less

GPON FTTH trial: lessons learned

NASA Astrophysics Data System (ADS)

Weis, Erik; Hölzl, Rainer; Breuer, Dirk; Lange, Christoph

2009-11-01

This paper reports on a FTTH field trial with GPON (Gigabit-capable passive optical network) technology in the network of Deutsche Telekom in the region of the cities of Berlin and Potsdam. Focus of this trial was to gain practical experience regarding GPON technology, fibre installation in existing ducts with micro duct technology, fibre cabling in customer buildings and impact on operational processes. Furthermore it is reported on an initial Deutsche Telekom FTTB deployment based on GPON technology in the city of Dresden with the main targets to obtain practical deployment and operation experiences with fibre-based access networks and to provide broadband access to a part of the city formerly not servable by DSL (digital subscriber line) technology.

Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions.

PubMed

Bertram, Stefanie; Padden, Juliet; Kälsch, Julia; Ahrens, Maike; Pott, Leona; Canbay, Ali; Weber, Frank; Fingas, Christian; Hoffmann, Andreas C; Vietor, Antonie; Schlaak, Joerg F; Eisenacher, Martin; Reis, Henning; Sitek, Barbara; Baba, Hideo A

2016-07-01

The distinction between intrahepatic cholangiocarcinoma (ICC) and benign bile duct lesions can be challenging. Using our previously identified potential biomarkers for ICC, we examined whether these are useful for the differential diagnosis of ICC, bile duct adenoma and reactive bile duct proliferations in an immunohistochemical approach and identified a diagnostic marker panel including known biomarkers. Subjects included samples from 77 patients with ICC, 33 patients with bile duct adenoma and 47 patients with ductular reactions in liver cirrhosis. Our previously identified biomarkers (stress-induced phosphoprotein 1 (STIP1), SerpinH1, 14-3-3Sigma) were tested immunohistochemically following comparison with candidates from the literature (cluster of differentiation 56, heat shock protein (HSP)27, HSP70, B-cell-lymphoma2, p53, ki67). The expression of SerpinH1 and 14-3-3Sigma was significantly higher in ICC than in bile duct adenomas and ductular reactions (p<0.05), whereas STIP1 expression was significantly higher (p<0.05) in ICC than in ductular reactions, but the difference to the bile duct adenoma group was not significant. A panel of the biomarker SerpinH1, 14-3-3Sigma and ki67 (≥2 marker positive) showed a high diagnostic accuracy (sensitivity 87.8%, specificity 95.9%, accuracy 91.8%) in the differential diagnosis of ICC versus non-malignant bile duct lesions. This suggests that 14-3-3Sigma and SerpinH1 may be useful in the differential diagnosis of malignant, benign and reactive bile duct lesions in addition to ki67 where a cut-off of >5% might be used for the distinction of malignant and non-malignant lesions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Fatigue failure in metal bellows due to flow-induced vibrations

NASA Technical Reports Server (NTRS)

Daniels, C. M.; Fargo, C. G.

1969-01-01

To prevent fatigue due to flow-induced vibrations in metal bellows connected to ducts carrying liquid hydrogen, a study was made which shows that the flexure lines are in general a function of the vibration coupling between the fluid and bellows structure, and the nature of the external environment.

EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-01-15

Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Uterine Sarcoma; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Progenitor cell domains in the developing and adult pancreas

PubMed Central

Kopp, Janel L; Dubois, Claire L; Hao, Ergeng; Thorel, Fabrizio; Herrera, Pedro L

2011-01-01

Unlike organs with defined stem cell compartments, such as the intestine, the pancreas has limited capacity to regenerate. The question of whether the adult pancreas harbors facultative stem/progenitor cells has been a prime subject of debate. Cumulative evidence from recent genetic lineage tracing studies, in which specific cell populations were marked and traced in adult mice, suggests that endocrine and acinar cells are no longer generated from progenitors in the adult pancreas. These studies further indicate that adult pancreatic ductal cells are not a source for endocrine cells following pancreatic injury, as previously suggested. Our own studies have shown that adult ductal cells reinitiate expression of some endocrine progenitor markers, including Ngn3, after injury by partial duct ligation (PDL), but that these cells do not undergo endocrine cell differentiation. Here, we present additional evidence that endocrine cells do not arise from ducts following β-cell ablation by streptozotocin or by a diphtheria toxin-expressing transgene or when β-cell ablation is combined with PDL. In this review, we discuss findings from recent lineage tracing studies of embryonic and adult pancreatic ductal cells. Based upon the combined evidence from these studies, we propose that multipotency is associated with a specific transcriptional signature. PMID:21558806

The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals.

PubMed

Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

2017-07-01

The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development.

The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals

PubMed Central

Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

2018-01-01

The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development. PMID:28581486

Is endoscopic therapy the treatment of choice in all patients with chronic pancreatitis?

PubMed

Jabłońska, Beata

2013-01-07

Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas characterized by destruction of the pancreatic parenchyma with subsequent fibrosis that leads to pancreatic exocrine and endocrine insufficiency. Abdominal pain and local complications (bile duct or duodenal stenosis and pancreatic tumor) secondary to CP are indications for therapy. At the beginning, medical therapy is used. More invasive treatment is recommended for patients with pancreatic duct stones (PDS) and pancreatic obstruction in whom standard medical therapy is not sufficient. Recently, Clarke et al assessed the long-term effectiveness of endoscopic therapy (ET) in CP patients. The authors compared ET with medical treatment. They reported that ET was clinically successful in 50% of patients with symptomatic CP. In this commentary, current CP treatment, including indications for ET and surgery in CP patients, is discussed. Recommendations for endoscopic treatment of CP according to the European Society of Gastrointestinal Endoscopy Clinical Guidelines are reviewed. Different surgical methods used in the treatment of CP patients are also discussed. ET is the most useful in patients with large PDS, pancreatic duct obstruction and dilation. It should be the first-line option because it is less invasive than surgery. Surgery should be the first-line option in patients in whom ET has failed or in those with a pancreatic mass with suspicion of malignancy. ET is a very effective and less invasive procedure, but it cannot be recommended as the treatment of choice in all CP patients.

Overview of Lung Development in the Newborn Human.

PubMed

Warburton, David

2017-01-01

In human neonates rapid adaptation from an aqueous intrauterine environment to permanent air breathing is the rate-limiting step for extrauterine life, failure of which justifies the existence of neonatal intensive care units. The lung develops at about 4-6 weeks' gestation in humans as a ventral outpouching of the primitive foregut into the surrounding ventral mesenchyme, termed the laryngotracheal groove. At its posterior end lie progenitor cells that form a pair of bronchial tubes, from which arise all the distal epithelial structures of the lung. In humans, formation of the distal gas exchange surfaces begins in utero at about 20 weeks' gestation and is substantially established by term. Stereotypic branching of the proximal airway ends relatively early at 16-18 weeks at the bronchoalveolar duct junctions. Distally, about 5 finger-like alveolar ducts arise from each bronchoalveolar duct junction and ramify outwards towards the pleura. The majority of alveolar air sacs arise from the sides of the alveolar ducts and each of these alveoli can have up to 5 daughter alveoli arising from the outer surface as subsequent buds. At the end of each alveolar duct lie the mouths of 5 interconnected alveoli. Each family of alveoli arising from each bronchoalveolar duct junction has a different shape depending upon the limitations imposed by the pleural surface as well as the interstitial fascial planes. © 2017 S. Karger AG, Basel.

Isolation of major pancreatic cell types and long-term culture-initiating cells using novel human surface markers.

PubMed

Dorrell, Craig; Abraham, Stephanie L; Lanxon-Cookson, Kelsea M; Canaday, Pamela S; Streeter, Philip R; Grompe, Markus

2008-09-01

We have developed a novel panel of cell-surface markers for the isolation and study of all major cell types of the human pancreas. Hybridomas were selected after subtractive immunization of Balb/C mice with intact or dissociated human islets and assessed for cell-type specificity and cell-surface reactivity by immunohistochemistry and flow cytometry. Antibodies were identified by specific binding of surface antigens on islet (panendocrine or alpha-specific) and nonislet pancreatic cell subsets (exocrine and duct). These antibodies were used individually or in combination to isolate populations of alpha, beta, exocrine, or duct cells from primary human pancreas by FACS and to characterize the detailed cell composition of human islet preparations. They were also employed to show that human islet expansion cultures originated from nonendocrine cells and that insulin expression levels could be increased to up to 1% of normal islet cells by subpopulation sorting and overexpression of the transcription factors Pdx-1 and ngn3, an improvement over previous results with this culture system. These methods permit the analysis and isolation of functionally distinct pancreatic cell populations with potential for cell therapy.

Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments.

PubMed

Koulouris, Andreas I; Banim, Paul; Hart, Andrew R

2017-04-01

Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.

Upregulation of transferrin receptor-1 induces cholangiocarcinoma progression via induction of labile iron pool.

PubMed

Jamnongkan, Wassana; Thanan, Raynoo; Techasen, Anchalee; Namwat, Nisana; Loilome, Watcharin; Intarawichian, Piyapharom; Titapun, Attapol; Yongvanit, Puangrat

2017-07-01

Labile iron pool is a cellular source of ions available for Fenton reactions resulting in oxidative stress. Living organisms avoid an excess of free irons by a tight control of iron homeostasis. We investigated the altered expression of iron regulatory proteins and iron discrimination in the development of liver fluke-associated cholangiocarcinoma. Additionally, the levels of labile iron pool and the functions of transferrin receptor-1 on cholangiocarcinoma development were also identified. Iron deposition was determined using the Prussian blue staining method in human cholangiocarcinoma tissues. We investigated the alteration of iron regulatory proteins including transferrin, transferrin receptor-1, ferritin, ferroportin, hepcidin, and divalent metal transporter-1 in cholangiocarcinoma tissues using immunohistochemistry. The clinicopathological data of cholangiocarcinoma patients and the expressions of proteins were analyzed. Moreover, the level of intracellular labile iron pool in cholangiocarcinoma cell lines was identified by the RhoNox-1 staining method. We further demonstrated transferrin receptor-1 functions on cell proliferation and migration upon small interfering RNA for human transferrin receptor 1 transfection. Results show that Iron was strongly stained in tumor tissues, whereas negative staining was observed in normal bile ducts of healthy donors. Interestingly, high iron accumulation was significantly correlated with poor prognosis of cholangiocarcinoma patients. The expressions of iron regulatory proteins in human cholangiocarcinoma tissues and normal liver from cadaveric donors revealed that transferrin receptor-1 expression was increased in the cancer cells of cholangiocarcinoma tissues when compared with the adjacent normal bile ducts and was significantly correlated with cholangiocarcinoma metastasis. Labile iron pool level and transferrin receptor-1 expression were significantly increased in KKU-214 and KKU-213 when compared with cholangiocyte cells (MMNK1). Additionally, the suppression of transferrin receptor-1 expression significantly decreased intracellular labile iron pool, cholangiocarcinoma migration, and cell proliferation when compared with control media and control small interfering RNA. In Conclusion, high expression of transferrin receptor-1 resulting in iron uptake contributes to increase in the labile iron pool which plays roles in cholangiocarcinoma progression with aggressive clinical outcomes.

Role of cholangiocyte bile Acid transporters in large bile duct injury after rat liver transplantation.

PubMed

Cheng, Long; Zhao, Lijin; Li, Dajiang; Liu, Zipei; Chen, Geng; Tian, Feng; Li, Xiaowu; Wang, Shuguang

2010-07-27

The pathogenesis of nonanastomotic strictures with a patent hepatic artery remains to be investigated. This study focuses on the role of cholangiocyte bile acid transporters in bile duct injury after liver transplantation. Sprague-Dawley rats were divided into three groups (n=20 for each): the sham-operated group (Sham), the transplant group with 1-hr donor liver cold preservation (CP-1h), and the transplant group with 12-hr donor liver cold preservation (CP-12h). Bile was collected for biochemical analysis. The histopathologic evaluation of bile duct injury was performed and the cholangiocyte bile acid transporters apical sodium-dependent bile acid transporter (ASBT), ileal lipid binding protein (ILBP), and Ostalpha/Ostbeta were investigated. RESULTS.: The immunohistochemical assay suggested that ASBT and ILBP were expressed exclusively on large bile duct epithelial cells, whereas Ostalpha and Ostbeta were expressed on both small and large bile ducts. Western blot and quantitative polymerase chain reaction analysis showed that the expression levels of these transporters dramatically decreased after transplantation. It took seven to 14 days for ILBP, Ostalpha, and Ostbeta to recover, whereas ASBT recovered within 3 days and even reached a peak above the normal level seven days after operation. In the CP-12h group, the ratios of the ASBT/ILBP, ASBT/Ostalpha and ASBT/Ostbeta expression levels were correlated with the injury severity scores of large but not small bile ducts. The results suggest that the unparallel alteration of cholangiocyte bile acid transporters may play a potential role in large bile duct injury after liver transplantation with prolonged donor liver preservation.

Experimental Study of Poly-l-Lactic Acid Biodegradable Stents in Normal Canine Bile Ducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, Kiyosei, E-mail: yamakiyo@zg7.so-net.ne.jp; Yoshioka, Tetsuya; Furuichi, Kinya

Purpose: This study was designed to clarify the advantages of biodegradable stents in terms of mucosal reaction and biodegradation after placement. We designed a biodegradable stent and assessed stent degradation and changes in the normal bile ducts of dogs. Methods: The biodegradable stent is a balloon-expandable Z stent consisting of poly-l-lactic acid (PLLA) with a diameter of 6 mm and a length of 15 mm. We assessed four groups of three beagle dogs each at 1, 3, 6, and 9 months of follow-up. After evaluating stent migration by radiography and stent and bile duct patency by cholangiography, the dogs weremore » sacrificed to remove the bile duct together with the stent. The bile duct lumen was examined macroscopically and histologically, and the stent degradation was examined macroscopically and by scanning electron microscopy (SEM). Results: Bile duct obstruction was absent and none of the stents migrated. Macroscopic evaluation showed moderate endothelial proliferation in the bile ducts at the implant sites at 3 and 6 months and a slight change at 9 months. Slight mononuclear cell infiltration was histologically identified at all time points and epithelial hyperplasia that was moderate at 3 months was reduced to slight at 6 and 9 months. Stent degradation was macroscopically evident in all animals at 9 months and was proven by SEM in two dogs at 6 months and in all of them at 9 months. Conclusions: Our results suggest that PLLA bioabsorbable stents seems to be useful for implantation in the biliary system with further investigation.« less

Spermatodesm reorganization in the spermatophore and in the spermatheca of the bushcricket Tylopsis liliifolia (Fabricius) (Orthoptera, Tettigoniidae).

PubMed

Viscuso, Renata; Vitale, Danilo G M

2015-05-01

Spermatozoa of Tettigoniidae are usually transferred to the female by means of a spermatophore which is also the site of feather-shaped spermatodesm formation. These spermatodesms are then transferred to a spermatheca, composed of a spermathecal duct and of a seminal receptacle, involved in storing spermatozoa. In order to extend the knowledge about sperm transfer and spermatodesms reorganization in the Tettigoniidae, a morpho-structural investigation was carried out on spermatophore and spermatheca of Tylopsis liliifolia and on the reorganization of the gametes from the spermatophore. Our results show that the spermatodesms undergo disorganization in the spermatophore; unlike other Tettigoniidae, however, feather-shaped spermatodesms are never found. The epithelium of the spermatheca consists of two cell types, the cuticle-forming and the gland cells, with secretory features. The gland cells, absent in the distal tract of the seminal receptacle, release their secretion in a "reservoir" where an efferent duct opens. In the distal tract of the spermathecal duct, adjacent epithelial cells show diversified ultrastructural characteristics whose probable role is discussed. A particular feature of T. liliifolia is the genesis of the feather-shaped spermatodesms in the seminal receptacle. This feature and the peculiar organization of the feather-shaped spermatodesm are a possible autapomorphy of T. liliifolia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phosphorylated Akt/PKB controls cell growth and apoptosis in intraductal papillary-mucinous tumor and invasive ductal adenocarcinoma of the pancreas.

PubMed

Semba, Shuho; Moriya, Toshiyuki; Kimura, Wataru; Yamakawa, Mitsunori

2003-04-01

Akt/PKB promotes cell proliferation and rescues cells from apoptosis. To evaluate the role of Akt/PKB, a key molecule in phosphatidylinositol 3-OH kinase (PI3K) signaling, during the development of pancreatic duct neoplasias such as intraductal papillary-mucinous tumor (IPMT) and invasive ductal adenocarcinoma (IDAC) of the pancreas. In PK-45H pancreatic cancer cells, the growth-inhibitory and apoptosis-inducing effects of LY294002, a PI3K inhibitor, were detected in a concentration-dependent manner, followed by the reduction of phosphorylated Akt levels. Immunohistochemical analyses revealed that frequent overexpression of phosphorylated Akt (Ser473) was detected in 10 (63%) of 16 IPMTs and 14 (70%) of 20 IDACs. It is interesting that the incidence of Akt phosphorylation closely correlated with Ki-67 immunoreactivity and had an inverse association with the number of cases of apoptotic bodies in both IPMT and IDAC. Although there was no good correlation with other clinicopathologic parameters, the two patients with recurrent IPMT had high levels of phosphorylated Akt. Our findings suggest that activation of Akt plays an important role during the progression of these pancreatic duct neoplasias at the early stage. Furthermore, inhibition of the PI3K-Akt/PKB pathway may have therapeutic potential in the treatment of pancreatic duct tumors.

Characterisation of glycoconjugate sugar residues in the vomeronasal organ of the armadillo Chaetophractus villosus (Mammalia, xenarthra)

PubMed Central

CARMANCHAHI, P. D.; FERRARI, C. C.; ALDANA MARCOS, H. J.; AFFANNI, J. M.; SONEZ, C. A.; PAZ, D. A.

2000-01-01

Conventional carbohydrate histochemistry and the binding patterns of 21 lectins were analysed to characterise the glycoconjugate content in the components of the vomeronasal organ of the armadillo Chaetophractus villosus. The mucomicrovillous complex of the sensory epithelium bound most of the lectins studied. No reaction was observed with Con A, PSA, S-Con A and SBA, and the sustentacular cells were stained with UEA-I, DSL, LEL, STL and Con A. The vomeronasal receptor neurons were labelled with S-WGA, WGA, PNA, UEA-I, STL, Con A, S-Con A, ECL and RCA120. The basal cell layer reacted with S-WGA, WGA, LCA, UEA-I, DSL, LEL, STL, Con A, JAC and VVA. The nonsensory epithelium exhibited a differential staining in relation to the different components. The mucociliary complex stained with ECL, DBA, JAC, RCA120, STL, LCA, PHA-E, PHA-L, LEL, BSL-I and VVA. However, SJA and UEA-I stained the mucus complex lining a subpopulation of columnar cells. The cytoplasm and cell membranes of columnar cells was labelled with DBA, DSL and LCA. The apical region of these cells exhibited moderate reactivity with LEL and SJA. None of the lectins bound specifically to secretory granules of the nonsecretory cells. Basal cells of the nonsensory epithelium were labelled with DSL, LEL, LCA, BSL-I and STL. The vomeronasal glands showed a positive reaction with WGA, DSL, LEL, LCA, DBA, PNA, RCA120 and SBA. Subpopulations of acinar cells were observed with ECL, S-WGA, Con A, S-Con A and DBA. PNA and RCA120 stained the cells lining the glandular ducts. In comparison with previous results obtained in the olfactory mucosa of the same group of armadillos, the carbohydrate composition of the vomeronasal organ sensory epithelium differed from the olfactory sensory epithelium. This is probably related to the different nature of molecules involved in the perireceptor processes. PMID:10853958

Decreased collagen types I and IV, laminin, CK-19 and α-SMA expression after bone marrow cell transplantation in rats with liver fibrosis.

PubMed

Carvalho, S N; Lira, D C; Oliveira, G P; Thole, A A; Stumbo, A C; Caetano, C E; Marques, R G; Carvalho, L

2010-11-01

Bone marrow cells have frequently been tested in animal models of liver fibrosis to assess their role in hepatic regeneration. The mononuclear fraction of bone marrow cells is of particular interest, as many studies show that these cells may be beneficial to treat hepatic fibrosis. In this study, we used the bile duct ligation model to induce hepatic fibrosis in an irreversible manner, and rats were treated with bone marrow mononuclear (BMMN) cells after fibrosis was established. Analysis of collagen types I and IV, laminin and α-SMA showed a decreased expression of these proteins in fibrotic livers after 7 days of BMMN cell injection. Moreover, cytokeratin-19 analysis showed a reduction in bile ducts in the BMMN cell-treated group. These results were accompanied by ameliorated levels of hepatic enzymes GPT (Glutamic-pyruvic transaminase), GOT (glutamic-oxaloacetic transaminase) and alkaline phosphatase (AP). Therefore, we showed that BMMN cells decrease hepatic fibrosis by significantly reducing myofibroblast numbers and through reduction of the collagen and laminin-rich extracellular matrix of fibrotic septa and hepatic sinusoids.

Potential application of in vivo imaging of impaired lymphatic duct to evaluate the severity of pressure ulcer in mouse model

NASA Astrophysics Data System (ADS)

Kasuya, Akira; Sakabe, Jun-Ichi; Tokura, Yoshiki

2014-02-01

Ischemia-reperfusion (IR) injury is a cause of pressure ulcer. However, a mechanism underlying the IR injury-induced lymphatic vessel damage remains unclear. We investigated the alterations of structure and function of lymphatic ducts in a mouse cutaneous IR model. And we suggested a new method for evaluating the severity of pressure ulcer. Immunohistochemistry showed that lymphatic ducts were totally vanished by IR injury, while blood vessels were relatively preserved. The production of harmful reactive oxygen species (ROS) was increased in injured tissue. In vitro study showed a high vulnerability of lymphatic endothelial cells to ROS. Then we evaluated the impaired lymphatic drainage using an in vivo imaging system for intradermally injected indocyanine green (ICG). The dysfunction of ICG drainage positively correlated with the severity of subsequent cutaneous changes. Quantification of the lymphatic duct dysfunction by this imaging system could be a useful strategy to estimate the severity of pressure ulcer.

Apoptosis in Early Salivary Gland Duct Morphogenesis and Lumen Formation.

PubMed

Teshima, T H N; Wells, K L; Lourenço, S V; Tucker, A S

2016-03-01

Salivary glands are essential for the maintenance of oral health by providing lubrication and antimicrobial protection to the mucosal and tooth surfaces. Saliva is modified and delivered to the oral cavity by a complex multifunctional ductal system. During development, these ducts form as solid tubes, which undergo cavitation to create lumens. Apoptosis has been suggested to play a role in this cavitation process along with changes in cell polarity. Here, we show that apoptosis occurs from the very earliest stages of mouse salivary gland development, much earlier than previously reported. Apoptotic cells were observed in the center of the first epithelial stalk at early-stage embryonic day 12.5 (E12.5) according to both TUNEL staining and cleaved caspase 3 immunofluorescence. The presumptive lumen space was highlighted by the colocalization of a predictive lumen marker, cytokeratin 7. At E14.5, as lumens start to form throughout the glands, apoptotic expression decreased while cytokeratin 7 remained positive. In vitro inhibition of all caspases in E12.5 and E13.5 salivary glands resulted in wider ducts, as compared with the controls, and a defect in lumen formation. In contrast, no such defect in lumen formation was observed at E14.5. Our data indicate that apoptosis is involved during early stages of gland formation (E12.5 onward) and appears important for shaping the forming ducts. © International & American Associations for Dental Research 2015.

Disruption of IFT Complex A Causes Cystic Kidneys without Mitotic Spindle Misorientation

PubMed Central

Jonassen, Julie A.; SanAgustin, Jovenal; Baker, Stephen P.

2012-01-01

Intraflagellar transport (IFT) complexes A and B build and maintain primary cilia. In the mouse, kidney-specific or hypomorphic mutant alleles of IFT complex B genes cause polycystic kidneys, but the influence of IFT complex A proteins on renal development is not well understood. In the present study, we found that HoxB7-Cre–driven deletion of the complex A gene Ift140 from collecting ducts disrupted, but did not completely prevent, cilia assembly. Mutant kidneys developed collecting duct cysts by postnatal day 5, with rapid cystic expansion and renal dysfunction by day 15 and little remaining parenchymal tissue by day 20. In contrast to many models of polycystic kidney disease, precystic Ift140-deleted collecting ducts showed normal centrosomal positioning and no misorientation of the mitotic spindle axis, suggesting that disruption of oriented cell division is not a prerequisite to cyst formation in these kidneys. Precystic collecting ducts had an increased mitotic index, suggesting that cell proliferation may drive cyst expansion even with normal orientation of the mitotic spindle. In addition, we observed significant increases in expression of canonical Wnt pathway genes and mediators of Hedgehog and tissue fibrosis in highly cystic, but not precystic, kidneys. Taken together, these studies indicate that loss of Ift140 causes pronounced renal cystic disease and suggest that abnormalities in several different pathways may influence cyst progression. PMID:22282595

Design and demonstration of a pumpless 14 compartment microphysiological system.

PubMed

Miller, Paula G; Shuler, Michael L

2016-10-01

We describe a human "Body-on-a-chip" device (or microphysiological system) that could be used to emulate drug distribution, metabolism, and action in the body. It is based upon a physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model, where multiple chambers representing different organs are connected with fluidic channels to mimic multi-organ interactions within the body. Here we describe a pumpless 14 chamber (13 organs) microfluidic cell culture device that provides a separation between barrier and nonbarrier types of cell cultures. Our barrier chamber layer (skin, GI tract, and lung) allows for direct access and/or exposures to chemical or biological reagents forcing these reagents to pass through a barrier of cells established on a microfabricated membrane before exposing the nonbarrier tissue chambers (fat, kidney, heart, adrenal glands, liver, spleen, pancreas, bone marrow, brain, muscle) or entering the microfluidic circulation within the device. Our nonbarrier tissue chambers were created as three-dimensional configurations by resuspending cells in hydrogel (PGMatrix). We used cell lines to represent five of these organs (barrier lines-A549 [lung] and Caco2 [GI]) (nonbarrier lines-HepG2 C3A [liver], Meg01 [bone marrow], and HK2 [kidney]). The dimensions of our straight duct-like channels to each organ chamber were designed to provide the appropriate flow of a culture medium. The organ volumes and organ flow rates that have been reported for an average human male were used to estimate the desired fluid retention times in each organ chamber. The flow through the channels was induced by gravity on a custom programmed rocker platform which enabled pumpless operation and minimized bubble entrapment. The purpose of this paper is to describe the design and operation of a 14 chamber multi-organ system representing 13 tissues/organs with both barrier and nonbarrier tissue chambers and to study the interactive responses among the various cell lines. We demonstrate that five different cell lines survived with high viability (above 85%) for 7 days. We compared the individual observed flow rates to the compartments to the desired or estimated flow rates. This work demonstrates the feasibility of constructing, operating and maintaining a simple, gravity-driven, multi-organ microphysiological system with the capability of measuring cellular functions such as CYP1A1 and CYP3A4 activities, albumin release, urea, maintenance of tight junctions, and presence of surfactant for a sustained period. Biotechnol. Bioeng. 2016;113: 2213-2227. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Heterotransplantation of human breast carcinomas in nude mice. Correlation between successful heterotransplants, poor prognosis and amplification of the HER-2/neu oncogene.

PubMed

Giovanella, B C; Vardeman, D M; Williams, L J; Taylor, D J; de Ipolyi, P D; Greeff, P J; Stehlin, J S; Ullrich, A; Cailleau, R; Slamon, D J

1991-01-02

Four hundred and thirty-three human breast carcinomas and 23 cell lines derived from human breast carcinomas were heterotransplanted in nude mice. Twenty-eight tumors and 13 cell lines took and could be serially transplanted. Their human origin was established by isozyme analysis performed on successive passages. Sixteen primary infiltrating duct-cell carcinomas (PIDC) took, from a total of 262 transplanted (6.1%). This is in striking contrast to the greater than 50% rate of takes of most major cancers of epithelial origin. All 16 PIDC growing in nude mice were highly cellular and lacked desmoplastic hyperplasia. The clinical prognosis of the PIDC patients whose tumors were successfully transplanted was poor. Ten of 16 (63%) died of their disease within 3 years, compared to only 49 (20%) of the 246 PIDC patients whose tumors did not take in nude mice. This could not be attributed to later stage disease of the tumors that took, because only 15% of these patients had 4 or more positive axillary lymph nodes as opposed to 28% of the patients whose tumors did not take. Sixty-four percent of the breast carcinomas growing in nude mice exhibited amplification of the HER-2/neu oncogene which is also correlated with poor prognosis in human breast cancer. It is possible that the nude mouse is more susceptible to a population of highly invasive and lethal breast carcinomas.

Natural Flow Air Cooled Photovoltaics

NASA Astrophysics Data System (ADS)

Tanagnostopoulos, Y.; Themelis, P.

2010-01-01

Our experimental study aims to investigate the improvement in the electrical performance of a photovoltaic installation on buildings through cooling of the photovoltaic panels with natural air flow. Our experimental study aims to investigate the improvement in the electrical performance of a photovoltaic installation on buildings through cooling of the photovoltaic panels with natural air flow. We performed experiments using a prototype based on three silicon photovoltaic modules placed in series to simulate a typical sloping building roof with photovoltaic installation. In this system the air flows through a channel on the rear side of PV panels. The potential for increasing the heat exchange from the photovoltaic panel to the circulating air by the addition of a thin metal sheet (TMS) in the middle of air channel or metal fins (FIN) along the air duct was examined. The operation of the device was studied with the air duct closed tightly to avoid air circulation (CLOSED) and the air duct open (REF), with the thin metal sheet (TMS) and with metal fins (FIN). In each case the experiments were performed under sunlight and the operating parameters of the experimental device determining the electrical and thermal performance of the system were observed and recorded during a whole day and for several days. We collected the data and form PV panels from the comparative diagrams of the experimental results regarding the temperature of solar cells, the electrical efficiency of the installation, the temperature of the back wall of the air duct and the temperature difference in the entrance and exit of the air duct. The comparative results from the measurements determine the improvement in electrical performance of the photovoltaic cells because of the reduction of their temperature, which is achieved by the naturally circulating air.

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

PubMed

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

2016-06-01

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

Image-guided intervention in the human bile duct using scanning fiber endoscope system

NASA Astrophysics Data System (ADS)

Seibel, Eric J.; Jo, Javier A.; Melville, C. David; Johnston, Richard S.; Naumann, Christopher R.; Saunders, Michael D.

2012-01-01

Bile duct cancers are increasing in frequency while being difficult to diagnose. Currently available endoscopic imaging devices used in the biliary tree are low resolution with poor image quality, leading to inadequate evaluation of indeterminate biliary strictures. However, a new ultrathin and flexible cholangioscope system has been successfully demonstrated in a human subject. This mini-cholangioscope system uses a scanning fiber endoscope (SFE) as a forward-imaging guidewire, dimensions of 1.2-mm diameter and 3-m length. Full color video (500-line resolution at 30Hz) is the standard SFE imaging mode using spiral scanning of red, green, and blue laser light at low power. Image-guided operation of the biopsy forceps was demonstrated in healthy human bile ducts with and without saline flushing. The laser-based video imaging can be switched to various modes to enhance tissue markers of disease, such as widefield fluorescence and enhanced spectral imaging. In parallel work, biochemical discrimination of tissue health in pig bile duct has been accomplished using fiberoptic delivery of pulsed UV illumination and time-resolved autofluorescence spectroscopic measurements. Implementation of time-resolved fluorescence spectroscopy for biochemical assessment of the bile duct wall is being done through a secondary endoscopic channel. Preliminary results indicate that adequate SNR levels (> 30 dB) can be achieved through a 50 micron fiber, which could serve as an optical biopsy probe. The SFE is an ideal mini-cholangioscope for integration of both tissue and molecular specific image contrast in the future. This will provide the physician with unprecedented abilities to target biopsy locations and perform endoscopically-guided therapies.

The Environmental Assessment and Management (TEAM) Guide: West Virginia Supplement

DTIC Science & Technology

2010-01-01

WVCSR 45-21-19) [Citation Revised January 2008]. • Paper Coating Line - a web coating line where coating is applied to paper . Printing presses are...from a ny stack, pi pe, a ir pol lution c ontrol de vice, or f rom a ny ot her equipment or facilities associated with a c hemical processing unit...to, hoods, ducts, fans, booths, ovens, dryers , e tc.) that contains, collects, and transports an air pollutant to a control device (WVCSR 45-21-2.9

Space platform utilities distribution study

NASA Technical Reports Server (NTRS)

Lefever, A. E.

1980-01-01

Generic concepts for the installation of power data and thermal fluid distribution lines on large space platforms were discussed. Connections with central utility subsystem modules and pallet interfaces were also considered. Three system concept study platforms were used as basepoints for the detail development. The tradeoff of high voltage low voltage power distribution and the impact of fiber optics as a data distribution mechanism were analyzed. Thermal expansion and temperature control of utility lines and ducts were considered. Technology developments required for implementation of the generic distribution concepts were identified.

Cross-Species Analysis of Nicotine-Induced Proteomic Alterations in Pancreatic Cells

PubMed Central

Paulo, Joao A.; Urrutia, Raul; Kadiyala, Vivek; Banks, Peter

2014-01-01

Background Toxic compounds in tobacco, such as nicotine, may have adversely affect pancreatic function. We aim to determine nicotine-induced protein alterations in pancreatic cells, which may reveal a link between nicotine exposure and pancreatic disease. Methods We compared the proteomic alterations induced by nicotine treatment in cultured pancreatic cells (mouse, rat and human stellate cells and human duct cells) using mass spectrometry-based techniques, specifically GeLC-MS/MS and spectral counting. Results We identified thousands of proteins in pancreatic cells, hundreds of which were identified exclusively or in higher abundance in either nicotine-treated or untreated cells. Inter-species comparisons of stellate cell proteins revealed several differentially-abundant proteins (in nicotine treated versus untreated cells) common among the 3 species. Proteins appearing in all nicotine-treated stellate cells include amyloid beta (A4), procollagen type VI alpha 1, integral membrane protein 2B,and Toll interacting protein. Conclusions Proteins which were differentially expressed upon nicotine treatment across cell lines, were enriched in certain pathways, including nAChR, cytokine, and integrin signaling. At this analytical depth, we conclude that similar pathways are affected by nicotine, but alterations at the protein level among stellate cells of different species vary. Further interrogation of such pathways will lead to insights into the potential effect of nicotine on pancreatic cells at the biomolecular level and the extension of this concept to the effect of nicotine on pancreatic disease. PMID:23456891

Induction of biliary cholangiocarcinoma cell apoptosis by 103Pd cholangial radioactive stent gamma-rays.

PubMed

He, Gui-jin; Sun, Dan-dan; Ji, Da-wei; Sui, Dong-ming; Yu, Fa-qiang; Gao, Qin-yi; Dai, Xian-wei; Gao, Hong; Jiang, Tao; Dai, Chao-liu

2008-06-05

In recent years, interventional tumor therapy, involving implantation of intra-cholangial metal stents through percutaneous trans-hepatic punctures, has provided a new method for treating cholangiocarcinoma. (103)Pd cholangial radioactive stents can concentrate high radioactive dosages into the malignant tumors and kill tumor cells effectively, in order to prevent re-stenosis of the lumen caused by a relapsed tumor. The aim of the present study was to investigate the efficacy of gamma-rays released by the (103)Pd biliary duct radioactive stent in treating cholangiocarcinoma via induction of biliary cholangiocarcinoma cell apoptosis. A group of biliary duct cancer cells was collectively treated with a dose of gamma-rays. Cells were then examined by the 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl terazolium-bromide (MTT) technique for determining the inhibition rate of the biliary duct cancer cells, as well as with other methods including electron microscopy, DNA agarose gel electrophoresis, and flow cytometry were applied for the evaluation of their morphological and biochemical characteristics. The growth curve and the growth inhibition rate of the cells were determined, and the changes in the ultrastructure of the cholangiocarcinoma cells and the DNA electrophoresis bands were examined under a UV-lamp. The gamma-ray released by (103)Pd inhibited cholangiocarcinoma cell growth, as demonstrated when the growth rate of the cells was stunned by a gamma-ray with a dosage larger than 197.321 MBq. Typical features of cholangiocarcinoma cell apoptosis were observed in the 197.321 MBq dosage group, while cell necrosis was observed when irradiated by a dosage above 245.865 MBq. DNA agarose gel electrophoresis results were different between the 197.321 MBq irradiation dosage group, the 245.865 MBq irradiation dosage group, and the control group. (103)Pd radioactive stents which provide a radioactive dosage of 197.321 MBq are effective in the treatment of cholangiocarcinoma; (103)Pd radioactive stents should be useful for the clinical treatment of cholangiocarcinoma.

Ultrastructure of the labrum and foregut of Derocheilocaris remanei (Crustacea, Mystacocarida).

PubMed

Herrera-Alvarez, Letizia; Fernández, Isabel; Benito, Jesús; Pardos, Fernando

1996-11-01

The cuticle-lined foregut of Derocheilocaris remanei consists of the mouth with its associated labrum, and an undifferentiated esophagus. It is separated from the midgut by an esophageal valve. The labrum is a conspicuous structure moved by five pairs of muscles (four dorsoventral and one longitudinal). Four pairs of subcuticular glands open to its inner face forming two longitudinal, lateral rows of cuticular pores. Each secretory unit is composed of a glandular component (with one or two secretory cells), a neck cell, and a duct cell. In addition, a single gland cell opens mesially into the buccal cavity. The ventrally located mouth is a complex structure characterized by a filter-like system, a sensory organ, and epithelial cells with highly developed microvilli. The esophagus is a simple tube with a characteristic curvature following the mouth. It has a rounded cross section and a triradiate lumen. A layer of circular musculature surrounds this region. The end of the esophagus protrudes into the midgut lumen forming the so-called esophageal valve. The ultrastructural features of the foregut, with the presence of a mucus-trapping mechanism, a relatively well-developed filter system and associated structures and an esophagus lacking glands confirm the microphagic feeding habits of mystacocarids. © 1996 Wiley-Liss, Inc. Copyright © 1996 Wiley-Liss, Inc.

Structure and function of the digestive system of solen grandis dunker

NASA Astrophysics Data System (ADS)

Sheng, Xiuzhen; Zhan, Wenbin; Ren, Sulian

2003-10-01

Structure and function of the digestive system of a bivalve mollusc, Solen grandis, were studied using light microscopy and histochemical methods. The wall of digestive tube consists of four layers: the mucosal epithelium, connective tissue, muscular and fibrosa or serosa (only in the portion of rectum) from the inner to the outer. The ciliated columnar epithelial cells, dispersed by cup-shaped mucous cells, rest on a thin base membrane. There are abundant blood spaces in connective tissue layer. The digestive diverticula are composed of multi-branched duct and digestive tubules. The digestive tubules are lined with digestive and basophilic secretory cells, and surrounded by a layer of smooth muscle fibers and connective tissues. Activities of acid and alkaline phosphatases, esterase and lipase are detected in the digestive cells, and the epithelia of stomach and intestine, suggesting that these cells are capable of intracellular digesting of food materials and absorbing. Besides, acid phosphatase and esterase activities are present in the posterior portion of esophagus. Phagocytes are abundant in blood spaces and the lumens of stomach and intestine, containing brown granules derived from the engulfed food materials. The present work indicates that phagocytes play important roles in ingestion and digestion of food materials, which is supported as well by the activities of acid phosphatase, esterase and lipase detected in blood spaces.

Simulation System for Training in Laparoscopic Surgery

NASA Technical Reports Server (NTRS)

Basdogan, Cagatay; Ho, Chih-Hao

2003-01-01

A computer-based simulation system creates a visual and haptic virtual environment for training a medical practitioner in laparoscopic surgery. Heretofore, it has been common practice to perform training in partial laparoscopic surgical procedures by use of a laparoscopic training box that encloses a pair of laparoscopic tools, objects to be manipulated by the tools, and an endoscopic video camera. However, the surgical procedures simulated by use of a training box are usually poor imitations of the actual ones. The present computer-based system improves training by presenting a more realistic simulated environment to the trainee. The system includes a computer monitor that displays a real-time image of the affected interior region of the patient, showing laparoscopic instruments interacting with organs and tissues, as would be viewed by use of an endoscopic video camera and displayed to a surgeon during a laparoscopic operation. The system also includes laparoscopic tools that the trainee manipulates while observing the image on the computer monitor (see figure). The instrumentation on the tools consists of (1) position and orientation sensors that provide input data for the simulation and (2) actuators that provide force feedback to simulate the contact forces between the tools and tissues. The simulation software includes components that model the geometries of surgical tools, components that model the geometries and physical behaviors of soft tissues, and components that detect collisions between them. Using the measured positions and orientations of the tools, the software detects whether they are in contact with tissues. In the event of contact, the deformations of the tissues and contact forces are computed by use of the geometric and physical models. The image on the computer screen shows tissues deformed accordingly, while the actuators apply the corresponding forces to the distal ends of the tools. For the purpose of demonstration, the system has been set up to simulate the insertion of a flexible catheter in a bile duct. [As thus configured, the system can also be used to simulate other endoscopic procedures (e.g., bronchoscopy and colonoscopy) that include the insertion of flexible tubes into flexible ducts.] A hybrid approach has been followed in developing the software for real-time simulation of the visual and haptic interactions (1) between forceps and the catheter, (2) between the forceps and the duct, and (3) between the catheter and the duct. The deformations of the duct are simulated by finite-element and modalanalysis procedures, using only the most significant vibration modes of the duct for computing deformations and interaction forces. The catheter is modeled as a set of virtual particles uniformly distributed along the center line of the catheter and connected to each other via linear and torsional springs and damping elements. The interactions between the forceps and the duct as well as the catheter are simulated by use of a ray-based haptic-interaction- simulating technique in which the forceps are modeled as connected line segments.

Fibroblast growth factor receptor inhibition induces loss of matrix MCL1 and necrosis in cholangiocarcinoma.

PubMed

Kabashima, Ayano; Hirsova, Petra; Bronk, Steven F; Hernandez, Matthew C; Truty, Mark J; Rizvi, Sumera; Kaufmann, Scott H; Gores, Gregory J

2018-03-08

Myeloid cell leukemia 1 (MCL1), a prosurvival member of the BCL2 protein family, has a pivotal role in human cholangiocarcinoma (CCA) cell survival. We previously reported that fibroblast growth factor receptor (FGFR) signalling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays. Mitochondrial oxidative metabolism was examined using a XF24 extracellular flux analyser. The efficiency of FGFR inhibition in patient-derived xenografts (PDX) was also assessed. CCA cells expressed two species of MCL1, a full-length form localised to the outer mitochondrial membrane, and an N terminus-truncated species compartmentalised within the mitochondrial matrix. The pan-FGFR inhibitor LY2874455 induced non-apoptotic cell death in the CCA cell lines associated with cellular depletion of both MCL1 species. The cell death was accompanied by failure of mitochondrial oxidative metabolism and was most consistent with necrosis. Enforced expression of N terminus-truncated MCL1 targeted to the mitochondrial matrix, but not full-length MCL1 targeted to the outer mitochondrial membrane, rescued cell death and mitochondrial function. LY2874455 treatment of PDX-bearing mice was associated with tumour cell loss of MCL1 and cell necrosis. FGFR inhibition induces loss of matrix MCL1, resulting in cell necrosis. These observations support a heretofore unidentified, alternative MCL1 survival function, namely prevention of cell necrosis, and have implications for treatment of human CCA. Herein, we report that therapeutic inhibition of a cell receptor expressed by bile duct cancer cells resulted in the loss of a critical survival protein termed MCL1. Cellular depletion of MCL1 resulted in the death of the cancer cells by a process characterised by cell rupture. Cell death by this process can stimulate the immune system and has implications for combination therapy using receptor inhibition with immunotherapy. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Adult human pancreas-derived cells expressing stage-specific embryonic antigen 4 differentiate into Sox9-expressing and Ngn3-expressing pancreatic ducts in vivo.

PubMed

Lee, Song; Lee, Chan Mi; Kim, Song Cheol

2016-11-11

Tissue-specific stem/progenitor cells are found in various adult tissues and may have the capacity for lineage-specific differentiation, facilitating applications in autologous transplantation. Stage-specific embryonic antigen 4 (SSEA-4), an early embryonic glycolipid antigen, is expressed in cells derived from adult human pancreas exocrine tissue. Here, we examined the characteristics and lineage-specific differentiation capacity of SSEA-4 + cells. Human adult partial pancreas tissues were obtained from different donors and cultured in vitro. SSEA-4 + and CA19-9 + cells were isolated from adult human pancreas exocrine cells using magnetic-activated cell sorting, and gene expression was validated by quantitative polymerase chain reaction. To confirm in-vivo differentiation, SSEA-4 + and CA19-9 + cells were transplanted into the dorsal subcutaneous region of mice. Finally, morphological features of differentiated areas were confirmed by immunostaining and morphometric analysis. SSEA-4-expressing cells were detected in isolated pancreas exocrine cells from adult humans. These SSEA-4 + cells exhibited coexpression of CA19-9, a marker of pancreatic duct cells, but not amylase expression, as shown by immunostaining and flow cytometry. SSEA-4 + cells exhibited higher relative expression of Oct4, Nanog, Klf4, Sox2, and c-Myc mRNAs than CA19-9 + cells. Pancreatic intralobular ducts (PIDs) were generated from SSEA-4 + or CA19-9 + cells in vivo at 5 weeks after transplantation. However, newly formed PIDs from CA19-9 + cells were less abundant and showed an incomplete PID morphology. In contrast, newly formed PIDs from SSEA-4 + cells were abundant in the transplanted area and showed a crowded morphology, typical of PIDs. Sox9 and Ngn3, key transcription factors associated with pancreatic development and regeneration, were expressed in PIDs from SSEA-4 + cells. SSEA-4-expressing cells in the adult human pancreas may have the potential for regeneration of the pancreas and may be used as a source of stem/progenitor cells for pancreatic cell lineage-specific differentiation.

Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

PubMed Central

Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

2017-01-01

Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres. After pancreatic transplantation, mutant clones form lesions histologically similar to native PanINs, including prominent stromal responses. Gene expression profiling reveals molecular similarities of mutant clones with native PanINs, and identifies potential PanIN biomarker candidates including Neuromedin U, a circulating peptide hormone. Prospective reconstitution of human PanIN development from primary cells provides experimental opportunities to investigate pancreas cancer development, progression and early-stage detection. PMID:28272465

A Comparative Immunohistochemical Study of Anal Canal Epithelium in Humans and Swine, Focusing on the Anal Transitional Zone Epithelium and the Anal Glands.

PubMed

Muranaka, Futoshi; Nakajima, Tomoyuki; Iwaya, Mai; Ishii, Keiko; Higuchi, Kayoko; Ogiwara, Naoko; Miyagawa, Shinichi; Ota, Hiroyoshi

2018-05-01

To better understand the cellular origins and differentiation of anal canal epithelial neoplasms, the immunohistochemical profiles of the anal canal epithelium in humans and swine were evaluated. Formalin-fixed tissue sections were immunostained for mucin (MUC: MUC2, MUC5AC, MUC5B), desmoglein 3 (DGS3), p63, CDX2, SOX2, and α-smooth muscle actin (α-SMA). The anal transitional zone (ATZ) epithelium covered the anal sinus and consisted of a stratified epithelium with mucous cells interspersed within the surface lining. Anal glands opened into the anal sinus. Ducts and acini of intraepithelial or periepithelial mucous type were the main structures of human anal glands, whereas those of swine were compound tubuloacinar mixed glands. Distal to the ATZ epithelium, non-keratinized stratified squamous epithelium merged with the keratinized stratified squamous epithelium of the perianal skin. MUC5AC expression predominated over MUC5B expression in the ATZ epithelium, while MUC5B expression was higher in the anal glands. SOX2 was positive in the ATZ epithelium, anal glands, and squamous epithelium except in the perianal skin. In humans, DGS3 was expressed in the ATZ epithelium, anal gland ducts, and squamous epithelium. p63 was detected in the ATZ epithelium, anal glands, and squamous epithelium. Myoepithelial cells positive for α-SMA and p63 were present in the anal glands of swine. Colorectal columnar cells were MUC5B + /MUC2 + /CDX2 + /MUC5AC - /SOX2 - . The ATZ epithelium seems to be a distinctive epithelium, with morphological and functional features allowing smooth defecation. The MUC5AC + /SOX2 + /MUC2 - /CDX2 - profile of the ATZ epithelium and anal glands is a useful feature for diagnosing adenocarcinoma arising from these regions. Anat Rec, 301:796-805, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Pathological Studies of “Sudden Death Syndrome” in Broiler Chickens

PubMed Central

Ononiwu, J.C.; Thomson, R.G.; Carlson, H.C.; Julian, R.J.

1979-01-01

Sudden death syndrome usually occurs in heavy, fast-growing and healthy-looking broilers. Most of the affected birds are males. The characteristic necropsy changes are seen in well-fleshed broilers with edema and generalized pulmonary congestion, recently ingested feed in the crop and gizzard, distended intestine with creamy content and empty gall bladder. The liver and kidneys are slightly enlarged and the latter have patchy areas of subcapsular hemorrhage. The heart contains clotted blood in the atria but the ventricles are often empty and the left ventricle in particular assumes a hypertrophied appearance. Microscopic examination of heart muscle reveals degeneration of fibers, separation of cardiac muscle fibers by edema and infiltration of heterophils. The lungs have severe vascular congestion, inflammatory cell infiltration in the mucosa of the secondary bronchi and edema fluid in the tertiary bronchi and interlobular connective tissue. The liver has moderate bile duct hyperplasia, periportal hepatitis and mononuclear cell infiltration adjacent to bile ducts which possibly leads to bile duct constriction. The kidneys have subcapsular and parenchymatous hemorrhage. ImagesFIGURE 1.FIGURE 2. PMID:436100

The physiology of a local renin-angiotensin system in the pancreas.

PubMed

Leung, Po Sing

2007-04-01

The systemic renin-angiotensin system (RAS) plays an important role in regulating blood pressure, electrolyte and fluid homeostasis. However, local RASs also exist in diverse tissues and organs, where they play a multitude of autocrine, paracrine and intracrine physiological roles. The existence of a local RAS is now recognized in pancreatic acinar, islet, duct, endothelial and stellate cells, the expression of which is modulated in response to physiological and pathophysiological stimuli such as hypoxia, pancreatitis, islet transplantation, hyperglycaemia, and diabetes mellitus. This pancreatic RAS has been proposed to have important endocrine and exocrine roles in the pancreas, regulating local blood flow, duct cell sodium bicarbonate secretion, acinar cell digestive enzyme secretion, islet beta-cell (pro)insulin biosynthesis, and thus, glucose-stimulated insulin release, delta-cell somatostatin secretion, and pancreatic cell proliferation and differentiation. It may further mediate oxidative stress-induced cell inflammation, apoptosis and fibrosis. Further exploration of this system would probably offer new insights into the pathogenesis of pancreatitis, diabetes, cystic fibrosis and pancreatic cancer formation. New therapeutic targets and strategies might thus be suggested.

The physiology of a local renin–angiotensin system in the pancreas

PubMed Central

Leung, Po Sing

2007-01-01

The systemic renin–angiotensin system (RAS) plays an important role in regulating blood pressure, electrolyte and fluid homeostasis. However, local RASs also exist in diverse tissues and organs, where they play a multitude of autocrine, paracrine and intracrine physiological roles. The existence of a local RAS is now recognized in pancreatic acinar, islet, duct, endothelial and stellate cells, the expression of which is modulated in response to physiological and pathophysiological stimuli such as hypoxia, pancreatitis, islet transplantation, hyperglycaemia, and diabetes mellitus. This pancreatic RAS has been proposed to have important endocrine and exocrine roles in the pancreas, regulating local blood flow, duct cell sodium bicarbonate secretion, acinar cell digestive enzyme secretion, islet beta-cell (pro)insulin biosynthesis, and thus, glucose-stimulated insulin release, delta-cell somatostatin secretion, and pancreatic cell proliferation and differentiation. It may further mediate oxidative stress-induced cell inflammation, apoptosis and fibrosis. Further exploration of this system would probably offer new insights into the pathogenesis of pancreatitis, diabetes, cystic fibrosis and pancreatic cancer formation. New therapeutic targets and strategies might thus be suggested. PMID:17218353

Zebrafish no isthmus reveals a role for pax2.1 in tubule differentiation and patterning events in the pronephric primordia.

PubMed

Majumdar, A; Lun, K; Brand, M; Drummond, I A

2000-05-01

Pax genes are important developmental regulators and function at multiple stages of vertebrate kidney organogenesis. In this report, we have used the zebrafish pax2.1 mutant no isthmus to investigate the role for pax2.1 in development of the pronephros. We demonstrate a requirement for pax2.1 in multiple aspects of pronephric development including tubule and duct epithelial differentiation and cloaca morphogenesis. Morphological analysis demonstrates that noi(- )larvae specifically lack pronephric tubules while glomerular cell differentiation is unaffected. In addition, pax2.1 expression in the lateral cells of the pronephric primordium is required to restrict the domains of Wilms' tumor suppressor (wt1) and vascular endothelial growth factor (VEGF) gene expression to medial podocyte progenitors. Ectopic podocyte-specific marker expression in pronephric duct cells correlates with loss of expression of the pronephric tubule and duct-specific markers mAb 3G8 and a Na(+)/K(+) ATPase (&agr;)1 subunit. The results suggest that the failure in pronephric tubule differentiation in noi arises from a patterning defect during differentiation of the pronephric primordium and that mutually inhibitory regulatory interactions play an important role in defining the boundary between glomerular and tubule progenitors in the forming nephron.

IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth

PubMed Central

Ayars, Michael; O’Sullivan, Eileen; Macgregor-Das, Anne; Shindo, Koji; Kim, Haeryoung; Borges, Michael; Yu, Jun; Hruban, Ralph H.; Goggins, Michael

2017-01-01

Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNA-sequencing analysis of laser capture microdissected PanINs and normal pancreatic duct cells to identify differentially expressed genes between PanINs and normal pancreatic duct, and between low-grade and high-grade PanINs. One of the most highly overexpressed transcripts identified in PanIN is interleukin-2 receptor subunit gamma (IL2RG) encoding the common gamma chain, IL2Rγ. CRISPR-mediated knockout of IL2RG in orthotopically implanted pancreatic cancer cells resulted in attenuated tumor growth in mice and reduced JAK3 expression in orthotopic tumors. These results indicate that IL2Rγ/JAK3 signaling contributes to pancreatic cancer cell growth in vivo. PMID:29137350

Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function.

PubMed

Drummond, I A; Majumdar, A; Hentschel, H; Elger, M; Solnica-Krezel, L; Schier, A F; Neuhauss, S C; Stemple, D L; Zwartkruis, F; Rangini, Z; Driever, W; Fishman, M C

1998-12-01

The zebrafish pronephric kidney provides a simplified model of nephron development and epithelial cell differentiation which is amenable to genetic analysis. The pronephros consists of two nephrons with fused glomeruli and paired pronephric tubules and ducts. Nephron formation occurs after the differentiation of the pronephric duct with both the glomeruli and tubules being derived from a nephron primordium. Fluorescent dextran injection experiments demonstrate that vascularization of the zebrafish pronephros and the onset of glomerular filtration occurs between 40 and 48 hpf. We isolated fifteen recessive mutations that affect development of the pronephros. All have visible cysts in place of the pronephric tubule at 2-2.5 days of development. Mutants were grouped in three classes: (1) a group of twelve mutants with defects in body axis curvature and manifesting the most rapid and severe cyst formation involving the glomerulus, tubule and duct, (2) the fleer mutation with distended glomerular capillary loops and cystic tubules, and (3) the mutation pao pao tang with a normal glomerulus and cysts limited to the pronephric tubules. double bubble was analyzed as a representative of mutations that perturb the entire length of the pronephros and body axis curvature. Cyst formation begins in the glomerulus at 40 hpf at the time when glomerular filtration is established suggesting a defect associated with the onset of pronephric function. Basolateral membrane protein targeting in the pronephric duct epithelial cells is also severely affected, suggesting a failure in terminal epithelial cell differentiation and alterations in electrolyte transport. These studies reveal the similarity of normal pronephric development to kidney organogenesis in all vertebrates and allow for a genetic dissection of genes needed to establish the earliest renal function.

Computation of transonic potential flow about 3 dimensional inlets, ducts, and bodies

NASA Technical Reports Server (NTRS)

Reyhner, T. A.

1982-01-01

An analysis was developed and a computer code, P465 Version A, written for the prediction of transonic potential flow about three dimensional objects including inlet, duct, and body geometries. Finite differences and line relaxation are used to solve the complete potential flow equation. The coordinate system used for the calculations is independent of body geometry. Cylindrical coordinates are used for the computer code. The analysis is programmed in extended FORTRAN 4 for the CYBER 203 vector computer. The programming of the analysis is oriented toward taking advantage of the vector processing capabilities of this computer. Comparisons of computed results with experimental measurements are presented to verify the analysis. Descriptions of program input and output formats are also presented.

Optimum wall impedance for spinning modes: A correlation with mode cut-off ratio

NASA Technical Reports Server (NTRS)

Rice, E. J.

1978-01-01

A correlating equation relating the optimum acoustic impedance for the wall lining of a circular duct to the acoustic mode cut-off ratio, is presented. The optimum impedance was correlated with cut-off ratio because the cut-off ratio appears to be the fundamental parameter governing the propagation of sound in the duct. Modes with similar cut-off ratios respond in a similar way to the acoustic liner. The correlation is a semi-empirical expression developed from an empirical modification of an equation originally derived from sound propagation theory in a thin boundary layer. This correlating equation represents a part of a simplified liner design method, based upon modal cut-off ratio, for multimodal noise propagation.

Correlated alterations in prostate basal cell layer and basement membrane

PubMed Central

Liu, Aijun; Wei, Lixin; Gardner, William A.; Deng, Chu-Xia; Man, Yan-Gao

2009-01-01

Our recent studies revealed that focal basal cell layer disruption (FBCLD) induced auto-immunoreactions represented a contributing factor for human prostate tumor progression and invasion. As the basement membrane surrounds and attaches to the basal cell layer, our current study assessed whether FBCLD would impact the physical integrity of the associated basement membrane. Paraffin sections from 25-human prostate tumors were subjected to double immunohistochemistry to simultaneously elucidate the basal cell layer and the basement membrane with corresponding biomarkers. The physical integrity of the basement membrane overlying FBCLD was examined to determine the extent of correlated alterations. Of a total of 89 FBCLD encountered, 76 (85 %) showed correlated alterations in the overlying basement membrane, which included distinct focal disruptions or fragmentations. In the remaining 13 (15%) FBCLD, the overlying basement membrane showed significant attenuation or reduction of the immunostaining intensity. The basement membrane in all or nearly all ducts or acini with p63 positive basal cells was substantially thicker and more uniform than that in ducts or acini without p63 positive basal cells, and also, a vast majority of the focal disruptions occurred near basal cells that lack p63 expression. These findings suggest that focal disruptions in the basal cell layer and alterations in the basement membrane are correlated events and that the physical and functional status of the basal cells could significantly impact the physical integrity of the overlying basement membrane. As the degradation of both the basal cell layer and the basement membrane is a pre-requisite for prostate tumor invasion or progression, ducts or acini with focally disrupted basal cell layer and basement membrane are likely at greater risk to develop invasive lesions. Thus, further elucidation of the specific molecules and mechanism associated with these events may lead to the development of a more effective alternative for repeat biopsy to monitor tumor progression and invasion. PMID:19343113

Accumulation of Clostridium perfringens epsilon-toxin in the mouse kidney and its possible biological significance.

PubMed

Tamai, Eiji; Ishida, Tetsuya; Miyata, Shigeru; Matsushita, Osamu; Suda, Hirofumi; Kobayashi, Shoji; Sonobe, Hiroshi; Okabe, Akinobu

2003-09-01

In this paper we show that Clostridium perfringens epsilon-toxin accumulates predominantly in the mouse kidney, where it is distributed mainly in glomeruli, capillaries, and collecting ducts. Although some pycnotic and exfoliated epithelial cells were observed in distal tubuli and collecting ducts, there were no findings indicative of severe renal injury. Bilateral nephrectomy increased the mouse lethality of the toxin, suggesting that the kidney contributes to the host defense against the lethal toxicity of epsilon-toxin.

15. ELECTRICAL REACTOR SHELVES, CONSTRUCTED OF CONCRETE IN THE BASEMENT ...

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

15. ELECTRICAL REACTOR SHELVES, CONSTRUCTED OF CONCRETE IN THE BASEMENT ALONG EAST WALL, WITH REACTOR PADS BEHIND FRAMED AND SCREENED CAGE, AND PORCELAIN-LINED CABLE DUCTS VISIBLE IN WALL NEAR FLOOR AT REAR - Bonneville Power Administration South Bank Substation, I-84, South of Bonneville Dam Powerhouse, Bonneville, Multnomah County, OR

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... The final waterline, in the final condition of sinkage, heel, and trim, must be below the lower edge...) Heel angle. The maximum angle of heel must not exceed 30 degrees. (c) Range of stability. Through an... lines may not be considered for reducing the angle of heel. Spaces joined by ducts of large cross...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... The final waterline, in the final condition of sinkage, heel, and trim, must be below the lower edge...) Heel angle. The maximum angle of heel must not exceed 30 degrees. (c) Range of stability. Through an... lines may not be considered for reducing the angle of heel. Spaces joined by ducts of large cross...

Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

ClinicalTrials.gov

2014-05-28

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

Culture of porcine hepatocytes or bile duct epithelial cells by inductive serum-free media

USDA-ARS?s Scientific Manuscript database

A serum-free, feeder-cell-dependent, selective culture system for the long-term culture of porcine hepatocytes or cholangiocytes was developed. Liver cells were isolated from 1 wk old pigs or young adult pigs (25 and 63 kg live weight) and were placed in primary culture on feeder-cell layers of mit...

Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium?

PubMed

Singhi, Aatur D; Norwood, Stephanie; Liu, Ta-Chiang; Sharma, Rajni; Wolfgang, Christopher L; Schulick, Richard D; Zeh, Herbert J; Hruban, Ralph H

2013-09-01

Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non-neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic transformation." In subsequent studies, these lesions were given the designation of "-oma," despite the relative lack of evidence supporting a neoplastic process. To characterize these lesions further, we examined the clinical, pathologic, and immunohistochemical features of 8 ACAs. The majority of patients were female (7 of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15 cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of acinar and ductal epithelium. Immunolabeling, including double-labeling for cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and acinar cells lining the cysts. In some areas, the cysts with patches of acinar and ductal differentiation formed larger locules with incomplete septa as they appeared to fuse with other cysts. In contrast, the unilocular cases were lined by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium. Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated invasive carcinoma were absent in all cases. In addition, we assessed the clonal versus polyclonal nature of ACAs, occurring in women, using X-chromosome inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases were informative and demonstrated a random X-chromosome inactivation pattern. Clinical follow-up information was available for all patients, and follow-up ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence or malignant transformation. We hypothesize that early lesions are marked by acinar dilatation that expands into and incorporates smaller ductules and later larger ducts. As the cysts increase in size, they fuse forming larger cysts. Later lesions demonstrate a unilocular cyst lined by predominantly acinar epithelium with scattered ductal cells. The term cystadenoma, with its neoplastic connotation, does not seem to accurately reflect the histologic, immunohistochemical, or molecular features of these lesions. We suggest readopting the term "acinar cystic transformation" until the non-neoplastic versus neoplastic origin of these lesions can be resolved.

Experiments in dilution jet mixing

NASA Technical Reports Server (NTRS)

Holdeman, J. D.; Srinivasan, R.; Berenfeld, A.

1983-01-01

Experimental results are presented on the mixing of a single row of jets with an isothermal mainstream in a straight duct, with flow and geometric variations typical of combustion chambers in gas turbine engines included. It is found that at a constant momentum ratio, variations in the density ratio have only a second-order effect on the profiles. A first-order approximation to the mixing of jets with a variable temperature mainstream can, it is found, be obtained by superimposing the jets-in-an-isothermal-crossflow and mainstream profiles. Another finding is that the flow area convergence, especially injection-wall convergence, significantly improves the mixing. For opposed rows of jets with the orifice cone centerlines in-line, the optimum ratio of orifice spacing to duct height is determined to be 1/2 of the optimum value for single injection at the same momentum ratio. For opposed rows of jets with the orifice centerlines staggered, the optimum ratio of orifice spacing to duct height is found to be twice the optimum value for single side injection at the same momentum ratio.

[Bile duct obstruction due to non-Hodkin's lymphoma in patients with HIV infection].

PubMed

Gómez-Domínguez, E; Rodríguez Serrano, D A; Mendoza, J; Iscar, T; Sarriá, C; García-Buey, L

2003-12-01

Acquired immune deficiency syndrome increases the risk of developing non-Hodgkin's B-cell lymphoma (NHL) (relative risk over 100). NHL tend to be high-grade and to affect the central nervous system and digestive tract. Biliary tract compression is usually due to external compression from enlarged lymph nodes, but is not usually the first manifestation.We describe 2 cases of bile duct obstruction secondary to NHL in patients diagnosed with HIV infection. Histological diagnosis of the lymphoma can be difficult but is necessary so that these patients do not undergo highly aggressive surgical treatment instead of chemotherapy, which currently produces the best results. Therefore, we emphasize the importance of including lymphomas in the differential diagnosis of bile duct obstruction in patients with HIV infection.

Investigation of the potential antimicrobial efficacy of sealants used in HVAC systems.

PubMed

Foarde, K K; VanOsdell, D W; Menetrez, M Y

2001-08-01

Recent experiments confirm field experience that duct cleaning alone may not provide adequate protection from regrowth of fungal contamination on fiberglass duct liner (FGDL). Current recommendations for remediation of fungally contaminated fiberglass duct materials specify complete removal of the materials. But removal of contaminated materials can be extremely expensive. Therefore, a common practice in the duct-cleaning industry is the postcleaning use of antimicrobial surface coatings with the implication that they may contain or limit regrowth. Little information is available on the efficacy of these treatments. This paper describes a study to evaluate whether three commercially available antimicrobial coatings, placed on a cleaned surface that 1 year previously had been actively growing microorganisms, would be able to prevent regrowth. The three coatings contained different active antimicrobial compounds. All three of the coatings were designed for use on heating, ventilation, and air conditioning (HVAC) system components or interior surfaces of lined and unlined duct systems. Coating I was a polyacrylate copolymer containing zinc oxide and borates. Coating II was an acrylic coating containing decabromodiphenyl oxide and antimony trioxide. Coating III was an acrylic primer containing a phosphated quaternary amine complex. The study included field and laboratory assessments. The three treatments were evaluated in an uncontrolled field setting in an actual duct system. The laboratory study broadened the field study to include a range of humidities under controlled conditions. Both static and dynamic chamber laboratory experiments were performed. The results showed that two of the three antimicrobial coatings limited the regrowth of fungal contamination, at least in the short term (the 3-month time span of the study); the third did not. Before use in the field, testing of the efficacy of antimicrobial coatings under realistic use conditions is recommended because antimicrobials have different baseline activities and interact differently with the substrate that contains them and their local environment.

New developments in diagnosis and non-surgical treatment of chronic pancreatitis.

PubMed

Inui, Kazuo; Yoshino, Junji; Miyoshi, Hironao; Yamamoto, Satoshi; Kobayashi, Takashi

2013-12-01

Chronic pancreatitis is progressive and irreversible, leading to digestive and absorptive disorders by destruction of the exocrine pancreas and to diabetes mellitus by destruction of the endocrine pancreas. When complications such as pancreatolithiasis and pseudocyst occur, elevated pancreatic ductal pressure exacerbates pain and induces other complications, worsening the patient's general condition. Combined treatment with extracorporeal shock-wave lithotripsy and endoscopic lithotripsy is a useful, minimally invasive, first-line treatment approach that can preserve pancreatic exocrine function. Pancreatic duct stenosis elevates intraductal pressure and favor both pancreatolithiasis and pseudocyst formation, making effective treatment vitally important. Endoscopic treatment of benign pancreatic duct stenosis stenting frequently decreases pain in chronic pancreatitis. Importantly, stenosis of the main pancreatic duct increases risk of stone recurrence after treatment of pancreatolithiasis. Recently, good results were reported in treating pancreatic duct stricture with a fully covered self-expandable metallic stent, which shows promise for preventing stone recurrence after lithotripsy in patients with pancreatic stricture. Chronic pancreatitis has many complications including pancreatic carcinoma, pancreatic atrophy, and loss of exocrine and endocrine function, as well as frequent recurrence of stones after treatment of pancreatolithiasis. As early treatment of chronic pancreatitis is essential, the new concept of early chronic pancreatitis, including characteristics findings in endoscopic ultrasonograms, is presented. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Outcomes of endo-radiological approach to management of bile leakage after right lobe living donor liver transplantation.

PubMed

Chok, Kenneth S H; Chan, Albert C Y; Sharr, William W; Cheung, Tan To; Fung, James Y Y; Chan, See Ching; Lo, Chung Mau

2016-01-01

Bile leakage is a major complication after right lobe living donor liver transplantation (RLDLT). It can result in significant morbidities and, occasionally, mortalities. Endo-radiology is a non-surgical means that has been used to manage this complication. This study reviews the outcomes of the endo-radiological approach to the management of bile leakage after RLDLT with duct-to-duct anastomosis (DDA) at a high-volume center. A retrospective study was conducted on all adult patients who received RLDLT at our center between January 2001 and December 2013. There were 496 RLDLTs performed during the study period. Only patients who had DDA as the only bile duct reconstruction method were included in the study. Twelve (3.7%) out of the 328 study subjects developed bile leakage after RLDLT. Six out of these 12 patients were successfully treated with the endo-radiological approach without the need for laparotomy. They had endoscopic retrograde cholangiography with stenting followed by percutaneous drainage of biloma. One of the 12 patients died from recurrence of hepatocellular carcinoma 37 months after transplantation. The remaining 11 patients are all alive. The endo-radiological approach should be the first-line management for bile leakage for selected patients with DDA as the bile duct reconstruction method. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Differentiation of benign and malignant hilar bile duct stenosis.

PubMed

Liu, Xiaolei; Yang, Zhiying; Tan, Haidong; Shao, Chen; Liu, Liguo; Si, Shuang; Xu, Li; Sun, Yongliang

2016-06-15

Failure to differentiate benign and malignant hilar bile duct stenosis may lead to inappropriate treatment. We retrospectively analyzed the methods for differentiation. A total of 53 patients with hilar bile duct stenosis were included, comprising 41 malignant cases (hilar cholangiocarcinoma) and 12 benign cases (six primary sclerosing cholangitis and six IgG4-associated sclerosing cholangitis). Data of clinical histories, laboratory tests, imaging studies, and liver pathologies were collected, and comparison was made between benign and malignant groups. Compared with malignant group, patients in the benign group were more likely to have multiorgan involvement of clinical histories (P < 0.001). There was no difference on bilirubin, liver enzyme, and serum tumor marker between the two groups, whereas serum IgG4 levels were higher in the benign group (P = 0.003). Patients in the benign group were more likely to have pancreatic changes (P < 0.001) and multiple-segmental bile duct stenosis (P < 0.001) on imaging. Compared with the malignant group, patients in the benign group were more likely to show severe periportal inflammation in noninvolved liver (P < 0.001), fibrosis around intrahepatic bile duct (P < 0.001), and more IgG4-positive plasma cells (P < 0.001) on liver pathology. Benign lesion should be considered for patients with history of multiorgan involvement, pancreas changes, or multiple-segmental bile duct stenosis on imaging. Liver biopsy could be helpful for differential diagnosis before surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Defects in hepatic Notch signaling result in disruption of the communicating intrahepatic bile duct network in mice.

PubMed

Sparks, Erin E; Perrien, Daniel S; Huppert, Kari A; Peterson, Todd E; Huppert, Stacey S

2011-05-01

Abnormal Notch signaling in humans results in Alagille syndrome, a pleiotropic disease characterized by a paucity of intrahepatic bile ducts (IHBDs). It is not clear how IHBD paucity develops as a consequence of atypical Notch signaling, whether by a developmental lack of bile duct formation, a post-natal lack of branching and elongation or an inability to maintain formed ducts. Previous studies have focused on the role of Notch in IHBD development, and demonstrated a dosage requirement of Notch signaling for proper IHBD formation. In this study, we use resin casting and X-ray microtomography (microCT) analysis to address the role of Notch signaling in the maintenance of formed IHBDs upon chronic loss or gain of Notch function. Our data show that constitutive expression of the Notch1 intracellular domain in bi-potential hepatoblast progenitor cells (BHPCs) results in increased IHBD branches at post-natal day 60 (P60), which are maintained at P90 and P120. By contrast, loss of Notch signaling via BHPC-specific deletion of RBP-J (RBP KO), the DNA-binding partner for all Notch receptors, results in progressive loss of intact IHBD branches with age. Interestingly, in RBP KO mice, we observed a reduction in bile ducts per portal vein at P60; no further reduction had occurred at P120. Thus, bile duct structures are not lost with age; instead, we propose a model in which BHPC-specific loss of Notch signaling results in an initial developmental defect resulting in fewer bile ducts being formed, and in an acquired post-natal defect in the maintenance of intact IHBD architecture as a result of irresolvable cholestasis. Our studies reveal a previously unappreciated role for Notch signaling in the post-natal maintenance of an intact communicating IHBD structure, and suggest that liver defects observed in Alagille syndrome patients might be more complex than bile duct paucity.

Defects in hepatic Notch signaling result in disruption of the communicating intrahepatic bile duct network in mice

PubMed Central

Sparks, Erin E.; Perrien, Daniel S.; Huppert, Kari A.; Peterson, Todd E.; Huppert, Stacey S.

2011-01-01

SUMMARY Abnormal Notch signaling in humans results in Alagille syndrome, a pleiotropic disease characterized by a paucity of intrahepatic bile ducts (IHBDs). It is not clear how IHBD paucity develops as a consequence of atypical Notch signaling, whether by a developmental lack of bile duct formation, a post-natal lack of branching and elongation or an inability to maintain formed ducts. Previous studies have focused on the role of Notch in IHBD development, and demonstrated a dosage requirement of Notch signaling for proper IHBD formation. In this study, we use resin casting and X-ray microtomography (microCT) analysis to address the role of Notch signaling in the maintenance of formed IHBDs upon chronic loss or gain of Notch function. Our data show that constitutive expression of the Notch1 intracellular domain in bi-potential hepatoblast progenitor cells (BHPCs) results in increased IHBD branches at post-natal day 60 (P60), which are maintained at P90 and P120. By contrast, loss of Notch signaling via BHPC-specific deletion of RBP-J (RBP KO), the DNA-binding partner for all Notch receptors, results in progressive loss of intact IHBD branches with age. Interestingly, in RBP KO mice, we observed a reduction in bile ducts per portal vein at P60; no further reduction had occurred at P120. Thus, bile duct structures are not lost with age; instead, we propose a model in which BHPC-specific loss of Notch signaling results in an initial developmental defect resulting in fewer bile ducts being formed, and in an acquired post-natal defect in the maintenance of intact IHBD architecture as a result of irresolvable cholestasis. Our studies reveal a previously unappreciated role for Notch signaling in the post-natal maintenance of an intact communicating IHBD structure, and suggest that liver defects observed in Alagille syndrome patients might be more complex than bile duct paucity. PMID:21282722

The role of lymph factors in lung injury, bone marrow suppression, and endothelial cell dysfunction in a primate model of trauma-hemorrhagic shock.

PubMed

Deitch, Edwin A; Forsythe, Raquel; Anjaria, Dev; Livingston, David H; Lu, Qi; Xu, Da-Zhong; Redl, Heinz

2004-09-01

Studies in rodent models of trauma-hemorrhagic shock (T/HS) have shown that factors contained in the intestinal lymph are responsible for acute lung injury and bone marrow suppression, and that they contribute to a systemic inflammatory state. Because results observed in rodent T/HS models may not fully reflect the response of injured patients, it is necessary to determine if these results can be replicated in primates before the institution of invasive studies in humans. Thus, the three goals of this study were to determine if diversion of thoracic duct lymph reduced T/HS-induced lung injury; to compare the biologic activity of thoracic duct lymph from baboons subjected to T/HS or trauma sham-shock (T/SS); and to compare the biologic activity and composition of plasma from baboons subjected to T/SS, T/HS, and T/HS with thoracic duct lymph drainage. Three groups of baboons were studied: T/SS plus lymph diversion via a thoracic duct catheter, T/HS, and T/HS plus lymph diversion (T/HS-LD). The trauma component consisted of a neck dissection with resection of the proximal clavicle plus a laparotomy. HS was to a mean arterial pressure of 40 mmHg and was maintained at 40 mmHg until the base excess reached -5 mEq or the total shock period reached 3 h. Volume resuscitation was carried out by reinfusing the shed blood plus crystalloids. Before, during, and after the T/HS or T/SS period, blood and lymph samples were obtained for analysis, and lung samples were harvested for measurement of lung wet-to-dry ratio at 5 h after the end of the shock period. Diversion of thoracic duct lymph prevented T/HS-induced lung injury as reflected in lung wet-to-dry weight ratios (T/SS = 4.6 +/- 0.5; T/HS+LD = 4.8 +/- 0.7; T/HS = 5.4 +/- 0.6; P < 0.05). Lymph from the T/HS group collected during the early postshock period was cytotoxic for human endothelial cells (HUVECs; 16% vs. 100% survival in T/SS lymph) and increased HUVEC monolayer permeability almost 2-fold (P < 0.01). T/HS lymph and plasma also suppressed red blood cell (erythroid burst-forming unit) and white blood cell (granulocyte-monocyte colony-forming unit) progenitor cell growth of human bone marrow to approximately 50% of control, whereas T/SS lymph and plasma were not suppressive (P < 0.05). Plasma cytokine levels were increased to a similar degree in the two T/HS groups. Thus, in a primate model of T/HS, gut-derived factors carried in the lymph potentiates lung injury and endothelial dysfunction, and suppresses bone marrow progenitor cell growth.

Histochemical carbonic anhydrase in rat inner medullary collecting duct

NASA Technical Reports Server (NTRS)

Kleinman, J. G.; Bain, J. L.; Fritsche, C.; Riley, D. A.

1992-01-01

Rat inner medullary collecting duct (IMCD) secretes substantial amounts of H+. However, carbonic anhydrase (CA), a concomitant of H+ secretion, has been generally reported absent in this segment. To reexamine this problem, we investigated CA and the morphological phenotypes of cells comprising the IMCD by CA histochemistry, using a modified Hansson technique with light and electron microscopy. Throughout the medulla, tubule cells exhibit histochemical CA activity. In the initial third of the inner medulla, a small proportion have features of intercalated cells and demonstrate some degree of CA activity. However, the majority population in the early portions of the IMCD appears to consist of principal cells. These also show CA staining of widely variable intensity, both among and within cells. A third cell type, previously called "IMCD cells", appears in the middle portion of the IMCD and is the only cell type present near the papilla tip. In contrast to previous reports, these "IMCD cells" have histochemical CA staining, also of highly variable intensity. These results demonstrate that stainable carbonic anhydrase to support acidification is present throughout the rat IMCD, both in intercalated cells and in some cells clearly not of this type. Therefore, the presence of CA is not specific for the intercalated cell type and suggests that other cell types may participate in acid secretion in IMCD.

Serine 269 phosphorylated aquaporin-2 is targeted to the apical membrane of collecting duct principal cells

PubMed Central

Moeller, Hanne B.; Knepper, Mark A.; Fenton, Robert A.

2012-01-01

Trafficking of the water channel aquaporin-2 to the apical plasma membrane of the collecting duct is mediated by arginine vasopressin, rendering the cell permeable to water. We recently identified a novel form of aquaporin-2 that is phosphorylated at serine-269 (pS269-AQP2). Using antibodies specific for this form of the water channel, we detected rat and mouse pS269-AQP2 in the connecting tubule and throughout the collecting duct system. Using confocal immunofluorescence microscopy with organelle-specific markers and immunogold electron microscopy, we found that pS269-AQP2 was found only on the apical plasma membrane of principal cells. In vasopressin-deficient Brattleboro rats, pS269-AQP2 was undetectable but dramatically increased in abundance after these rats were treated with [deamino-Cys-1, d-Arg-8]vasopressin (dDAVP). This increase occurred only at the apical plasma membrane, even after long-term dDAVP treatment. Following dDAVP there was a time-dependent redistribution of total aquaporin-2 from predominantly intracellular vesicles to the apical plasma membrane, clathrin-coated vesicles, early endosomal compartments, and lysosomes. However, pS269-AQP2 was found only on the apical plasma membrane at any time. Our results show that S269 phosphorylated aquaporin-2 is exclusively associated with the apical plasma membrane, where it escapes endocytosis to remain at the cell surface. PMID:18843259

Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.

PubMed

Kuo, Ying-Ju; Weinreb, Ilan; Perez-Ordonez, Bayardo

2013-07-01

Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.

Pulmonary response to inhaled Kevlar aramid synthetic fibers in rats.

PubMed

Lee, K P; Kelly, D P; Kennedy, G L

1983-11-01

Groups of male rats were exposed to specially prepared ultrafine Kevlar pulp fibers (du Pont's registered trademark for certain aramid fibers) at atmospheric concentrations of either 0.1, 0.5, 3.0, or 18 mg/m3 for 2 weeks. Rats were killed at 0 and 2 weeks and 3 and 6 months postexposure (PE) except the rats exposed to 18 mg/m3, which were killed 0, 4, and 14 days and 1, 3, and 6 months PE. Another group of male rats was exposed to 18 mg/m3 (respirable dust approximately 2.5 mg/m3) of commercial Kevlar fibers for 2 weeks and were killed at 0 and 2 weeks and 3 and 6 months PE. Inhaled ultrafine Kevlar fibers were mostly phagocytized by alveolar macrophages (dust cells) in the alveolar ducts and adjoining alveoli after exposure to either 0.1 or 0.5 micrograms/m3. Most dust cells had disappeared and lungs showed a normal appearance throughout 6 months PE. The pulmonary response almost satisfied the biological criteria for a nuisance dust. Rats exposed to 3 mg/m3 ultrafine Kevlar fibers revealed occasional patchy thickening of alveolar ducts with dust cells and inflammatory cells but with no collagen fibers deposited throughout 6 months PE. After exposure to 18 mg/m3 ultrafine Kevlar, the respiratory bronchioles, alveolar ducts, and adjoining alveoli showed granulomatous lesions with dust cells by 2 weeks PE. The granulomatous lesions converted to patchy fibrotic thickening with dust cells after 1 month PE. The fibrotic lesions were markedly reduced in cellularity, size, and numbers from 3 to 6 months PE but revealed networks of reticulum fibers with slight collagen fiber deposition.

Data integration in physiology using Bayes’ rule and minimum Bayes’ factors: deubiquitylating enzymes in the renal collecting duct

PubMed Central

Xue, Zhe; Chen, Jia-Xu; Zhao, Yue; Medvar, Barbara

2017-01-01

A major challenge in physiology is to exploit the many large-scale data sets available from “-omic” studies to seek answers to key physiological questions. In previous studies, Bayes’ theorem has been used for this purpose. This approach requires a means to map continuously distributed experimental data to probabilities (likelihood values) to derive posterior probabilities from the combination of prior probabilities and new data. Here, we introduce the use of minimum Bayes’ factors for this purpose and illustrate the approach by addressing a physiological question, “Which deubiquitylating enzymes (DUBs) encoded by mammalian genomes are most likely to regulate plasma membrane transport processes in renal cortical collecting duct principal cells?” To do this, we have created a comprehensive online database of 110 DUBs present in the mammalian genome (https://hpcwebapps.cit.nih.gov/ESBL/Database/DUBs/). We used Bayes’ theorem to integrate available information from large-scale data sets derived from proteomic and transcriptomic studies of renal collecting duct cells to rank the 110 known DUBs with regard to likelihood of interacting with and regulating transport processes. The top-ranked DUBs were OTUB1, USP14, PSMD7, PSMD14, USP7, USP9X, OTUD4, USP10, and UCHL5. Among these USP7, USP9X, OTUD4, and USP10 are known to be involved in endosomal trafficking and have potential roles in endosomal recycling of plasma membrane proteins in the mammalian cortical collecting duct. PMID:28039431

Data integration in physiology using Bayes' rule and minimum Bayes' factors: deubiquitylating enzymes in the renal collecting duct.

PubMed

Xue, Zhe; Chen, Jia-Xu; Zhao, Yue; Medvar, Barbara; Knepper, Mark A

2017-03-01

A major challenge in physiology is to exploit the many large-scale data sets available from "-omic" studies to seek answers to key physiological questions. In previous studies, Bayes' theorem has been used for this purpose. This approach requires a means to map continuously distributed experimental data to probabilities (likelihood values) to derive posterior probabilities from the combination of prior probabilities and new data. Here, we introduce the use of minimum Bayes' factors for this purpose and illustrate the approach by addressing a physiological question, "Which deubiquitylating enzymes (DUBs) encoded by mammalian genomes are most likely to regulate plasma membrane transport processes in renal cortical collecting duct principal cells?" To do this, we have created a comprehensive online database of 110 DUBs present in the mammalian genome (https://hpcwebapps.cit.nih.gov/ESBL/Database/DUBs/). We used Bayes' theorem to integrate available information from large-scale data sets derived from proteomic and transcriptomic studies of renal collecting duct cells to rank the 110 known DUBs with regard to likelihood of interacting with and regulating transport processes. The top-ranked DUBs were OTUB1, USP14, PSMD7, PSMD14, USP7, USP9X, OTUD4, USP10, and UCHL5. Among these USP7, USP9X, OTUD4, and USP10 are known to be involved in endosomal trafficking and have potential roles in endosomal recycling of plasma membrane proteins in the mammalian cortical collecting duct. Copyright © 2017 the American Physiological Society.

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands

PubMed Central

Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon

2015-01-01

Background Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. Objective To evaluate the basic physiological role of PAR-2 in skin. Methods We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Results Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Conclusion Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands. PMID:26273149

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands.

PubMed

Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon; Lee, Young Ho

2015-08-01

Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. To evaluate the basic physiological role of PAR-2 in skin. We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands.

Bilateral Leydig cell tumor in a six-year-old intersex goat affected by Polled Intersex Syndrome.

PubMed

Monteagudo, L V; Arruga, M V; Bonafonte, J I; Ordás, M; Whyte, A; Gallego, M; Bascuas, J A; Sierra, I

2008-01-01

A 6-year-old, sterile, Blanca Celtibérica breed adult doe was referred to our faculty. The doe had external female genitalia, a short anogenital distance, and normally shaped udders. Masculinization signs in the head shape and male behavior were also noted at the time of referral. Genetic analysis demonstrated normal 2n = 60 XX karyotype and an absence of the sex-determining region Y (SRY). The animal was homozygous for a DNA deletion responsible for the Polled Intersex Syndrome (PIS). A uterus and 2 uterine horns were present at the postmortem examination. Gartner's ducts and degenerated Wolffian derivatives persisted. There were 2 intra-abdominal testicle-like structures, one of which consisted of epididymal and deferent ducts. An advanced Leydig cell tumor, resulting in almost total destruction of the intratesticular structures, was also observed. Leydig cell tumors usually produce testosterone. Thus, these histologic findings are compatible with the evident virilization.

Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery

ClinicalTrials.gov

2018-01-05

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

40 CFR 260.10 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... electrochemical cells which is designed to receive, store, and deliver electric energy. An electrochemical cell is...) must be of integral design. To be of integral design, the combustion chamber and the primary energy...) are joined only by ducts or connections carrying flue gas is not integrally designed; however...

40 CFR 260.10 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... electrochemical cells which is designed to receive, store, and deliver electric energy. An electrochemical cell is...) must be of integral design. To be of integral design, the combustion chamber and the primary energy...) are joined only by ducts or connections carrying flue gas is not integrally designed; however...

Birth and death of human β-cells in pancreases from cadaver donors, autopsies, surgical specimens, and islets transplanted into mice.

PubMed

Caballero, Francisco; Siniakowicz, Karolina; Hollister-Lock, Jennifer; Duran, Luisa; Katsuta, Hitoshi; Yamada, Takatsugu; Lei, Ji; Deng, Shaoping; Westermark, Gunilla T; Markmann, James; Bonner-Weir, Susan; Weir, Gordon C

2014-02-01

There is great interest in the potential of the human endocrine pancreas for regeneration by β-cell replication or neogenesis. Our aim was to explore this potential in adult human pancreases and in both islet and exocrine tissue transplanted into mice. The design was to examine pancreases obtained from cadaver donors, autopsies, and fresh surgical specimens and compare these findings with those obtained from islet and duct tissue grafted into the kidney. Islets and exocrine tissue were transplanted into normoglycemic ICR-SCID mice and studied 4 and 14 weeks later. β-Cell replication, as assessed by double staining for insulin and Ki67, was 0.22 ± 0.03% at 4 weeks and 0.13 ± 0.03% at 14 weeks. In contrast, no evidence of β-cell replication could be found in 11 cadaver donor and 10 autopsy pancreases. However, Ki67 staining of β-cells in frozen sections obtained at surgery was comparable to that found in transplanted islets. Evidence for neogenesis in transplanted pancreatic exocrine tissue was supported by finding β-cells within the duct epithelium and the presence of cells double stained for insulin and cytokeratin 19 (CK19). However, β-cells within the ducts never constituted more than 1% of the CK19-positive cells. With confocal microscopy, 7 of 12 examined cells expressed both markers, consistent with a neogeneic process. Mice with grafts containing islet or exocrine tissue were treated with various combinations of exendin-4, gastrin, and epidermal growth factor; none increased β-cell replication or stimulated neogenesis. In summary, human β-cells replicate at a low level in islets transplanted into mice and in surgical pancreatic frozen sections, but rarely in cadaver donor or autopsy pancreases. The absence of β-cell replication in many adult cadaver or autopsy pancreases could, in part, be an artifact of the postmortem state. Thus, it appears that adult human β-cells maintain a low level of turnover through replication and neogenesis.

Birth and death of human β-cells in pancreas from cadaver donors, autopsies, surgical specimens, and islets transplanted into mice

PubMed Central

Caballero, Francisco; Siniakowicz, Karolina; Jennifer-Hollister-Lock; Duran, Luisa; Katsuta, Hitoshi; Yamada, Takatsugu; Lei, Ji; Deng, Shaoping; Westermark, Gunilla T.; Markmann, James; Bonner-Weir, Susan; Weir, Gordon C.

2013-01-01

There is great interest in the potential of the human endocrine pancreas for regeneration by β-cell replication or neogenesis. Our aim was to explore this potential in adult human pancreases and in both islet and exocrine tissue transplanted into mice. The design was to examine pancreases obtained from cadaver donors, autopsies and fresh surgical specimens and compare these findings with those obtained from islet and duct tissue grafted into the kidney. Islets and exocrine tissue were transplanted into normoglycemic ICR/SCID mice and studied 4 and 14 wk later. β-cell replication as assessed by double staining for insulin and Ki67 was 0.22 ± 0.03 % at 4 wk and 0.13 ± 0.03 % at 14 wk. In contrast, no evidence of β-cell replication could be found in 11 cadaver donor and 10 autopsy pancreases. However, Ki67 staining of β-cells in frozen sections obtained at surgery was comparable to that found in transplanted islets. Evidence for neogenesis in transplanted pancreatic exocrine tissue was supported by finding β-cells within the duct epithelium, and the presence of cells double stained for insulin and cytokeratin 19 (CK19). However, β-cells within the ducts never constituted more than 1% of the CK19 positive cells. With confocal microscopy, 7 of 12 examined cells expressed both markers, consistent with a neogeneic process. Mice with grafts containing islet or exocrine tissue were treated with various combinations exendin-4, gastrin and epidermal growth factor; none increased β-cell replication or stimulated neogenesis. In summary, human β-cells replicate at a low level in islets transplanted into mice and in surgical pancreatic frozen sections but rarely in cadaver donor or autopsy pancreases. The absence of β-cell replication in many adult cadaver or autopsy pancreases could, in part, be an artifact of the postmortem state. Thus, it appears that adult human β-cells maintain a low level of turnover through replication and neogenesis. PMID:23321263

DETAIL VIEW ON THE MAIN ASSEMBLY LEVEL OF A LADDER ...

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

DETAIL VIEW ON THE MAIN ASSEMBLY LEVEL OF A LADDER TO THE CATWALK AT COLUMN LINE AA-28 SHOWING VERTICAL MECHANICAL DUCT, RETURN AIR FLOOR GRILLE, STEEL INDUSTRIAL SASH WINDOWS AND CROSS BRACING OF SOUTH WALL. - Offutt Air Force Base, Glenn L. Martin-Nebraska Bomber Plant, Building D, Peacekeeper Drive, Bellevue, Sarpy County, NE

Pathfinder, v6 n2, Mar/Apr 2008. Strengthening NGA Partnerships Around the World

DTIC Science & Technology

2008-04-01

Office of International Affairs and Policy. What’s Next In fiscal year 2008, NGA plans to con- duct a gravity survey in an extremely remote and void...observer on Escudo de Veraguas Island. Perdue soon moved to Colombia as part of a team running a geodetic level line between Cali and Cartagena, walking

Gab1 regulates proliferation and migration through the PI3K/Akt signaling pathway in intrahepatic cholangiocarcinoma.

PubMed

Sang, Haiquan; Li, Tingting; Li, Hangyu; Liu, Jingang

2015-11-01

Intrahepatic cholangiocarcinoma is the second most common primary malignant tumor of the liver, and it originates from the intrahepatic biliary duct epithelium. Prognosis is poor due to lack of effective comprehensive treatments. In this study, we assessed the expression of Gab1, VEGFR-2, and MMP-9 in intrahepatic cholangiocarcinoma solid tumors by immunohistochemistry and determined whether their expression was associated with clinical and pathological features. We found that expression of Gab1, VEGFR-2, and MMP-9 was highly and positively correlated with each other and with lymph node metastasis and TNM stage in intrahepatic cholangiocarcinoma tissues. Interference of Gab1 and VEGFR-2 expression via siRNA in the intrahepatic cholangiocarcinoma cell line RBE resulted in decreased PI3K/Akt pathway activity. Inhibition of Gab1 and VEGFR-2 expression also caused decreased cell proliferation, cell cycle arrested in G1 phase, increased apoptosis, and decreased invasion in RBE cells. These results suggest that Gab1, VEGFR-2, and MMP-9 contribute significantly to the highly malignant behavior of intrahepatic cholangiocarcinoma. The regulation of growth, apoptosis, and invasion by Gab1 through the VEGFR-2/Gab1/PI3K/Akt signaling pathway may represent potential targets for improving the treatment of intrahepatic cholangiocarcinoma.

Microglandular adenosis of the breast: a deceptive and still misterious benign lesion.

PubMed

Foschini, Maria P; Eusebi, Vincenzo

2018-06-24

Microglandular adenosis of the breast (MA), a benign glandular proliferation, was originally described about 35years ago. The lesion, is constituted by small glands all of the same size. Glands are lined by one layer of cuboidal epithelial cells encircled by basal lamina without any evidence of interposed myoepithelial elements. Cells are positive for low weight keratins and S-100 protein and negative for ER, PR and HER 2. Since then, in the years, several malignant lesions all showing microglandular architecture have been regarded either as a precursor or an equivalent manifestation of MA. The latter has been associated to a large number of malignancies that include DCIS, LCIS, ademyoepithelioma, high grade basal like carcinoma, adenoid cystic carcinoma, matrix producing carcinoma, invasive duct carcinoma NOS, spindle cell carcinoma, not to mention acinic cell carcinoma. None of the above tumors were identical to MA. Differences mainly rested not only on the specific structure of the small glands but also on the cytological composition and immunohistochemical features of different lesions. Here a review of the features of MA together with the differential diagnosis with lesions showing microglandular structure is discussed. MA shows similarities with a lesion named microglandular hamartoma/adenosis (MH) of the nasal cavity. The relation of the two similar lesions is discussed. Copyright © 2018. Published by Elsevier Inc.

Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice.

PubMed

Ko, Kwang Suk; Tomasi, Maria Lauda; Iglesias-Ara, Ainhoa; French, Barbara A; French, Samuel W; Ramani, Komal; Lozano, Juan José; Oh, Pilsoo; He, Lina; Stiles, Bangyan L; Li, Tony W H; Yang, Heping; Martínez-Chantar, M Luz; Mato, José M; Lu, Shelly C

2010-12-01

Prohibitin 1 (PHB1) is a highly conserved, ubiquitously expressed protein that participates in diverse processes including mitochondrial chaperone, growth and apoptosis. The role of PHB1 in vivo is unclear and whether it is a tumor suppressor is controversial. Mice lacking methionine adenosyltransferase 1A (MAT1A) have reduced PHB1 expression, impaired mitochondrial function, and spontaneously develop hepatocellular carcinoma (HCC). To see if reduced PHB1 expression contributes to the Mat1a knockout (KO) phenotype, we generated liver-specific Phb1 KO mice. Expression was determined at the messenger RNA and protein levels. PHB1 expression in cells was varied by small interfering RNA or overexpression. At 3 weeks, KO mice exhibit biochemical and histologic liver injury. Immunohistochemistry revealed apoptosis, proliferation, oxidative stress, fibrosis, bile duct epithelial metaplasia, hepatocyte dysplasia, and increased staining for stem cell and preneoplastic markers. Mitochondria are swollen and many have no discernible cristae. Differential gene expression revealed that genes associated with proliferation, malignant transformation, and liver fibrosis are highly up-regulated. From 20 weeks on, KO mice have multiple liver nodules and from 35 to 46 weeks, 38% have multifocal HCC. PHB1 protein levels were higher in normal human hepatocytes compared to human HCC cell lines Huh-7 and HepG2. Knockdown of PHB1 in murine nontransformed AML12 cells (normal mouse hepatocyte cell line) raised cyclin D1 expression, increased E2F transcription factor binding to cyclin D1 promoter, and proliferation. The opposite occurred with PHB1 overexpression. Knockdown or overexpression of PHB1 in Huh-7 cells did not affect proliferation significantly or sensitize cells to sorafenib-induced apoptosis. Hepatocyte-specific PHB1 deficiency results in marked liver injury, oxidative stress, and fibrosis with development of HCC by 8 months. These results support PHB1 as a tumor suppressor in hepatocytes. Copyright © 2010 American Association for the Study of Liver Diseases.

Zonal hierarchy of differentiation markers and nestin expression during oval cell mediated rat liver regeneration.

PubMed

Koenig, Sarah; Probst, Irmelin; Becker, Heinz; Krause, Petra

2006-12-01

Oval cells constitute a heterogeneous population of proliferating progenitors found in rat livers following carcinogenic treatment (2-acetylaminofluorene and 70% hepatectomy). The aim of this study was to investigate the cellular pattern of various differentiation and cell type markers in this model of liver regeneration. Immunophenotypic characterisation revealed at least two subtypes emerging from the portal field. First, a population of oval cells formed duct-like structures and expressed bile duct (CD49f) as well as hepatocytic markers (alpha-foetoprotein, CD26). Second, a population of non-ductular oval cells was detected between and distally from the ductules expressing the neural marker nestin and the haematopoietic marker Thy1. Following oval cell isolation, a subset of the nestin-positive cells was shown to co-express hepatocytic and epithelial markers (albumin, CD26, pancytokeratin) and could be clearly distinguished from anti-desmin reactive hepatic stellate cells. The gene expression profiles (RT-PCR) of isolated oval cells and oval cell liver tissue were found to be similar to foetal liver (ED14). The present results suggest that the two oval cell populations are organised in a zonal hierarchy with a marker gradient from the inner (displaying hepatocytic and biliary markers) to the outer zone (showing hepatocytic and extrahepatic progenitor markers) of the proliferating progeny clusters.

Bronchobiliary Fistula Treated by Self-expanding ePTFE-Covered Nitinol Stent-Graft

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gandini, Roberto; Konda, Daniel; Tisone, Giuseppe

A 71-year-old man, who had undergone right hepatectomy extended to the caudate lobe with terminolateral Roux-en-Y left hepatojejunostomy for a Klatskin tumor, developed bilioptysis 3 weeks postoperatively due to bronchobiliary fistula. Percutaneous transhepatic cholangiography revealed a non-dilated biliary system with contrast medium extravasation to the right subphrenic space through a resected anomalous right posterior segmental duct. After initial unsuccessful internal-external biliary drainage, the fistula was sealed with a VIATORR covered self-expanding nitinol stent-graft placed with its distal uncovered region in the hepatojejunal anastomosis and the proximal ePTFE-lined region in the left hepatic duct. A 10-month follow-up revealed no recurrence ofmore » bilioptysis and confirmed the complete exclusion of the bronchobiliary fistula.« less

ARRANGEMENT FOR REPLACING FILTERS

DOEpatents

Blomgren, R.A.; Bohlin, N.J.C.

1957-08-27

An improved filtered air exhaust system which may be continually operated during the replacement of the filters without the escape of unfiltered air is described. This is accomplished by hermetically sealing the box like filter containers in a rectangular tunnel with neoprene covered sponge rubber sealing rings coated with a silicone impregnated pneumatic grease. The tunnel through which the filters are pushed is normal to the exhaust air duct. A number of unused filters are in line behind the filters in use, and are moved by a hydraulic ram so that a fresh filter is positioned in the air duct. The used filter is pushed into a waiting receptacle and is suitably disposed. This device permits a rapid and safe replacement of a radiation contaminated filter without interruption to the normal flow of exhaust air.

The diagnosis and management of pre-invasive breast disease: Flat epithelial atypia – classification, pathologic features and clinical significance

PubMed Central

Schnitt, Stuart J

2003-01-01

Flat epithelial atypia is a descriptive term that encompasses lesions of the breast terminal duct lobular units in which variably dilated acini are lined by one to several layers of epithelial cells, which are usually columnar in shape and which display low-grade cytologic atypia. Observational studies have suggested that at least some of these lesions may represent either a precursor of ductal carcinoma in situ (DCIS) or the earliest morphological manifestation of DCIS. In contrast, the limited available clinical follow-up data suggest that the risk of both local recurrence and progression of these lesions to invasive cancer is extremely low, supporting the notion that categorizing such lesions as 'clinging carcinoma' and managing them as if they were fully developed DCIS will result in overtreatment of many patients. Additional studies are needed to better understand the biological nature and clinical significance of these lesions. PMID:12927037

Calcified telangiectatic hyperplastic nodule associated with vascular malformation in a child: a case report.

PubMed

Marti, Josep; Trivedi, Anshu; D'Alessandro, Valentina; Roayaie, Sasan; Rosen, Ally; Arnon, Ronen; Thung, Swan

2015-04-01

This is a case report of an asymptomatic 4-year-old girl who was found to have a nodule at the lateral left lobe of the liver. She underwent transabdominal liver ultrasound and abdominal MRI that showed calcification and intense arterial enhancement but they failed to clearly exclude malignancy. The patient underwent an unremarkable laparoscopic wedge liver resection of the lesion because of its location and size. Pathological examination showed features compatible with a benign telangiectatic hyperplastic nodule with vascular malformation and calcification. CD34 immunostained the proliferative vascular lining cells while CK7 and CK19 highlighted the normal bile ducts present within the lesion. The diagnosis of a telangiectatic hyperplastic nodule associated with vascular malformation has been scarcely reported in children and our case shows for the first time that it can also present with calcifications.

Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid

PubMed Central

Wiemuth, Dominik; Sahin, Hacer; Lefèvre, Cathérine M.T.; Wasmuth, Hermann E.; Gründer, Stefan

2013-01-01

Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic acid, as agonists of rBASIC. Moreover, it seems that extracellular divalent cations stabilize the resting state of rBASIC, because removal of extracellular divalent cations opens the channel. In this addendum, we demonstrate that removal of extracellular divalent cations potentiates the activation of rBASIC by bile acids, suggesting an allosteric mechanism. Furthermore, we show that rBASIC is strongly activated by the anticholestatic bile acid ursodeoxycholic acid (UDCA), suggesting that BASIC might mediate part of the therapeutic effects of UDCA. PMID:23064163

Evolving concepts on regulation and function of renin in distal nephron

PubMed Central

Prieto, Minolfa C.; Gonzalez, Alexis A.

2012-01-01

Sustained stimulation of the intrarenal/intratubular renin–angiotensin system in a setting of elevated arterial pressure elicits renal vasoconstriction, increased sodium reabsorption, proliferation, fibrosis, and eventual renal injury. Activation of luminal AT1 receptors in proximal and distal nephron segments by local Ang II formation stimulates various transport systems. Augmented angiotensinogen (AGT) production by proximal tubule cells increases AGT secretion contributing to increased proximal Ang II levels and leading to spillover of AGT into the distal nephron segments, as reflected by increased urinary AGT excretion. The increased distal delivery of AGT provides substrate for renin, which is expressed in principal cells of the collecting tubule and collecting ducts, and is also stimulated by AT1 receptor activation. Renin and prorenin are secreted into the tubular lumen and act on the AGT delivered from the proximal tubule to form more Ang I. The catalytic actions of renin and or prorenin may be enhanced by binding to prorenin receptors on the intercalated cells or soluble prorenin receptor secreted into the tubular fluid. There is also increased luminal angiotensin converting enzyme in collecting ducts facilitating Ang II formation leading to stimulation of sodium reabsorption via sodium channel and sodium/chloride co-transporter. Thus, increased collecting duct renin contributes to Ang II-dependent hypertension by augmenting distal nephron intra-tubular Ang II formation leading to sustained stimulation of sodium reabsorption and progression of hypertension. PMID:22990760

47. ARAI. Interior view of operating wall of hot cell ...

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

47. ARA-I. Interior view of operating wall of hot cell in ARA-626. Note stands for operators at viewing windows. Manipulators with hand grips extend cables and other controls into hot cell through ducts above windows. Ineel photo no. 81-27. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

Microscopic anatomy of the lower respiratory tract of the grey short-tailed opossum (Monodelphis domestica).

PubMed

Cope, L A; Henry, R W; Reed, R B

2012-04-01

The respiratory tracts of seven grey short-tailed opossums were histologically examined. Six opossums were prepared by perfusion with buffered formalin. Opossum seven was perfused with gluteraldehyde. Samples taken from the respiratory passages and lungs of specimens 1-6 were stained with haematoxylin and eosin. A mixture of methylene and azure blue was used for specimen 7. The trachea and right and left principal bronchi are lined with a pseudostratified ciliated columnar epithelium with occasional goblet cells. The secondary and tertiary bronchi and the primary and secondary bronchioles are lined by a simple ciliated columnar epithelium. The terminal bronchioles and a portion of the respiratory bronchioles are lined by a simple ciliated cuboidal epithelium. The terminal portion of the respiratory bronchioles and the alveolar ducts are lined with simple squamous epithelium. Alveoli are lined by type I and II pneumocytes. Tracheal glands are present in the tela submucosa. The fibromusculocartilaginous tunic of the trachea consists of c-shaped cartilage rings and the trachealis muscle. A lamina muscularis mucosa begins in the intrapulmonary portion of the principal bronchus and continues into the respiratory bronchioles. Bronchial glands are present in the propria submucosa and tela submucosa of the principal bronchi. The musculocartilaginous tunic is localized to the extrapulmonary portion of the principal bronchus. The bronchial cartilages are irregular shaped plates and limited to the extrapulmonary portion of the principal bronchus. The visceral pleura is a simple squamous mesothelium covering the outer surface of the lung. © 2011 Blackwell Verlag GmbH.

Elastin Cables Define the Axial Connective Tissue System in the Murine Lung.

PubMed

Wagner, Willi; Bennett, Robert D; Ackermann, Maximilian; Ysasi, Alexandra B; Belle, Janeil; Valenzuela, Cristian D; Pabst, Andreas; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

2015-11-01

The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels. © 2015 Wiley Periodicals, Inc.

Early Palliative Care With Standard Care or Standard Care Alone in Improving Quality of Life of Patients With Incurable Lung or Non-colorectal Gastrointestinal Cancer and Their Family Caregivers

ClinicalTrials.gov

2017-04-19

Liver Cancer; Anxiety Disorder; Depression; Small Cell Lung Cancer; Extrahepatic Bile Duct Cancer; Malignant Mesothelioma; Pancreatic Cancer; Esophageal Cancer; Gastric Cancer; Non-small Cell Lung Cancer

Down-regulation of Gab1 inhibits cell proliferation and migration in hilar cholangiocarcinoma.

PubMed

Sang, Haiquan; Li, Tingting; Li, Hangyu; Liu, Jingang

2013-01-01

Hilar cholangiocarcinoma is a highly aggressive malignancy originating from the hilar biliary duct epithelium. Due to few effective comprehensive treatments, the prognosis of hilar cholangiocarcinoma is poor. In this study, immunohistochemistry was first used to detect and analyze the expression of Gab1, VEGFR-2, and MMP-9 in hilar cholangiocarcinoma solid tumors and the relationships to the clinical pathological features. Furthermore, Gab1 and VEGFR-2 siRNA were used to interfere the hilar cholangiocarcinoma cell line ICBD-1 and then detect the PI3K/Akt signaling pathway, MMP-9 levels and malignant biological behaviors of tumor cells. The data showed that 1. Gab1, VEGFR-2, and MMP-9 were highly expressed and positively correlated with each other in hilar cholangiocarcinoma tissues, which were related to lymph node metastasis and differentiation. 2. After Gab1 or VEGFR-2 siRNA interference, PI3K/Akt pathway activity and MMP-9 levels were decreased in ICBD-1 cells. At the same time, cell proliferation decreased, cell cycle arrested in G1 phase, apoptosis increased and invasion decreased. These results suggest that the expression of Gab1, VEGFR-2, and MMP-9 are significantly related to the malignant biological behavior of hilar cholangiocarcinoma. Gab1 regulates growth, apoptosis and invasion through the VEGFR-2/Gab1/PI3K/Akt signaling pathway in hilar cholangiocarcinoma cells and influences the invasion of tumor cells via MMP-9.

Down-Regulation of Gab1 Inhibits Cell Proliferation and Migration in Hilar Cholangiocarcinoma

PubMed Central

Sang, Haiquan; Li, Tingting; Li, Hangyu; Liu, Jingang

2013-01-01

Hilar cholangiocarcinoma is a highly aggressive malignancy originating from the hilar biliary duct epithelium. Due to few effective comprehensive treatments, the prognosis of hilar cholangiocarcinoma is poor. In this study, immunohistochemistry was first used to detect and analyze the expression of Gab1, VEGFR-2, and MMP-9 in hilar cholangiocarcinoma solid tumors and the relationships to the clinical pathological features. Furthermore, Gab1 and VEGFR-2 siRNA were used to interfere the hilar cholangiocarcinoma cell line ICBD-1 and then detect the PI3K/Akt signaling pathway, MMP-9 levels and malignant biological behaviors of tumor cells. The data showed that 1. Gab1, VEGFR-2, and MMP-9 were highly expressed and positively correlated with each other in hilar cholangiocarcinoma tissues, which were related to lymph node metastasis and differentiation. 2. After Gab1 or VEGFR-2 siRNA interference, PI3K/Akt pathway activity and MMP-9 levels were decreased in ICBD-1 cells. At the same time, cell proliferation decreased, cell cycle arrested in G1 phase, apoptosis increased and invasion decreased. These results suggest that the expression of Gab1, VEGFR-2, and MMP-9 are significantly related to the malignant biological behavior of hilar cholangiocarcinoma. Gab1 regulates growth, apoptosis and invasion through the VEGFR-2/Gab1/PI3K/Akt signaling pathway in hilar cholangiocarcinoma cells and influences the invasion of tumor cells via MMP-9. PMID:24312291

Salivary duct carcinoma treated with cetuximab-based targeted therapy: A case report.

PubMed

Kawahara, Kenta; Hiraki, Akimitsu; Yoshida, Ryoji; Arita, Hidetaka; Matsuoka, Yuichiro; Yamashita, Toshio; Koga, Kan-Ichi; Nagata, Masashi; Hirosue, Akiyuki; Fukuma, Daiki; Nakayama, Hideki

2017-06-01

Salivary duct carcinoma is a highly aggressive disease with a poor prognosis. Surgical resection is currently the only curative treatment, as there is no effective systemic therapy for this malignancy. Recently, trastuzumab has been shown to exhibit therapeutic efficacy in the treatment of salivary duct carcinoma; similarly, molecularly targeted agents, such as cetuximab, are expected to be useful for salivary duct carcinoma treatment. We herein describe the case of a 56-year-old man diagnosed with salivary duct carcinoma in the left submandibular region, with ipsilateral multiple metastases to the neck lymph nodes. Radical resection of the tumor and submandibular gland with neck dissection were performed. One month after radical surgery, computed tomography (CT) scans indicated metastasis in the lower lobe of the left lung. CT-guided transthoracic fine-needle aspiration biopsy revealed a single metastasis and lung metastasectomy was immediately performed. The tumor cells of the primary lesion and those of the lung metastasis were immunohistochemically positive for epidermal growth factor receptor. One month later, multiple right lung metastases appeared, and the patient was treated with cisplatin/5-fluorouracil (5-FU) chemotherapy plus cetuximab, achieving a complete radiographic response. However, multiple lung metastases developed during adjuvant weekly cetuximab monotherapy. Subsequently, treatment with S-1 and weekly cetuximab was initiated, and the multiple lung metastases have been maintained as stable disease for 5 months. To the best of our knowledge, this is the first report of cetuximab use for the treatment of salivary duct carcinoma. Although cisplatin/5-FU chemotherapy plus cetuximab was efficacious in treating the lung metastasis, cetuximab monotherapy was insufficient for controlling tumor growth.

Unique Aspects of Cryptochrome in Chronobiology and Metabolism, Pancreatic β-Cell Dysfunction, and Regeneration: Research into Cysteine414-Alanine Mutant CRY1.

PubMed

Okano, Satoshi

2016-01-01

Cryptochrome proteins (CRYs), which can bind noncovalently to cofactor (chromophore) flavin adenine dinucleotide (FAD), occur widely among organisms. CRYs play indispensable roles in the generation of circadian rhythm in mammals. Transgenic mice (Tg mice), ubiquitously expressing mouse CRY1 having a mutation in which cysteine414 (the zinc-binding site of CRY1) being replaced with alanine, display unique phenotypes in their circadian rhythms. Moreover, male Tg mice exhibit symptoms of diabetes characterized by beta-cell dysfunction, resembling human maturity onset diabetes of the young (MODY). The lowered proliferation of β -cells is a primary cause of age-dependent β -cell loss. Furthermore, unusually enlarged duct-like structures developed prominently in the Tg mice pancreases. The duct-like structures contained insulin-positive cells, suggesting neogenesis of β -cells in the Tg mice. This review, based mainly on the author's investigation of the unique features of Tg mice, presents reported results and recent findings related to molecular processes associated with mammalian cryptochromes, especially their involvement in the regulation of metabolism. New information is described with emphasis on the aspects of islet architecture, pancreatic β -cell dysfunction, and regeneration.

Adult bile duct strictures: differentiating benign biliary stenosis from cholangiocarcinoma.

PubMed

Nguyen Canh, Hiep; Harada, Kenichi

2016-12-01

Biliary epithelial cells preferentially respond to various insults under chronic pathological conditions leading to reactively atypical changes, hyperplasia, or the development of biliary neoplasms (such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and cholangiocarcinoma). Moreover, benign biliary strictures can be caused by a variety of disorders (such as IgG4-related sclerosing cholangitis, eosinophilic cholangitis, and follicular cholangitis) and often mimic malignancies, despite their benign nature. In addition, primary sclerosing cholangitis is a well-characterized precursor lesion of cholangiocarcinoma and many other chronic inflammatory disorders increase the risk of malignancies. Because of these factors and the changes in biliary epithelial cells, biliary strictures frequently pose a diagnostic challenge. Although the ability to differentiate neoplastic from non-neoplastic biliary strictures has markedly progressed with the advance in radiological modalities, brush cytology and bile duct biopsy examination remains effective. However, no single modality is adequate to diagnose benign biliary strictures because of the low sensitivity. Therefore, understanding the underlying causes by compiling the entire clinical, laboratory, and imaging data; considering the under-recognized causes; and collaborating between experts in various fields including cytopathologists with multiple approaches is necessary to achieve an accurate diagnosis.

[Nephrogenic diabetes insipidus].

PubMed

Velásquez-Jones, Luis; Medeiros-Domingo, Mara

The anti-diuretic hormone arginine-vasopressin (AVP) is released from the pituitary and regulates water reabsorption in the principal cells of the kidney collecting duct. Binding of AVP to the arginine-vasopressin receptor type-2 in the basolateral membrane leads to translocation of aquaporin-2 water channels to the apical membrane of the principal cells of the collecting duct, inducing water permeability of the membrane. This results in water reabsorption in the collecting duct of the nephron following an osmotic gradient. Nephrogenic diabetes insipidus is caused by partial or complete renal resistance to the effects of AVP. Congenital nephrogenic diabetes insipidus is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their urine. Acquired nephrogenic diabetes insipidus can be caused by electrolyte imbalances (e.g., hypercalcemia, hypokalemia), renal/extra-renal diseases and drugs (e.g., lithium toxicity). This article reviews the causes, clinical manifestations, diagnosis and treatment of patients with nephrogenic diabetes insipidus. Based on more in-depth mechanistic understanding, new therapeutic strategies are current being explored. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

The immunophenotypic relationship between the submucosal gland unit, columnar metaplasia and squamous islands in the columnar-lined oesophagus.

PubMed

Lörinc, Ester; Mellblom, Lennart; Öberg, Stefan

2015-12-01

To characterize the immunophenotypic relationship between the squamous and the glandular compartments in the oesophagus of patients with columnar-lined oesophagus (CLO). Eight tissue blocks from three oesophageal resection specimens from patients who underwent oesophagectomy for adenocarcinoma of the oesophagus were selected for immunohistochemical analysis. The markers of intestinal differentiation [CK20, CDX2 and MUC2] were all expressed in the expected pattern, solely in the glandular compartment of the resection specimens. CK4, CK17 and lysozyme were expressed in both the glandular and the squamous compartments. In addition, CK17 expression was found on both the squamous and glandular margins of the squamocolumnar transformation zones and in the submucosal gland (SMG) intraglandular and excretory ducts. There is an immunophenotypic relationship between the squamous and the glandular compartments of the CLO, with expression of lysozyme, CK4 and CK17 in both squamous and columnar cells. These overlapping immunophenotypes indicate similar differentiation paths, and link the SMG unit with the columnar metaplasia and the neosquamous islands in CLO. Our findings support the theory of a cellular origin of CLO and neosquamous islands from the SMG unit. © 2015 John Wiley & Sons Ltd.

Local immune response to primary infection and re-infection by Clonorchis sinensis in FVB mice.

PubMed

Kim, Eun-Min; Yu, Hak Sun; Jin, Yan; Choi, Min-Ho; Bae, Young Mee; Hong, Sung-Tae

2017-08-01

Although Clonorchis sinensis lives in the bile duct, few studies have investigated the local immune response in the liver and bile duct. To investigate the local immune response to C. sinensis, we investigated the activation and recruitment of various immune cells and cytokine levels in the liver and bile duct lymph nodes (BLN) in FVB mice after primary infection and re-infection. Male 4-week-old FVB mice were divided into 6 experimental groups: uninfected controls, primary infection lasting 1week (PI 1w), primary infection lasting 4weeks (PI 4w), praziquantel treatment after PI 4w (Tx), re-infection lasting 1week after Tx (RI 1w), and re-infection lasting 4weeks after Tx (RI 4w). Recovery rates were 80.0% and 73.0% in PI 1w and PI 4w mice, respectively, but significantly decreased during re-infection to 26.6% in RI 1w and 13.3% in RI 4w. This result suggested that the mice were resistant to re-infection. In the liver, Kupffer cells were augmented 70-fold in PI 1w mice (P<0.001). Kupffer cells expressed Th2-related cytokines (IL-10 and IL-13) during primary infection. In addition, serum levels of C. sinensis-specific IgG1 and IgG2a strongly increased in RI 1w mice. Secretion of C. sinensis-specific IgE reached a plateau at 4weeks after primary infection, and remained elevated in all infected groups. In conclusion, during infection with C. sinensis, Kupffer cells likely act as antigen-presenting cells, stimulating the Th2 cytokine production system. Copyright © 2016. Published by Elsevier B.V.

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

PubMed Central

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

2017-01-01

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

Computational Aerodynamic Simulations of an 840 ft/sec Tip Speed Advanced Ducted Propulsor Fan System Model for Acoustic Methods Assessment and Development

NASA Technical Reports Server (NTRS)

Tweedt, Daniel L.

2014-01-01

Computational Aerodynamic simulations of an 840 ft/sec tip speed, Advanced Ducted Propulsor fan system were performed at five different operating points on the fan operating line, in order to provide detailed internal flow field information for use with fan acoustic prediction methods presently being developed, assessed and validated. The fan system is a sub-scale, lownoise research fan/nacelle model that has undergone extensive experimental testing in the 9- by 15- foot Low Speed Wind Tunnel at the NASA Glenn Research Center, resulting in quality, detailed aerodynamic and acoustic measurement data. Details of the fan geometry, the computational fluid dynamics methods, the computational grids, and various computational parameters relevant to the numerical simulations are discussed. Flow field results for three of the five operating conditions simulated are presented in order to provide a representative look at the computed solutions. Each of the five fan aerodynamic simulations involved the entire fan system, excluding a long core duct section downstream of the core inlet guide vane. As a result, only fan rotational speed and system bypass ratio, set by specifying static pressure downstream of the core inlet guide vane row, were adjusted in order to set the fan operating point, leading to operating points that lie on a fan operating line and making mass flow rate a fully dependent parameter. The resulting mass flow rates are in good agreement with measurement values. The computed blade row flow fields for all five fan operating points are, in general, aerodynamically healthy. Rotor blade and fan exit guide vane flow characteristics are good, including incidence and deviation angles, chordwise static pressure distributions, blade surface boundary layers, secondary flow structures, and blade wakes. Examination of the computed flow fields reveals no excessive boundary layer separations or related secondary-flow problems. A few spanwise comparisons between computational and measurement data in the bypass duct show that they are in good agreement, thus providing a partial validation of the computational results.

40 CFR 63.1657 - Monitoring requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... pressure drop across each baghouse cell, or across the baghouse if it is not possible to monitor each cell individually, to ensure the pressure drop is within the normal operating range identified in the baghouse... detection system if the furnace primary and/or tapping emissions are ducted to a negative pressure baghouse...

Breast Cancer—Health Professional Version

Cancer.gov

The most common type of breast cancer is ductal carcinoma, which begins in the cells of the ducts. Breast cancer can also begin in the cells of a lobule and in other tissues of the breast. Find evidence-based information on breast cancer treatment, causes and prevention, genetics, screening, research, and statistics.

Basolateral membrane K+ channels in renal epithelial cells

PubMed Central

Devor, Daniel C.

2012-01-01

The major function of epithelial tissues is to maintain proper ion, solute, and water homeostasis. The tubule of the renal nephron has an amazingly simple structure, lined by epithelial cells, yet the segments (i.e., proximal tubule vs. collecting duct) of the nephron have unique transport functions. The functional differences are because epithelial cells are polarized and thus possess different patterns (distributions) of membrane transport proteins in the apical and basolateral membranes of the cell. K+ channels play critical roles in normal physiology. Over 90 different genes for K+ channels have been identified in the human genome. Epithelial K+ channels can be located within either or both the apical and basolateral membranes of the cell. One of the primary functions of basolateral K+ channels is to recycle K+ across the basolateral membrane for proper function of the Na+-K+-ATPase, among other functions. Mutations of these channels can cause significant disease. The focus of this review is to provide an overview of the basolateral K+ channels of the nephron, providing potential physiological functions and pathophysiology of these channels, where appropriate. We have taken a “K+ channel gene family” approach in presenting the representative basolateral K+ channels of the nephron. The basolateral K+ channels of the renal epithelia are represented by members of the KCNK, KCNJ, KCNQ, KCNE, and SLO gene families. PMID:22338089

TMEM16A regulates portal vein smooth muscle cell proliferation in portal hypertension.

PubMed

Zeng, Xi; Huang, Ping; Chen, Mingkai; Liu, Shiqian; Wu, Nannan; Wang, Fang; Zhang, Jing

2018-01-01

The aim of the present study was to elucidate the effect of transmembrane protein 16A (TMEM16A) on portal vein smooth muscle cell (PVSMC) proliferation associated with portal vein remodeling in portal hypertension (PHT). Sprague-Dawley rats were subjected to bile duct ligation to establish a rat model of liver cirrhosis and PHT. Sham-operated animals served as controls. At 8 weeks after bile duct ligation, the extent of liver fibrosis and the portal vein wall thickness were assessed using hematoxylin-eosin staining. The protein expression levels of TMEM16A, extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) in the portal vein were detected by immunohistochemistry and western blotting. In vitro , the lentivirus vectors were constructed and transfected into PVSMCs to upregulate the expression of TMEM16A. Isolated rat primary PVSMCs were treated with a small molecule inhibitor of TMEM16A, T16A-inhA01. Cell cycle was detected by flow cytometry. The activity of TMEM16A in the portal vein isolated from bile duct ligated rats was decreased, while the expression level of p-ERK1/2 was increased. However, in vitro , upregulation of TMEM16A promoted the proliferation PVSMCs, while inhibition of TMEM16A channels inhibited the proliferation of PVSMCs. The results indicated that TMEM16A contributes to PVSMCs proliferation in vitro , but in vivo , it may be a negative regulator of cell proliferation influenced by numerous factors.

Commandant’s International Technical Series. Volume 8. Fire Aboard the M.S. SCANDINAVIAN SEA on March 9, 1984. Technical Assessment

DTIC Science & Technology

1985-01-01

Bulkheads - 5/8" asbestos cement panels Ceilings - 3/8" asbestos cement panels Structural insulation - mineral wool Ducting and Hull Insulation-fibrous...glass/ mineral wool D6ryks - steel Linings - 3/4" and 5/8" asbestos cement panels Interior finish - melamine plastic laminate Furnishings - wood and

14. BUILDING NO. 445, PHYSICS LAB (FORMERLY GUN BAG LOADING), ...

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

14. BUILDING NO. 445, PHYSICS LAB (FORMERLY GUN BAG LOADING), LOOKING EAST AT SOUTHWEST END OF BUILDING. HVAC EQUIPMENT LOCATED OUTDOORS IN FOREGROUND. DUCTS CONDUCT HOT OR COLD AIR INDOORS. ROUND PIPES ARE INSULATED STEAM LINES. BUILDING NO. 448, ORDNANCE FACILITY, IN BACKGROUND. - Picatinny Arsenal, 400 Area, Gun Bag Loading District, State Route 15 near I-80, Dover, Morris County, NJ

40 CFR 86.109-94 - Exhaust gas sampling system; Otto-cycle vehicles not requiring particulate emission measurements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... concentration and total flow over the test period. (2) Vehicle tailpipe to CVS Duct. For methanol-fueled... proportional samples for the bag sample, and for methanol-fueled vehicles, the methanol sample (Figure B94-2... methanol-fueled vehicles, the sample lines for the methanol and formaldehyde samples are heated to prevent...

Adrenocortical and adrenomedullary homologs in eight species of adult and developing teleosts: morphology, histology, and immunohistochemistry.

PubMed

Grassi Milano, E; Basari, F; Chimenti, C

1997-12-01

Morphology, histology, and immunohistochemistry of the adrenocortical and adrenomedullary homologs (adrenal glands) of the following developing and adult teleosts were examined: Salmoniformes-Oncorhynchus mykiss (rainbow trout), Salmo trutta fario (brown trout), Coregonus lavaretus (white fish); Cyprinodontiformes-Gambusia affinis (mosquito fish). Perciformes-Dicentrarchus labrax (sea bass), Sparus aurata (sea bream), Diplodus sargus (white bream), Oblada melanura (saddled bream). The anatomical relationships of the gland with the renal system and venous vessels were also noted. In adults of all species steroidogenic and catecholaminergic chromaffin cells were found in the head kidney, which is pronephric in origin and subsequently transformed into a hematopoietic lymphatic organ. In Perciformes, chromaffin cells are distributed around the anterior and posterior cardinal veins and ducts of Cuvier; in Salmoniformes, around the posterior cardinal veins and in the hematopoietic tissue; and in G. affinis, around the ducts of Cuvier and posterior cardinal veins, while a few are visible also around the sinus venosus. In Perciformes and Salmoniformes, numerous chromaffin cells are also present in the posterior kidney, derived from the opisthonephros, in contact with the caudal vein. Steroidogenic cells are always confined to the head kidney. During development chromaffin and steroidogenic cells appear early after hatching in the pronephric kidney, at the level of the ducts of Cuvier and of the cephalic part of the posterior cardinal veins. Later, chromaffin cells in Perciformes reach the anterior cardinal veins, and subsequently, in both Perciformes and Salmoniformes, they reach the developing posterior kidney. Their localization along the posterior kidney is still in progress about 4 months after hatching and is completed about a year after hatching. These findings support the concept that the structure of the adrenal gland in teleosts is intermediate between that of the other actinopterygians and that of tetrapods. The development differs from that of tetrapods in that it occurs mainly in the pronephros and only later do chromaffin cells reach the opisthonephric kidney. Copyright 1997 Academic Press.

Antimicrobial efficacy and longevity of silver+zeolite incorporating preinsulated ducts installed in real healthcare settings.

PubMed

Tinteri, C; Potenza, M; Rizzetto, R

2012-12-01

The values of microbial growth in the air exiting from the heating, ventilation and air conditioning (HVAC) ducts treated with silver/zeolite have been shown to be lower than those in the air coming out the traditional metal ones. This study aims to verify how long this antimicrobial activity lasts. All the tests were performed according to US ASTM E2180-01 and ISO-JIZ 22196 standards. Samples of aluminum cladding panels of different thickness and incorporating silver-zeolite were tested in order to verify their thickness depending antibacterial activity. The same kind of linings samples were analyzed after a simulated and accelerated ageing process. Ag-zeolite incorporating HVAC duct panels linings were tested after years from their installation, in order to verify the maintenance of their bactericidal power during time. For laminates containing different amounts of silver+Zeolite it was shown that also in panels with minimum thickness tested, the lowest germicidal effect (GE) found was still very good (GE of 5,76 ULog10). After their wearing and tearing the antimicrobial activity tended to increase passing from 7.2081 to 8.29922 LogUnits in panels 80 microns thick. For still hospital working aluminium foils incorporating Silver/Zeolite on panels installed through 2006 and 2008, the antimicrobial action of zeolite was still firmly present even after two years and three years.The germicidal effect standards were maintained even during time on constant values between 7.477 and 7.086 LogUnits. The persistence of bactericidal efficacy of Ag+zeolite treatment in all the materials used for the construction of HVAC ductworks can be confirmed.

Intercalated cell-specific Rh B glycoprotein deletion diminishes renal ammonia excretion response to hypokalemia

PubMed Central

Bishop, Jesse M.; Lee, Hyun-Wook; Handlogten, Mary E.; Han, Ki-Hwan; Verlander, Jill W.

2013-01-01

The ammonia transporter family member, Rh B Glycoprotein (Rhbg), is an ammonia-specific transporter heavily expressed in the kidney and is necessary for the normal increase in ammonia excretion in response to metabolic acidosis. Hypokalemia is a common clinical condition in which there is increased renal ammonia excretion despite the absence of metabolic acidosis. The purpose of this study was to examine Rhbg's role in this response through the use of mice with intercalated cell-specific Rhbg deletion (IC-Rhbg-KO). Hypokalemia induced by feeding a K+-free diet increased urinary ammonia excretion significantly. In mice with intact Rhbg expression, hypokalemia increased Rhbg protein expression in intercalated cells in the cortical collecting duct (CCD) and in the outer medullary collecting duct (OMCD). Deletion of Rhbg from intercalated cells inhibited hypokalemia-induced changes in urinary total ammonia excretion significantly and completely prevented hypokalemia-induced increases in urinary ammonia concentration, but did not alter urinary pH. We conclude that hypokalemia increases Rhbg expression in intercalated cells in the cortex and outer medulla and that intercalated cell Rhbg expression is necessary for the normal increase in renal ammonia excretion in response to hypokalemia. PMID:23220726

Biological Therapy in Treating Patients With Metastatic Cancer

ClinicalTrials.gov

2013-02-21

Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

A non-cell-autonomous role for Ras signaling in C. elegans neuroblast delamination

PubMed Central

Parry, Jean M.; Sundaram, Meera V.

2014-01-01

Receptor tyrosine kinase (RTK) signaling through Ras influences many aspects of normal cell behavior, including epithelial-to-mesenchymal transition, and aberrant signaling promotes both tumorigenesis and metastasis. Although many such effects are cell-autonomous, here we show a non-cell-autonomous role for RTK-Ras signaling in the delamination of a neuroblast from an epithelial organ. The C. elegans renal-like excretory organ is initially composed of three unicellular epithelial tubes, namely the canal, duct and G1 pore cells; however, the G1 cell later delaminates from the excretory system to become a neuroblast and is replaced by the G2 cell. G1 delamination and G2 intercalation involve cytoskeletal remodeling, interconversion of autocellular and intercellular junctions and migration over a luminal extracellular matrix, followed by G1 junction loss. LET-23/EGFR and SOS-1, an exchange factor for Ras, are required for G1 junction loss but not for initial cytoskeletal or junction remodeling. Surprisingly, expression of activated LET-60/Ras in the neighboring duct cell, but not in the G1 or G2 cells, is sufficient to rescue sos-1 delamination defects, revealing that Ras acts non-cell-autonomously to permit G1 delamination. We suggest that, similarly, oncogenic mutations in cells within a tumor might help create a microenvironment that is permissive for other cells to detach and ultimately metastasize. PMID:25371363

Annexin A5 binds to lipopolysaccharide and reduces its endotoxin activity.

PubMed

Rand, Jacob H; Wu, Xiao-Xuan; Lin, Elaine Y; Griffel, Alexander; Gialanella, Philip; McKitrick, John C

2012-01-01

Annexin A5 (AnxA5) has a high affinity for phosphatidylserine. The protein is widely used to detect apoptotic cells because phosphatidylserine, a phospholipid that is normally present in the inner leaflets of cytoplasmic membranes, becomes translocated to the outer leaflets during programmed cell death. Here we report the novel observation that AnxA5 binds to Gram-negative bacteria via the lipid A domain of lipopolysaccharide (LPS). Binding of AnxA5 to bacteria was measured quantitatively, confirmed by fluorescence microscopy, and found to be inhibited by antibodies against lipid A. AnxA5 also bound to purified dot-blotted LPS and lipid A. Through ellipsometry, we found that the binding of AnxA5 to purified LPS was calcium dependent and rapid and showed a high affinity-characteristics similar to those of AnxA5 binding to phosphatidylserine. Initial functional studies indicated that AnxA5 can affect LPS activities. AnxA5 inhibited LPS-mediated gelation in the Limulus amebocyte lysate assay. Incubation of LPS with the protein reduced the quantity of tumor necrosis factor alpha (TNF-α) released by cultured monocytes compared to that released upon incubation with LPS alone. Initial in vivo experiments indicated that injection of mice with LPS preincubated with AnxA5 produced serum TNF-α levels lower than those seen after injection of LPS alone. These data demonstrate that AnxA5 binds to LPS and open paths to investigation of the potential biological and therapeutic implications of this interaction. AnxA5 is highly expressed in cells that have a barrier function-including, among others, vascular endothelium, placental trophoblasts, and epithelial cells lining bile ducts, renal tubules, mammary ducts, and nasal epithelium. The protein has been well characterized for its binding to phospholipid bilayers that contain phosphatidylserine. This report of a previously unrecognized activity of AnxA5 opens the door to investigation of the possibility that this binding may have biological and therapeutic ramifications. In view of the tissue expression of the protein, the present results suggest the possibility that AnxA5 plays a role in modulating the host defense against lipopolysaccharide at these anatomic sites, where cells may interface with microorganisms. These results also raise the intriguing possibility that AnxA5 or analogous proteins or peptides could provide novel approaches to addressing the difficult clinical problem of Gram-negative sepsis.

Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.

PubMed

Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

2016-07-01

Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

Intraductal Therapy of Ductal Carcinoma In Situ: A Presurgery Study

PubMed Central

Mahoney, M. Ellen; Gordon, Eva J.; Rao, Jian Yu; Jin, Yusheng; Hylton, Nola; Love, Susan M.

2014-01-01

Many women with ductal carcinoma in situ (DCIS) are treated with extensive surgery, radiation, and hormone therapy due to the inability to monitor the disease and to determine which cases will progress to invasive cancer. We assessed the safety and feasibility of administering chemotherapy directly into DCIS-containing ducts in 13 women before definitive surgery. The treatment was safe, feasible, and well tolerated, supporting further development of this strategy for management of DCIS. Introduction Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer wherein malignant cells are confined within a ductal lobular unit. Although less than half the cases of DCIS will progress to invasive disease, most women are treated aggressively with surgery, radiation, and/or hormone therapy due to the inability to clinically evaluate the extent and location of the disease. Intraductal therapy, in which a drug is administered directly into the mammary duct through the nipple, is a promising approach for treating DCIS, but the feasibility of instilling drug into a diseased duct has not been established. Patients and Methods Four to 6 weeks before their scheduled surgery, 13 women diagnosed with DCIS were subjected to cannulation of the affected duct. After both the absence of perforation and presence of dye in the duct were confirmed by ductogram, pegylated liposomal doxorubicin was instilled. Histopathologic assessment was performed after surgery to assess the treatment effects. Results Of the 13 women enrolled in the study, 6 had their DCIS duct successfully cannulated without perforation and instilled with the drug. The treatment was well tolerated, and no serious adverse events have been reported. Biomarker studies indicated a general decrease in Ki-67 levels but an increase in annexin-1 and 8-hydroxydeoxyguanosine in the lumen of DCIS-containing ducts, which suggests a local response to pegylated liposomal doxorubicin treatment. Conclusions Intraductal therapy offers a nonsurgical strategy to treat DCIS at the site of disease, potentially minimizing the adverse effects of systemic treatment while preventing development of invasive cancer. PMID:23664819

Reproductive biology in Anophelinae mosquitoes (Diptera, Culicidae): Fine structure of the female accessory gland.

PubMed

Laghezza Masci, Valentina; Di Luca, Marco; Gambellini, Gabriella; Taddei, Anna Rita; Belardinelli, Maria Cristina; Guerra, Laura; Mazzini, Massimo; Fausto, Anna Maria

2015-07-01

The morphology and ultrastructure of female accessory reproductive glands of Anopheles maculipennis s.s., Anopheles labranchiae and Anopheles stephensi were investigated by light and electron microscopy. The reproductive system in these species is characterized by two ovaries, two lateral oviducts, a single spermatheca and a single accessory gland. The gland is globular and has a thin duct which empties into the vagina, near the opening of the spermathecal duct. Significant growth of the accessory reproductive gland is observed immediately after blood meal, but not at subsequent digestion steps. At ultrastructural level, the gland consists of functional glandular units belonging to type 3 ectodermal glands. The secretory cells are elongated and goblet shaped, with most of their cytoplasm and large nucleus in the basal part, close to the basement lamella. Finely fibrous electron-transparent material occupies the secretory cavity that is in contact with the end of a short efferent duct (ductule) emerging from the gland duct. The present study is the first detailed description of female accessory gland ultrastructure in Anophelinae and provides insights into the gland's functional role in the reproductive biology of these insects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Examination of Duct Physiology in the Human Mammary Gland

PubMed Central

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

2016-01-01

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

Toll-Like Receptors in Secondary Obstructive Cholangiopathy

PubMed Central

Miranda-Díaz, A. G.; Alonso-Martínez, H.; Hernández-Ojeda, J.; Arias-Carvajal, O.; Rodríguez-Carrizalez, A. D.; Román-Pintos, L. M.

2011-01-01

Secondary obstructive cholangiopathy is characterized by intra- or extrahepatic bile tract obstruction. Liver inflammation and structural alterations develop due to progressive bile stagnation. Most frequent etiologies are biliary atresia in children, and hepatolithiasis, postcholecystectomy bile duct injury, and biliary primary cirrhosis in adults, which causes chronic biliary cholangitis. Bile ectasia predisposes to multiple pathogens: viral infections in biliary atresia; Gram-positive and/or Gram-negative bacteria cholangitis found in hepatolithiasis and postcholecystectomy bile duct injury. Transmembrane toll-like receptors (TLRs) are activated by virus, bacteria, fungi, and parasite stimuli. Even though TLR-2 and TLR-4 are the most studied receptors related to liver infectious diseases, other TLRs play an important role in response to microorganism damage. Acquired immune response is not vertically transmitted and reflects the infectious diseases history of individuals; in contrast, innate immunity is based on antigen recognition by specific receptors designated as pattern recognition receptors and is transmitted vertically through the germ cells. Understanding the mechanisms for bile duct inflammation is essential for the future development of therapeutic alternatives in order to avoid immune-mediated destruction on secondary obstructive cholangiopathy. The role of TLRs in biliary atresia, hepatolithiasis, bile duct injury, and primary biliary cirrhosis is described in this paper. PMID:22114589

New look inside human breast ducts with Raman imaging. Raman candidates as diagnostic markers for breast cancer prognosis: Mammaglobin, palmitic acid and sphingomyelin.

PubMed

Abramczyk, Halina; Brozek-Pluska, Beata

2016-02-25

Looking inside the human body fascinated mankind for thousands of years. Current diagnostic and therapy methods are often limited by inadequate sensitivity, specificity and spatial resolution. Raman imaging may bring revolution in monitoring of disease and treatment. The main advantage of Raman imaging is that it gives spatial information about various chemical constituents in defined cellular organelles in contrast to conventional methods (liquid chromatography/mass spectrometry, NMR, HPLC) that rely on bulk or fractionated analyses of extracted components. We demonstrated how Raman imaging can drive the progress on breast cancer just unimaginable a few years ago. We looked inside human breast ducts answering fundamental questions about location and distribution of various biochemical components inside the lumen, epithelial cells of the duct and the stroma around the duct during cancer development. We have identified Raman candidates as diagnostic markers for breast cancer prognosis: carotenoids, mammaglobin, palmitic acid and sphingomyelin as key molecular targets in ductal breast cancer in situ, and propose the molecular mechanisms linking oncogenes with lipid programming. Copyright © 2016 Elsevier B.V. All rights reserved.

Atypia and DNA methylation in nipple duct lavage in relation to predicted breast cancer risk.

PubMed

Euhus, David M; Bu, Dawei; Ashfaq, Raheela; Xie, Xian-Jin; Bian, Aihua; Leitch, A Marilyn; Lewis, Cheryl M

2007-09-01

Tumor suppressor gene (TSG) methylation is identified more frequently in random periareolar fine needle aspiration samples from women at high risk for breast cancer than women at lower risk. It is not known whether TSG methylation or atypia in nipple duct lavage (NDL) samples is related to predicted breast cancer risk. 514 NDL samples obtained from 150 women selected to represent a wide range of breast cancer risk were evaluated cytologically and by quantitative multiplex methylation-specific PCR for methylation of cyclin D2, APC, HIN1, RASSF1A, and RAR-beta2. Based on methylation patterns and cytology, NDL retrieved cancer cells from only 9% of breasts ipsilateral to a breast cancer. Methylation of >/=2 genes correlated with marked atypia by univariate analysis, but not multivariate analysis, that adjusted for sample cellularity and risk group classification. Both marked atypia and TSG methylation independently predicted abundant cellularity in multivariate analyses. Discrimination between Gail lower-risk ducts and Gail high-risk ducts was similar for marked atypia [odds ratio (OR), 3.48; P = 0.06] and measures of TSG methylation (OR, 3.51; P = 0.03). However, marked atypia provided better discrimination between Gail lower-risk ducts and ducts contralateral to a breast cancer (OR, 6.91; P = 0.003, compared with methylation OR, 4.21; P = 0.02). TSG methylation in NDL samples does not predict marked atypia after correcting for sample cellularity and risk group classification. Rather, both methylation and marked atypia are independently associated with highly cellular samples, Gail model risk classifications, and a personal history of breast cancer. This suggests the existence of related, but independent, pathogenic pathways in breast epithelium.