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Sample records for protocols lymphatic system

  1. Imaging the lymphatic system.

    PubMed

    Munn, Lance L; Padera, Timothy P

    2014-11-01

    Visualization of the lymphatic system is clinically necessary during diagnosis or treatment of many conditions and diseases; it is used for identifying and monitoring lymphedema, for detecting metastatic lesions during cancer staging and for locating lymphatic structures so they can be spared during surgical procedures. Imaging lymphatic anatomy and function also plays an important role in experimental studies of lymphatic development and function, where spatial resolution and accessibility are better. Here, we review technologies for visualizing and imaging the lymphatic system for clinical applications. We then describe the use of lymphatic imaging in experimental systems as well as some of the emerging technologies for improving these methodologies.

  2. Imaging the lymphatic system

    PubMed Central

    Munn, Lance L.; Padera, Timothy P.

    2014-01-01

    Visualization of the lymphatic system is clinically necessary during diagnosis or treatment of many conditions and diseases; it is used for identifying and monitoring lymphedema, for detecting metastatic lesions during cancer staging and for locating lymphatic structures so they can be spared during surgical procedures. Imaging lymphatic anatomy and function also plays an important role in experimental studies of lymphatic development and function, where spatial resolution and accessibility are better. Here, we review technologies for visualizing and imaging the lymphatic system for clinical applications. We then describe the use of lymphatic imaging in experimental systems as well as some of the emerging technologies for improving these methodologies. PMID:24956510

  3. Lymphatic System in Cardiovascular Medicine.

    PubMed

    Aspelund, Aleksanteri; Robciuc, Marius R; Karaman, Sinem; Makinen, Taija; Alitalo, Kari

    2016-02-01

    The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease.

  4. The Lymphatic System in Disease Processes and Cancer Progression.

    PubMed

    Padera, Timothy P; Meijer, Eelco F J; Munn, Lance L

    2016-07-11

    Advances in our understanding of the structure and function of the lymphatic system have made it possible to identify its role in a variety of disease processes. Because it is involved not only in fluid homeostasis but also in immune cell trafficking, the lymphatic system can mediate and ultimately alter immune responses. Our rapidly increasing knowledge of the molecular control of the lymphatic system will inevitably lead to new and effective therapies for patients with lymphatic dysfunction. In this review, we discuss the molecular and physiological control of lymphatic vessel function and explore how the lymphatic system contributes to many disease processes, including cancer and lymphedema.

  5. Development of the lymphatic system: new questions and paradigms.

    PubMed

    Semo, Jonathan; Nicenboim, Julian; Yaniv, Karina

    2016-03-15

    The lymphatic system is a blind-ended network of vessels that plays important roles in mediating tissue fluid homeostasis, intestinal lipid absorption and the immune response. A profound understanding of the development of lymphatic vessels, as well as of the molecular cues governing their formation and morphogenesis, might prove essential for our ability to treat lymphatic-related diseases. The embryonic origins of lymphatic vessels have been debated for over a century, with a model claiming a venous origin for the lymphatic endothelium being predominant. However, recent studies have provided new insights into the origins of lymphatic vessels. Here, we review the molecular mechanisms controlling lymphatic specification and sprouting, and we discuss exciting findings that shed new light on previously uncharacterized sources of lymphatic endothelial cells.

  6. Demonstrating the lymphatic system in rats with microinjection.

    PubMed

    Suami, Hiroo; Chang, David W; Matsumoto, Kumiko; Kimata, Yoshihiro

    2011-09-01

    The lymphatic system plays an important role in human health and disease. In addition to a role in the immune response, the lymphatics can serve as a pathway for cancer metastasis. Visualizing the lymphatic system has been a difficult part of anatomic dissection studies. Anatomists have attempted to map the lymphatic system using various methods and materials; vivisection of dogs, injection of mercury into the skin and lymphatic vessel in cadavers, and injection of dye indirectly into the skin of dead and living specimens. In this study, we introduce a method of using a mixture of acrylic blue dye and hydrogen peroxide to visualize the lymphatic system in rats. The lymphatic vessels were cannulated with micropipettes, and radio-opaque orange lead oxide was selectively injected. The lymphatic system became visible from the dorsal side of the hand and foot, and distal region of the tail to their termination at the left and right subclavicular veins via lymph nodes. Cisterna chyli in the abdominal cavity and thoracic duct ran along with the aorta. The advantage of this technique is that lymph nodes as well as lymphatic channels could be recorded not only photographically but also radiographically. This microinjection technique is useful for demonstrating the lymphatic system in rats and may provide further information that will help in cancer metastasis research.

  7. Lymphatic system: an active pathway for immune protection.

    PubMed

    Liao, Shan; von der Weid, P Y

    2015-02-01

    Lymphatic vessels are well known to participate in the immune response by providing the structural and functional support for the delivery of antigens and antigen presenting cells to draining lymph nodes. Recent advances have improved our understanding of how the lymphatic system works and how it participates to the development of immune responses. New findings suggest that the lymphatic system may control the ultimate immune response through a number of ways which may include guiding antigen/dendritic cells (DC) entry into initial lymphatics at the periphery; promoting antigen/DC trafficking through afferent lymphatic vessels by actively facilitating lymph and cell movement; enabling antigen presentation in lymph nodes via a network of lymphatic endothelial cells and lymph node stroma cell and finally by direct lymphocytes exit from lymph nodes. The same mechanisms are likely also important to maintain peripheral tolerance. In this review we will discuss how the morphology and gene expression profile of the lymphatic endothelial cells in lymphatic vessels and lymph nodes provides a highly efficient pathway to initiate immune responses. The fundamental understanding of how lymphatic system participates in immune regulation will guide the research on lymphatic function in various diseases.

  8. Communication between lymphatic and venous systems in mice.

    PubMed

    Shao, Lenan; Takeda, Kazu; Kato, Shigeki; Mori, Shiro; Kodama, Tetsuya

    2015-09-01

    The lymphatic system in mice consists of lymphatic vessels and 22 types of lymph nodes. Metastatic tumor cells in the lymphatic system spread to distant organs through the venous system. However, the communication routes between the lymphatic and venous systems have not been fully elucidated. Here, we identify the communication routes between the lymphatic and venous systems in the axillary and subiliac regions of MXH10/Mo-lpr/lpr inbred mice, which develop systemic swelling of lymph nodes up to 10mm in diameter, allowing investigation of the topography of the lymph nodes and lymphatic vessels. Using a gross anatomy dissection approach, the efferent lymphatic vessels of the proper axillary lymph node were shown to communicate with the subclavian vein. Furthermore, we found that the thoracoepigastric vein, which connects the subclavian vein and inferior vena cava, runs adjacent to the subiliac and proper axillary lymph nodes, and receives venous blood from these lymph nodes routed through small branches. The direction of blood flow in the thoracoepigastric vein occurred in two directions in the intermediate region between the proper axillary lymph node and subiliac lymph node; one to the subclavian vein, the other to the inferior vena cava. This paper reveals the anatomy of the communication between the lymphatic and venous systems in the axillary and subiliac regions of the mouse, and provides new insights relevant to the investigation of the mechanisms of lymph node metastasis and cancer immunology, and the development of diagnostic and treatment methods for lymph node metastasis, including drug delivery systems.

  9. Heterogeneity in the lymphatic vascular system and its origin.

    PubMed

    Ulvmar, Maria H; Mäkinen, Taija

    2016-09-01

    Lymphatic vessels have historically been viewed as passive conduits for fluid and immune cells, but this perspective is increasingly being revised as new functions of lymphatic vessels are revealed. Emerging evidence shows that lymphatic endothelium takes an active part in immune regulation both by antigen presentation and expression of immunomodulatory genes. In addition, lymphatic vessels play an important role in uptake of dietary fat and clearance of cholesterol from peripheral tissues, and they have been implicated in obesity and arteriosclerosis. Lymphatic vessels within different organs and in different physiological and pathological processes show a remarkable plasticity and heterogeneity, reflecting their functional specialization. In addition, lymphatic endothelial cells (LECs) of different organs were recently shown to have alternative developmental origins, which may contribute to the development of the diverse lymphatic vessel and endothelial functions seen in the adult. Here, we discuss recent developments in the understanding of heterogeneity within the lymphatic system considering the organ-specific functional and molecular specialization of LECs and their developmental origin. PMID:27357637

  10. Heterogeneity in the lymphatic vascular system and its origin.

    PubMed

    Ulvmar, Maria H; Mäkinen, Taija

    2016-09-01

    Lymphatic vessels have historically been viewed as passive conduits for fluid and immune cells, but this perspective is increasingly being revised as new functions of lymphatic vessels are revealed. Emerging evidence shows that lymphatic endothelium takes an active part in immune regulation both by antigen presentation and expression of immunomodulatory genes. In addition, lymphatic vessels play an important role in uptake of dietary fat and clearance of cholesterol from peripheral tissues, and they have been implicated in obesity and arteriosclerosis. Lymphatic vessels within different organs and in different physiological and pathological processes show a remarkable plasticity and heterogeneity, reflecting their functional specialization. In addition, lymphatic endothelial cells (LECs) of different organs were recently shown to have alternative developmental origins, which may contribute to the development of the diverse lymphatic vessel and endothelial functions seen in the adult. Here, we discuss recent developments in the understanding of heterogeneity within the lymphatic system considering the organ-specific functional and molecular specialization of LECs and their developmental origin.

  11. Heterogeneity in the lymphatic vascular system and its origin

    PubMed Central

    Ulvmar, Maria H.; Mäkinen, Taija

    2016-01-01

    Lymphatic vessels have historically been viewed as passive conduits for fluid and immune cells, but this perspective is increasingly being revised as new functions of lymphatic vessels are revealed. Emerging evidence shows that lymphatic endothelium takes an active part in immune regulation both by antigen presentation and expression of immunomodulatory genes. In addition, lymphatic vessels play an important role in uptake of dietary fat and clearance of cholesterol from peripheral tissues, and they have been implicated in obesity and arteriosclerosis. Lymphatic vessels within different organs and in different physiological and pathological processes show a remarkable plasticity and heterogeneity, reflecting their functional specialization. In addition, lymphatic endothelial cells (LECs) of different organs were recently shown to have alternative developmental origins, which may contribute to the development of the diverse lymphatic vessel and endothelial functions seen in the adult. Here, we discuss recent developments in the understanding of heterogeneity within the lymphatic system considering the organ-specific functional and molecular specialization of LECs and their developmental origin. PMID:27357637

  12. Lymphatic Diseases

    MedlinePlus

    The lymphatic system is a network of tissues and organs. It is made up of Lymph - a fluid that contains ... They are part of the system, too. The lymphatic system clears away infection and keeps your body fluids ...

  13. An investigation of the topography of the lymphatic system of the grey kangaroo (Macropus giganteus). 1. The superficial lymphatic system.

    PubMed Central

    Hopwood, P R

    1988-01-01

    The superficial lymphatic system of the grey kangaroo, Macropus giganteus is described. The description is based on dissections of 130 eastern grey kangaroos. The most significant difference found between the superficial lymphatic drainage pattern of kangaroos and that of the domestic species was the existence of large inguino-axillary lymphatic trunks in the kangaroo. Thus in the kangaroo, instead of lymph passing from the inguinal lymphocentre to the lumbar lymphatic trunks as is the situation in the domestic animals, lymph passes from the inguinal lymphocentre to the axillary lymphocentre. Apart from the lymph draining from the head and ventral neck (which passes to the superficial cervical lymphocentre) and lymph which may pass from the superficial lymphatic vessels to deeper lymphatic vessels, all the superficial lymphatic drainage of the kangaroo passes through the axillary lymphocentre. From the viewpoint of the meat inspection of the carcasses of kangaroos taken as game meat animals, pathology of the axillary lymphocentre may reflect disease in a much wider range of body regions than it would in a domestic animal. PMID:3198478

  14. The surgical anatomy of the lymphatic system of the pancreas.

    PubMed

    Cesmebasi, Alper; Malefant, Jason; Patel, Swetal D; Du Plessis, Maira; Renna, Sarah; Tubbs, R Shane; Loukas, Marios

    2015-05-01

    The lymphatic system of the pancreas is a complex, intricate network of lymphatic vessels and nodes responsible for the drainage of the head, neck, body, and tail of the pancreas. Its anatomical divisions and embryological development have been well described in the literature with emphasis on its clinical relevance in regards to pancreatic pathologies. A thorough knowledge and understanding of the lymphatic system surrounding the pancreas is critical for physicians in providing diagnostic and treatment strategies for patients with pancreatic cancer and pancreatitis. Pancreatic cancer has an extremely poor prognosis and is a notable cause of morbidity and mortality worldwide. Although a surgeon may try to predict the routes for metastasis for pancreatic cancer, the complexity of this system presents difficulty due to variable drainage patterns. Pancreatitis also presents as another severe disease which has been shown to have an association with the lymphatics. The aim of this article is to review the literature on the lymphatics of the pancreas, pancreatic pathologies, and the available imaging methodologies used to study the pancreatic lymphatics.

  15. Lymphatic obstruction

    MedlinePlus

    ... certain directions based on the structure of the lymphatic system. This helps the lymph fluid drain through the ... always appropriate or effective. Alternative Names Lymphedema Images Lymphatic system Yellow nail syndrome References Kurklinsky AK, Rooke TW. ...

  16. Stress-driven lymphatic dissemination: An unanticipated consequence of communication between the sympathetic nervous system and lymphatic vasculature.

    PubMed

    Le, Caroline P; Sloan, Erica K

    2016-07-01

    Chronic stress drives cancer progression, but the routes of metastasis are unclear. We recently demonstrated that chronic stress activates a neural-inflammatory signaling axis to remodel lymphatic vasculature and increase lymph flow. This unanticipated crosstalk between stress and the lymphatic system provides pathways of tumor cell dissemination and accelerates metastasis. PMID:27652324

  17. Structural and functional features of central nervous system lymphatic vessels.

    PubMed

    Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

    2015-07-16

    One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

  18. Disorders of the lymphatic system of the abdomen.

    PubMed

    Patil, A R; Nandikoor, S; De Marco, J; Bhat, R; Shivakumar, S; Mallrajapatna, G

    2016-10-01

    The lymphatic system of the abdomen comprises of the cisterna chyli, its major and minor lymphatic tributaries, and lymph nodes. Disorders of the lymphatic system of the abdomen are rarely encountered and consist of primary and secondary types. Abdominal lymphangiomas constitute the majority and have characteristic imaging features. Complicated lymphangiomas may pose a diagnostic dilemma. Generalised systemic lymphangiomatosis is a rare condition and affects major organs with a poor prognosis. Retroperitoneal lymphangiectasia in the appropriate setting might predict underlying infection, such as filariasis. Other acquired conditions include iatrogenic or treatment-induced chylocoele. Chylous ascites can be secondary to multiple causes and can be confirmed by biochemical testing and lymphangiogram in appropriate settings. PMID:27450410

  19. [Lymphatic vascular system, development and lymph formation. Review].

    PubMed

    Bernaudin, J-F; Kambouchner, M; Lacave, R

    2013-04-01

    The lymphatic vascular system is widely developed among vertebrates. Lymphatic vessels provide the interstitial fluid (20% of the body weight) drainage through interstitial prelymphatic channels, capillaries, precollectors and collectors flowing into the venous blood. Endothelial cells of capillaries are overlapped and fixed to interstitial collagen and elastic fibres by anchoring filaments facilitating the fluid transfer. Precollectors and collectors have valves controlling the lymph flux direction. In addition to external mechanisms, the lymphangions of collectors have contracting muscle cells driving the flow. Lymphatic endothelial cells are routinely identified by the expression of podoplanin, LYVE-1 and VEGFR3. In the embryo, prelymphatic endothelial cells emerge from the cardinal veins and migrate into the mesenchyma forming embryonic lymphatic sacs. Prox1, Sox18 and COUP-TFII play a major role in the endothelial speciation, VEGFC as VEGFD combined to VEGFR3 in cell migration and proliferation and FoxC2 in valves development. In cancer or inflammation, various factors secreted by cancer cells and/or inflammatory cells induce a neolymphangiogenesis. Recently it has been shown that cells from the bone marrow could be potential precursors for lymphatic endothelial cells.

  20. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  1. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  2. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  3. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  4. 38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and lymphatic systems. 4.117 Section 4.117 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Hemic and Lymphatic Systems § 4.117 Schedule of ratings—hemic and lymphatic systems. Rating 7700Anemia, hypochromic-microcytic...

  5. From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity.

    PubMed

    Trevaskis, Natalie L; Kaminskas, Lisa M; Porter, Christopher J H

    2015-11-01

    The lymphatic system serves an integral role in fluid homeostasis, lipid metabolism and immune control. In cancer, the lymph nodes that drain solid tumours are a primary site of metastasis, and recent studies have suggested intrinsic links between lymphatic function, lipid deposition, obesity and atherosclerosis. Advances in the current understanding of the role of the lymphatics in pathological change and immunity have driven the recognition that lymph-targeted delivery has the potential to transform disease treatment and vaccination. In addition, the design of lymphatic delivery systems has progressed from simple systems that rely on passive lymphatic access to sophisticated structures that use nanotechnology to mimic endogenous macromolecules and lipid conjugates that 'hitchhike' onto lipid transport processes. Here, we briefly summarize the lymphatic system in health and disease and the varying mechanisms of lymphatic entry and transport, as well as discussing examples of lymphatic delivery that have enhanced therapeutic utility. We also outline future challenges to effective lymph-directed therapy.

  6. The meningeal lymphatic system: a route for HIV brain migration?

    PubMed

    Lamers, Susanna L; Rose, Rebecca; Ndhlovu, Lishomwa C; Nolan, David J; Salemi, Marco; Maidji, Ekaterina; Stoddart, Cheryl A; McGrath, Michael S

    2016-06-01

    Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4(+) T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system.

  7. Recent advances in lymphatic targeted drug delivery system for tumor metastasis

    PubMed Central

    Zhang, Xiao-Yu; Lu, Wei-Yue

    2014-01-01

    The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers. PMID:25610710

  8. The New Era of the Lymphatic System: No Longer Secondary to the Blood Vascular System

    PubMed Central

    Choi, Inho; Lee, Sunju; Hong, Young-Kwon

    2012-01-01

    The blood and lymphatic systems are the two major circulatory systems in our body. Although the blood system has been studied extensively, the lymphatic system has received much less scientific and medical attention because of its elusive morphology and mysterious pathophysiology. However, a series of landmark discoveries made in the past decade has begun to change the previous misconception of the lymphatic system to be secondary to the more essential blood vascular system. In this article, we review the current understanding of the development and pathology of the lymphatic system. We hope to convince readers that the lymphatic system is no less essential than the blood circulatory system for human health and well-being. PMID:22474611

  9. Preclinical lymphatic imaging.

    PubMed

    Zhang, Fan; Niu, Gang; Lu, Guangming; Chen, Xiaoyuan

    2011-08-01

    Noninvasive in vivo imaging of lymphatic vessels and lymphatic nodes is expected to fulfill the purpose of analyzing lymphatic vessels and their function, understanding molecular mechanisms of lymphangiogenesis and lymphatic spread of tumors, and utilizing lymphatic molecular markers as a prognostic or diagnostic indicator. In this review, we provide a comprehensive summary of in vivo imaging modalities for detecting lymphatic vessels, lymphatic drainage, and lymphatic nodes, which include conventional lymphatic imaging techniques such as dyes and radionuclide scintigraphy as well as novel techniques for lymphatic imaging such as optical imaging, computed tomography, magnetic resonance imaging, ultrasound, positron emission tomography using lymphatic biomarkers, photoacoustic imaging, and combinations of multiple modalities. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve the research of lymphatic vascular system in health and disease states as well as to improve the accuracy of diagnosis in the relevant diseases.

  10. Preclinical Lymphatic Imaging

    PubMed Central

    Zhang, Fan; Niu, Gang; Lu, Guangming; Chen, Xiaoyuan

    2011-01-01

    Non-invasive in vivo imaging of lymphatic vessels and lymphatic nodes is expected to fulfill the purpose of analyzing lymphatic vessels and their function, understanding molecular mechanisms of lymphangiogenesis and lymphatic spread of tumors, and utilizing lymphatic molecular markers as a prognostic or diagnostic indicator. In this review, we provide a comprehensive summary of in vivo imaging modalities for detecting lymphatic vessels, lymphatic drainage, lymphatic nodes, which include conventional lymphatic imaging techniques such as dyes and radionuclide scintigraphy as well as novel techniques for lymphatic imaging such as optical imaging, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET) using lymphatic biomarkers, photoacoustic imaging and combinations of multiple modalities. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve the research of lymphatic vascular system in health and disease states as well as to improve the accuracy of diagnosis in the relevant diseases. PMID:20862613

  11. Orofacial lymphatic malformation: management with a three steps diode laser protocol

    NASA Astrophysics Data System (ADS)

    Miccoli, Simona; Tempesta, Angela; Limongelli, Luisa; Caporusso, Concetta; Di Venere, Daniela; Petruzzi, Massimo; Lacaita, Mariagrazia; Maiorano, Eugenio; Favia, Gianfranco

    2014-01-01

    Lymphatic Malformation (LM) according to ISSVA Classification, is a rare benign disorder with unknown aetiology. LM may grow slowly over years or develop rapidly over the course of days becoming a bulky lump, infected or bleeding. We propose our three steps Diode Laser protocol for LM management, based on its persistent vascular blood component. 1. Histological and cytological examination, to evaluate the vascular blood component (10-40%), shows mature lymphocytes with red blood cells and endothelial cells. 2. Diode Laser Photocoagulation (DLP) in pulsed mode (on 100ms / off 400ms) at 10W and 800nm with a 300μm fibre kept 2-3mm from the tissues, to reduce the lesion. 3. Diode Laser surgical excision in pulsed mode (on 50ms / off 200ms) at 8W and 800nm with a 300 μm fibre in close contact with tissues, and histological intraoperative margins control on frozen sections. Even if it has inconstant results (lesions decreasing rate is 10% to 40% proportionally to vascular blood component), DLP simplifies the last and the most important step. Use of Diode Laser also in surgical excision reduces intra and postoperatory complications.

  12. The lymphatic vascular system in liver diseases: its role in ascites formation.

    PubMed

    Chung, Chuhan; Iwakiri, Yasuko

    2013-06-01

    The lymphatic system is part of the circulatory system and plays a key role in normal vascular function. Its failure plays a crucial role in the development and maintenance of various diseases including liver diseases. Lymphangiogenesis (the growth of lymphatic vessels) and changes in the properties of lymphatic vessels are associated with pathogenesis of tumor metastases, ascites formation, liver fibrosis/cirrhosis and portal hypertension. Despite its significant role in liver diseases and its importance as a potential therapeutic target for those diseases, the lymphatic vascular system of the liver is poorly understood. Therefore, how the lymphatic vascular system in general and lymphangiogenesis in particular are mechanistically related to the pathogenesis and maintenance of liver diseases are largely unknown. This article summarizes: 1) the lymphatic vascular system; 2) its role in liver tumors, liver fibrosis/cirrhosis and portal hypertension; and 3) its role in ascites formation.

  13. Spleen and Lymphatic System (For Parents)

    MedlinePlus

    ... How A Healthy Lymph System Works Carrying Away Waste Lymph fluid drains into lymph capillaries, which are ... crowd out healthy cells and may cause tumors (solid growths) in other parts of the body. Splenomegaly ( ...

  14. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations.

    PubMed

    Ali Khan, Arshad; Mudassir, Jahanzeb; Mohtar, Noratiqah; Darwis, Yusrida

    2013-01-01

    The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects uptake of drug into the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes

  15. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations

    PubMed Central

    Khan, Arshad Ali; Mudassir, Jahanzeb; Mohtar, Noratiqah; Darwis, Yusrida

    2013-01-01

    The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects uptake of drug into the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes

  16. The role of the lymphatic system in endometriosis: a comprehensive review of the literature.

    PubMed

    Jerman, Laila F; Hey-Cunningham, Alison J

    2015-03-01

    Endometriosis is a benign gynecological disorder characterized by the presence of tissue resembling the endometrium in locations outside the uterus. The pathogenesis of endometriosis is still unknown; however, it is believed that the lymphatic system plays major roles in the development and progression of the disease. The lymphatic dissemination theory has been proposed to explain the presence of endometrial and/or endometriotic tissue in lymphatic vessels, lymph nodes, and rare sites, as well as high reoccurrence rates following treatment. Despite the importance of the lymphatic system in many aspects of endometriosis, there has been no previous thorough scientific update on its role in the disease. A review of scientific literature on the lymphatic system, lymphangiogenesis, and immunological changes associated with endometriosis was conducted. Lymphangiogenic potential is disturbed and lymphatic vessel density increased in the eutopic endometrium of women with endometriosis, likely promoting the entry of endometrial tissues into the lymphatic circulation. Endometriotic lesions and endometrial-like cells are present in uterine-draining nodes and various other pelvic lymph nodes. Immune responses are impaired in uterine-draining nodes, likely favoring the survival of endometrial cells and lesion establishment. In addition, lymphangiogenesis in endometriotic lesions may contribute to lesion growth and persistence, and promote the spread of endometrial cells to draining lymph nodes. The evidence reviewed in this paper supports the theory of lymphatic dissemination of endometriosis and highlights the roles of the lymphatic system in the pathogenesis and persistence of endometriosis. Understanding these roles is crucial for establishment of novel therapeutic approaches.

  17. Anatomy of the lymphatics.

    PubMed

    Skandalakis, John E; Skandalakis, Lee J; Skandalakis, Panagiotis N

    2007-01-01

    The lymphatic system is perhaps the most complicated system of Homo sapiens. An introduction to the anatomy, embryology, and anomalies of the lymphatics is presented. The overall anatomy and drainage of the lymphatic vessels in outlined. The topographic anatomy, relations, and variations of the principle vessels of the lymphatic system (the right lymphatic duct, the thoracic duct, and the cisterna chyli) are presented in detail.

  18. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules.

    PubMed

    Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge; Alitalo, Kari

    2015-06-29

    The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.

  19. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules

    PubMed Central

    Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T.; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge

    2015-01-01

    The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease. PMID:26077718

  20. A Systemic Route for Drug Loading to Lymphatic Phagocytes

    PubMed Central

    Papisov, M. I.; Yurkovetskiy, A.; Syed, S.; Koshkina, N.; Yin, M.; Hiller, A.; Fischman, A. J.

    2015-01-01

    Lymph nodes are primary germination and proliferation sites for many types of pathogens. Maintaining therapeutic levels of appropriate chemotherapeutic agents in the lymph node tissue is critical for the treatment of both infection and cancer. This study was intended to develop a systemic route for loading lymph node phagocytes with drugs, using a lymph node specific nanocarrier. The latter is assembled as a 10–15 nm particle with a drug-carrying core and a phagocyte-homing poly(1→6)-α-d-glucose based interface. Biokinetics and microdistribution of the model carrier were investigated in vivo. Nanocarrier accumulation in lymph nodes reached 30–35% dose/g in central lymph nodes, with deposition in various phagocytic cell populations. The latter included cells harboring inhaled microparticles translocated to lymph nodes from the lungs. In view of the nanocarrier ability to transport and release significant amounts of various drug substances, the data suggests feasibility of systemic drug loading to lymphatic phagocytes and, through drug release, to the neighboring cells. PMID:15804177

  1. Chronic lower limb wounds evoke systemic response of the lymphatic (immune) system

    PubMed Central

    Olszewski, W. L.; Jain, P.; Zaleska, M.; Stelmach, E.; Swoboda, E.

    2012-01-01

    Wound healing should not be considered as a process limited only to the damaged tissues. It is always accompanied by an intensive local immune response and in advanced stages, the systemic lymphatic (immune) structure. In this review we present evidence from our own studies as well as pertinent literature on the role of skin and subcutaneous tissue lymphatics at the wound site and of transport of antigens along with collecting afferent lymphatics to the lymph nodes. We also speculate the role of lymph nodes in raising cohorts of bacterial and own tissue antigen-specific lymphocytes and their participation in healing and not infrequently evoking uncontrolled chronic immune reaction causing a delay of healing. It is also speculated as to why there is a rapid response of lymph node cells to microbial antigens and tolerance to damaged-tissue-derived antigens occurs PMID:23162224

  2. Artificial lymphatic drainage systems for vascularized microfluidic scaffolds.

    PubMed

    Wong, Keith H K; Truslow, James G; Khankhel, Aimal H; Chan, Kelvin L S; Tien, Joe

    2013-08-01

    The formation of a stably perfused microvasculature continues to be a major challenge in tissue engineering. Previous work has suggested the importance of a sufficiently large transmural pressure in maintaining vascular stability and perfusion. Here we show that a system of empty channels that provides a drainage function analogous to that of lymphatic microvasculature in vivo can stabilize vascular adhesion and maintain perfusion rate in dense, hydraulically resistive fibrin scaffolds in vitro. In the absence of drainage, endothelial delamination increased as scaffold density increased from 6 to 30 mg/mL and scaffold hydraulic conductivity decreased by a factor of 20. Single drainage channels exerted only localized vascular stabilization, the extent of which depended on the distance between vessel and drainage as well as scaffold density. Computational modeling of these experiments yielded an estimate of 0.40-1.36 cm H2O for the minimum transmural pressure required for vascular stability. We further designed and constructed fibrin patches (0.8 × 0.9 cm(2)) that were perfused by a parallel array of vessels and drained by an orthogonal array of drainage channels; only with the drainage did the vessels display long-term stability and perfusion. This work underscores the importance of drainage in vascularization, especially when a dense, hydraulically resistive scaffold is used. PMID:23281125

  3. Current Status of Optical Imaging for Evaluating Lymph Nodes and Lymphatic System

    PubMed Central

    Lee, Eun Seong; Kim, Tae Sung

    2015-01-01

    Optical imaging techniques use visual and near infrared rays. Despite their considerably poor penetration depth, they are widely used due to their safe and intuitive properties and potential for intraoperative usage. Optical imaging techniques have been actively investigated for clinical imaging of lymph nodes and lymphatic system. This article summarizes a variety of optical tracers and techniques used for lymph node and lymphatic imaging, and reviews their clinical applications. Emerging new optical imaging techniques and their potential are also described. PMID:25598672

  4. Clinical Protocol Information System

    PubMed Central

    Wirtschafter, David D.; Gams, Richard; Ferguson, Carol; Blackwell, William; Boackle, Paul

    1980-01-01

    The Clinical Protocol Information System (CPIS) supports the clinical research and patient care objectives of the SouthEastern Cancer Study Group (SEG). The information system goals are to improve the evaluability of clinical trials, decrease the frequency of adverse patient events, implement drug toxicity surveillance, improve the availability of study data and demonstrate the criteria for computer networks that can impact on the general medical care of the community. Nodes in the network consist of Data General MicroNova MP-100 minicomputers that drive the interactive data dialogue and communicate with the network concentrator (another DG MicroNova) in Birmingham. Functions supported include: source data editing, care “advice,” care “audit,” care “explanation,” and treatment note printing. The complete database is updated nightly and resides on UAB's IBM 370/158-AP.

  5. The role of the lymphatic system in cholesterol transport

    PubMed Central

    Huang, Li-Hao; Elvington, Andrew; Randolph, Gwendalyn J.

    2015-01-01

    Reverse cholesterol transport (RCT) is the pathway for removal of peripheral tissue cholesterol and involves transport of cholesterol back to liver for excretion, starting from cellular cholesterol efflux facilitated by lipid-free apolipoprotein A1 (ApoA1) or other lipidated high-density lipoprotein (HDL) particles within the interstitial space. Extracellular cholesterol then is picked up and transported through the lymphatic vasculature before entering into bloodstream. There is increasing evidence supporting a role for enhanced macrophage cholesterol efflux and RCT in ameliorating atherosclerosis, and recent data suggest that these processes may serve as better diagnostic biomarkers than plasma HDL levels. Hence, it is important to better understand the processes governing ApoA1 and HDL influx into peripheral tissues from the bloodstream, modification and facilitation of cellular cholesterol removal within the interstitial space, and transport through the lymphatic vasculature. New findings will complement therapeutic strategies for the treatment of atherosclerotic vascular disease. PMID:26388772

  6. Pelvic irradiation modulates the pharmacokinetics of cisplatin in the plasma and lymphatic system

    PubMed Central

    Tsai, Tung-Hu; Chen, Yu-Jen; Hou, Mei-Ling; Wang, Li-Ying; Tai, Hung-Chi; Hsieh, Chen-Hsi

    2015-01-01

    Background: Cisplatin (CDDP) is employed to enhance radiotherapy’s (RT) effect for various cancers. However, the effects of local RT on chemotherapeutics in the plasma and lymphatic system remain unclear. Here, we evaluated the influence of pelvic irradiation on the pharmacokinetics (PK) of CDDP using rats as an experimental model. Methods and Materials: RT with 2 Gy and 0.5 Gy were delivered to the whole pelvis of Sprague-Dawley rats. CDDP at 5 mg/kg and 10 mg/kg was intravenously infused 24 hours after radiation for the plasma and lymphatic system, respectively. The pharmacokinetics of CDDP in the plasma and lymphatic system were calculated. Results: Compared with sham-irradiated controls, the whole pelvic irradiation increased the area under the concentration versus time curve (AUC) of CDDP (5 mg/kg) in the plasma by 80% at 0.5 Gy and 87% at 2 Gy, respectively. In contrast, the AUC of CDDP decreased in bile by 13% at both dose levels. Intriguingly, RT could also increase the AUC of CDDP (10 mg/kg) in the lymphatic fluid by 87% at 2 Gy. In addition, the AUC in CDDP without and with RT was 2.8-fold and 3.4-fold greater for the lymph system than for the plasma, respectively. Conclusions: A local pelvic RT could modulate the systemic PK of CDDP in both the plasma and lymphatic fluids of the rats. The RT-PK phenomena are worth further investigation. PMID:25901204

  7. Essential role of the coxsackie- and adenovirus receptor (CAR) in development of the lymphatic system in mice.

    PubMed

    Mirza, Momina; Pang, Mei-Fong; Zaini, Mohamad Amr; Haiko, Paula; Tammela, Tuomas; Alitalo, Kari; Philipson, Lennart; Fuxe, Jonas; Sollerbrant, Kerstin

    2012-01-01

    The coxsackie- and adenovirus receptor (CAR) is a cell adhesion molecule predominantly associated with epithelial tight junctions in adult tissues. CAR is also expressed in cardiomyocytes and essential for heart development up to embryonic day 11.5, but not thereafter. CAR is not expressed in vascular endothelial cells but was recently detected in neonatal lymphatic vessels, suggesting that CAR could play a role in the development of the lymphatic system. To address this, we generated mice carrying a conditional deletion of the CAR gene (Cxadr) and knocked out CAR in the mouse embryo at different time points during post-cardiac development. Deletion of Cxadr from E12.5, but not from E13.5, resulted in subcutaneous edema, hemorrhage and embryonic death. Subcutaneous lymphatic vessels were dilated and structurally abnormal with gaps and holes present at lymphatic endothelial cell-cell junctions. Furthermore, lymphatic vessels were filled with erythrocytes showing a defect in the separation between the blood and lymphatic systems. Regionally, erythrocytes leaked out into the interstitium from leaky lymphatic vessels explaining the hemorrhage detected in CAR-deficient mouse embryos. The results show that CAR plays an essential role in development of the lymphatic vasculature in the mouse embryo by promoting appropriate formation of lymphatic endothelial cell-cell junctions.

  8. Monitoring the primo vascular system in lymphatic vessels by using window chambers.

    PubMed

    Kim, Jungdae; Kim, Dong-Hyun; Jung, Sharon Jiyoon; Gil, Hyun-Ji; Yoon, Seung Zhoo; Kim, Young-Il; Soh, Kwang-Sup

    2016-04-01

    This study aims to develop a window chamber system in the skin of rats and to monitor the primo vascular system (PVS) inside the lymphatic vessels along the superficial epigastric vessels. The PVS in lymphatic vessels has been observed through many experiments under in vivo conditions, but monitoring the in vivo PVS in situ inside lymphatic vessels for a long time is difficult. To overcome the obstacles, we adapted the window chamber system for monitoring the PVS and Alcian blue (AB) staining dye solution for the contrast agent. The lymphatic vessels in the skin on the lateral side of the body, connecting the inguinal lymph nodes to the axillary lymph nodes, were the targets for setting the window system. After AB had been injected into the inguinal lymph nodes with a glass capillary, the morphological changes of the stained PVS were monitored through the window system for up to twenty hours, and the changes in the AB intensity in the PVS were quantified by using image processing. The results and histological images are presented in this study.

  9. Monitoring the primo vascular system in lymphatic vessels by using window chambers.

    PubMed

    Kim, Jungdae; Kim, Dong-Hyun; Jung, Sharon Jiyoon; Gil, Hyun-Ji; Yoon, Seung Zhoo; Kim, Young-Il; Soh, Kwang-Sup

    2016-04-01

    This study aims to develop a window chamber system in the skin of rats and to monitor the primo vascular system (PVS) inside the lymphatic vessels along the superficial epigastric vessels. The PVS in lymphatic vessels has been observed through many experiments under in vivo conditions, but monitoring the in vivo PVS in situ inside lymphatic vessels for a long time is difficult. To overcome the obstacles, we adapted the window chamber system for monitoring the PVS and Alcian blue (AB) staining dye solution for the contrast agent. The lymphatic vessels in the skin on the lateral side of the body, connecting the inguinal lymph nodes to the axillary lymph nodes, were the targets for setting the window system. After AB had been injected into the inguinal lymph nodes with a glass capillary, the morphological changes of the stained PVS were monitored through the window system for up to twenty hours, and the changes in the AB intensity in the PVS were quantified by using image processing. The results and histological images are presented in this study. PMID:27446651

  10. Monitoring the primo vascular system in lymphatic vessels by using window chambers

    PubMed Central

    Kim, Jungdae; Kim, Dong-Hyun; Jung, Sharon Jiyoon; Gil, Hyun-Ji; Yoon, Seung Zhoo; Kim, Young-Il; Soh, Kwang-Sup

    2016-01-01

    This study aims to develop a window chamber system in the skin of rats and to monitor the primo vascular system (PVS) inside the lymphatic vessels along the superficial epigastric vessels. The PVS in lymphatic vessels has been observed through many experiments under in vivo conditions, but monitoring the in vivo PVS in situ inside lymphatic vessels for a long time is difficult. To overcome the obstacles, we adapted the window chamber system for monitoring the PVS and Alcian blue (AB) staining dye solution for the contrast agent. The lymphatic vessels in the skin on the lateral side of the body, connecting the inguinal lymph nodes to the axillary lymph nodes, were the targets for setting the window system. After AB had been injected into the inguinal lymph nodes with a glass capillary, the morphological changes of the stained PVS were monitored through the window system for up to twenty hours, and the changes in the AB intensity in the PVS were quantified by using image processing. The results and histological images are presented in this study. PMID:27446651

  11. Roles of dextrans on improving lymphatic drainage for liposomal drug delivery system.

    PubMed

    Feng, Linglin; Zhang, Lei; Liu, Min; Yan, Zhiqiang; Wang, Chenyu; Gu, Bing; Liu, Yu; Wei, Gang; Zhong, Gaoren; Lu, Weiyue

    2010-04-01

    Our aim was to develop a novel liposomal drug delivery system containing dextrans to reduce undesirable retention of antineoplastic agents and thus alleviate local tissue damage. At the cell level, diethylaminoethyl-dextran (DEAE-Dx) showed the strongest inhibiting effect on liposome uptake by macrophages among tested dextrans. The distribution of radiolabeled liposomes mixed with dextrans in injection site and draining lymph node was investigated in rats after subcutaneous injection. DEAE-Dx substantially reduced the undesired local retention and promoted the draining of liposome into lymphatics, which was further confirmed by confocal microscopy images revealing the substantial prevention of rhodamine B-labelled liposome sequestration by macrophages in normal lymph node in rats. Pharmacokinetic data indicated the accelerated drainage of liposome through lymphatics back to systemic circulation by mixing with DEAE-Dx. In the toxicological study in rabbits, DEAE-Dx alleviated the local tissue damage caused by liposomal doxorubicin. In conclusion, dextrans, particularly DEAE-Dx, could efficiently enhanced liposomes drainage into lymphatics, which proves themselves as promising adjuvants for lymphatic-targeted liposomal drug delivery system.

  12. An in situ optical imaging system for measuring lipid uptake, vessel contraction, and lymph flow in small animal lymphatic vessels

    NASA Astrophysics Data System (ADS)

    Kassis, Timothy; Weiler, Michael J.; Dixon, J. Brandon

    2012-03-01

    All dietary lipids are transported to venous circulation through the lymphatic system, yet the underlying mechanisms that regulate this process remain unclear. Understanding how the lymphatics functionally respond to changes in lipid load is important in the diagnosis and treatment of lipid and lymphatic related diseases such as obesity, hypercholesterolemia, and lymphedema. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. A custom-built optical set-up provides us with the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. This is achieved by dividing the light path into two optical bands. Utilizing high-speed and back-illuminated CCD cameras and post-acquisition image processing algorithms, we have the potential quantify correlations between vessel contraction, lymph flow and lipid concentration of mesenteric lymphatic vessels in situ. Local flow velocity is measured through lymphocyte tracking, vessel contraction through measurements of the vessel walls and lipid uptake through fluorescence intensity tracking of a fluorescent long chain fatty acid analogue, Bodipy FL C16. This system will prove to be an invaluable tool for both scientists studying lymphatic function in health and disease, and those investigating strategies for targeting the lymphatic system with orally delivered drugs.

  13. Dual-channel in-situ optical imaging system for quantifying lipid uptake and lymphatic pump function

    NASA Astrophysics Data System (ADS)

    Kassis, Timothy; Kohan, Alison B.; Weiler, Michael J.; Nipper, Matthew E.; Cornelius, Rachel; Tso, Patrick; Brandon Dixon, J.

    2012-08-01

    Nearly all dietary lipids are transported from the intestine to venous circulation through the lymphatic system, yet the mechanisms that regulate this process remain unclear. Elucidating the mechanisms involved in the functional response of lymphatics to changes in lipid load would provide valuable insight into recent implications of lymphatic dysfunction in lipid related diseases. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. The imaging platform provides the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. Utilizing post-acquisition image processing algorithms, we can quantify correlations between vessel pump function, lymph flow, and lipid concentration of mesenteric lymphatic vessels in situ. All image analysis is automated with customized LabVIEW virtual instruments; local flow is measured through lymphocyte velocity tracking, vessel contraction through measurements of the vessel wall displacement, and lipid uptake through fluorescence intensity tracking of an orally administered fluorescently labelled fatty acid analogue, BODIPY FL C16. This system will prove to be an invaluable tool for scientists studying intestinal lymphatic function in health and disease, and those investigating strategies for targeting the lymphatics with orally delivered drugs to avoid first pass metabolism.

  14. Dual-channel in-situ optical imaging system for quantifying lipid uptake and lymphatic pump function

    PubMed Central

    Kassis, Timothy; Kohan, Alison B.; Weiler, Michael J.; Nipper, Matthew E.; Cornelius, Rachel; Tso, Patrick

    2012-01-01

    Abstract. Nearly all dietary lipids are transported from the intestine to venous circulation through the lymphatic system, yet the mechanisms that regulate this process remain unclear. Elucidating the mechanisms involved in the functional response of lymphatics to changes in lipid load would provide valuable insight into recent implications of lymphatic dysfunction in lipid related diseases. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. The imaging platform provides the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. Utilizing post-acquisition image processing algorithms, we can quantify correlations between vessel pump function, lymph flow, and lipid concentration of mesenteric lymphatic vessels in situ. All image analysis is automated with customized LabVIEW virtual instruments; local flow is measured through lymphocyte velocity tracking, vessel contraction through measurements of the vessel wall displacement, and lipid uptake through fluorescence intensity tracking of an orally administered fluorescently labelled fatty acid analogue, BODIPY FL C16. This system will prove to be an invaluable tool for scientists studying intestinal lymphatic function in health and disease, and those investigating strategies for targeting the lymphatics with orally delivered drugs to avoid first pass metabolism. PMID:23224192

  15. Peri-articular lymphatic system and "Bi" theory of Chinese medicine in the pathogenesis and treatment of arthritis.

    PubMed

    Liang, Qian-Qian; Shi, Qi; Wood, Ronald W; Xing, Lian-Ping; Wang, Yong-Jun

    2015-09-01

    Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most common joint diseases, and they have characterization of synovial inflammation and cartilage destruction, associated with the accumulation of numerous catabolic mediators and inflammatory cells in the synovial space and surrounding soft tissues. How these factors are cleared and if the "clearance" process contributes to pathogenesis of arthritis are not known. Recently, we found the existence of the peri-articular lymphatic system in mouse joints. The blockade of lymphangiogenesis and lymphatic draining function accelerates while stimulation of lymphatic function attenuates the severity of joint tissue lesions in mouse models of RA and OA. More importantly, we noticed the similarity between the dysfunction of lymphatic drainage in arthritic joints and "Bi" theory of Chinese medicine (CM), and demonstrated that several Bi disease-treated herbal drugs directly affect the function of lymphatic endothelial cells. Here we review the advances about the interactions between joint inflammation and changes in the peri-articular lymphatic system and discuss our view of linking "Bi" theory of CM to lymphatic dysfunction in arthritis.

  16. Use of a whole-slide imaging system to assess the presence and alteration of lymphatic vessels in joint sections of arthritic mice.

    PubMed

    Shi, J X; Liang, Q Q; Wang, Y J; Mooney, R A; Boyce, B F; Xing, L

    2013-11-01

    We investigated the presence and alteration of lymphatic vessels in joints of arthritic mice using a whole-slide imaging system. Joints and long bone sections were cut from paraffin blocks of two mouse models of arthritis: meniscal-ligamentous injury (MLI)-induced osteoarthritis (OA) and TNF transgene (TNF-Tg)-induced rheumatoid arthritis (RA). MLI-OA mice were fed a high fat diet to accelerate OA development. TNF-Tg mice were treated with lymphatic growth factor VEGF-C virus to stimulate lymphangiogenesis. Sections were double immunofluorescence stained with anti-podoplanin and alpha-smooth muscle actin antibodies. The area and number of lymphatic capillaries and mature lymphatic vessels were determined using a whole-slide imaging system and its associated software. Lymphatic vessels in joints were distributed in soft tissues mainly around the joint capsule, ligaments, fat pads and muscles. In long bones, enriched lymphatic vessels were present in the periosteal areas adjacent to the blood vessels. Occasionally, lymphatic vessels were observed in the cortical bone. Increased lymphatic capillaries, but decreased mature lymphatic vessels, were detected in both OA and RA joints. VEGF-C treatment increased lymphatic capillary and mature vessel formation in RA joints. Our findings suggest that the lymphatic system may play an important role in arthritis pathogenesis and treatment.

  17. Mechanobiology of lymphatic contractions.

    PubMed

    Munn, Lance L

    2015-02-01

    The lymphatic system is responsible for controlling tissue fluid pressure by facilitating flow of lymph (i.e. the plasma and cells that enter the lymphatic system). Because lymph contains cells of the immune system, its transport is not only important for fluid homeostasis, but also immune function. Lymph drainage can occur via passive flow or active pumping, and much research has identified the key biochemical and mechanical factors that affect output. Although many studies and reviews have addressed how tissue properties and fluid mechanics (i.e. pressure gradients) affect lymph transport [1-3] there is less known about lymphatic mechanobiology. As opposed to passive mechanical properties, mechanobiology describes the active coupling of mechanical signals and biochemical pathways. Lymphatic vasomotion is the result of a fascinating system affected by mechanical forces exerted by the flowing lymph, including pressure-induced vessel stretch and flow-induced shear stresses. These forces can trigger or modulate biochemical pathways important for controlling the lymphatic contractions. Here, I review the current understanding of lymphatic vessel function, focusing on vessel mechanobiology, and summarize the prospects for a comprehensive understanding that integrates the mechanical and biomechanical control mechanisms in the lymphatic system.

  18. Lymphatics and the breast

    MedlinePlus

    ... is often referred to as the body's "secondary circulatory system." The lymphatic system collects excess fluid in ... the exchange of fluid and molecules between the blood circulation and body tissues, blood capillaries may not reabsorb ...

  19. Ex-Vivo Lymphatic Perfusion System for Independently Controlling Pressure Gradient and Transmural Pressure in Isolated Vessels

    PubMed Central

    Kornuta, Jeffrey A.; Dixon, J. Brandon

    2015-01-01

    In addition to external forces, collecting lymphatic vessels intrinsically contract to transport lymph from the extremities to the venous circulation. As a result, the lymphatic endothelium is routinely exposed to a wide range of dynamic mechanical forces, primarily fluid shear stress and circumferential stress, which have both been shown to affect lymphatic pumping activity. Although various ex-vivo perfusion systems exist to study this innate pumping activity in response to mechanical stimuli, none are capable of independently controlling the two primary mechanical forces affecting lymphatic contractility: transaxial pressure gradient, ΔP, which governs fluid shear stress; and average transmural pressure, Pavg, which governs circumferential stress. Hence, the authors describe a novel ex-vivo lymphatic perfusion system (ELPS) capable of independently controlling these two outputs using a linear, explicit model predictive control (MPC) algorithm. The ELPS is capable of reproducing arbitrary waveforms within the frequency range observed in the lymphatics in vivo, including a time-varying ΔP with a constant Pavg, time-varying ΔP and Pavg, and a constant ΔP with a time-varying Pavg. In addition, due to its implementation of syringes to actuate the working fluid, a post-hoc method of estimating both the flow rate through the vessel and fluid wall shear stress over multiple, long (5 sec) time windows is also described. PMID:24809724

  20. Mapping superficial lymphatic territories in the rabbit.

    PubMed

    Soto-Miranda, Miguel A; Suami, Hiroo; Chang, David W

    2013-06-01

    Little is known about the anatomy of the lymphatic system in the rabbit with regard to relationships between the lymphatic vessel and lymph node. According to our previous studies in human cadavers and canines, the superficial lymphatic system could be divided into lymphatic territories. The aim of this study was to completely map the superficial lymphatic system in the rabbit. We used our microinjection technique and histological analysis for dissecting studies and recently developed indocyanine green (ICG) fluorescent lymphography for demonstrating dynamic lymph flow in living rabbits. Real-time ICG fluorescent lymphography was performed in two living New Zealand White rabbits, and direct dye microinjection of the lymphatic vessels was performed in eight dead rabbits. To assess the relationships between the vascular and lymphatic systems in rabbits, we performed radiocontrast injection into arteries in two dead rabbits prior to the lymphatic injection. The ICG fluorescent lymphography revealed eight lymphatic territories in the preauricular, submandibular, root of the lateral neck, axillary, lumbar, inguinal, root of the tail, and popliteal regions. We injected blue acrylic dye into every lymphatic vessel 0.1 mm in diameter or larger. We then dissected and chased the stained lymphatic vessels proximally until the vessels connected to the first tier lymph node. This procedure was repeated throughout the body until all the relationships between the lymphatic vessels and lymph nodes were defined. The lymphatic system of the rabbit could be defined as eight lymphatic territories, each with its own lymphatic vessels and lymph node.

  1. Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system.

    PubMed

    Kodama, Tetsuya; Hatakeyama, Yuriko; Kato, Shigeki; Mori, Shiro

    2015-01-01

    Curing/preventing micrometastasis to lymph nodes (LNs) located outside the surgically resected area is essential for improving the morbidity and mortality associated with breast cancer and head and neck cancer. However, no lymphatic therapy system exists that can deliver drugs to LNs located outside the dissection area. Here, we demonstrate proof of concept for a drug delivery system using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs being as large as 10 mm in diameter. We report that a fluorescent solution injected into the subiliac LN (defined as the upstream LN within the dissection area) was delivered successfully to the proper axillary LN (defined as the downstream LN outside the dissection area) through the lymphatic vessels. Our results suggest that this approach could be used before surgical resection to deliver drugs to downstream LNs outside the dissection area. We anticipate that our methodology could be applied clinically, before surgical resection, to cure/prevent micrometastasis in LNs outside the dissection area, using techniques such as ultrasound-guided internal jugular vein catheterization. PMID:25657881

  2. Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system.

    PubMed

    Kodama, Tetsuya; Hatakeyama, Yuriko; Kato, Shigeki; Mori, Shiro

    2015-01-01

    Curing/preventing micrometastasis to lymph nodes (LNs) located outside the surgically resected area is essential for improving the morbidity and mortality associated with breast cancer and head and neck cancer. However, no lymphatic therapy system exists that can deliver drugs to LNs located outside the dissection area. Here, we demonstrate proof of concept for a drug delivery system using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs being as large as 10 mm in diameter. We report that a fluorescent solution injected into the subiliac LN (defined as the upstream LN within the dissection area) was delivered successfully to the proper axillary LN (defined as the downstream LN outside the dissection area) through the lymphatic vessels. Our results suggest that this approach could be used before surgical resection to deliver drugs to downstream LNs outside the dissection area. We anticipate that our methodology could be applied clinically, before surgical resection, to cure/prevent micrometastasis in LNs outside the dissection area, using techniques such as ultrasound-guided internal jugular vein catheterization.

  3. Absence of Lymphatic Vessels in PCNSL May Contribute to Confinement of Tumor Cells to the Central Nervous System.

    PubMed

    Deckert, Martina; Brunn, Anna; Montesinos-Rongen, Manuel; Siebert, Reiner

    2016-06-01

    Primary central nervous system (CNS) lymphoma (PCNSL) is a mature lymphoma of the diffuse large B-cell lymphoma (DLBCL) type confined to the CNS. Despite cytomorphological similarities between PCNSL and systemic DLBCL, molecular differences between both entities have been identified. The exclusively topographical restriction of PCNSL to the CNS is an unexplained mystery. To address the question of whether the unique lymphatic drainage system of the CNS, which differs from that of other organs, may play a role for this peculiar behavior, we investigated a series of 20 PCNSLs for the presence of lymphatic vessels by immunohistochemistry for Lyve-1, podoplanin, and Prox-1 expression. All PCNSLs lacked lymphatic vessels and, in this regard, were similar to 20 glioblastoma multiforme samples. In contrast to these tumors, all of which were located in the deep brain parenchyma, dural and meningeal DLBCL harbored lymphatic vessels that expressed Lyve-1 (3/8 tumors), podoplanin (5/8 tumors), and Prox-1 (5/8 tumors) in areas where the tumors had invaded the fibrous tissue of the dura. These data indicate that local topographical characteristics of the specific lymphatic drainage system may contribute to confinement of the tumor cells in PCNSL and malignant gliomas.

  4. Absence of Lymphatic Vessels in PCNSL May Contribute to Confinement of Tumor Cells to the Central Nervous System.

    PubMed

    Deckert, Martina; Brunn, Anna; Montesinos-Rongen, Manuel; Siebert, Reiner

    2016-06-01

    Primary central nervous system (CNS) lymphoma (PCNSL) is a mature lymphoma of the diffuse large B-cell lymphoma (DLBCL) type confined to the CNS. Despite cytomorphological similarities between PCNSL and systemic DLBCL, molecular differences between both entities have been identified. The exclusively topographical restriction of PCNSL to the CNS is an unexplained mystery. To address the question of whether the unique lymphatic drainage system of the CNS, which differs from that of other organs, may play a role for this peculiar behavior, we investigated a series of 20 PCNSLs for the presence of lymphatic vessels by immunohistochemistry for Lyve-1, podoplanin, and Prox-1 expression. All PCNSLs lacked lymphatic vessels and, in this regard, were similar to 20 glioblastoma multiforme samples. In contrast to these tumors, all of which were located in the deep brain parenchyma, dural and meningeal DLBCL harbored lymphatic vessels that expressed Lyve-1 (3/8 tumors), podoplanin (5/8 tumors), and Prox-1 (5/8 tumors) in areas where the tumors had invaded the fibrous tissue of the dura. These data indicate that local topographical characteristics of the specific lymphatic drainage system may contribute to confinement of the tumor cells in PCNSL and malignant gliomas. PMID:27142645

  5. An Experimental Investigation of the Lymphatic System of the Teeth and Jaws

    PubMed Central

    MacGregor, Alexander

    1936-01-01

    A review of the literature is given, followed by a consideration of the available methods of demonstrating the lymphatic system in the area of the teeth and jaws. A new method of demonstrating this system by the injection or application of lead acetate intra vitam, is described, and the technique is explained. The method can be employed to reveal macroscopic or microscopic lymph channels in any part of the body, and is especially of value where decalcification of the hard tissues has to be carried out in the preparation of the sections. The various types of experiments which have been performed are described, and the macroscopic and microscopic results dealt with separately. Among the macroscopic results, the lymphatic drainage of various parts the jaws is described, and the large amount of anastomosis and cross anastomosis between the vessels is shown. A comparison of the lymphatic system in this region in the guinea-pig, cat, dog, and monkey is given, and it is demonstrated that the guinea-pig and monkey possess submental and supraclavicular lymph nodes which assist in the drainage of this area in addition to the submaxillary and cervical groups of nodes possessed by the cat and the dog. Among the microscopic results, the way in which the mass makes its way from the gingival tissues through the bone, and is found in the pulp, dentine, and cementum of the tooth, even where no pressure is applied, is described. The communication of the lymphatic vessels of the pulp with those of the periodontal membrane and the path of the mass down the periodontal membrane from the gingival trough, and its entry into the alveolar bone from this situation are demonstrated, and the way in which the mass reaches the pulp, dentine, and cementum of the tooth from the gingival tissues is discussed. The significance of various concentrations of the mass in the tissues, particularly the dentine, is also discussed. Control experiments are described, the conclusions which have been reached

  6. Lymphatic Filariasis

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Parasites - Lymphatic Filariasis Note: Javascript is disabled or is ... this? Submit Button Information For: Travelers Related Links Parasites A-Z Index Parasites Glossary Neglected Tropical Diseases ...

  7. The lymphatic vasculature in disease.

    PubMed

    Alitalo, Kari

    2011-11-07

    Blood vessels form a closed circulatory system, whereas lymphatic vessels form a one-way conduit for tissue fluid and leukocytes. In most vertebrates, the main function of lymphatic vessels is to collect excess protein-rich fluid that has extravasated from blood vessels and transport it back into the blood circulation. Lymphatic vessels have an important immune surveillance function, as they import various antigens and activated antigen-presenting cells into the lymph nodes and export immune effector cells and humoral response factors into the blood circulation. Defects in lymphatic function can lead to lymph accumulation in tissues, dampened immune responses, connective tissue and fat accumulation, and tissue swelling known as lymphedema. This review highlights the most recent developments in lymphatic biology and how the lymphatic system contributes to the pathogenesis of various diseases involving immune and inflammatory responses and its role in disseminating tumor cells.

  8. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies.

    PubMed

    Han, Sifei; Quach, Tim; Hu, Luojuan; Wahab, Anisa; Charman, William N; Stella, Valentino J; Trevaskis, Natalie L; Simpson, Jamie S; Porter, Christopher J H

    2014-03-10

    A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may enhance immunomodulatory effects. Two classes of lymph-directing prodrugs were synthesised. Alkyl chain derivatives (octyl mycophenolate, MPA-C8E; octadecyl mycophenolate, MPA-C18E; and octadecyl mycophenolamide, MPA-C18AM), to promote passive partitioning into lipids in lymphatic transport pathways, and a triglyceride mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) to facilitate metabolic integration into triglyceride deacylation-reacylation pathways. Lymphatic transport, lymphocyte uptake and plasma pharmacokinetics were assessed in mesenteric lymph and carotid artery cannulated rats following intraduodenal infusion of lipid-based formulations containing MPA or MPA prodrugs. Patterns of prodrug hydrolysis in rat digestive fluid, and cellular re-esterification in vivo, were evaluated to examine the mechanisms responsible for lymphatic transport. Poor enzyme stability and low absorption appeared to limit lymphatic transport of the alkyl derivatives, although two of the three alkyl chain prodrugs - MPA-C18AM (6-fold) and MPA-C18E (13-fold) still increased lymphatic drug transport when compared to MPA. In contrast, 2-MPA-TG markedly increased lymphatic drug transport (80-fold) and drug concentrations in lymphocytes (103-fold), and this was achieved via biochemical incorporation into triglyceride deacylation-reacylation pathways. The prodrug was hydrolysed rapidly to 2-mycophenoloyl glycerol (2-MPA-MG) in the presence of rat digestive fluid, and 2-MPA-MG was subsequently re-esterified in the enterocyte with oleic acid (most likely originating from the co-administered formulation) prior to accessing the

  9. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies.

    PubMed

    Han, Sifei; Quach, Tim; Hu, Luojuan; Wahab, Anisa; Charman, William N; Stella, Valentino J; Trevaskis, Natalie L; Simpson, Jamie S; Porter, Christopher J H

    2014-03-10

    A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may enhance immunomodulatory effects. Two classes of lymph-directing prodrugs were synthesised. Alkyl chain derivatives (octyl mycophenolate, MPA-C8E; octadecyl mycophenolate, MPA-C18E; and octadecyl mycophenolamide, MPA-C18AM), to promote passive partitioning into lipids in lymphatic transport pathways, and a triglyceride mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) to facilitate metabolic integration into triglyceride deacylation-reacylation pathways. Lymphatic transport, lymphocyte uptake and plasma pharmacokinetics were assessed in mesenteric lymph and carotid artery cannulated rats following intraduodenal infusion of lipid-based formulations containing MPA or MPA prodrugs. Patterns of prodrug hydrolysis in rat digestive fluid, and cellular re-esterification in vivo, were evaluated to examine the mechanisms responsible for lymphatic transport. Poor enzyme stability and low absorption appeared to limit lymphatic transport of the alkyl derivatives, although two of the three alkyl chain prodrugs - MPA-C18AM (6-fold) and MPA-C18E (13-fold) still increased lymphatic drug transport when compared to MPA. In contrast, 2-MPA-TG markedly increased lymphatic drug transport (80-fold) and drug concentrations in lymphocytes (103-fold), and this was achieved via biochemical incorporation into triglyceride deacylation-reacylation pathways. The prodrug was hydrolysed rapidly to 2-mycophenoloyl glycerol (2-MPA-MG) in the presence of rat digestive fluid, and 2-MPA-MG was subsequently re-esterified in the enterocyte with oleic acid (most likely originating from the co-administered formulation) prior to accessing the

  10. Polyaminoacid nanocapsules for drug delivery to the lymphatic system: Effect of the particle size.

    PubMed

    Abellan-Pose, Raquel; Teijeiro-Valiño, Carmen; Santander-Ortega, Manuel J; Borrajo, Erea; Vidal, Anxo; Garcia-Fuentes, Marcos; Csaba, Noémi; Alonso, María José

    2016-07-25

    Previous work by our group showed the possibility to reduce the toxicity of docetaxel upon its encapsulation in polyaminoacid nanocapsules with a size of 200nm. The objective of this study was to elucidate whether a reduction in the nanocapsules size might facilitate their access to the lymphatic system. To do so, we analyzed the effect of several formulation parameters on the characteristics of polyglutamic acid, PEGylated polyglutamic acid and polyasparagine nanocapsules. From these experiments, we could identify the best conditions to produce nanocapsules with a small size (close to 100nm) and adequate capacity to encapsulate and sustain the release of the antitumor drug docetaxel. Moreover, the results of the stability study made evident the critical role of the polyaminoacid shell on the colloidal stability of the nanocapsules in biologically relevant media. Finally, we studied the influence of the particle size (100nm vs. 200nm) on the biodistribution of PGA-PEG nanocapsules following subcutaneous injection. The results showed that the 100 nm-size nanocapsules accumulate faster in the lymph nodes, than those with a size of 200nm. In summary, these data suggest the potential of 100nm-size polyaminoacid nanocapsules as lymphatic drug delivery carriers. PMID:27210735

  11. Application of geographical information system for lymphatic filariasis and malaria control in Nigeria.

    PubMed

    Okorie, P N

    2014-06-01

    Geographical Information System (GIS) is defined as an information system used to capture, store, edit, retrieve, analyze and visualize geographically referenced data. The use of GIS is one technology that is very useful in the prevention and control of Vector Borne Diseases (VBDs) such as lymphatic filariasis (LF) and malaria which cause high morbidity and mortality in Nigeria. This paper focuses on how the use of Geographical Information System (GIS) can be harnessed for surveillance, prevention and control of LF and malaria in Nigeria. GIS can be used as an operational tool to assist with resource allocation, as a monitoring and evaluation tool and as a tool to investigate various research projects on spatial aspects of LF and malaria epidemiology. This paper provides information on the benefits and potential of using GIS as a tool for the national malaria and LF control programmes with particular reference to Nigeria.

  12. lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic vessel development in zebrafish.

    PubMed

    Okuda, Kazuhide S; Astin, Jonathan W; Misa, June P; Flores, Maria V; Crosier, Kathryn E; Crosier, Philip S

    2012-07-01

    We have generated novel transgenic lines that brightly mark the lymphatic system of zebrafish using the lyve1 promoter. Facilitated by these new transgenic lines, we generated a map of zebrafish lymphatic development up to 15 days post-fertilisation and discovered three previously uncharacterised lymphatic vessel networks: the facial lymphatics, the lateral lymphatics and the intestinal lymphatics. We show that a facial lymphatic vessel, termed the lateral facial lymphatic, develops through a novel developmental mechanism, which initially involves vessel growth through a single vascular sprout followed by the recruitment of lymphangioblasts to the vascular tip. Unlike the lymphangioblasts that form the thoracic duct, the lymphangioblasts that contribute to the lateral facial lymphatic vessel originate from a number of different blood vessels. Our work highlights the additional complexity of lymphatic vessel development in the zebrafish that may increase its versatility as a model of lymphangiogenesis.

  13. A study of the topography of the lymphatic system of the Australian brushtail possum (Trichosurus vulpecula).

    PubMed Central

    Jackson, R; Morris, R S

    1996-01-01

    The superficial and deep lymphatic systems of the Australian brushtail possum (Trichosurus vulpecula) are described. In common with other marsupials studied to date and in contrast with most eutherians, there were no popliteal lymph nodes and efferent drainage from the inguinal lymph centre passed directly to the deep axillary group of lymph nodes via an inguinoaxillary trunk. Efferent vessels from the tonsil passed directly to the deep cervical lymph node, which was drained by the tracheal trunk. The mandibular and parotid lymph nodes drained independently to the superficial cervical lymph node. All subcutaneous lymph drainage passed either through the superficial cervical or the axillary lymph centres before entering the venous system, an arrangement which is also found in kangaroos. The significance of the patterns of lesion distributions in possums with naturally occurring tuberculosis caused by Mycobacterium bovis is discussed. PMID:8763477

  14. Vascular, glial, and lymphatic immune gateways of the central nervous system.

    PubMed

    Engelhardt, Britta; Carare, Roxana O; Bechmann, Ingo; Flügel, Alexander; Laman, Jon D; Weller, Roy O

    2016-09-01

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer's disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

  15. Vascular, glial, and lymphatic immune gateways of the central nervous system.

    PubMed

    Engelhardt, Britta; Carare, Roxana O; Bechmann, Ingo; Flügel, Alexander; Laman, Jon D; Weller, Roy O

    2016-09-01

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer's disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system. PMID:27522506

  16. Vascular Endothelial Growth Factor D Is Dispensable for Development of the Lymphatic System

    PubMed Central

    Baldwin, Megan E.; Halford, Michael M.; Roufail, Sally; Williams, Richard A.; Hibbs, Margaret L.; Grail, Dianne; Kubo, Hajime; Stacker, Steven A.; Achen, Marc G.

    2005-01-01

    Vascular endothelial growth factor receptor 3 (Vegfr-3) is a tyrosine kinase that is expressed on the lymphatic endothelium and that signals for the growth of the lymphatic vessels (lymphangiogenesis). Vegf-d, a secreted glycoprotein, is one of two known activating ligands for Vegfr-3, the other being Vegf-c. Vegf-d stimulates lymphangiogenesis in tissues and tumors; however, its role in embryonic development was previously unknown. Here we report the generation and analysis of mutant mice deficient for Vegf-d. Vegf-d-deficient mice were healthy and fertile, had normal body mass, and displayed no pathologic changes consistent with a defect in lymphatic function. The lungs, sites of strong Vegf-d gene expression during embryogenesis in wild-type mice, were normal in Vegf-d-deficient mice with respect to tissue mass and morphology, except that the abundance of the lymphatics adjacent to bronchioles was slightly reduced. Dye uptake experiments indicated that large lymphatics under the skin were present in normal locations and were functional. Smaller dermal lymphatics were similar in number, location, and function to those in wild-type controls. The lack of a profound lymphatic phenotype in Vegf-d-deficient mice suggests that Vegf-d does not play a major role in lymphatic development or that Vegf-c or another, as-yet-unknown activating Vegfr-3 ligand can compensate for Vegf-d during development. PMID:15743836

  17. Design of lipid-based delivery systems for improving lymphatic transport and bioavailability of delta-tocopherol and nobiletin

    NASA Astrophysics Data System (ADS)

    Xia, Chunxin

    Lymphatic drug transport can confer bioavailability advantage by avoiding the first-pass metabolism normally observed in the portal vein hepatic route. It was reported that long chain lipid-based delivery systems can stimulate the formation of chylomicron and thus promote the lymphatic transport of drugs. In this study, a novel delta-tocopherol (delta-T) loaded Solid Lipid Nanoparticle (SLN) system was developed to investigate its effect on promoting the lymphatic transport of delta-T. The delta-T SLN was prepared with hot melt emulsification method by using glyceryl behenate (compritol RTM888) as the lipid phase and lecithin (PC75) as the emulsifier. Formula configuration, processing condition and loading capacity were carefully optimized. Physicochemical properties (particle size, surface charge, morphology) were also characterized. Moreover, excellent stability of the developed delta-T SLN in the gastrointestinal environment was observed by using an in vitro digestion model. Further investigations of the SLN in stimulating delta-T lymphatic transport were performed on mice without cannulation. Compared with the control group (delta-T corn oil dispersion), much lower delta-T levels in both blood and liver indicated reduced portal vein and hepatic transport of delta-T in the form of SLN. On the other hand, significantly higher concentrations of delta-T were observed in thymus, a major lymphatic tissue, indicating improved lymphatic transport of delta-T with the SLN delivery system. Finally, the far less excreted delta-T level in feces further confirmed improved lymphatic transport and overall bioavailability of delta-T by using SLN system. Nobiletin (NOB), one of most abundant polymethoxyflavones (PMFs) found in Citrus genus, has a low solubility in both water and oil at ambient temperatures. Thus it tends to form crystals when the loading exceeds its saturation level in the carrier system. This character greatly impaired its bioavailability and application. To

  18. TGF-β1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis.

    PubMed

    Pang, M-F; Georgoudaki, A-M; Lambut, L; Johansson, J; Tabor, V; Hagikura, K; Jin, Y; Jansson, M; Alexander, J S; Nelson, C M; Jakobsson, L; Betsholtz, C; Sund, M; Karlsson, M C I; Fuxe, J

    2016-02-11

    Tumor cells frequently disseminate through the lymphatic system during metastatic spread of breast cancer and many other types of cancer. Yet it is not clear how tumor cells make their way into the lymphatic system and how they choose between lymphatic and blood vessels for migration. Here we report that mammary tumor cells undergoing epithelial-mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β1) become activated for targeted migration through the lymphatic system, similar to dendritic cells (DCs) during inflammation. EMT cells preferentially migrated toward lymphatic vessels compared with blood vessels, both in vivo and in 3D cultures. A mechanism of this targeted migration was traced to the capacity of TGF-β1 to promote CCR7/CCL21-mediated crosstalk between tumor cells and lymphatic endothelial cells. On one hand, TGF-β1 promoted CCR7 expression in EMT cells through p38 MAP kinase-mediated activation of the JunB transcription factor. Blockade of CCR7, or treatment with a p38 MAP kinase inhibitor, reduced lymphatic dissemination of EMT cells in syngeneic mice. On the other hand, TGF-β1 promoted CCL21 expression in lymphatic endothelial cells. CCL21 acted in a paracrine fashion to mediate chemotactic migration of EMT cells toward lymphatic endothelial cells. The results identify TGF-β1-induced EMT as a mechanism, which activates tumor cells for targeted, DC-like migration through the lymphatic system. Furthermore, it suggests that p38 MAP kinase inhibition may be a useful strategy to inhibit EMT and lymphogenic spread of tumor cells.

  19. Fluid-solid modeling of lymphatic valves

    NASA Astrophysics Data System (ADS)

    Caulk, Alexander; Ballard, Matthew; Nepiyushchikh, Zhanna; Dixon, Brandon; Alexeev, Alexander

    2015-11-01

    The lymphatic system performs important physiological functions such as the return of interstitial fluid to the bloodstream to maintain tissue fluid balance, as well as the transport of immune cells in the body. It utilizes contractile lymphatic vessels, which contain valves that open and close to allow flow in only one direction, to directionally pump lymph against a pressure gradient. We develop a fluid-solid model of geometrically representative lymphatic valves. Our model uses a hybrid lattice-Boltzmann lattice spring method to capture fluid-solid interactions with two-way coupling between a viscous fluid and lymphatic valves in a lymphatic vessel. We use this model to investigate the opening and closing of lymphatic valves, and its effect on lymphatic pumping. This helps to broaden our understanding of the fluid dynamics of the lymphatic system.

  20. Communication protocol standards for space data systems

    NASA Technical Reports Server (NTRS)

    Hooke, Adrian J.; Desjardins, Richard

    1990-01-01

    The main elements and requirements of advanced space data networks are identified. The communication protocol standards for use on space missions during the coming decades are described. In particular, the blending of high-performance space-unique data transmission techniques with off-the-shelf open systems interconnection (OSI) protocols is described.

  1. A verification system of RMAP protocol controller

    NASA Astrophysics Data System (ADS)

    Khanov, V. Kh; Shakhmatov, A. V.; Chekmarev, S. A.

    2015-01-01

    The functional verification problem of IP blocks of RMAP protocol controller is considered. The application of the verification method using fully- functional models of the processor and the internal bus of a system-on-chip is justified. Principles of construction of a verification system based on the given approach are proposed. The practical results of creating a system of verification of IP block of RMAP protocol controller is presented.

  2. Clear-cut observation of clearance of sustainable upconverting nanoparticles from lymphatic system of small living mice

    PubMed Central

    Park, Hye Sun; Nam, Sang Hwan; Kim, Jongwoo; Shin, Hyung Seon; Suh, Yung Doug; Hong, Kwan Soo

    2016-01-01

    The significance of lymphatic system has gathered great attention for immunotechnology related to cancer metastasis and immunotherapy. To develop innovative immunodiagnostics and immunotherapy in in vivo environments, it is very important to understand excretion pathways and clearance of injected cargoes. Herein, we employed Tm3+-doped upconverting nanoparticles (UCNPs) with versatile advantages suitable for long-term non-invasive in vivo optical imaging and tracking. Transport and retention of the UCNPs in the lymphatic system were evaluated with high-quality NIR-to-NIR upconversion luminescence (UCL) imaging. We obtained their kinetic luminescence profiles for the injection site and sentinel lymph node (SLN) and observed luminescence signals for one month; we also examined UCL images in SLN tissues, organs, and faeces at each time point. We speculate that the injected UCNPs in a footpad of a small mouse are transported rapidly from the lymphatic system to the blood system and then eventually result in an efficient excretion by the hepatobiliary route. These results will support development of novel techniques for SLN biopsy as well as immunotechnology. PMID:27265267

  3. Clear-cut observation of clearance of sustainable upconverting nanoparticles from lymphatic system of small living mice

    NASA Astrophysics Data System (ADS)

    Park, Hye Sun; Nam, Sang Hwan; Kim, Jongwoo; Shin, Hyung Seon; Suh, Yung Doug; Hong, Kwan Soo

    2016-06-01

    The significance of lymphatic system has gathered great attention for immunotechnology related to cancer metastasis and immunotherapy. To develop innovative immunodiagnostics and immunotherapy in in vivo environments, it is very important to understand excretion pathways and clearance of injected cargoes. Herein, we employed Tm3+-doped upconverting nanoparticles (UCNPs) with versatile advantages suitable for long-term non-invasive in vivo optical imaging and tracking. Transport and retention of the UCNPs in the lymphatic system were evaluated with high-quality NIR-to-NIR upconversion luminescence (UCL) imaging. We obtained their kinetic luminescence profiles for the injection site and sentinel lymph node (SLN) and observed luminescence signals for one month; we also examined UCL images in SLN tissues, organs, and faeces at each time point. We speculate that the injected UCNPs in a footpad of a small mouse are transported rapidly from the lymphatic system to the blood system and then eventually result in an efficient excretion by the hepatobiliary route. These results will support development of novel techniques for SLN biopsy as well as immunotechnology.

  4. Clear-cut observation of clearance of sustainable upconverting nanoparticles from lymphatic system of small living mice.

    PubMed

    Park, Hye Sun; Nam, Sang Hwan; Kim, Jongwoo; Shin, Hyung Seon; Suh, Yung Doug; Hong, Kwan Soo

    2016-01-01

    The significance of lymphatic system has gathered great attention for immunotechnology related to cancer metastasis and immunotherapy. To develop innovative immunodiagnostics and immunotherapy in in vivo environments, it is very important to understand excretion pathways and clearance of injected cargoes. Herein, we employed Tm(3+)-doped upconverting nanoparticles (UCNPs) with versatile advantages suitable for long-term non-invasive in vivo optical imaging and tracking. Transport and retention of the UCNPs in the lymphatic system were evaluated with high-quality NIR-to-NIR upconversion luminescence (UCL) imaging. We obtained their kinetic luminescence profiles for the injection site and sentinel lymph node (SLN) and observed luminescence signals for one month; we also examined UCL images in SLN tissues, organs, and faeces at each time point. We speculate that the injected UCNPs in a footpad of a small mouse are transported rapidly from the lymphatic system to the blood system and then eventually result in an efficient excretion by the hepatobiliary route. These results will support development of novel techniques for SLN biopsy as well as immunotechnology. PMID:27265267

  5. Lymphatic Territories (Lymphosomes) in a Canine: An Animal Model for Investigation of Postoperative Lymphatic Alterations

    PubMed Central

    Suami, Hiroo; Yamashita, Shuji; Soto-Miranda, Miguel A.; Chang, David W.

    2013-01-01

    Background Lymph node dissection is often performed as a part of surgical treatment for breast cancer and malignant melanoma to prevent malignant cells from traveling via the lymphatic system. Currently little is known about postoperative lymphatic drainage pattern alterations. This knowledge may be useful for management of recurrent cancer and prevention of breast cancer related lymphedema. We mapped the complete superficial lymphatic system of a dog and used this canine model to perform preliminary studies of lymphatic architectural changes in postoperative condition. Methods Lymphatic territories (lymphosomes) were mapped with 4 female mongrel carcasses using an indocyanine green (ICG) fluorescent lymphography and a radiographic microinjection technique. Two live dogs were then subjected to unilateral lymph node dissection of lymph basins of the forelimb, and ICG lymphography and lymphangiogram were performed 6 months after the surgery to investigate lymphatic changes. Lymphatic patterns in the carcass were then compared with postoperative lymphatic patterns in the live dogs. Results Ten lymphosomes were identified, corresponding with ten lymphatic basins. Postoperative fluorescent lymphographic images and lymphangiograms in the live dogs revealed small caliber lymphatic network fulfilling gaps in the surgical area and collateral lymphatic vessels arising from the network connecting to lymph nodes in the contralateral and ipsilateral neck in one dog and the ipsilateral subclavicular vein in another dog. Conclusion Our canine lymphosome map allowed us to observe lymphatic collateral formations after lymph node dissection in live dogs. This canine model may help clarify our understanding of postoperative lymphatic changes in humans in future studies. PMID:23894435

  6. Oncotherapy: A System for Requesting Chemotherapy Protocols.

    PubMed

    Righi, Laura Vera

    2015-01-01

    A clinical decision support system is able to provide oncologists with suitable treatment options at the moment of decision making regarding which chemotherapy protocol is the best to apply to a particular oncological case. The National Cancer Institute has created a Guidelines Committee that establishes therapeutical options for each clinical case. The Health Informatics Department has developed Oncotherapy, a knowledge database that incorporates information provided by the Guidelines Committee. Oncotherapy includes a tailored information repository to provide oncologists in the public health system with the chemotherapy protocols available given three types of data: clinical diagnosis, clinical stage and therapy criteria. The protocol selected by the treating oncologist is sent back to Oncotherapy, which may create new knowledge that can be incorporated into the knowledge database. In this way, the system supports making the best decision according to the chemotherapy protocol options available. Furthermore, it can warn of errors that could result from mistakenly chosen therapies. PMID:26262420

  7. A Novel Treatment Method for Lymph Node Metastasis Using a Lymphatic Drug Delivery System with Nano/Microbubbles and Ultrasound

    PubMed Central

    Kato, Shigeki; Mori, Shiro; Kodama, Tetsuya

    2015-01-01

    Chemotherapy based on hematogenous administration of drugs to lymph nodes (LNs) located outside the surgically resected area shows limited tissue selectivity and inadequate response rates, resulting in poor prognosis. Here, we demonstrate proof of concept for a lymphatic drug delivery system using nano/microbubbles (NMBs) and ultrasound (US) to achieve sonoporation in LNs located outside the dissection area. First, we demonstrated the in vitro effectiveness of doxorubicin (Dox) delivered into three different tumor cell lines by sonoporation. Sonoporation increased the Dox autofluorescence signal and resulted in a subsequent decrease in cell viability. Next, we verified the antitumor effects of Dox in vivo using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs reaching 10 mm in diameter. We defined the subiliac LN (SiLN) as the upstream LN within the dissection area, and the proper axillary LN (PALN) as the downstream LN outside the dissection area. Dox and NMBs were injected into the SiLN and delivered to the PALN via lymphatic vessels; the PALN was then exposed to US when it had filled with solution. We found that sonoporation enhanced the intracellular uptake of Dox leading to high cytotoxicity. We also found that sonoporation induced extravasation of Dox from lymphatic endothelia and penetration of Dox into tumor tissues within the PALN. Furthermore, our method inhibited tumor growth and diminished blood vessels in the PALN while avoiding systemic toxic effects of Dox. Our findings indicate that a lymphatic drug delivery system with sonoporation represents a promising method for treating metastatic LNs located outside the dissection area. PMID:26640589

  8. Lymphatic Anomalies Registry

    ClinicalTrials.gov

    2016-07-26

    Lymphatic Malformation; Generalized Lymphatic Anomaly (GLA); Central Conducting Lymphatic Anomaly; CLOVES Syndrome; Gorham-Stout Disease ("Disappearing Bone Disease"); Blue Rubber Bleb Nevus Syndrome; Kaposiform Lymphangiomatosis; Kaposiform Hemangioendothelioma/Tufted Angioma; Klippel-Trenaunay Syndrome; Lymphangiomatosis

  9. Dynamics of some parameters of the endocrine and lymphatic systems in rats during cold adaptation

    SciTech Connect

    Borodin, Yu.I.; Sedova, L.A.; Selyatitskaya, V.G.; Shorin, Yu.P.

    1986-02-01

    This paper examines the combined behavior of the endocrine and lymphatic systems in rats at stages of long-term adaptation of the animals to moderate cold. After decapitation of male Wister rats, the corticosterone concentration in the blood plasma was determined by saturation analysis and serum levels of thyroxine (T/sub 4/) and triiodothyronine (T/sub 3/) were determined by radioimmunoassay. The thymus was weighed and the structure of the popliteal lymph nodes (LN) was studied in histological sections stained with hematoxylin and eosin and with azure II-eosin. Morphometry of the structural components of LN was undertaken and the numbers of the various cell forms per 1000 cells were counted in different zones of LN. The increase in activity of the lymphoid tissue in the phase of adaptation may be connected with intensification of the peripheral action of thyroid hormones. During long-term adaptation, in the phase of consistently increased specific resistance, a new type of endocrine-lymphoid relation is formed, and it differs significantly both in the original state and in the acute phase of stress.

  10. Anatomical Mercury: Changing Understandings of Quicksilver, Blood, and the Lymphatic System, 1650-1800.

    PubMed

    Hendriksen, Marieke M A

    2015-10-01

    The use of mercury as an injection mass in anatomical experiments and preparations was common throughout Europe in the long eighteenth century, and refined mercury-injected preparations as well as plates of anatomical mercury remain today. The use and meaning of mercury in related disciplines such as medicine and chemistry in the same period have been studied, but our knowledge of anatomical mercury is sparse and tends to focus on technicalities. This article argues that mercury had a distinct meaning in anatomy, which was initially influenced by alchemical and classical understandings of mercury. Moreover, it demonstrates that the choice of mercury as an anatomical injection mass was deliberate and informed by an intricate cultural understanding of its materiality, and that its use in anatomical preparations and its perception as an anatomical material evolved with the understanding of the circulatory and lymphatic systems. By using the material culture of anatomical mercury as a starting point, I seek to provide a new, object-driven interpretation of complex and strongly interrelated historiographical categories such as mechanism, vitalism, chemistry, anatomy, and physiology, which are difficult to understand through a historiography that focuses exclusively on ideas.

  11. A case of liver cirrhosis with chylous ascites and multiple cystic dilatation of the abdominal lymphatic system.

    PubMed

    Watanabe, M; Taketa, K; Yonei, J; Kubota, M; Nagashima, H; Akamutsu, K; Awai, M

    1980-10-01

    A 51-year-old male suffering from abdominal distension and diagnosed by laparoscopic and histological examination as a liver cirrhosis patient, had a chylous ascites with a negative Gordon test. The content of chylomicron in ascites decreased by restriction of dietary fat, although the ascites retention was resistant to salt restriction, diuretics and intravenous re-infusion of ascites. Lymphangiography revealed dysplasia of the retroperitoneal lymphatic system and dilatation of the thoracic duct. Main autopsy findings were liver cirrhosis (post-necrotic type) without malignancy and marked cystic dilatations of the lymphatic duct. The lymph congestion in the intestine was more remarkable in the subserosal space and the leakage of the chyle into the abdominal cavity was also proved by histological examination.

  12. Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish

    PubMed Central

    Dahl Ejby Jensen, Lasse; Cao, Renhai; Hedlund, Eva-Maria; Söll, Iris; Lundberg, Jon O.; Hauptmann, Giselbert; Steffensen, John Fleng; Cao, Yihai

    2009-01-01

    The blood and lymphatic vasculatures are structurally and functionally coupled in controlling tissue perfusion, extracellular interstitial fluids, and immune surveillance. Little is known, however, about the molecular mechanisms that underlie the regulation of bloodlymphatic vessel connections and lymphatic perfusion. Here we show in the adult zebrafish and glass catfish (Kryptopterus bicirrhis) that blood-lymphatic conduits directly connect arterial vessels to the lymphatic system. Under hypoxic conditions, arterial-lymphatic conduits (ALCs) became highly dilated and linearized by NO-induced vascular relaxation, which led to blood perfusion into the lymphatic system. NO blockage almost completely abrogated hypoxia-induced ALC relaxation and lymphatic perfusion. These findings uncover mechanisms underlying hypoxia-induced oxygen compensation by perfusion of existing lymphatics in fish. Our results might also imply that the hypoxia-induced NO pathway contributes to development of progression of pathologies, including promotion of lymphatic metastasis by modulating arterial-lymphatic conduits, in the mammalian system. PMID:19822749

  13. Lipid-Calcium Phosphate Nanoparticles for Delivery to the Lymphatic System and SPECT/CT Imaging of Lymph Node Metastases

    PubMed Central

    Tseng, Yu-Cheng; Xu, Zhenghong; Guley, Kevin; Yuan, Hong; Huang, Leaf

    2014-01-01

    A lipid/calcium/phosphate (LCP) nanoparticle (NP) formulation (particle diameter ~25 nm) with superior siRNA delivery efficiency was developed and reported previously. Here, we describe the successful formulation of 111In into LCP for SPECT/CT imaging. Imaging and biodistribution studies showed that, polyethylene glycol grafted 111In-LCP preferentially accumulated in the lymph nodes at ~70% ID/g in both C57BL/6 and nude mice when the improved surface coating method was used. Both the liver and spleen accumulated only ~25% ID/g. Larger LCP (diameter ~67 nm) was less lymphotropic. These results indicate that 25 nm LCP was able to penetrate into tissues, enter the lymphatic system, and accumulate in the lymph nodes via lymphatic drainage due to 1) small size, 2) a well-PEGylated lipid surface, and 3) a slightly negative surface charge. The capability of intravenously injected 111In-LCP to visualize an enlarged, tumor-loaded sentinel lymph node was demonstrated using a 4T1 breast cancer lymph node metastasis model. Systemic gene delivery to the lymph nodes after IV injection was demonstrated by the expression of red fluorescent protein cDNA. The potential of using LCP for lymphatic drug delivery is discussed. PMID:24613050

  14. Implementation and evaluation of a protocol management system for automated review of CT protocols.

    PubMed

    Grimes, Joshua; Leng, Shuai; Zhang, Yi; Vrieze, Thomas; McCollough, Cynthia

    2016-09-08

    Protocol review is important to decrease the risk of patient injury and increase the consistency of CT image quality. A large volume of CT protocols makes manual review labor-intensive, error-prone, and costly. To address these challenges, we have developed a software system for automatically managing and monitoring CT proto-cols on a frequent basis. This article describes our experiences in the implementation and evaluation of this protocol monitoring system. In particular, we discuss various strategies for addressing each of the steps in our protocol-monitoring workflow, which are: maintaining an accurate set of master protocols, retrieving protocols from the scanners, comparing scanner protocols to master protocols, reviewing flagged differences between the scanner and master protocols, and updating the scanner and/or master protocols. In our initial evaluation focusing only on abdo-men and pelvis protocols, we detected 309 modified protocols in a 24-week trial period. About one-quarter of these modified protocols were determined to contain inappropriate (i.e., erroneous) protocol parameter modifications that needed to be corrected on the scanner. The most frequently affected parameter was the series description, which was inappropriately modified 47 times. Two inappropriate modifications were made to the tube current, which is particularly important to flag as this parameter impacts both radiation dose and image quality. The CT protocol changes detected in this work provide strong motivation for the use of an automated CT protocol quality control system to ensure protocol accuracy and consistency.

  15. Implementation and evaluation of a protocol management system for automated review of CT protocols.

    PubMed

    Grimes, Joshua; Leng, Shuai; Zhang, Yi; Vrieze, Thomas; McCollough, Cynthia

    2016-01-01

    Protocol review is important to decrease the risk of patient injury and increase the consistency of CT image quality. A large volume of CT protocols makes manual review labor-intensive, error-prone, and costly. To address these challenges, we have developed a software system for automatically managing and monitoring CT proto-cols on a frequent basis. This article describes our experiences in the implementation and evaluation of this protocol monitoring system. In particular, we discuss various strategies for addressing each of the steps in our protocol-monitoring workflow, which are: maintaining an accurate set of master protocols, retrieving protocols from the scanners, comparing scanner protocols to master protocols, reviewing flagged differences between the scanner and master protocols, and updating the scanner and/or master protocols. In our initial evaluation focusing only on abdo-men and pelvis protocols, we detected 309 modified protocols in a 24-week trial period. About one-quarter of these modified protocols were determined to contain inappropriate (i.e., erroneous) protocol parameter modifications that needed to be corrected on the scanner. The most frequently affected parameter was the series description, which was inappropriately modified 47 times. Two inappropriate modifications were made to the tube current, which is particularly important to flag as this parameter impacts both radiation dose and image quality. The CT protocol changes detected in this work provide strong motivation for the use of an automated CT protocol quality control system to ensure protocol accuracy and consistency. PMID:27685112

  16. Functional imaging in tumor-associated lymphatics

    NASA Astrophysics Data System (ADS)

    Kwon, Sunkuk; Sevick-Muraca, Eva M.

    2011-03-01

    The lymphatic system plays an important role in cancer cell dissemination; however whether lymphatic drainage pathways and function change during tumor progression and metastasis remains to be elucidated. In this report, we employed a non-invasive, dynamic near-infrared (NIR) fluorescence imaging technique for functional lymphatic imaging. Indocyanine green (ICG) was intradermally injected into tumor-free mice and mice bearing C6/LacZ rat glioma tumors in the tail or hindlimb. Our imaging data showed abnormal lymphatic drainage pathways and reduction/loss of lymphatic contractile function in mice with lymph node (LN) metastasis, indicating that cancer metastasis to the draining LNs is accompanied by transient changes of the lymphatic architectural network and its function. Therefore, functional lymphatic imaging may provide a role in the clinical staging of cancer.

  17. Treatment of lymphatic malformations of head and neck with OK-432 sclerotherapy induce systemic inflammatory response.

    PubMed

    Närkiö-Mäkelä, Mervi; Mäkelä, Teppo; Saarinen, Pia; Salminen, Päivi; Julkunen, Ilkka; Pitkäranta, Anne

    2011-01-01

    Systemic immune responses after OK-432 (Picibanil) sclerotherapy in patients with head and neck lymphatic malformations (LM) were examined to achieve a better understanding of the mechanism of OK-432 sclerotherapy and to evaluate the long-term treatment outcome. Serum samples from 17 consecutive patients with head and neck LMs were collected during a total of 26 OK-432 treatment episodes. Serum C-reactive protein (CRP), interleukins (IL) 1β, 6, 8, 10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, RANTES, immune protein (IP)-10 and macrophage chemoattractant protein (MCP)-1 as well as blood leukocyte counts were determined. Clinical outcome of the treatment was evaluated at the last visit and from patient files. Elevated serum levels of IP-10 (means at baseline 702 ng/L, after 1 day 1180 ng/L, after 4 weeks 691 ng/L) were seen on day one after OK-432 sclerotherapy (p < 0.05). C-reactive protein and leukocyte counts 1 day after treatment differed statistically significantly (p < 0.05) from the baseline. No significant differences with other cytokines investigated were observed. Patients with macrocystic LM responded better than patients with microcystic LM (p = 0.01). The elevated levels of IP-10, C-reactive protein and leukocyte levels indicate that OK-432 sclerotherapy induces systemic immune responses in patients with LM. The mechanisms of OK-432 sclerotherapy are still not precisely understood, but the IP-10 elevation may reflect local antiangiogenetic properties of immunoactivation induced by OK-432.

  18. An overview of lymphatic vessels and their emerging role in cardiovascular disease.

    PubMed

    Jones, Dennis; Min, Wang

    2011-07-01

    Over the past decade, molecular details of lymphatic vessels (lymphatics) have been rapidly acquired due to the identification of lymphatic endothelial-specific markers. Separate from the cardiovascular system, the lymphatic system is also an elaborate network of vessels that are important in normal physiology. Lymphatic vessels have the unique task to regulate fluid homeostasis, assist in immune surveillance, and transport dietary lipids. However, dysfunctional lymphatic vessels can cause pathology, while normal lymphatics can exacerbate pathology. This review summarizes the development and growth of lymphatic vessels in addition to highlighting their critical roles in physiology and pathology. Also, we discuss recent work that suggests a connection between lymphatic dysfunction and cardiovascular disease.

  19. Oral delivery system prolongs blood circulation of docetaxel nanocapsules via lymphatic absorption.

    PubMed

    Attili-Qadri, Suha; Karra, Nour; Nemirovski, Alina; Schwob, Ouri; Talmon, Yeshayahu; Nassar, Taher; Benita, Simon

    2013-10-22

    An original oral formulation of docetaxel nanocapsules (NCs) embedded in microparticles elicited in rats a higher bioavailability compared with the i.v. administration of the commercial docetaxel solution, Taxotere. In the present study, various animal studies were designed to elucidate the absorption process of docetaxel from such a delivery system. Again, the docetaxel NC formulation elicited a marked enhanced absorption compared with oral Taxotere in minipigs, resulting in relative bioavailability and Cmax values 10- and 8.4-fold higher, respectively, confirming the previous rat study results. It was revealed that orally absorbed NCs altered the elimination and distribution of docetaxel, as shown in the organ biodistribution rat study, due to their reinforced coating, while transiting through the enterocytes by surface adsorption of apoproteins and phospholipids. These findings were demonstrated by the cryogenic-temperature transmission electron microscopy results and confirmed by the use of a chylomicron flow blocker, cycloheximide, that prevented the oral absorption of docetaxel from the NC formulation in an independent pharmacokinetic study. The lipoproteinated NCs reduced the docetaxel release in plasma and its distribution among the organs. The improved anticancer activity compared with i.v. Taxotere, observed in the metastatic lung cancer model in Severe Combined Immune Deficiency-beige (SCID-bg) mice, should be attributed to the extravasation effect, leading to the lipoproteinated NC accumulation in lung tumors, where they exert a significant therapeutic action. To the best of our knowledge, no study has reported that the absorption of NCs was mediated by a lymphatic process and reinforced during their transit.

  20. Lymphatic regulation in nonmammalian vertebrates.

    PubMed

    Hedrick, Michael S; Hillman, Stanley S; Drewes, Robert C; Withers, Philip C

    2013-08-01

    All vertebrate animals share in common the production of lymph through net capillary filtration from their closed circulatory system into their tissues. The balance of forces responsible for net capillary filtration and lymph formation is described by the Starling equation, but additional factors such as vascular and interstitial compliance, which vary markedly among vertebrates, also have a significant impact on rates of lymph formation. Why vertebrates show extreme variability in rates of lymph formation and how nonmammalian vertebrates maintain plasma volume homeostasis is unclear. This gap hampers our understanding of the evolution of the lymphatic system and its interaction with the cardiovascular system. The evolutionary origin of the vertebrate lymphatic system is not clear, but recent advances suggest common developmental factors for lymphangiogenesis in teleost fishes, amphibians, and mammals with some significant changes in the water-land transition. The lymphatic system of anuran amphibians is characterized by large lymphatic sacs and two pairs of lymph hearts that return lymph into the venous circulation but no lymph vessels per se. The lymphatic systems of reptiles and some birds have lymph hearts, and both groups have extensive lymph vessels, but their functional role in both lymph movement and plasma volume homeostasis is almost completely unknown. The purpose of this review is to present an evolutionary perspective in how different vertebrates have solved the common problem of the inevitable formation of lymph from their closed circulatory systems and to point out the many gaps in our knowledge of this evolutionary progression.

  1. Lymphatic regulation in nonmammalian vertebrates.

    PubMed

    Hedrick, Michael S; Hillman, Stanley S; Drewes, Robert C; Withers, Philip C

    2013-08-01

    All vertebrate animals share in common the production of lymph through net capillary filtration from their closed circulatory system into their tissues. The balance of forces responsible for net capillary filtration and lymph formation is described by the Starling equation, but additional factors such as vascular and interstitial compliance, which vary markedly among vertebrates, also have a significant impact on rates of lymph formation. Why vertebrates show extreme variability in rates of lymph formation and how nonmammalian vertebrates maintain plasma volume homeostasis is unclear. This gap hampers our understanding of the evolution of the lymphatic system and its interaction with the cardiovascular system. The evolutionary origin of the vertebrate lymphatic system is not clear, but recent advances suggest common developmental factors for lymphangiogenesis in teleost fishes, amphibians, and mammals with some significant changes in the water-land transition. The lymphatic system of anuran amphibians is characterized by large lymphatic sacs and two pairs of lymph hearts that return lymph into the venous circulation but no lymph vessels per se. The lymphatic systems of reptiles and some birds have lymph hearts, and both groups have extensive lymph vessels, but their functional role in both lymph movement and plasma volume homeostasis is almost completely unknown. The purpose of this review is to present an evolutionary perspective in how different vertebrates have solved the common problem of the inevitable formation of lymph from their closed circulatory systems and to point out the many gaps in our knowledge of this evolutionary progression. PMID:23640588

  2. Role of lymphatic vasculature in regional and distant metastases.

    PubMed

    Podgrabinska, Simona; Skobe, Mihaela

    2014-09-01

    In cancer, lymphatic vasculature has been traditionally viewed only as a transportation system for metastatic cells. It has now become clear that lymphatics perform many additional functions which could influence cancer progression. Lymphangiogenesis, induced at the primary tumor site and at distant sites, potently augments metastasis. Lymphatic endothelial cells (LECs) control tumor cell entry and exit from the lymphatic vessels. LECs also control immune cell traffic and directly modulate adaptive immune responses. This review highlights advances in our understanding of the mechanisms by which lymphatic vessels, and in particular lymphatic endothelium, impact metastasis.

  3. Lymphovenous hemostasis and the role of platelets in regulating lymphatic flow and lymphatic vessel maturation.

    PubMed

    Welsh, John D; Kahn, Mark L; Sweet, Daniel T

    2016-09-01

    Aside from the established role for platelets in regulating hemostasis and thrombosis, recent research has revealed a discrete role for platelets in the separation of the blood and lymphatic vascular systems. Platelets are activated by interaction with lymphatic endothelial cells at the lymphovenous junction, the site in the body where the lymphatic system drains into the blood vascular system, resulting in a platelet plug that, with the lymphovenous valve, prevents blood from entering the lymphatic circulation. This process, known as "lymphovenous hemostasis," is mediated by activation of platelet CLEC-2 receptors by the transmembrane ligand podoplanin expressed by lymphatic endothelial cells. Lymphovenous hemostasis is required for normal lymph flow, and mice deficient in lymphovenous hemostasis exhibit lymphedema and sometimes chylothorax phenotypes indicative of lymphatic insufficiency. Unexpectedly, the loss of lymph flow in these mice causes defects in maturation of collecting lymphatic vessels and lymphatic valve formation, uncovering an important role for fluid flow in driving endothelial cell signaling during development of collecting lymphatics. This article summarizes the current understanding of lymphovenous hemostasis and its effect on lymphatic vessel maturation and synthesizes the outstanding questions in the field, with relationship to human disease. PMID:27385789

  4. A study of the three-dimensional organization of the human diaphragmatic lymphatic lacunae and lymphatic drainage units.

    PubMed

    Li, J; Zhao, Z; Zhou, J; Yu, S

    1996-12-01

    The peritoneal stomata, lymphatic drainage units and subperitoneal terminal lymphatics, called lymphatic lacunae, form a specialized drainage system in the diaphragm, by which absorption of fluid in bulk, particles and cells is carried out in the peritoneal cavity. The aim of this study is to elucidate the three-dimensional organization and function of the subperitoneal lymphatic lacunae and lymphatic drainage units by using lymphatic casts in the scanning electron microscope (SEM), ODO (OsO4-DMSO-OsO4) freeze fracture, conventional SEM and the transmission electron microscope (TEM). The subperitoneal lymphatic lacuna is unique for its large size and its multiple morphology and can be recognized by its broad, flattened enlargement and the blind-ends of lymphatic vessels, from which extend numerous main lymphatic vessels and side branches. These lymphatic vessels communicate with each other and form a rich lymphatic plexus under the diaphragmatic peritoneum. Two layers of lymphatic networks, i.e. the subperitoneal plexus and the deeper plexus are found in the muscular portion. Only one layer is present in the tendinous portion of the human diaphragm. The lymphatic plexus is denser in the tendinous portion than that in the muscular portion. The lymphatic lacunae occur exclusively in the muscular portion of the human diaphragm. The lumina of lymphatic lacunae are separated from the peritoneal cavity by a barrier consisting of cuboidal mesothelial cells, endothelial cells of the lymphatic lacunae and intervening connective tissue forming a lymphatic drainage unit. All these three components of the lymphatic drainage unit abut upon each other, but are not linked by specialized junctions. The cuboidal mesothelial cells frequently extend valve-like cytoplasmic processes that bridge the subperitoneal channel and make give it a tortuous course. The fibrous layer of the connective tissue is arranged in fiber bundles and gives a three-dimensional network forming the floor of

  5. Organization and developmental aspects of lymphatic vessels.

    PubMed

    Ohtani, Osamu; Ohtani, Yuko

    2008-05-01

    The lymphatic system plays important roles in maintaining tissue fluid homeostasis, immune surveillance of the body, and the taking up dietary fat and fat-soluble vitamins A, D, E and K. The lymphatic system is involved in many pathological conditions, including lymphedema, inflammatory diseases, and tumor dissemination. A clear understanding of the organization of the lymphatic vessels in normal conditions would be critically important to develop new treatments for diseases involving the lymphatic vascular system. Therefore, the present paper reviews the organization of the lymphatic vascular system of a variety of organs, including the thyroid gland, lung and pleura, small intestine, cecum and colon in the rat, the diaphragm in the rat, monkey, and human, Peyer's patches and the appendix in the rabbit, and human tonsils. Methods employed include scanning electron microscopy of lymphatic corrosion casts and tissues with or without treatment of alkali maceration technique, transmission electron microscopy of intact tissues, confocal microscopy in conjunction with immunohistochemistry to some lymphatic-specific markers (i.e., LYVE-1 and VEGFR-3), and light microscopy in conjunction with enzyme-histochemistry to 5'-nucleotidase. Some developmental aspects of the lymphatic vessels and lymphedema are also discussed.

  6. Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction.

    PubMed

    Lynskey, Nicola N; Banerji, Suneale; Johnson, Louise A; Holder, Kayla A; Reglinski, Mark; Wing, Peter A C; Rigby, David; Jackson, David G; Sriskandan, Shiranee

    2015-09-01

    The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human pathogen group A streptococcus has a predilection to induce pathology in the lymphatic system and draining lymph nodes, however the underlying basis and subsequent consequences for disease outcome are currently unknown. Here we report that the hyaluronan capsule of group A streptococci is a crucial virulence determinant for lymphatic tropism in vivo, and further, we identify the lymphatic vessel endothelial receptor-1 as the critical host receptor for capsular hyaluronan in the lymphatic system. Interference with this interaction in vivo impeded bacterial dissemination to local draining lymph nodes and, in the case of a hyper-encapsulated M18 strain, redirected streptococcal entry into the blood circulation, suggesting a pivotal role in the manifestation of streptococcal infections. Our results reveal a novel function for bacterial capsular polysaccharide in directing lymphatic tropism, with potential implications for disease pathology.

  7. Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction

    PubMed Central

    Johnson, Louise A.; Holder, Kayla A.; Reglinski, Mark; Wing, Peter A. C.; Rigby, David; Jackson, David G.; Sriskandan, Shiranee

    2015-01-01

    The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human pathogen group A streptococcus has a predilection to induce pathology in the lymphatic system and draining lymph nodes, however the underlying basis and subsequent consequences for disease outcome are currently unknown. Here we report that the hyaluronan capsule of group A streptococci is a crucial virulence determinant for lymphatic tropism in vivo, and further, we identify the lymphatic vessel endothelial receptor-1 as the critical host receptor for capsular hyaluronan in the lymphatic system. Interference with this interaction in vivo impeded bacterial dissemination to local draining lymph nodes and, in the case of a hyper-encapsulated M18 strain, redirected streptococcal entry into the blood circulation, suggesting a pivotal role in the manifestation of streptococcal infections. Our results reveal a novel function for bacterial capsular polysaccharide in directing lymphatic tropism, with potential implications for disease pathology. PMID:26352587

  8. Lymphatic anatomy and biomechanics.

    PubMed

    Negrini, Daniela; Moriondo, Andrea

    2011-06-15

    Lymph formation is driven by hydraulic pressure gradients developing between the interstitial tissue and the lumen of initial lymphatics. While in vessels equipped with lymphatic smooth muscle cells these gradients are determined by well-synchronized spontaneous contractions of vessel segments, initial lymphatics devoid of smooth muscles rely on tissue motion to form lymph and propel it along the network. Lymphatics supplying highly moving tissues, such as skeletal muscle, diaphragm or thoracic tissues, undergo cyclic compression and expansion of their lumen imposed by local stresses arising in the tissue as a consequence of cardiac and respiratory activities. Active muscle contraction and not passive tissue displacement is required to support an efficient lymphatic drainage, as suggested by the fact that the respiratory activity promotes lymph formation during spontaneous, but not mechanical ventilation. The mechanical properties of the lymphatic wall and of the surrounding tissue also play an important role in lymphatic function. Modelling of stress distribution in the lymphatic wall suggests that compliant vessels behave as reservoirs accommodating absorbed interstitial fluid, while lymphatics with stiffer walls, taking advantage of a more efficient transmission of tissue stresses to the lymphatic lumen, propel fluid through the lumen of the lymphatic circuit.

  9. [Chylous reflux and chylous ascites in lymphatic dysplasia, with the lymphographic demonstration of mediastinal and retroperitoneal lymphatic cysts].

    PubMed

    Hermanutz, K D; Boldt, I; Frotscher, U

    1975-01-01

    Two patients with congenital dysplasia of the lymphatic system and with chylous ascites are described. In one 24-year old woman with this rare condition, it was possible to demonstrate for the first time numerous mediastinal lymphatic cysts during lymphangiography. Both patients showed an abnormality of the retroperitoneal lymphatics, consisting of lymphatic dilatation and cysts. In the investigation of chylous ascites, direct lymphangiography must be regarded as a valuable and necessary investigation.

  10. A Wiki Based CT Protocol Management System.

    PubMed

    Szczykutowicz, Timothy P; Rubert, Nicholas; Belden, Daryn; Ciano, Amanda; Duplissis, Andrew; Hermanns, Ashley; Monette, Stephen; Saldivar, Elliott Janssen

    2015-01-01

    At the University of Wisconsin Madison Department of Radiology, CT protocol management requires maintenance of thousands of parameters for each scanner. Managing CT protocols is further complicated by the unique configurability of each scanner. Due to recent Joint Commission requirements, now all CT protocol changes must be documented and reviewed by a site's CT protocol optimization team. The difficulty of managing the CT protocols was not in assembling the protocols, but in managing and implementing changes. This is why a wiki based solution for protocol management was implemented. A wiki inherently keeps track of all changes, logging who made the changes and when, allowing for editing and viewing permissions to be controlled, as well as allowing protocol changes to be instantly relayed to all scanner locations.

  11. How Do Meningeal Lymphatic Vessels Drain the CNS?

    PubMed

    Raper, Daniel; Louveau, Antoine; Kipnis, Jonathan

    2016-09-01

    The many interactions between the nervous and the immune systems, which are active in both physiological and pathological states, have recently become more clearly delineated with the discovery of a meningeal lymphatic system capable of carrying fluid, immune cells, and macromolecules from the central nervous system (CNS) to the draining deep cervical lymph nodes. However, the exact localization of the meningeal lymphatic vasculature and the path of drainage from the cerebrospinal fluid (CSF) to the lymphatics remain poorly understood. Here, we discuss the potential differences between peripheral and CNS lymphatic vessels and examine the purported mechanisms of CNS lymphatic drainage, along with how these may fit into established patterns of CSF flow.

  12. The embryonic origins of lymphatic vessels: an historical review.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2010-06-01

    Work on the lymphatic system began in the 17th century, and by the beginning of the 19th century the anatomy of most of the lymphatic system had been described. One of the most important questions in this field has been the determination of the embryological origin of the lymphatic endothelium. Two theories were proposed. The first suggested that lymphatic endothelium derived by sprouting from venous endothelium, the so-called centrifugal theory. The second, the so-called centripetal theory, suggested that lymphatic endothelium differentiates in situ from primitive mesenchyme, and secondarily acquires connection with the vascular system. More recent evidence has provided support for both hypotheses.

  13. Lymphatic response to depilation-induced inflammation assessed with label-free optical lymphangiography

    PubMed Central

    Qin, Wan; Baran, Utku; Wang, Ruikang

    2015-01-01

    Background and Objectives Optical microangiography (OMAG) is a noninvasive technique capable of imaging 3D microvasculature. OMAG-based optical lymphangiography has been developed for 3D visualization of lymphatic vessels without the need for exogenous contrast agents. In this study, we utilize the optical lymphangiography to investigate dynamic changes in lymphatic response within skin tissue to depilation-induced inflammation by using mouse ear as a simple tissue model. Materials and Methods A spectral-domain optical coherence tomography (OCT) system is used in this study to acquire volumetric images of mouse ear. The system operates under the ultrahigh-sensitive OMAG scanning protocol with 5 repetitions for each B frame. An improved adaptive-threshold-based method is proposed to segment lymphatic vessels from OCT microstructure images. Depilation is achieved by placing hair removal lotion on mouse ear pinna for 5 minutes. 3 acquisitions are made before depilation, 3-minute and 30-minute post-depilation, respectively. Results Right after the application of depilation lotion on the skin, we observe that the blind-ended sacs of initial lymphatics are mainly visible in a specific area of the normal tissue. At 5 minutes, more collecting lymphatic vessels start to form, evidenced by their valve structure that only exists in collecting lymphatic vessels. The lymphangiogenesis is almost completed within 8 minutes in the inflammatory tissue. Conclusions Our experimental results demonstrate that the OMAG-based optical lymphangiography has great potential to improve the understanding of lymphatic system in response to various physiological conditions, thus would benefit the development of effective therapeutics. PMID:26224650

  14. Lymphatics, Cancer and Zebrafish.

    PubMed

    Astin, Jonathan W; Crosier, Philip S

    2016-01-01

    Many solid tumors are known to metastasize through the lymphatic vasculature. This process is facilitated by the generation of new lymphatic vessels (tumor lymphangiogenesis) and also by the remodelling of existing lymphatics. Together these processes enable the spread of tumor cells to distant sites. Currently our understanding of tumor lymphangiogenesis has been informed from mouse tumor models and from studies of developmental lymphangiogenesis. Since the discovery of bona fide lymphatic vessels in zebrafish in 2006, zebrafish have become a well-established model of developmental lymphangiogenesis. The attributes that make zebrafish such an important model of blood vessel development-the ability to live image developing vessels, genetic tractability and the conserved nature of development-also make fish an attractive model of lymphatic vessel development. In particular, zebrafish have made important contributions to our understanding of the processes of lymphatic vessel sprouting from veins and the mechanisms by which lymphatic precursors remodel into mature vessels. To date, zebrafish have not been used to directly model tumor lymphangiogenesis. In this chapter we will summarise the contributions zebrafish have made to our understanding of lymphangiogenesis and investigate the possibilities of combining zebrafish transgenic cancer lines or tumor transplantation models with existing lymphatic reporter lines, which could provide valuable insights into the process of tumor-induced lymphangiogenesis. In addition the utility of using the zebrafish lymphatic model as a platform to screen and develop novel anti-lymphatic therapeutics will also be discussed.

  15. Lymphatics, Cancer and Zebrafish.

    PubMed

    Astin, Jonathan W; Crosier, Philip S

    2016-01-01

    Many solid tumors are known to metastasize through the lymphatic vasculature. This process is facilitated by the generation of new lymphatic vessels (tumor lymphangiogenesis) and also by the remodelling of existing lymphatics. Together these processes enable the spread of tumor cells to distant sites. Currently our understanding of tumor lymphangiogenesis has been informed from mouse tumor models and from studies of developmental lymphangiogenesis. Since the discovery of bona fide lymphatic vessels in zebrafish in 2006, zebrafish have become a well-established model of developmental lymphangiogenesis. The attributes that make zebrafish such an important model of blood vessel development-the ability to live image developing vessels, genetic tractability and the conserved nature of development-also make fish an attractive model of lymphatic vessel development. In particular, zebrafish have made important contributions to our understanding of the processes of lymphatic vessel sprouting from veins and the mechanisms by which lymphatic precursors remodel into mature vessels. To date, zebrafish have not been used to directly model tumor lymphangiogenesis. In this chapter we will summarise the contributions zebrafish have made to our understanding of lymphangiogenesis and investigate the possibilities of combining zebrafish transgenic cancer lines or tumor transplantation models with existing lymphatic reporter lines, which could provide valuable insights into the process of tumor-induced lymphangiogenesis. In addition the utility of using the zebrafish lymphatic model as a platform to screen and develop novel anti-lymphatic therapeutics will also be discussed. PMID:27165355

  16. Exercise countermeasure protocol management expert system

    NASA Technical Reports Server (NTRS)

    Webster, L.; Chen, J. G.; Flores, L.; Tan, S.

    1993-01-01

    Exercise will be used primarily to countermeasure against deconditioning on extended space flight. In this paper we describe the development and evaluation of an expert system for exercise countermeasure protocol management. Currently, the system includes two major subsystems: baseline prescription and prescription adjustment. The baseline prescription subsystem is designed to provide initial exercise prescriptions while prescription adjustment subsystem is designed to modify the initial prescription based on the exercised progress. The system runs under three different environments: PC, SUN workstation, and Symbolic machine. The inference engine, baseline prescription module, prescription adjustment module and explanation module are developed under the Symbolic environment by using the ART (Automated Reasoning Tool) software. The Sun environment handles database management features and interfaces with PC environment to obtain physical and physiological data from exercise units on-board during the flight. Eight subjects' data have been used to evaluate the system performance by comparing the prescription of nine experienced exercise physiologists and the one prescribed by the expert system. The results of the validation test indicated that the performance of the expert system was acceptable.

  17. [Morphogenesis, structure and properties of lymphatic vessels].

    PubMed

    Ratajska, Anna; Jankowska-Steifer, Ewa; Czarnowska, Elżbieta; Flaht, Aleksandra; Radomska-Leśniewska, Dorota

    2012-11-19

    In this paper, we present literature results related to structure and various manners of lymphatic vessel formation during embryonic development and in pathological events, such as tumorigenesis, wound healing, and other diseases. The functions of the lymphatic system include the collection of fluids that enter tissues from the circulation, absorption of lipids and lipid-soluble vitamins from the intestine and their subsequent transport, participation in antigen, dendritic cell, and lymphocyte migration. The lymphatic system is also a route for tumor cell and inflammatory cell transport. Native lymphatic capillaries differ from blood capillaries by having an irregular lumen, a discontinuous basement membrane, absence of pericytes, and a strong anchorage of their endothelial cells to the extracellular matrix via microfibrils built of emilin and fibrillin. Lymphatic endothelial cells express surface antigens such as Lyve-1, podoplanin, VEGFR3 (Flk4) and transcription factor Prox-1, as well as molecules which are common for blood endothelial cells and lymphatic endothelial cells (CD31, CD34, Flk-1, Tie-1, Tie-2, neuropilin 2). Lymphatic vessel formation during embryonic development starts with the occurrence of lymphatic sacs sprouting from systemic jugular veins and/or by co-option of lymphangioblasts or hematopoietic-derived cells. It can also proceed by dedifferentiation of venous endothelial cells after their detachment from the venous system, migration to the target places within the body and assembly in the lymphatic lumen. Mechanisms of lymphatic vessel formation during embryonic development and in pathological conditions, such as tumorigenesis, wound healing, and metastasis, is regulated by a plethora of growth factors and molecules, among which the most important are VEGF-C, VEGF-D, HGF, FGF, retinoic acid, IL-3, and IL-7. Macrophages and cells bearing CD45 phenotype seem to take part in the formation of lymphatics. Macrophages might act as a source of growth

  18. Spacelab system analysis: The modified free access protocol: An access protocol for communication systems with periodic and Poisson traffic

    NASA Technical Reports Server (NTRS)

    Ingels, Frank; Owens, John; Daniel, Steven

    1989-01-01

    The protocol definition and terminal hardware for the modified free access protocol, a communications protocol similar to Ethernet, are developed. A MFA protocol simulator and a CSMA/CD math model are also developed. The protocol is tailored to communication systems where the total traffic may be divided into scheduled traffic and Poisson traffic. The scheduled traffic should occur on a periodic basis but may occur after a given event such as a request for data from a large number of stations. The Poisson traffic will include alarms and other random traffic. The purpose of the protocol is to guarantee that scheduled packets will be delivered without collision. This is required in many control and data collection systems. The protocol uses standard Ethernet hardware and software requiring minimum modifications to an existing system. The modification to the protocol only affects the Ethernet transmission privileges and does not effect the Ethernet receiver.

  19. Immunopathogenesis of lymphatic filarial disease.

    PubMed

    Babu, Subash; Nutman, Thomas B

    2012-11-01

    Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ~40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process-the first initiated by the parasite and host innate immune system and the second propagated mainly by the host's adaptive immune system and by other factors (including secondary infections). PMID:23053393

  20. Survivability validation protocol issues for a system-of-systems

    SciTech Connect

    Brock, G.; Ianacone, K.J.; Stringer, T.A.

    1993-08-01

    This paper illuminates the various issues confronting a protocol developer as he attempts to construct a system-of-systems (SOS) survivability validation protocol. These issues are considered in the context of a Battle Management Command, Control, and Communications (BMC{sup 3}) network in the form of a Hypothetical System Architecture consisting of air, sea, ground, and space platforms. The purpose of the protocol of concem is to validate the nuclear survivability of the BMC{sup 3} SOS. To achieve this validation, the combined susceptibilities of the SOS platforms and communications links must be considered. A basic SOS simulation concept is described, which assumes individual platform survivability. The nuclear environments to be considered in the simulation are outlined with a discussion of the relationship to basic system susceptibility. Various validation concepts for the SOS protocol are summarized in relation to the life cycle phase during which they would be utilized. Computer simulation issues are discussed, including the environments to be modeled, validation of the codes, documentation, and configuration control. Concluding remarks center on the most likely way of simulating nuclear effects and on treating simulation tools like mission critical items.

  1. Lymphatic Filariasis: Frequently Asked Questions (FAQs)

    MedlinePlus

    ... a parasitic disease caused by microscopic, thread-like worms. The adult worms only live in the human lymph system. The ... South America. You cannot get infected with the worms in the United States. How is lymphatic filariasis ...

  2. Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2.

    PubMed

    Liebl, Johanna; Zhang, Siwei; Moser, Markus; Agalarov, Yan; Demir, Cansaran Saygili; Hager, Bianca; Bibb, James A; Adams, Ralf H; Kiefer, Friedemann; Miura, Naoyuki; Petrova, Tatiana V; Vollmar, Angelika M; Zahler, Stefan

    2015-01-01

    The lymphatic system maintains tissue fluid balance, and dysfunction of lymphatic vessels and valves causes human lymphedema syndromes. Yet, our knowledge of the molecular mechanisms underlying lymphatic vessel development is still limited. Here, we show that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of lymphatic vessel development. Endothelial-specific Cdk5 knockdown causes congenital lymphatic dysfunction and lymphedema due to defective lymphatic vessel patterning and valve formation. We identify the transcription factor Foxc2 as a key substrate of Cdk5 in the lymphatic vasculature, mechanistically linking Cdk5 to lymphatic development and valve morphogenesis. Collectively, our findings show that Cdk5-Foxc2 interaction represents a critical regulator of lymphatic vessel development and the transcriptional network underlying lymphatic vascular remodeling. PMID:26027726

  3. Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2.

    PubMed

    Liebl, Johanna; Zhang, Siwei; Moser, Markus; Agalarov, Yan; Demir, Cansaran Saygili; Hager, Bianca; Bibb, James A; Adams, Ralf H; Kiefer, Friedemann; Miura, Naoyuki; Petrova, Tatiana V; Vollmar, Angelika M; Zahler, Stefan

    2015-06-01

    The lymphatic system maintains tissue fluid balance, and dysfunction of lymphatic vessels and valves causes human lymphedema syndromes. Yet, our knowledge of the molecular mechanisms underlying lymphatic vessel development is still limited. Here, we show that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of lymphatic vessel development. Endothelial-specific Cdk5 knockdown causes congenital lymphatic dysfunction and lymphedema due to defective lymphatic vessel patterning and valve formation. We identify the transcription factor Foxc2 as a key substrate of Cdk5 in the lymphatic vasculature, mechanistically linking Cdk5 to lymphatic development and valve morphogenesis. Collectively, our findings show that Cdk5-Foxc2 interaction represents a critical regulator of lymphatic vessel development and the transcriptional network underlying lymphatic vascular remodeling.

  4. Short time effects of radiotherapy on lymphatic vessels and restorative lymphatic pathways: experimental approaches ina mouse model.

    PubMed

    Pastouret, F; Lievens, P; Leduc, O; Bourgeois, P; Tournel, K; Lamote, J; Zirak, C; Leduc, A

    2014-06-01

    Radiotherapy (RT) is an important component in the therapeutic approach to oncologic conditions. This study presents the investigative results on the impact of RT on lymphatic vessels and on the regenerative response of the lymphatic system in a mouse model. We first irradiated 3 groups of ten mice using brachytherapy in a single treatment of 20 Gy. We then performed morphological examination of the irradiated lymphatic vessels using an in vivo microscopic transillumination technique at 2, 4, and 6 weeks. Next we evaluated lymphatic flow using lymphoscintigraphy and in vivo microscopy at 6 to 11 weeks in: 10 additional mice following irradiation as above (IR), in 10 mice following incision of a lymphatic vessel (I), and in a non-treated control group of 10 mice (N). Intact lymphatic vessels were observed in all mice at 2, 4, and 8 weeks following the single dose of radiotherapy in the first group of mice and normal lymphatic flow was fully restored in the irradiated (IR) and incised (I) mice indicating that the reparative substitution lymphatic pathways are functioning normally. We found that following irradiation with one dose of 20 Gy, lymphatic vessels were not visibly damaged and also that lymphatic flow was consistently restored and substitutive lymphatic pathways formed.

  5. Comparison of approaches for microscopic imaging of skin lymphatic vessels.

    PubMed

    Wu, Xiufeng; Yu, Zheyuan; Liu, Ningfei

    2012-01-01

    Assessment of skin lymphatic vessels is of great significance in understanding their roles in many pathological conditions. Our aim was to identify the optimal approach for investigation of cutaneous lymphatic system. We performed comparative studies on skin lymphatic vessels using immunohistochemistry of tissue sections, computer graphic reconstruction method together with immunohistochemically stained serial sections and whole mount fluorescence in human lower limb. Lymphatic vessels were identified with podoplanin antibody. The relative merits and drawbacks of each method in evaluation of structure, spatial organization, and distribution of cutaneous lymphatic vessels were described. Immunohistology of tissue sections enabled the investigation of the structure and distribution of the whole cutaneous lymphatic system in two-dimensional slices, whereas three-dimensional morphology of only the most superficial lymph capillary network immediately under the epidermis could be evaluated with the whole mount technique. Meanwhile, only little segmentation of skin lymphatic vessel from five immunohistochemically stained serial sections was reconstructed and evaluated due to expense and special skills required using computer graphic three-dimensional reconstruction. Furthermore, a great number of artifacts and special skills required in its processes leaded to less accurate structure of skin lymphatic vessels. Our findings demonstrated that the use of either of the proposed techniques alone could not allow a comprehensive analysis of the skin lymphatic system due to their relative drawbacks. Combination of immunohistology of tissue sections and three-dimensional whole-mount preparations appears to be the best candidate for comprehensive evaluation of skin lymphatic system.

  6. In vivo dual-modality imaging of lymphatic systems using indocyanine green in rats: three-dimensional photoacoustic imaging and planar fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Song, Kwang Hyun; Wang, Lihong V.

    2010-02-01

    The purpose of this study is to map non-invasively sentinel lymph nodes (SLNs) and lymphatic vessels of rats in vivo using FDA-approved indocyanine green (ICG) and two non-ionizing imaging modalities: volumetric spectroscopic photoacoustic (PA) imaging, which measures optical absorption, and planar fluorescence imaging, which measures fluorescent emission. SLNs and lymphatic vessels were clearly visible after a 0.2 ml-intradermal-injection of 1 mM ICG in both imaging systems. We also imaged deeply positioned lymph nodes in vivo by layering biological tissues on top of rats. These two modalities, when used together with ICG, have the potential to map SLNs in axillary staging and to study tumor metastasis in breast cancer patients.

  7. Immunohistochemical detection of somatostatin sst2a receptors in the lymphatic, smooth muscular, and peripheral nervous systems of the human gastrointestinal tract: facts and artifacts.

    PubMed

    Reubi, J C; Laissue, J A; Waser, B; Steffen, D L; Hipkin, R W; Schonbrunn, A

    1999-08-01

    The cellular distribution of the somatostatin sst2A receptor protein was investigated in the lymphatic, smooth muscular, and nervous components of the human gastrointestinal tract using subtype-specific antibody R2-88 for immunohistochemical staining of cryostat and formalin-fixed, paraffin-embedded tissue sections. Germinal centers of intestinal lymphatic follicles were immunostained, exhibiting a predominantly plasma membrane localization of the receptor. Similarly, nerve fibers and cells in the submucosal and myenteric plexus were stained for sst2A. Antibody preabsorption with 100 nmol/L antigen peptide abolished staining in all of these tissues, and immunohistochemical staining correlated with the labeling observed after receptor autoradiography using the sst2-preferring radioligand 125I-[Tyr3]octreotide. Cytoplasmic immunostaining was detected in gastrointestinal smooth muscle cells and was inhibited by antibody pre-absorption with antigen peptide. However, 125I-[Tyr3]octreotide autoradiography was negative, and Western blots showed no band at the usual 70-90 kDa location for sst2A. Instead, a band was observed at 205 kDa. This band comigrated with the rabbit myosin standard, which was also stained with R2-88, although antibody sensitivity for myosin was less than 0.002% of that for the sst2A receptor. Rigorous computer-based sequence analysis demonstrated the peptide sequence chosen for antibody production was unique. Moreover, standard sequence alignment protocols were unable to identify the sequences in myosin responsible for the observed reactivity with the R2-88 antiserum. The observed cross-reactivity emphasizes the need for extensive controls to prove the specificity of immunostaining for such low abundance proteins as receptors even when the peptide sequence chosen for antibody production is unique. This study demonstrates for the first time the presence of specific sst2A receptor protein by immunohistochemistry in the human gastrointestinal lymphatic

  8. Advances in Lymphatic Imaging and Drug Delivery

    SciTech Connect

    Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

    2011-09-10

    Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.

  9. Imaging methods for the local lymphatic system of the axilla in early breast cancer in patients qualified for sentinel lymph node biopsy

    PubMed Central

    Kurylcio, Andrzej; Polkowski, Wojciech; Zegarski, Wojciech

    2016-01-01

    Breast cancer is the most common malignancy in women in well-developed countries. Despite a constant increase in its incidence, the percentage of patients diagnosed with the disease in the non-invasive stage is also rising. This allows more frequently for the use of breast-preserving surgical techniques, involving the breast and the regional lymphatic system. According to current guidelines of expert panels and research societies, the recommended method of identifying the sentinel lymph node is the use of an isotope marker with a dye (a combined isotope and dye method). Cooperation with a nuclear medicine unit is essential (performing a preoperative lymphoscintigraphic scan to identify the lymphatic drainage basin and sentinel lymph node). In the case of smaller centers treating breast cancer, it can be associated with a number of difficulties, including organizational ones, and also increasing general treatment costs. A possible solution to these problems is to use alternative techniques of visualizing the sentinel lymph node, which do not require a radiotracer. In this paper we discuss the currently available methods of mapping the lymphatic system of the axillary region in patients with early breast cancer. The review is limited to reporting on methods of proven (based on clinical research) high diagnostic value. PMID:27095960

  10. Imaging methods for the local lymphatic system of the axilla in early breast cancer in patients qualified for sentinel lymph node biopsy.

    PubMed

    Nowikiewicz, Tomasz; Kurylcio, Andrzej; Polkowski, Wojciech; Zegarski, Wojciech

    2016-03-01

    Breast cancer is the most common malignancy in women in well-developed countries. Despite a constant increase in its incidence, the percentage of patients diagnosed with the disease in the non-invasive stage is also rising. This allows more frequently for the use of breast-preserving surgical techniques, involving the breast and the regional lymphatic system. According to current guidelines of expert panels and research societies, the recommended method of identifying the sentinel lymph node is the use of an isotope marker with a dye (a combined isotope and dye method). Cooperation with a nuclear medicine unit is essential (performing a preoperative lymphoscintigraphic scan to identify the lymphatic drainage basin and sentinel lymph node). In the case of smaller centers treating breast cancer, it can be associated with a number of difficulties, including organizational ones, and also increasing general treatment costs. A possible solution to these problems is to use alternative techniques of visualizing the sentinel lymph node, which do not require a radiotracer. In this paper we discuss the currently available methods of mapping the lymphatic system of the axillary region in patients with early breast cancer. The review is limited to reporting on methods of proven (based on clinical research) high diagnostic value. PMID:27095960

  11. The lymphatic vasculature: development and role in shaping immunity.

    PubMed

    Betterman, Kelly L; Harvey, Natasha L

    2016-05-01

    The lymphatic vasculature is an integral component of the immune system. Lymphatic vessels are a key highway via which immune cells are trafficked, serving not simply as a passive route of transport, but to actively shape and coordinate immune responses. Reciprocally, immune cells provide signals that impact the growth, development, and activity of the lymphatic vasculature. In addition to immune cell trafficking, lymphatic vessels are crucial for fluid homeostasis and lipid absorption. The field of lymphatic vascular research is rapidly expanding, fuelled by rapidly advancing technology that has enabled the manipulation and imaging of lymphatic vessels, together with an increasing recognition of the involvement of lymphatic vessels in a myriad of human pathologies. In this review we provide an overview of the genetic pathways and cellular processes important for development and maturation of the lymphatic vasculature, discuss recent work revealing important roles for the lymphatic vasculature in directing immune cell traffic and coordinating immune responses and highlight the involvement of lymphatic vessels in a range of pathological settings.

  12. The lymphatic vasculature: development and role in shaping immunity.

    PubMed

    Betterman, Kelly L; Harvey, Natasha L

    2016-05-01

    The lymphatic vasculature is an integral component of the immune system. Lymphatic vessels are a key highway via which immune cells are trafficked, serving not simply as a passive route of transport, but to actively shape and coordinate immune responses. Reciprocally, immune cells provide signals that impact the growth, development, and activity of the lymphatic vasculature. In addition to immune cell trafficking, lymphatic vessels are crucial for fluid homeostasis and lipid absorption. The field of lymphatic vascular research is rapidly expanding, fuelled by rapidly advancing technology that has enabled the manipulation and imaging of lymphatic vessels, together with an increasing recognition of the involvement of lymphatic vessels in a myriad of human pathologies. In this review we provide an overview of the genetic pathways and cellular processes important for development and maturation of the lymphatic vasculature, discuss recent work revealing important roles for the lymphatic vasculature in directing immune cell traffic and coordinating immune responses and highlight the involvement of lymphatic vessels in a range of pathological settings. PMID:27088921

  13. Lymph flow regulates collecting lymphatic vessel maturation in vivo.

    PubMed

    Sweet, Daniel T; Jiménez, Juan M; Chang, Jeremy; Hess, Paul R; Mericko-Ishizuka, Patricia; Fu, Jianxin; Xia, Lijun; Davies, Peter F; Kahn, Mark L

    2015-08-01

    Fluid shear forces have established roles in blood vascular development and function, but whether such forces similarly influence the low-flow lymphatic system is unknown. It has been difficult to test the contribution of fluid forces in vivo because mechanical or genetic perturbations that alter flow often have direct effects on vessel growth. Here, we investigated the functional role of flow in lymphatic vessel development using mice deficient for the platelet-specific receptor C-type lectin-like receptor 2 (CLEC2) as blood backfills the lymphatic network and blocks lymph flow in these animals. CLEC2-deficient animals exhibited normal growth of the primary mesenteric lymphatic plexus but failed to form valves in these vessels or remodel them into a structured, hierarchical network. Smooth muscle cell coverage (SMC coverage) of CLEC2-deficient lymphatic vessels was both premature and excessive, a phenotype identical to that observed with loss of the lymphatic endothelial transcription factor FOXC2. In vitro evaluation of lymphatic endothelial cells (LECs) revealed that low, reversing shear stress is sufficient to induce expression of genes required for lymphatic valve development and identified GATA2 as an upstream transcriptional regulator of FOXC2 and the lymphatic valve genetic program. These studies reveal that lymph flow initiates and regulates many of the key steps in collecting lymphatic vessel maturation and development.

  14. Emerging trends in the pathophysiology of lymphatic contractile function.

    PubMed

    Chakraborty, Sanjukta; Davis, Michael J; Muthuchamy, Mariappan

    2015-02-01

    Lymphatic contractile dysfunction is central to a number of pathologies that affect millions of people worldwide. Due to its critical role in the process of inflammation, a dysfunctional lymphatic system also compromises the immune response, further exacerbating a number of inflammation related diseases. Despite the critical physiological functions accomplished by the transport of lymph, a complete understanding of the contractile machinery of the lymphatic system lags far behind that of the blood vasculature. However, there has been a surge of recent research focusing on different mechanisms that underlie both physiological and pathophysiological aspects of lymphatic contractile function. This review summarizes those emerging paradigms that shed some novel insights into the contractile physiology of the lymphatics in normal as well as different disease states. In addition, this review emphasizes the recent progress made in our understanding of various contractile parameters and regulatory elements that contribute to the normal functioning of the lymphatics.

  15. Determinants of valve gating in collecting lymphatic vessels from rat mesentery.

    PubMed

    Davis, Michael J; Rahbar, Elaheh; Gashev, Anatoliy A; Zawieja, David C; Moore, James E

    2011-07-01

    Secondary lymphatic valves are essential for minimizing backflow of lymph and are presumed to gate passively according to the instantaneous trans-valve pressure gradient. We hypothesized that valve gating is also modulated by vessel distention, which could alter leaflet stiffness and coaptation. To test this hypothesis, we devised protocols to measure the small pressure gradients required to open or close lymphatic valves and determine if the gradients varied as a function of vessel diameter. Lymphatic vessels were isolated from rat mesentery, cannulated, and pressurized using a servo-control system. Detection of valve leaflet position simultaneously with diameter and intraluminal pressure changes in two-valve segments revealed the detailed temporal relationships between these parameters during the lymphatic contraction cycle. The timing of valve movements was similar to that of cardiac valves, but only when lymphatic vessel afterload was elevated. The pressure gradients required to open or close a valve were determined in one-valve segments during slow, ramp-wise pressure elevation, either from the input or output side of the valve. Tests were conducted over a wide range of baseline pressures (and thus diameters) in passive vessels as well as in vessels with two levels of imposed tone. Surprisingly, the pressure gradient required for valve closure varied >20-fold (0.1-2.2 cmH(2)O) as a passive vessel progressively distended. Similarly, the pressure gradient required for valve opening varied sixfold with vessel distention. Finally, our functional evidence supports the concept that lymphatic muscle tone exerts an indirect effect on valve gating.

  16. Lymphatic imaging: Lymphography, computed tomography and scintigraphy, 2nd ed

    SciTech Connect

    Close, M.E.; Wallace, S.

    1985-01-01

    The latest addition to the Golden's Diagnostic Radiology series deals not only with imaging of the lymphatic system but also with lymphatic anatomy, its pathophysiology, and treatment of disorders. The first two chapters deal with the history of the discovery of the lymphatic system and its normal anatomy. The section on technique contains practical information and discussion of lymphatic physiology and the pathology of lymphomas. Half of the book's 16 chapters are devoted to problems encountered in clinical imaging. The approach is both by anatomy (thorax, neck, abdomen) and pathology (benign disease, lymphoma, solid tumors).

  17. Lymphatic vessels arise from specialized angioblasts within a venous niche.

    PubMed

    Nicenboim, J; Malkinson, G; Lupo, T; Asaf, L; Sela, Y; Mayseless, O; Gibbs-Bar, L; Senderovich, N; Hashimshony, T; Shin, M; Jerafi-Vider, A; Avraham-Davidi, I; Krupalnik, V; Hofi, R; Almog, G; Astin, J W; Golani, O; Ben-Dor, S; Crosier, P S; Herzog, W; Lawson, N D; Hanna, J H; Yanai, I; Yaniv, K

    2015-06-01

    How cells acquire their fate is a fundamental question in developmental and regenerative biology. Multipotent progenitors undergo cell-fate restriction in response to cues from the microenvironment, the nature of which is poorly understood. In the case of the lymphatic system, venous cells from the cardinal vein are thought to generate lymphatic vessels through trans-differentiation. Here we show that in zebrafish, lymphatic progenitors arise from a previously uncharacterized niche of specialized angioblasts within the cardinal vein, which also generates arterial and venous fates. We further identify Wnt5b as a novel lymphatic inductive signal and show that it also promotes the ‘angioblast-to-lymphatic’ transition in human embryonic stem cells, suggesting that this process is evolutionarily conserved. Our results uncover a novel mechanism of lymphatic specification, and provide the first characterization of the lymphatic inductive niche. More broadly, our findings highlight the cardinal vein as a heterogeneous structure, analogous to the haematopoietic niche in the aortic floor.

  18. Mechanical forces and lymphatic transport.

    PubMed

    Breslin, Jerome W

    2014-11-01

    This review examines the current understanding of how the lymphatic vessel network can optimize lymph flow in response to various mechanical forces. Lymphatics are organized as a vascular tree, with blind-ended initial lymphatics, precollectors, prenodal collecting lymphatics, lymph nodes, postnodal collecting lymphatics and the larger trunks (thoracic duct and right lymph duct) that connect to the subclavian veins. The formation of lymph from interstitial fluid depends heavily on oscillating pressure gradients to drive fluid into initial lymphatics. Collecting lymphatics are segmented vessels with unidirectional valves, with each segment, called a lymphangion, possessing an intrinsic pumping mechanism. The lymphangions propel lymph forward against a hydrostatic pressure gradient. Fluid is returned to the central circulation both at lymph nodes and via the larger lymphatic trunks. Several recent developments are discussed, including evidence for the active role of endothelial cells in lymph formation; recent developments on how inflow pressure, outflow pressure, and shear stress affect the pump function of the lymphangion; lymphatic valve gating mechanisms; collecting lymphatic permeability; and current interpretations of the molecular mechanisms within lymphatic endothelial cells and smooth muscle. An improved understanding of the physiological mechanisms by which lymphatic vessels sense mechanical stimuli, integrate the information, and generate the appropriate response is key for determining the pathogenesis of lymphatic insufficiency and developing treatments for lymphedema. PMID:25107458

  19. Mechanical Forces and Lymphatic Transport

    PubMed Central

    Breslin, Jerome W.

    2014-01-01

    This review examines current understanding of how the lymphatic vessel network can optimize lymph flow in response to various mechanical forces. Lymphatics are organized as a vascular tree, with blind-ended initial lymphatics, precollectors, prenodal collecting lymphatics, lymph nodes, postnodal collecting lymphatics and the larger trunks (thoracic duct and right lymph duct) that connect to the subclavian veins. The formation of lymph from interstitial fluid depends heavily on oscillating pressure gradients to drive fluid into initial lymphatics. Collecting lymphatics are segmented vessels with unidirectional valves, with each segment, called a lymphangion, possessing an intrinsic pumping mechanism. The lymphangions propel lymph forward against a hydrostatic pressure gradient. Fluid is returned to the central circulation both at lymph nodes and via the larger lymphatic trunks. Several recent developments are discussed, including: evidence for the active role of endothelial cells in lymph formation; recent developments on how inflow pressure, outflow pressure, and shear stress affect pump function of the lymphangion; lymphatic valve gating mechanisms; collecting lymphatic permeability; and current interpretations of the molecular mechanisms within lymphatic endothelial cells and smooth muscle. Improved understanding of the physiological mechanisms by lymphatic vessels sense mechanical stimuli, integrate the information, and generate the appropriate response is key for determining the pathogenesis of lymphatic insufficiency and developing treatments for lymphedema. PMID:25107458

  20. Mechanical forces and lymphatic transport.

    PubMed

    Breslin, Jerome W

    2014-11-01

    This review examines the current understanding of how the lymphatic vessel network can optimize lymph flow in response to various mechanical forces. Lymphatics are organized as a vascular tree, with blind-ended initial lymphatics, precollectors, prenodal collecting lymphatics, lymph nodes, postnodal collecting lymphatics and the larger trunks (thoracic duct and right lymph duct) that connect to the subclavian veins. The formation of lymph from interstitial fluid depends heavily on oscillating pressure gradients to drive fluid into initial lymphatics. Collecting lymphatics are segmented vessels with unidirectional valves, with each segment, called a lymphangion, possessing an intrinsic pumping mechanism. The lymphangions propel lymph forward against a hydrostatic pressure gradient. Fluid is returned to the central circulation both at lymph nodes and via the larger lymphatic trunks. Several recent developments are discussed, including evidence for the active role of endothelial cells in lymph formation; recent developments on how inflow pressure, outflow pressure, and shear stress affect the pump function of the lymphangion; lymphatic valve gating mechanisms; collecting lymphatic permeability; and current interpretations of the molecular mechanisms within lymphatic endothelial cells and smooth muscle. An improved understanding of the physiological mechanisms by which lymphatic vessels sense mechanical stimuli, integrate the information, and generate the appropriate response is key for determining the pathogenesis of lymphatic insufficiency and developing treatments for lymphedema.

  1. [Medical treatment of lymphatic filariasis].

    PubMed

    Hovette, P; Laroche, R; Verrot, D; Molinier, S; Touze, J E

    1991-01-01

    Lymphatic filariasis remains in 1991 a major health problem. Ivermectine revolutionizes their treatment and, by suppressing microfilaremia, provides a new method of helping to control the vector-borne transmission of lymphatic filariasis. PMID:2072855

  2. Visualization of lymphatic vessel development, growth, and function.

    PubMed

    Pollmann, Cathrin; Hägerling, René; Kiefer, Friedemann

    2014-01-01

    Despite their important physiological and pathophysiological functions, lymphatic endothelial cells and lymphatic vessels remain less well studied compared to the blood vascular system. Lymphatic endothelium differentiates from venous blood vascular endothelium after initial arteriovenous differentiation. Only recently by the use of light sheet microscopy, the precise mechanism of separation of the first lymphatic endothelial progenitors from the cardinal vein has been described as delamination followed by mesenchymal cell migration of lymphatic endothelial cells. Dorsolaterally of the embryonic cardinal vein, lymphatic endothelial cells reaggregate to form the first lumenized lymphatic vessels, the dorsal peripheral longitudinal vessel and the more ventrally positioned primordial thoracic duct. Despite this progress in our understanding of the first lymph vessel formation, intravital observation of lymphatic vessel behavior in the intact organism, during development and in the adult, is prerequisite to a precise understanding of this tissue. Transgenic models and two-photon microscopy, in combination with optical windows, have made live intravital imaging possible: however, new imaging modalities and novel approaches promise gentler, more physiological, and longer intravital imaging of lymphatic vessels.

  3. Osteopathic lymphatic pump techniques to enhance immunity and treat pneumonia

    PubMed Central

    Hodge, Lisa M.

    2012-01-01

    Pneumonia is a common cause of morbidity and mortality worldwide. While antibiotics are generally effective for the treatment of infection, the emergence of resistant strains of bacteria threatens their success. The osteopathic medical profession has designed a set of manipulative techniques called lymphatic pump techniques (LPT), to enhance the flow of lymph through the lymphatic system. Clinically, LPT is used to treat infection and oedemaand might be an effective adjuvant therapy in patients with pneumonia.The immune system uses the lymphatic and blood systems to survey to rid the body of pathogens; however, only recently have the effects of LPT on the lymphatic and immune systems been investigated. This short review highlightsclinical and basic science research studies that support the use of LPT to enhance the lymphatic and immune systems and treat pneumonia, and discusses the potential mechanisms by which LPT benefits patients with pneumonia. PMID:22977459

  4. The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems.

    PubMed

    Wu, Min; Frieboes, Hermann B; Chaplain, Mark A J; McDougall, Steven R; Cristini, Vittorio; Lowengrub, John S

    2014-08-21

    Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response

  5. The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems.

    PubMed

    Wu, Min; Frieboes, Hermann B; Chaplain, Mark A J; McDougall, Steven R; Cristini, Vittorio; Lowengrub, John S

    2014-08-21

    Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response

  6. The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems

    PubMed Central

    Wu, Min; Frieboes, Hermann B.; Chaplain, Mark A.J.; McDougall, Steven R.; Cristini, Vittorio; Lowengrub, John

    2014-01-01

    Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but leads to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the

  7. Spleen and Lymphatic System

    MedlinePlus

    ... destroy damaged cells. How It Works Carrying Away Waste Lymph fluid drains into tiny vessels called lymph ... crowd out healthy cells and may cause tumors (solid growths) in other parts of the body. Splenomegaly ( ...

  8. Anatomy and development of the cardiac lymphatic vasculature: Its role in injury and disease.

    PubMed

    Norman, Sophie; Riley, Paul R

    2016-04-01

    Lymphatic vessels are present throughout the entire body in all mammals and function to regulate tissue fluid balance, lipid transport and survey the immune system. Despite the presence of an extensive lymphatic plexus within the heart, until recently the importance of the cardiac lymphatic vasculature and its origins were unknown. Several studies have described the basic anatomy of the developing cardiac lymphatic vasculature and more recently the detailed development of the murine cardiac lymphatics has been documented, with important insight into their cellular sources during embryogenesis. In this review we initially describe the development of systemic lymphatic vasculature, to provide the background for a comparative description of the spatiotemporal development of the cardiac lymphatic vessels, including detail of both canonical, typically venous, and noncanonical (hemogenic endothelium) cellular sources. Subsequently, we address the response of the cardiac lymphatic network to myocardial infarction (heart attack) and the therapeutic potential of targeting cardiac lymphangiogenesis.

  9. Anatomy and development of the cardiac lymphatic vasculature: Its role in injury and disease.

    PubMed

    Norman, Sophie; Riley, Paul R

    2016-04-01

    Lymphatic vessels are present throughout the entire body in all mammals and function to regulate tissue fluid balance, lipid transport and survey the immune system. Despite the presence of an extensive lymphatic plexus within the heart, until recently the importance of the cardiac lymphatic vasculature and its origins were unknown. Several studies have described the basic anatomy of the developing cardiac lymphatic vasculature and more recently the detailed development of the murine cardiac lymphatics has been documented, with important insight into their cellular sources during embryogenesis. In this review we initially describe the development of systemic lymphatic vasculature, to provide the background for a comparative description of the spatiotemporal development of the cardiac lymphatic vessels, including detail of both canonical, typically venous, and noncanonical (hemogenic endothelium) cellular sources. Subsequently, we address the response of the cardiac lymphatic network to myocardial infarction (heart attack) and the therapeutic potential of targeting cardiac lymphangiogenesis. PMID:26443964

  10. Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles

    PubMed Central

    Cai, Shuang; Zhang, Qiuhong; Bagby, Taryn; Forrest, M. Laird

    2011-01-01

    The lymphatic system plays a crucial role in the immune system’s recognition and response to disease, and most solid cancers initially spread from the primary site via the tumor’s surrounding lymphatics before hematological dissemination. Hence, the lymphatic system is an important target for developing new vaccines, cancer treatments, and diagnostic agents. Targeting the lymphatic system by subcutaneous, intestinal, and pulmonary routes has been evaluated and subsequently utilized to improve lymphatic penetration and retention of drug molecules, reduce drug-related systemic toxicities, and enhance bioavailability of poorly soluble and unstable drugs. Lymphatic imaging is an essential tool for the detection and staging of cancer. New nano-based technologies offer improved detection and characterization of the nodal diseases, while new delivery devices can better target and confine treatments to tumors within the nodal space while sparing healthy tissues. This manuscript reviews recent advances in the field of lymphatic drug delivery and imaging and focuses specifically on the development ofliposomes and solid lipid nanoparticles for lymphatic introduction via the subcutaneous, intestinal, and pulmonary routes. PMID:21712055

  11. An Electronic System for Home Care Protocols

    PubMed Central

    Saba, Virginia K.; Irwin, Ruth Galten

    2001-01-01

    This is demonstration of an Electronic Tracking System being implemented in several Home Health Agencies in the US. It uses the Home Health Care Classification (HHCC) System, a standardized terminology designed and developed to document patient care. The goal it to take the coded data to design the Electronic Tracking System as a method for predicting resource requirements, tracking care needs, and measuring the outcomes of the care.

  12. The School System Transformation (SST) Protocol

    ERIC Educational Resources Information Center

    Duffy, Francis M.; Reigeluth, Charles M., Ed.

    2008-01-01

    This is the second in a series of articles about creating and sustaining systemic transformational change in school districts. The first article described the "AECT FutureMinds: Transforming America's School Systems" initiative for helping state education agencies (SEAs) facilitate paradigm change in their school districts. This article describes…

  13. How Do Meningeal Lymphatic Vessels Drain the CNS?

    PubMed

    Raper, Daniel; Louveau, Antoine; Kipnis, Jonathan

    2016-09-01

    The many interactions between the nervous and the immune systems, which are active in both physiological and pathological states, have recently become more clearly delineated with the discovery of a meningeal lymphatic system capable of carrying fluid, immune cells, and macromolecules from the central nervous system (CNS) to the draining deep cervical lymph nodes. However, the exact localization of the meningeal lymphatic vasculature and the path of drainage from the cerebrospinal fluid (CSF) to the lymphatics remain poorly understood. Here, we discuss the potential differences between peripheral and CNS lymphatic vessels and examine the purported mechanisms of CNS lymphatic drainage, along with how these may fit into established patterns of CSF flow. PMID:27460561

  14. Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage

    PubMed Central

    Iolyeva, Maria; Aebischer, David; Proulx, Steven T.; Willrodt, Ann-Helen; Ecoiffier, Tatiana; Häner, Simone; Bouchaud, Grégory; Krieg, Carsten; Onder, Lucas; Ludewig, Burkhard; Santambrogio, Laura; Boyman, Onur; Chen, Lu; Finke, Daniela

    2013-01-01

    The cytokine interleukin (IL)-7 exerts essential roles in lymph node (LN) organogenesis and lymphocyte development and homeostasis. Recent studies have identified lymphatic endothelial cells (LECs) as a major source of IL-7 in LNs. Here, we report that LECs not only produce IL-7, but also express the IL-7 receptor chains IL-7Rα and CD132. Stimulation with recombinant IL-7 enhanced LEC in vitro activity and induced lymphangiogenesis in the cornea of wild-type (WT) mice. Whereas in IL-7Rα−/− mice, dermal lymphatic vessels (LVs) were abnormally organized and lymphatic drainage was compromised, transgenic overexpression of IL-7 in mice resulted in an expanded dermal LV network with increased drainage function. Moreover, systemic treatment with recombinant IL-7 enhanced lymphatic drainage in the skin of WT mice and of mice devoid of lymphocytes. Experiments in IL-7Rα−/− bone marrow chimeras demonstrated that the drainage-enhancing activity of IL-7 was exclusively dependent on IL-7Rα expression in stromal but not in hematopoietic cells. Finally, near-infrared in vivo imaging performed in IL-7Rα−/− mice revealed that the pumping activity of collecting vessels was normal but fluid uptake into lymphatic capillaries was defective. Overall, our data point toward an unexpected new role for IL-7 as a potential autocrine mediator of lymphatic drainage. PMID:23963040

  15. Assessment of The Lymphatic System of the Genitalia Using Magnetic Resonance Lymphography Before and After Treatment of Male Genital Lymphedema.

    PubMed

    Lu, Qing; Jiang, Zhaohua; Zhao, Zizhou; Wu, Lianming; Wu, Guangyu; Suo, Shiteng; Xu, Jianrong

    2016-05-01

    Treatment for chronic male genital lymphedema (GL) is limited. No standard treatment or validated instrument to assess GL is available. The aim of this study was to explore whether magnetic resonance lymphography (MRL) could be used to assess GL, select proper treatment for patients, and monitor postoperative progress.This is a retrospective analysis of a prospectively acquired cohort of men with GL presenting for MRL over a 7-year period. Thirty-six of 47 eligible men were included. All men were offered preoperative and postoperative MRL and assigned a morphology and function classification. Men with mild, moderate, and severe nodal dysfunction underwent complex decongestive physiotherapy (CDP), lymphoveneous microsurgery, and surgical excision, respectively. The volume reductions in the genitalia of patients with mild and moderate nodal dysfunction were recorded and compared using Student t test.The abnormal superficial and deep lymphatic vessels in the lymphedematous genitalia were detected by MRL, and inguinal lymph node dysfunction was classified by MRL. Seven patients with mild dysfunction who underwent CDP showed a more significant mean volume reduction in the genitalia than did 9 patients with moderate dysfunction. Three patients with hyperplasia and moderate dysfunction who underwent microsurgical operations and 17 patients with hypoplasia and moderate or severe nodal dysfunction who underwent surgical excision had excellent cosmetic results with no lymphedema at the 3- to 5-year follow-up.MRL can be used to assess morphological and functional lymphatic abnormalities in GL, preoperatively select appropriate treatment, and postoperatively evaluate treatment outcomes. PMID:27227943

  16. Assessment of The Lymphatic System of the Genitalia Using Magnetic Resonance Lymphography Before and After Treatment of Male Genital Lymphedema

    PubMed Central

    Lu, Qing; Jiang, Zhaohua; Zhao, Zizhou; Wu, Lianming; Wu, Guangyu; Suo, Shiteng; Xu, Jianrong

    2016-01-01

    Abstract Treatment for chronic male genital lymphedema (GL) is limited. No standard treatment or validated instrument to assess GL is available. The aim of this study was to explore whether magnetic resonance lymphography (MRL) could be used to assess GL, select proper treatment for patients, and monitor postoperative progress. This is a retrospective analysis of a prospectively acquired cohort of men with GL presenting for MRL over a 7-year period. Thirty-six of 47 eligible men were included. All men were offered preoperative and postoperative MRL and assigned a morphology and function classification. Men with mild, moderate, and severe nodal dysfunction underwent complex decongestive physiotherapy (CDP), lymphoveneous microsurgery, and surgical excision, respectively. The volume reductions in the genitalia of patients with mild and moderate nodal dysfunction were recorded and compared using Student t test. The abnormal superficial and deep lymphatic vessels in the lymphedematous genitalia were detected by MRL, and inguinal lymph node dysfunction was classified by MRL. Seven patients with mild dysfunction who underwent CDP showed a more significant mean volume reduction in the genitalia than did 9 patients with moderate dysfunction. Three patients with hyperplasia and moderate dysfunction who underwent microsurgical operations and 17 patients with hypoplasia and moderate or severe nodal dysfunction who underwent surgical excision had excellent cosmetic results with no lymphedema at the 3- to 5-year follow-up. MRL can be used to assess morphological and functional lymphatic abnormalities in GL, preoperatively select appropriate treatment, and postoperatively evaluate treatment outcomes. PMID:27227943

  17. Quantitative imaging of lymphatic function with liposomal indocyanine green.

    PubMed

    Proulx, Steven T; Luciani, Paola; Derzsi, Stefanie; Rinderknecht, Matthias; Mumprecht, Viviane; Leroux, Jean-Christophe; Detmar, Michael

    2010-09-15

    Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C-expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer. PMID:20823159

  18. Lymphatic vessels: new targets for the treatment of inflammatory diseases.

    PubMed

    Dieterich, Lothar C; Seidel, Catharina D; Detmar, Michael

    2014-04-01

    The lymphatic system plays an important role in the physiological control of the tissue fluid balance and in the initiation of immune responses. Recent studies have shown that lymphangiogenesis, the growth of new lymphatic vessels and/or the expansion of existing lymphatic vessels, is a characteristic feature of acute inflammatory reactions and of chronic inflammatory diseases. In these conditions, lymphatic vessel expansion occurs at the tissue level but also within the draining lymph nodes. Surprisingly, activation of lymphatic vessel function by delivery of vascular endothelial growth factor-C exerts anti-inflammatory effects in several models of cutaneous and joint inflammation. These effects are likely mediated by enhanced drainage of extravasated fluid and inflammatory cells, but also by lymphatic vessel-mediated modulation of immune responses. Although some of the underlying mechanisms are just beginning to be identified, lymphatic vessels have emerged as important targets for the development of new therapeutic strategies to treat inflammatory conditions. In this context, it is of great interest that some of the currently used anti-inflammatory drugs also potently activate lymphatic vessels.

  19. Advanced information processing system: Authentication protocols for network communication

    NASA Technical Reports Server (NTRS)

    Harper, Richard E.; Adams, Stuart J.; Babikyan, Carol A.; Butler, Bryan P.; Clark, Anne L.; Lala, Jaynarayan H.

    1994-01-01

    In safety critical I/O and intercomputer communication networks, reliable message transmission is an important concern. Difficulties of communication and fault identification in networks arise primarily because the sender of a transmission cannot be identified with certainty, an intermediate node can corrupt a message without certainty of detection, and a babbling node cannot be identified and silenced without lengthy diagnosis and reconfiguration . Authentication protocols use digital signature techniques to verify the authenticity of messages with high probability. Such protocols appear to provide an efficient solution to many of these problems. The objective of this program is to develop, demonstrate, and evaluate intercomputer communication architectures which employ authentication. As a context for the evaluation, the authentication protocol-based communication concept was demonstrated under this program by hosting a real-time flight critical guidance, navigation and control algorithm on a distributed, heterogeneous, mixed redundancy system of workstations and embedded fault-tolerant computers.

  20. Thymus cell antigen 1 (Thy1, CD90) is expressed by lymphatic vessels and mediates cell adhesion to lymphatic endothelium.

    PubMed

    Jurisic, Giorgia; Iolyeva, Maria; Proulx, Steven T; Halin, Cornelia; Detmar, Michael

    2010-10-15

    The lymphatic vascular system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined by comparative transcriptional profiling studies of ex vivo isolated mouse intestinal lymphatic endothelial cells versus blood vascular endothelial cells, thymus cell antigen 1 (Thy1, CD90) was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative PCR, and at the protein level by FACS and immunofluorescence analyses. Thy1 was also strongly expressed by tumor-associated lymphatic vessels, as evaluated in a B16 melanoma footpad model in mice. Blockade of Thy1 inhibited tumor cell adhesion to cultured mouse lymphatic endothelial cells. Importantly, treatment of human dermal microvascular endothelial cells with tumor necrosis factor or phorbol 12-myristate 13-acetate resulted in Thy1 upregulation in podoplanin-expressing lymphatic endothelial cells, but not in podoplanin-negative blood vascular endothelial cells. Moreover, adhesion of human polymorphonuclear and mononuclear leukocytes to human lymphatic endothelial cells was Thy1-dependent. Together, these results identify Thy1 as a novel lymphatic vessel expressed gene and suggest its potential role in the cell adhesion processes required for tumor progression and inflammation.

  1. Lymphatic disorders after renal transplantation: new insights for an old complication

    PubMed Central

    Ranghino, Andrea; Segoloni, Giuseppe Paolo; Lasaponara, Fedele; Biancone, Luigi

    2015-01-01

    In renal transplanted patients, lymphoceles and lymphorrhea are well-known lymphatic complications. Surgical damage of the lymphatics of the graft during the procurement and of the lymphatic around the iliac vessels of the recipients has been associated with development of lymphatic complications. However, lymphatic complications may be related to medical factors such as diabetes, obesity, blood coagulation abnormalities, anticoagulation prophylaxis, high dose of diuretics, delay in graft function and immunosuppressive drugs. Consistently, immunosuppression regimens based on the use of mTOR inhibitors, especially in association with steroids and immediately after transplantation, has been associated with a high risk to develop lymphocele or lymphorrhea. In addition, several studies have demonstrated the association between rejection episodes and lymphatic complications. However, before the discovery of reliable markers of lymphatic vessels, the pathogenic mechanisms underlining the development of lymphatic complications during rejection and the influence of mTOR inhibitors remained not fully understood. The recent findings on the lymphatic systems of either native or transplanted kidneys together with the advances achieved on lymphangiogenesis shared some lights on the pathogenesis of lymphatic complications after renal transplantation. In this review, we describe the surgical and medical causes of lymphatic complications focusing on the rejection and immunosuppressive drugs as causes of lymphatic complications. PMID:26413290

  2. Development of diaphragmatic lymphatics: the process of their direct connection to the peritoneal cavity.

    PubMed

    Shao, X J; Ohtani, O; Saitoh, M; Ohtani, Y

    1998-05-01

    The development of the lymphatic system in the rat diaphragm was studied from embryonic day 16 to 25 weeks after birth by histochemistry for 5'-nucleotidase, scanning electron microscopy of KOH-treated or intact tissues, and transmission electron microscopy of thin sections. On embryonic day 16, distinct lymphatics were noted in the subpleural space of the diaphragm periphery. The endothelial cells at this stage contained an abundance of rough endoplasmic reticulum, a developed Golgi apparatus and mitochondria, and fewer pinocytotic vesicles than those in adults. The subpleural lymphatics subsequently increased and formed a polygonal network. They possessed many valves, and by postnatal week 6, some thick collecting lymphatics became endowed with smooth muscle cells. On embryonic day 19, some lymphatics appeared in the subperitoneal space. They extended centripetally and had many lateral projections that subsequently became elongated and connected with those from adjacent lymphatics, thus forming a lattice-like network. During the early postnatal days, the subperitoneal lymphatics projected many bulges that subsequently became elongated, and came into contact with the pores among the mesothelial cells, thus forming lymphatic stomata connecting the lymphatic lacunae to the peritoneal cavity. The lymphatic stomata increased until postnatal week 10. The results show that lymphatics appear as early as embryonic day 16 in the subpleural space of the diaphragm periphery, and develop with age by sprouting to form networks in both the subpleural and the subperitoneal spaces, and that the direct connection of the lymphatic lacunae to the peritoneal cavity is formed after birth.

  3. System level traffic shaping in disk servers with heterogeneous protocols

    NASA Astrophysics Data System (ADS)

    Cano, Eric; Kruse, Daniele Francesco

    2014-06-01

    Disk access and tape migrations compete for network bandwidth in CASTORs disk servers, over various protocols: RFIO, Xroot, root and GridFTP. As there are a limited number of tape drives, it is important to keep them busy all the time, at their nominal speed. With potentially 100s of user read streams per server, the bandwidth for the tape migrations has to be guaranteed to a controlled level, and not the fair share the system gives by default. Xroot provides a prioritization mechanism, but using it implies moving exclusively to the Xroot protocol, which is not possible in short to mid-term time frame, as users are equally using all protocols. The greatest commonality of all those protocols is not more than the usage of TCP/IP. We investigated the Linux kernel traffic shaper to control TCP/ IP bandwidth. The performance and limitations of the traffic shaper have been understood in test environment, and satisfactory working point has been found for production. Notably, TCP offload engines' negative impact on traffic shaping, and the limitations of the length of the traffic shaping rules were discovered and measured. A suitable working point has been found and the traffic shaping is now successfully deployed in the CASTOR production systems at CERN. This system level approach could be transposed easily to other environments.

  4. Nonmalignant Adult Thoracic Lymphatic Disorders.

    PubMed

    Itkin, Maxim; McCormack, Francis X

    2016-09-01

    The thoracic lymphatic disorders are a heterogeneous group of uncommon conditions that are associated with thoracic masses, interstitial pulmonary infiltrates, and chylous complications. Accurate diagnosis of the thoracic lymphatic disorders has important implications for the newest approaches to management, including embolization and treatment with antilymphangiogenic drugs. New imaging techniques to characterize lymphatic flow, such as dynamic contrast-enhanced magnetic resonance lymphangiogram, are redefining approaches to disease classification and therapy. PMID:27514588

  5. The dual role of tumor lymphatic vessels in dissemination of metastases and immune response development.

    PubMed

    Stachura, Joanna; Wachowska, Malgorzata; Kilarski, Witold W; Güç, Esra; Golab, Jakub; Muchowicz, Angelika

    2016-07-01

    Lymphatic vasculature plays a crucial role in the immune response, enabling transport of dendritic cells (DCs) and antigens (Ags) into the lymph nodes. Unfortunately, the lymphatic system has also a negative role in the progression of cancer diseases, by facilitating the metastatic spread of many carcinomas to the draining lymph nodes. The lymphatics can promote antitumor immune response as well as tumor tolerance. Here, we review the role of lymphatic endothelial cells (LECs) in tumor progression and immunity and mechanism of action in the newest anti-lymphatic therapies, including photodynamic therapy (PDT).

  6. The dual role of tumor lymphatic vessels in dissemination of metastases and immune response development

    PubMed Central

    Stachura, Joanna; Wachowska, Malgorzata; Kilarski, Witold W.; Güç, Esra; Golab, Jakub; Muchowicz, Angelika

    2016-01-01

    ABSTRACT Lymphatic vasculature plays a crucial role in the immune response, enabling transport of dendritic cells (DCs) and antigens (Ags) into the lymph nodes. Unfortunately, the lymphatic system has also a negative role in the progression of cancer diseases, by facilitating the metastatic spread of many carcinomas to the draining lymph nodes. The lymphatics can promote antitumor immune response as well as tumor tolerance. Here, we review the role of lymphatic endothelial cells (LECs) in tumor progression and immunity and mechanism of action in the newest anti-lymphatic therapies, including photodynamic therapy (PDT).

  7. The dual role of tumor lymphatic vessels in dissemination of metastases and immune response development

    PubMed Central

    Stachura, Joanna; Wachowska, Malgorzata; Kilarski, Witold W.; Güç, Esra; Golab, Jakub; Muchowicz, Angelika

    2016-01-01

    ABSTRACT Lymphatic vasculature plays a crucial role in the immune response, enabling transport of dendritic cells (DCs) and antigens (Ags) into the lymph nodes. Unfortunately, the lymphatic system has also a negative role in the progression of cancer diseases, by facilitating the metastatic spread of many carcinomas to the draining lymph nodes. The lymphatics can promote antitumor immune response as well as tumor tolerance. Here, we review the role of lymphatic endothelial cells (LECs) in tumor progression and immunity and mechanism of action in the newest anti-lymphatic therapies, including photodynamic therapy (PDT). PMID:27622039

  8. The dual role of tumor lymphatic vessels in dissemination of metastases and immune response development.

    PubMed

    Stachura, Joanna; Wachowska, Malgorzata; Kilarski, Witold W; Güç, Esra; Golab, Jakub; Muchowicz, Angelika

    2016-07-01

    Lymphatic vasculature plays a crucial role in the immune response, enabling transport of dendritic cells (DCs) and antigens (Ags) into the lymph nodes. Unfortunately, the lymphatic system has also a negative role in the progression of cancer diseases, by facilitating the metastatic spread of many carcinomas to the draining lymph nodes. The lymphatics can promote antitumor immune response as well as tumor tolerance. Here, we review the role of lymphatic endothelial cells (LECs) in tumor progression and immunity and mechanism of action in the newest anti-lymphatic therapies, including photodynamic therapy (PDT). PMID:27622039

  9. Immunopathogenesis of lymphatic filarial disease1

    PubMed Central

    Babu, Subash; Nutman, Thomas B.

    2012-01-01

    Although two-thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ~ 40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process - the first initiated by the parasite and host innate immune system and the second propagated mainly by the host’s adaptive immune system and by other factors (including secondary infections). PMID:23053393

  10. Lipopolysaccharide modulates neutrophil recruitment and macrophage polarization on lymphatic vessels and impairs lymphatic function in rat mesentery.

    PubMed

    Chakraborty, Sanjukta; Zawieja, Scott D; Wang, Wei; Lee, Yang; Wang, Yuan J; von der Weid, Pierre-Yves; Zawieja, David C; Muthuchamy, Mariappan

    2015-12-15

    Impairment of the lymphatic system is apparent in multiple inflammatory pathologies connected to elevated endotoxins such as LPS. However, the direct mechanisms by which LPS influences the lymphatic contractility are not well understood. We hypothesized that a dynamic modulation of innate immune cell populations in mesentery under inflammatory conditions perturbs tissue cytokine/chemokine homeostasis and subsequently influences lymphatic function. We used rats that were intraperitoneally injected with LPS (10 mg/kg) to determine the changes in the profiles of innate immune cells in the mesentery and in the stretch-mediated contractile responses of isolated lymphatic preparations. Results demonstrated a reduction in the phasic contractile activity of mesenteric lymphatic vessels from LPS-injected rats and a severe impairment of lymphatic pump function and flow. There was a significant reduction in the number of neutrophils and an increase in monocytes/macrophages present on the lymphatic vessels and in the clear mesentery of the LPS group. This population of monocytes and macrophages established a robust M2 phenotype, with the majority showing high expression of CD163 and CD206. Several cytokines and chemoattractants for neutrophils and macrophages were significantly changed in the mesentery of LPS-injected rats. Treatment of lymphatic muscle cells (LMCs) with LPS showed significant changes in the expression of adhesion molecules, VCAM1, ICAM1, CXCR2, and galectin-9. LPS-TLR4-mediated regulation of pAKT, pERK pI-κB, and pMLC20 in LMCs promoted both contractile and inflammatory pathways. Thus, our data provide the first evidence connecting the dynamic changes in innate immune cells on or near the lymphatics and complex cytokine milieu during inflammation with lymphatic dysfunction.

  11. Primary and secondary lymphatic valve development: molecular, functional and mechanical insights.

    PubMed

    Bazigou, Eleni; Wilson, John T; Moore, James E

    2014-11-01

    Fluid homeostasis in vertebrates critically relies on the lymphatic system forming a hierarchical network of lymphatic capillaries and collecting lymphatics, for the efficient drainage and transport of extravasated fluid back to the cardiovascular system. Blind-ended lymphatic capillaries employ specialized junctions and anchoring filaments to encourage a unidirectional flow of the interstitial fluid into the initial lymphatic vessels, whereas collecting lymphatics are responsible for the active propulsion of the lymph to the venous circulation via the combined action of lymphatic muscle cells and intraluminal valves. Here we describe recent findings on molecular and physical factors regulating the development and maturation of these two types of valves and examine their role in tissue-fluid homeostasis.

  12. Cutaneous lymphatic sporotrichosis.

    PubMed

    Anandi, V; Kurien, T; Jacob, M; Koshi, G

    1994-01-01

    The first case of cutaneous lymphatic sporotrichosis from Nagaland and a case of cutaneous sporotrichosis from Kerala who had acquired infection from Assam are reported. The diagnosis in both cases were established by isolating Sporothrix schenckii from multiple cutaneous lesions. The dimorphic nature of fungus was established in vitro by demonstrating the mycelial phase at 25-30 degrees C and yeast phase at 37 degrees C and pathogenicity to white mice. Both the patients were successfully treated with oral administration of potassium iodide for 3 months. PMID:8088907

  13. Vascular endothelial growth factor receptor-2 promotes the development of the lymphatic vasculature.

    PubMed

    Dellinger, Michael T; Meadows, Stryder M; Wynne, Katherine; Cleaver, Ondine; Brekken, Rolf A

    2013-01-01

    Vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed by lymphatic endothelial cells and has been shown to stimulate lymphangiogenesis in adult mice. However, the role VEGFR2 serves in the development of the lymphatic vascular system has not been defined. Here we use the Cre-lox system to show that the proper development of the lymphatic vasculature requires VEGFR2 expression by lymphatic endothelium. We show that Lyve-1(wt/Cre);Vegfr2(flox/flox) mice possess significantly fewer dermal lymphatic vessels than Vegfr2(flox/flox) mice. Although Lyve-1(wt/Cre);Vegfr2(flox/flox) mice exhibit lymphatic hypoplasia, the lymphatic network is functional and contains all of the key features of a normal lymphatic network (initial lymphatic vessels and valved collecting vessels surrounded by smooth muscle cells (SMCs)). We also show that Lyve-1(Cre) mice display robust Cre activity in macrophages and in blood vessels in the yolk sac, liver and lung. This activity dramatically impairs the development of blood vessels in these tissues in Lyve-1(wt/Cre);Vegfr2(flox/flox) embryos, most of which die after embryonic day14.5. Lastly, we show that inactivation of Vegfr2 in the myeloid lineage does not affect the development of the lymphatic vasculature. Therefore, the abnormal lymphatic phenotype of Lyve-1(wt/Cre);Vegfr2(flox/flox) mice is due to the deletion of Vegfr2 in the lymphatic vasculature not macrophages. Together, this work demonstrates that VEGFR2 directly promotes the expansion of the lymphatic network and further defines the molecular mechanisms controlling the development of the lymphatic vascular system.

  14. Lymphatic vascular morphogenesis in development, physiology, and disease.

    PubMed

    Schulte-Merker, Stefan; Sabine, Amélie; Petrova, Tatiana V

    2011-05-16

    The lymphatic vasculature constitutes a highly specialized part of the vascular system that is essential for the maintenance of interstitial fluid balance, uptake of dietary fat, and immune response. Recently, there has been an increased awareness of the importance of lymphatic vessels in many common pathological conditions, such as tumor cell dissemination and chronic inflammation. Studies of embryonic development and genetically engineered animal models coupled with the discovery of mutations underlying human lymphedema syndromes have contributed to our understanding of mechanisms regulating normal and pathological lymphatic morphogenesis. It is now crucial to use this knowledge for the development of novel therapies for human diseases.

  15. Lymphatic vessel development: fluid flow and valve-forming cells.

    PubMed

    Kume, Tsutomu

    2015-08-01

    Hemodynamic forces regulate many aspects of blood vessel disease and development, including susceptibility to atherosclerosis and remodeling of primary blood vessels into a mature vascular network. Vessels of the lymphatic circulatory system are also subjected to fluid flow-associated forces, but the molecular and cellular mechanisms by which these forces regulate the formation and maintenance of lymphatic vessels remain largely uncharacterized. This issue of the JCI includes two articles that begin to address how fluid flow influences lymphatic vessel development and function. Sweet et al. demonstrate that lymph flow is essential for the remodeling of primary lymphatic vessels, for ensuring the proper distribution of smooth muscle cells (SMCs), and for the development and maturation of lymphatic valves. Kazenwadel et al. show that flow-induced lymphatic valve development is initiated by the upregulation of GATA2, which has been linked to lymphedema in patients with Emberger syndrome. Together, these observations and future studies inspired by these results have potential to lead to the development of strategies for the treatment of lymphatic disorders.

  16. Lymphangion coordination minimally affects mean flow in lymphatic vessels.

    PubMed

    Venugopal, Arun M; Stewart, Randolph H; Laine, Glen A; Dongaonkar, Ranjeet M; Quick, Christopher M

    2007-08-01

    The lymphatic system returns interstitial fluid to the central venous circulation, in part, by the cyclical contraction of a series of "lymphangion pumps" in a lymphatic vessel. The dynamics of individual lymphangions have been well characterized in vitro; their frequencies and strengths of contraction are sensitive to both preload and afterload. However, lymphangion interaction within a lymphatic vessel has been poorly characterized because it is difficult to experimentally alter properties of individual lymphangions and because the afterload of one lymphangion is coupled to the preload of another. To determine the effects of lymphangion interaction on lymph flow, we adapted an existing mathematical model of a lymphangion (characterizing lymphangion contractility, lymph viscosity, and inertia) to create a new lymphatic vessel model consisting of several lymphangions in series. The lymphatic vessel model was validated with focused experiments on bovine mesenteric lymphatic vessels in vitro. The model was then used to predict changes in lymph flow with different time delays between onset of contraction of adjacent lymphangions (coordinated case) and with different relative lymphangion contraction frequencies (noncoordinated case). Coordination of contraction had little impact on mean flow. Furthermore, orthograde and retrograde propagations of contractile waves had similar effects on flow. Model results explain why neither retrograde propagation of contractile waves nor the lack of electrical continuity between lymphangions adversely impacts flow. Because lymphangion coordination minimally affects mean flow in lymphatic vessels, lymphangions have flexibility to independently adapt to local conditions.

  17. Interaction of tumor cells and lymphatic vessels in cancer progression.

    PubMed

    Alitalo, A; Detmar, M

    2012-10-18

    Metastatic spread of cancer through the lymphatic system affects hundreds of thousands of patients yearly. Growth of new lymphatic vessels, lymphangiogenesis, is activated in cancer and inflammation, but is largely inactive in normal physiology, and therefore offers therapeutic potential. Key mediators of lymphangiogenesis have been identified in developmental studies. During embryonic development, lymphatic endothelial cells derive from the blood vascular endothelium and differentiate under the guidance of lymphatic-specific regulators, such as the prospero homeobox 1 transcription factor. Vascular endothelial growth factor-C (VEGF-C) and VEGF receptor 3 signaling are essential for the further development of lymphatic vessels and therefore they provide a promising target for inhibition of tumor lymphangiogenesis. Lymphangiogenesis is important for the progression of solid tumors as shown for melanoma and breast cancer. Tumor cells may use chemokine gradients as guidance cues and enter lymphatic vessels through intercellular openings between endothelial cell junctions or, possibly, by inducing larger discontinuities in the endothelial cell layer. Tumor-draining sentinel lymph nodes show enhanced lymphangiogenesis even before cancer metastasis and they may function as a permissive 'lymphovascular niche' for the survival of metastatic cells. Although our current knowledge indicates that the development of anti-lymphangiogenic therapies may be beneficial for the treatment of cancer patients, several open questions remain with regard to the frequency, mechanisms and biological importance of lymphatic metastases.

  18. Molecular and functional analyses of the contractile apparatus in lymphatic muscle

    NASA Technical Reports Server (NTRS)

    Muthuchamy, Mariappan; Gashev, Anatoliy; Boswell, Niven; Dawson, Nancy; Zawieja, David; Delp, Z. (Principal Investigator)

    2003-01-01

    Lymphatics are necessary for the generation and regulation of lymph flow. Lymphatics use phasic contractions and extrinsic compressions to generate flow; tonic contractions alter resistance. Lymphatic muscle exhibits important differences from typical vascular smooth muscle. In this study, the thoracic duct exhibited significant functional differences from mesenteric lymphatics. To understand the molecular basis for these differences, we examined the profiles of contractile proteins and their messages in mesenteric lymphatics, thoracic duct, and arterioles. Results demonstrated that mesenteric lymphatics express only SMB smooth muscle myosin heavy chain (SM-MHC), whereas thoracic duct and arterioles expressed both SMA and SMB isoforms. Both SM1 and SM2 isoforms of SM-MHC were detected in arterioles and mesenteric and thoracic lymphatics. In addition, the fetal cardiac/skeletal slow-twitch muscle-specific beta-MHC message was detected only in mesenteric lymphatics. All four actin messages, cardiac alpha-actin, vascular alpha-actin, enteric gamma-actin, and skeletal alpha-actin, were present in both mesenteric lymphatics and arterioles. However, in thoracic duct, predominantly cardiac alpha-actin and vascular alpha-actin were found. Western blot and immunohistochemical analyses corroborated the mRNA studies. However, in arterioles only vascular alpha-actin protein was detected. These data indicate that lymphatics display genotypic and phenotypic characteristics of vascular, cardiac, and visceral myocytes, which are needed to fulfill the unique roles of the lymphatic system.

  19. Smooth muscle–endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation

    PubMed Central

    Lutter, Sophie; Xie, Sherry; Tatin, Florence

    2012-01-01

    Active lymph transport relies on smooth muscle cell (SMC) contractions around collecting lymphatic vessels, yet regulation of lymphatic vessel wall assembly and lymphatic pumping are poorly understood. Here, we identify Reelin, an extracellular matrix glycoprotein previously implicated in central nervous system development, as an important regulator of lymphatic vascular development. Reelin-deficient mice showed abnormal collecting lymphatic vessels, characterized by a reduced number of SMCs, abnormal expression of lymphatic capillary marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and impaired function. Furthermore, we show that SMC recruitment to lymphatic vessels stimulated release and proteolytic processing of endothelium-derived Reelin. Lymphatic endothelial cells in turn responded to Reelin by up-regulating monocyte chemotactic protein 1 (MCP1) expression, which suggests an autocrine mechanism for Reelin-mediated control of endothelial factor expression upstream of SMC recruitment. These results uncover a mechanism by which Reelin signaling is activated by communication between the two cell types of the collecting lymphatic vessels—smooth muscle and endothelial cells—and highlight a hitherto unrecognized and important function for SMCs in lymphatic vessel morphogenesis and function. PMID:22665518

  20. Decline of lymphatic vessel density and function in murine skin during aging.

    PubMed

    Karaman, Sinem; Buschle, Dorina; Luciani, Paola; Leroux, Jean-Christophe; Detmar, Michael; Proulx, Steven T

    2015-10-01

    Lymphatic vessels play important roles in the pathogenesis of many conditions that have an increased prevalence in the elderly population. However, the effects of the aging process on the lymphatic system are still relatively unknown. We have applied non-invasive imaging and whole-mount staining techniques to assess the lymphatic vessel function and morphology in three different age groups of mice: 2 months (young), 7 months (middle-aged), and 18 months (aged). We first developed and validated a new method to quantify lymphatic clearance from mouse ear skin, using a lymphatic-specific near-infrared tracer. Using this method, we found that there is a prominent decrease in lymphatic vessel function during aging since the lymphatic clearance was significantly delayed in aged mice. This loss of function correlated with a decreased lymphatic vessel density and a reduced lymphatic network complexity in the skin of aged mice as compared to younger controls. The blood vascular leakage in the skin was slightly increased in the aged mice, indicating that the decreased lymphatic function was not caused by a reduced capillary filtration in aged skin. The decreased function of lymphatic vessels with aging might have implications for the pathogenesis of a number of aging-related diseases.

  1. Protocol care for hypertension supported by an expert system.

    PubMed

    Takahashi, E; Yoshida, K; Izuno, T; Miyakawa, M; Sugimori, H

    1995-01-01

    1. PURPOSE. Hypertension if one of the major prevalent diseases that influences the prognosis of chronic diseases. Primary care should attract much attention in the management of hypertension. The management of hypertension includes not only the use of antihypertensiove drugs, but also the modification of unhealthy lifestyles. Multi-dimensional approaches are required for the management of hypertensive patients. This system supports the standard protocol care for hypertensive patients and the database for clinical epidemiology. 2. DESIGN CONSIDERATIONS. This system has several functions that support the appropriate management of hypertensive patients. The first one is clinical database management. The second is the evaluation of the clinical conditions in hypertension. The third is the decision support system for the selection of treatments for hypertension. 3. SYSTEM DESCRIPTION. This system administers the clinical database, which includes symptoms and signs, laboratory data, and prescriptions. The database deals with the temporal course of the patient's status. The system that evaluates the patient's condition and the decision support system have some knowledge bases. The knowledge bases consist of the evaluation of the patient's condition, the appropriate selection of laboratory examinations, and suggestions for treatments, which involve a life-style modification and the proper prescription of medication. 4. STATUS REPORTS. The relational database was developed for handling the patient's records. These records were displayed on the terminal according to the temporal sequence. The graphical representations of the medical data were displayed in order to understand the patient's status. 5. LESSON LEARNED. This kind of protocol care system is expected to support the proper medical care of patients. Excess medications and laboratory examinations will be excluded under the protocol care, thus reducing unnecessary medical expense. The system will enhance the

  2. Streetlight Control System Based on Wireless Communication over DALI Protocol

    PubMed Central

    Bellido-Outeiriño, Francisco José; Quiles-Latorre, Francisco Javier; Moreno-Moreno, Carlos Diego; Flores-Arias, José María; Moreno-García, Isabel; Ortiz-López, Manuel

    2016-01-01

    Public lighting represents a large part of the energy consumption of towns and cities. Efficient management of public lighting can entail significant energy savings. This work presents a smart system for managing public lighting networks based on wireless communication and the DALI protocol. Wireless communication entails significant economic savings, as there is no need to install new wiring and visual impacts and damage to the facades of historical buildings in city centers are avoided. The DALI protocol uses bidirectional communication with the ballast, which allows its status to be controlled and monitored at all times. The novelty of this work is that it tackles all aspects related to the management of public lighting: a standard protocol, DALI, was selected to control the ballast, a wireless node based on the IEEE 802.15.4 standard with a DALI interface was designed, a network layer that considers the topology of the lighting network has been developed, and lastly, some user-friendly applications for the control and maintenance of the system by the technical crews of the different towns and cities have been developed. PMID:27128923

  3. Streetlight Control System Based on Wireless Communication over DALI Protocol.

    PubMed

    Bellido-Outeiriño, Francisco José; Quiles-Latorre, Francisco Javier; Moreno-Moreno, Carlos Diego; Flores-Arias, José María; Moreno-García, Isabel; Ortiz-López, Manuel

    2016-01-01

    Public lighting represents a large part of the energy consumption of towns and cities. Efficient management of public lighting can entail significant energy savings. This work presents a smart system for managing public lighting networks based on wireless communication and the DALI protocol. Wireless communication entails significant economic savings, as there is no need to install new wiring and visual impacts and damage to the facades of historical buildings in city centers are avoided. The DALI protocol uses bidirectional communication with the ballast, which allows its status to be controlled and monitored at all times. The novelty of this work is that it tackles all aspects related to the management of public lighting: a standard protocol, DALI, was selected to control the ballast, a wireless node based on the IEEE 802.15.4 standard with a DALI interface was designed, a network layer that considers the topology of the lighting network has been developed, and lastly, some user-friendly applications for the control and maintenance of the system by the technical crews of the different towns and cities have been developed. PMID:27128923

  4. Roles of transcriptional network during the formation of lymphatic vessels.

    PubMed

    Watabe, Tetsuro

    2012-09-01

    The lymphatic vascular system, also known as the second vascular system in vertebrates, plays crucial roles in various physiological and pathological processes. It participates in the maintenance of normal tissue fluid balance, trafficking of the immune cells and absorption of fatty acids in the gut. Furthermore, lymphatic system is associated with the pathogenesis of a number of diseases, including lymphedema, inflammatory diseases and tumour metastasis. Lymphatic vessels are comprised of lymphatic endothelial cells (LECs), which are differentiated from blood vascular endothelial cells. This review highlights recent advances in our understanding of the transcriptional control of LEC fate determination and reflects on efforts to understand the roles of transcriptional networks during this discrete developmental process.

  5. Immunology of lymphatic filariasis.

    PubMed

    Babu, S; Nutman, T B

    2014-08-01

    The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen-specific Th2 response and an expansion of IL-10 producing CD4(+) T cells that is accompanied by a muted Th1 response. This antigen-specific T-cell hyporesponsiveness appears to be crucial for the maintenance of the sustained, long-standing infection often with high parasite densities. While the correlates of protective immunity to lymphatic filariasis are still incompletely understood, primarily due to the lack of suitable animal models to study susceptibility, it is clear that T cells and to a certain extent B cells are required for protective immunity. Host immune responses, especially CD4(+) T-cell responses clearly play a role in mediating pathological manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main underlying defect in the development of clinical pathology appears to be a failure to induce T-cell hyporesponsiveness in the face of antigenic stimulation. Finally, another intriguing feature of filarial infections is their propensity to induce bystander effects on a variety of immune responses, including responses to vaccinations, allergens and to other infectious agents. The complexity of the immune response to filarial infection therefore provides an important gateway to understanding the regulation of immune responses to chronic infections, in general.

  6. Immunology of lymphatic filariasis

    PubMed Central

    Babu, Subash; Nutman, Thomas B.

    2013-01-01

    The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen - specific Th2 response and an expansion of IL-10 producing CD4+ T cells that is accompanied by a muted Th1 response. This antigen specific T cell hypo-responsiveness appears to be crucial for the maintenance of the sustained, long-standing infection often with high parasite densities. While the correlates of protective immunity to lymphatic filariasis are still incompletely understood, primarily due to the lack of suitable animal models to study susceptibility, it is clear that T cells and to a certain extent B cells are required for protective immunity. Host immune responses, especially CD4+ T cell responses clearly play a role in mediating pathological manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main underlying defect in the development of clinical pathology appears to be a failure to induce T cell hypo-responsiveness in the face of antigenic stimulation. Finally, another intriguing feature of filarial infections is their propensity to induce bystander effects on a variety of immune responses, including responses to vaccinations, allergens and to other infectious agents. The complexity of the immune response to filarial infection therefore provides an important gateway to understanding the regulation of immune responses to chronic infections, in general. PMID:24134686

  7. Measurement of cytosolic Ca2+ in isolated contractile lymphatics.

    PubMed

    Souza-Smith, Flavia M; Kurtz, Kristine M; Breslin, Jerome W

    2011-01-01

    Lymphatic vessels comprise a multifunctional transport system that maintains fluid homeostasis, delivers lipids to the central circulation, and acts as a surveillance system for potentially harmful antigens, optimizing mucosal immunity and adaptive immune responses. Lymph is formed from interstitial fluid that enters blind-ended initial lymphatics, and then is transported against a pressure gradient in larger collecting lymphatics. Each collecting lymphatic is made up of a series of segments called lymphangions, separated by bicuspid valves that prevent backflow. Each lymphangion possesses a contractile cycle that propels lymph against a pressure gradient toward the central circulation. This phasic contractile pattern is analogous to the cardiac cycle, with systolic and diastolic phases, and with a lower contraction frequency. In addition, lymphatic smooth muscle generates tone and displays myogenic constriction and dilation in response to increases and decreases in luminal pressure, respectively. A hybrid of molecular mechanisms that support both the phasic and tonic contractility of lymphatics are thus proposed. Contraction of smooth muscle is generally regulated by the cytosolic Ca(2+) concentration ([Ca(2+)](i)) plus sensitivity to Ca(2+) of the contractile elements in response to changes in the environment surrounding the cell. [Ca(2+)](i) is determined by the combination of the movement of Ca(2+) through plasma membrane ligand or voltage gated Ca(2+) channels and the release and uptake of Ca(2+) from internal stores. Cytosolic Ca(2+) binds to calmodulin and activates enzymes such as myosin light chain (MLC) kinase (MLCK), which in turn phosphorylates MLC leading to actin-myosin-mediated contraction. However, the sensitivity of this pathway to Ca(2+) can be regulated by the MLC phosphatase (MLCP). MLCP activity is regulated by Rho kinase (ROCK) and the myosin phosphatase inhibitor protein CPI-17. Here, we present a method to evaluate changes in [Ca(2+)](i

  8. Filaria monitoring visualization system: a geographical information system-based application to manage lymphatic filariasis in Andhra Pradesh, India.

    PubMed

    Upadhyayula, Suryanaryana Murty; Mutheneni, Srinivasa Rao; Kumaraswamy, Sriram; Kadiri, Madhusudhan Rao; Pabbisetty, Sampath Kumar; Yellepeddi, Venkata Suryanarayana Murthy

    2012-05-01

    Among various public health diseases, filariasis constitutes a major public health problem in India, wherein an estimated 553.7 million people are at risk of infection. The aim of this article is to present a spatial mapping and analysis of filariasis data over a 3-year period (2004-2007) from Karimnagar, Chittoor, East and West Godavari districts of Andhra Pradesh, India. The data include epidemiological and entomological studies (i.e., infection rate, infectivity rate, mosquito per man hour, and microfilaria rate). These parameters were customized on Geographical Information System (GIS) platform and developed filaria monitoring visualization system (FMVS) for identifying the endemic/risk areas of filariasis among these four districts. GIS map for filariasis transmission from the study areas was created and stratified into different spatial entities like low, medium, and high risk zones. On the basis of the data and FMVS maps, it was demonstrated that filariasis remained unevenly distributed within the districts. Balancing the intervention coverage in different villages with overall mass drug administration and continued promotion of the proper use of control measures are necessary for further reduction of filarial cases in these districts.

  9. Isolation and Characterization of Human Lung Lymphatic Endothelial Cells.

    PubMed

    Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

    2015-01-01

    Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

  10. Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

    PubMed Central

    Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M.; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

    2015-01-01

    Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

  11. Current and Future Lymphatic Imaging Modalities for Tumor Staging

    PubMed Central

    Gao, Kuo; Liu, Tiegang; Tariq, Imran; Sajjad, Ashif; Niu, Meiying; Liu, Guokai; Mehmood, Zahid; Tian, Guihua

    2014-01-01

    Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review. PMID:24757671

  12. Newborn intraabdominal cystic lymphatic malformations.

    PubMed

    Lin, J I; Fisher, J; Caty, M G

    2000-08-01

    Cystic lymphatic malformations are rare causes of abdominal masses in the newborn. Also known as mesenteric, omental, or retroperitoneal cysts, they can present in a variety of ways including, intestinal obstruction, volvulus, nonspecific abdominal pain, intracystic hemorrhage, or as an asymptomatic abdominal mass. Abdominal ultrasound scan provides a definitive diagnosis in most suspected cases. Complete resection is possible in most patients except those with extensive retroperitoneal involvement. Recurrence is unusual when complete resection is accomplished. Because most case series with complete data suggest that these entities are lymphatic malformations, the authors suggest the more specific term, cystic lymphatic malformations, be used to describe these lesions.

  13. An Immunological Fingerprint Differentiates Muscular Lymphatics from Arteries and Veins

    PubMed Central

    Bridenbaugh, Eric A.; Wang, Wei; Srimushnam, Maya; Cromer, Walter E.; Zawieja, Scott D.; Schmidt, Susan E.; Jupiter, Daniel C.; Huang, Hung-Chung; Van Buren, Vincent

    2013-01-01

    Abstract The principal function of the lymphatic system is to transport lymph from the interstitium to the nodes and then from the nodes to the blood. In doing so lymphatics play important roles in fluid homeostasis, macromolecular/antigen transport and immune cell trafficking. To better understand the genes that contribute to their unique physiology, we compared the transcriptional profile of muscular lymphatics (prenodal mesenteric microlymphatics and large, postnodal thoracic duct) to axillary and mesenteric arteries and veins isolated from rats. Clustering of the differentially expressed genes demonstrated that the lymph versus blood vessel differences were more profound than between blood vessels, particularly the microvessels. Gene ontology functional category analysis indicated that microlymphatics were enriched in antigen processing/presentation, IgE receptor signaling, catabolic processes, translation and ribosome; while they were diminished in oxygen transport, regulation of cell proliferation, glycolysis and inhibition of adenylate cyclase activity by G-proteins. We evaluated the differentially expressed microarray genes/products by qPCR and/or immunofluorescence. Immunofluorescence documented that multiple MHC class II antigen presentation proteins were highly expressed by an antigen-presenting cell (APC) type found resident within the lymphatic wall. These APCs also expressed CD86, a co-stimulatory protein necessary for T-cell activation. We evaluated the distribution and phenotype of APCs within the pre and postnodal lymphatic network. This study documents a novel population of APCs resident within the walls of muscular, prenodal lymphatics that indicates novel roles in antigen sampling and immune responses. In conclusion, these prenodal lymphatics exhibit a unique profile that distinguishes them from blood vessels and highlights the role of the lymphatic system as an immunovascular system linking the parenchymal interstitium, lymph nodes and the

  14. Lymphatic dysfunction after ligation surgery for varicose vein

    PubMed Central

    Hara, Hisako; Mihara, Makoto; Hasegawa, Kyoko; Yamanaka, Kazuko

    2016-01-01

    Objective: Although the lymphatic complications such as lymphocele sometimes occur after surgery for varicose veins, the lymphatic function of such patients has not been evaluated. In this case report, we present a case of lymphocele after ligation surgery for varicose vein. We also detected subclinical dysfunction in lower limb using indocyanine green (ICG) lymphography. Case report: A 76 year- old female underwent ligation surgery for right lower leg varicose vein, and she noticed the squashy lesion in the medial side of the right knee. Three years later, she consulted our clinic and we performed ICG lymphography. We observed dermal backflow around the mass, which indicated lymphatic dysfunction. After injecting additional ICG around the knee, we punctured and drained the clear, yellow fluid from the mass and it was contrasted with ICG during the examination and the involvement of the lymphatic system was proven. PMID:27757234

  15. A brief perspective on the diverging theories of lymphatic targeting with colloids

    PubMed Central

    Siram, Karthik; Marslin, Gregory; Raghavan, Chellan Vijaya; Balakumar, Krishnamoorthy; Rahman, Habibur; Franklin, Gregory

    2016-01-01

    For targeted delivery of colloids to the lymphatic system, the colloids should efficiently reach and remain in the lymphatics for a considerable period of time. As per the current knowledge, diffusion and phagocytosis are the two mechanisms through which colloids reach the lymphatic system. Several parameters including particle size and charge have been shown to affect the direct uptake of colloids by the lymphatic system. Although many researchers attached ligands on the surface of colloids to promote phagocytosis-mediated lymphatic delivery, another school of thought suggests avoidance of phagocytosis by use of carriers like polyethylene glycol (PEG)ylated colloids to impart stealth attributes and evade phagocytosis. In this perspective, we weigh up the paradoxical theories and approaches available in the literature to draw conclusions on the conditions favorable for achieving efficient lymphatic targeting of colloids. PMID:27366065

  16. A brief perspective on the diverging theories of lymphatic targeting with colloids.

    PubMed

    Siram, Karthik; Marslin, Gregory; Raghavan, Chellan Vijaya; Balakumar, Krishnamoorthy; Rahman, Habibur; Franklin, Gregory

    2016-01-01

    For targeted delivery of colloids to the lymphatic system, the colloids should efficiently reach and remain in the lymphatics for a considerable period of time. As per the current knowledge, diffusion and phagocytosis are the two mechanisms through which colloids reach the lymphatic system. Several parameters including particle size and charge have been shown to affect the direct uptake of colloids by the lymphatic system. Although many researchers attached ligands on the surface of colloids to promote phagocytosis-mediated lymphatic delivery, another school of thought suggests avoidance of phagocytosis by use of carriers like polyethylene glycol (PEG)ylated colloids to impart stealth attributes and evade phagocytosis. In this perspective, we weigh up the paradoxical theories and approaches available in the literature to draw conclusions on the conditions favorable for achieving efficient lymphatic targeting of colloids. PMID:27366065

  17. Step-up-to-Excellence: A Change Navigation Protocol for Transforming School Systems

    ERIC Educational Resources Information Center

    Duffy, Francis M.

    2006-01-01

    This article presents a protocol change leaders can use to navigate whole-system change in their school districts. The information describing the protocol will help change leaders in school districts and policymakers interested in whole-district change answer the question, "How do we transform our entire school system"? The protocol is…

  18. A knowledge-based care protocol system for ICU.

    PubMed

    Lau, F; Vincent, D D

    1995-01-01

    There is a growing interest in using care maps in ICU. So far, the emphasis has been on developing the critical path, problem/outcome, and variance reporting for specific diagnoses. This paper presents a conceptual knowledge-based care protocol system design for the ICU. It is based on the manual care map currently in use for managing myocardial infarction in the ICU of the Sturgeon General Hospital in Alberta. The proposed design uses expert rules, object schemas, case-based reasoning, and quantitative models as sources of its knowledge. Also being developed is a decision model with explicit linkages for outcome-process-measure from the care map. The resulting system is intended as a bedside charting and decision-support tool for caregivers. Proposed usage includes charting by acknowledgment, generation of alerts, and critiques on variances/events recorded, recommendations for planned interventions, and comparison with historical cases. Currently, a prototype is being developed on a PC-based network with Visual Basic, Level-Expert Object, and xBase. A clinical trial is also planned to evaluate whether this knowledge-based care protocol can reduce the length of stay of patients with myocardial infarction in the ICU. PMID:8591604

  19. The association of adult Onchocerca volvulus with lymphatic vessels.

    PubMed

    Mackenzie, C D; Huntington, M K; Wanji, S; Lovato, R V; Eversole, R R; Geary, T G

    2010-02-01

    Immunocytochemical examination of onchocercal nodule tissues containing adult Onchocerca volvulus using immuno-markers for blood and lymphatic vessels (vWF, D2-40, podoplanin, Prox-1, and Lyve1) shows a distinct pattern of distribution of these vessels within nodules. Blood vessels were commonly seen associated with organized lymphoid cellular aggregates in the both the outer and inner areas of the nodules. In contrast, the majority of the lymphatic vessel positivity was seen in the central zone in close apposition to the adult parasites, and the remainder usually associated with microfilariae in the outer areas of the nodule. These findings suggest an intimate relationship between adult O. volvulus and lymphatic vessels, including the likely proliferation of lymphatic endothelial cells (lymphangectasia) akin to that seen with other filariae. These findings indicate that adult O. volvulus may migrate via the lymphatic system, and that clinical manifestations of this disease that involve tissue edema may be the result of the location of these worms in the lymphatic system.

  20. Photoacoustic lymphatic imaging with high spatial-temporal resolution

    NASA Astrophysics Data System (ADS)

    Martel, Catherine; Yao, Junjie; Huang, Chih-Hsien; Zou, Jun; Randolph, Gwendalyn J.; Wang, Lihong V.

    2014-11-01

    Despite its critical function in coordinating the egress of inflammatory and immune cells out of tissues and maintaining fluid balance, the causative role of lymphatic network dysfunction in pathological settings is still understudied. Engineered-animal models and better noninvasive high spatial-temporal resolution imaging techniques in both preclinical and clinical studies will help to improve our understanding of different lymphatic-related pathologic disorders. Our aim was to take advantage of our newly optimized noninvasive wide-field fast-scanning photoacoustic (PA) microcopy system to coordinately image the lymphatic vasculature and its flow dynamics, while maintaining high resolution and detection sensitivity. Here, by combining the optical-resolution PA microscopy with a fast-scanning water-immersible microelectromechanical system scanning mirror, we have imaged the lymph dynamics over a large field-of-view, with high spatial resolution and advanced detection sensitivity. Depending on the application, lymphatic vessels (LV) were spectrally or temporally differentiated from blood vessels. Validation experiments were performed on phantoms and in vivo to identify the LV. Lymphatic flow dynamics in nonpathological and pathological conditions were also visualized. These results indicate that our newly developed PA microscopy is a promising tool for lymphatic-related biological research.

  1. Photoacoustic lymphatic imaging with high spatial-temporal resolution.

    PubMed

    Martel, Catherine; Yao, Junjie; Huang, Chih-Hsien; Zou, Jun; Randolph, Gwendalyn J; Wang, Lihong V

    2014-11-01

    Despite its critical function in coordinating the egress of inflammatory and immune cells out of tissues and maintaining fluid balance, the causative role of lymphatic network dysfunction in pathological settings is still understudied. Engineered-animal models and better noninvasive high spatial-temporal resolution imaging techniques in both preclinical and clinical studies will help to improve our understanding of different lymphatic-related pathologic disorders. Our aim was to take advantage of our newly optimized noninvasive wide-field fast-scanning photoacoustic (PA) microcopy system to coordinately image the lymphatic vasculature and its flow dynamics, while maintaining high resolution and detection sensitivity. Here, by combining the optical-resolution PA microscopy with a fast-scanning water-immersible microelectromechanical system scanning mirror, we have imaged the lymph dynamics over a large field-of-view, with high spatial resolution and advanced detection sensitivity. Depending on the application, lymphatic vessels (LV) were spectrally or temporally differentiated from blood vessels. Validation experiments were performed on phantoms and in vivo to identify the LV. Lymphatic flow dynamics in nonpathological and pathological conditions were also visualized. These results indicate that our newly developed PA microscopy is a promising tool for lymphatic-related biological research.

  2. Interactions of immune cells and lymphatic vessels.

    PubMed

    Kataru, Raghu P; Lee, Yulia G; Koh, Gou Young

    2014-01-01

    In addition to fluid and lipid absorption, immune cell trafficking has now become recognized as one of the major functions of the lymphatic system. Recently, several critical roles of the lymphatic vessels (LVs) in modulating immune reactions during both physiological and pathological conditions have been emerging. As LVs serve as conduits for immune cells, they come to closely interact with macrophages/monocytes, dendritic cells, and T and B lymphocytes. Accumulating evidences indicate that reciprocal interactions between the LVs and immune cells exist which cause considerable influence over the process of immune cell migration, LV growth, and ultimately certain immune reactions. This chapter discusses on the interactions of macrophages/monocytes and dendritic cells with peripheral LVs and on those of sinusoidal macrophages and T and B lymphocytes with lymph node LVs.

  3. Lymphatic spreading and lymphadenectomy for esophageal carcinoma

    PubMed Central

    Ji, Xiang; Cai, Jie; Chen, Yao; Chen, Long-Qi

    2016-01-01

    Esophageal carcinoma (EC) is a highly lethal malignancy with a poor prognosis. One of the most important prognostic factors in EC is lymph node status. Therefore, lymphadenectomy has been recognized as a key that influences the outcome of surgical treatment for EC. However, the lymphatic drainage system of the esophagus, including an abundant lymph-capillary network in the lamina propria and muscularis mucosa, is very complex with cervical, mediastinal and celiac node spreading. The extent of lymphadenectomy for EC has always been controversial because of the very complex pattern of lymph node spreading. In this article, published literature regarding lymphatic spreading was reviewed and the current lymphadenectomy trends for EC are discussed. PMID:26843917

  4. ASSESSMENT PROTOCOLS - DURABILITY OF PERFORMANCE OF A HOME RADON REDUCTION SYSTEM FOR SUB-SLAB DEPRESSURIZA- TION SYSTEMS

    EPA Science Inventory

    This handbook contains protocols that compare the immediate performance of subslab depressurization (SSD) mitigation system with performance months or years later. These protocols provide a methodology to test SSD radon mitigation systems in situ to determine long-term performanc...

  5. Lymphatic Regulation of Cellular Trafficking

    PubMed Central

    Jackson, David G.

    2016-01-01

    Lymphatic vessels play vital roles in immune surveillance and immune regulation by conveying antigen loaded dendritic cells, memory T cells, macrophages and neutrophils from the peripheral tissues to draining lymph nodes where they initiate as well as modify immune responses. Until relatively recently however, there was little understanding of how entry and migration through lymphatic vessels is organized or the specific molecular mechanisms that might be involved. Within the last decade, the situation has been transformed by an explosion of knowledge generated largely through the application of microscopic imaging, transgenic animals, specific markers and function blocking mAbs that is beginning to provide a rational conceptual framework. This article provides a critical review of the recent literature, highlighting seminal discoveries that have revealed the fascinating ultrastructure of leucocyte entry sites in lymphatic vessels, as well as generating controversies over the involvement of integrin adhesion, chemotactic and haptotactic mechanisms in DC entry under normal and inflamed conditions. It also discusses the major changes in lymphatic architecture that occur during inflammation and the different modes of leucocyte entry and trafficking within inflamed lymphatic vessels, as well as presenting a timely update on the likely role of hyaluronan and the major lymphatic endothelial hyaluronan receptor LYVE-1 in leucocyte transit.

  6. Sensitivity analysis of near-infrared functional lymphatic imaging

    NASA Astrophysics Data System (ADS)

    Weiler, Michael; Kassis, Timothy; Dixon, J. Brandon

    2012-03-01

    Background - Near-infrared (NIR) imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, offering better spatial and temporal resolution than competing imaging modalities. While NIR lymphatic imaging has begun to be reported in the literature, the technology is still in its infancy and its imaging capabilities have yet to be quantitatively characterized. The objective of this study, therefore, was to characterize the parameters of NIR lymphatic imaging to quantify its capabilities as a diagnostic tool for evaluating lymphatic disease. Methods - An NIR imaging system was developed using a laser diode for excitation, ICG as a fluorescent agent, and a CCD camera to detect emission. A tissue phantom with mock lymphatic vessels of known depths and diameters was used as an alternative to in vivo lymphatic vessels due to the greater degree of control with the phantom. Results and Conclusions - When dissolved in an albumin physiological salt solution (APSS) to mimic interstitial fluid, ICG experiences shifts in the excitation/emission wavelengths such that it is maximally excited at 805nm and produces peak fluorescence at 840nm. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being: 900μM (60g/L) albumin and 193.5μM (150μg/mL) ICG. ICG fluorescence can be detected as deep as 6mm, but spatial resolution deteriorates severely below 3mm, thus skewing vessel geometry measurements. ICG packet travel, a common measure of lymphatic transport, can be detected as deep as 5mm.

  7. Geographic information system (GIS) mapping of lymphatic filariasis endemic areas of Gampaha District, Sri Lanka based on epidemiological and entomological screening.

    PubMed

    Wijegunawardana, N D A D; Gunawardene, Y I N Silva; Manamperi, Aresha; Senarathne, H; Abeyewickreme, W

    2012-05-01

    The objective of this study was to develop a site directed geographic information system (GIS) map of lymphatic filariasis (LF) in Gampaha District, Sri Lanka as a guide for targeted control activities. Epidemiological and entomological screening of LF was carried out in nine pre-identified endemic areas in Gampaha District, using night blood screening and pool-screening PCR-ELISA. In total, 1,073 subjects (286 children, 787 adults) from 9 sites were examined. Positive cases were detected at 2 sites, with prevalence rates of 0.5% (Hekiththa) and 3.4% (Peliyagoda); the prevalence of microfilaria (mf) among adult Culex quinquefasciatus mosquitoes surveyed was 30%. The overall prevalence of mosquitoes with L1-L2 larvae of W. bancrofti ranged from 0% to 8.31% using dissection and point estimates of infection prevalence, and ranged from 0 to 32.4% using PCR-ELISA. The largest number of human cases was found at altitudes of 2.5-3.5 min highly populated areas, where transmission appears to have taken place. Questionnaires indicated that limited community awareness of LF may be a reason for the fairly static infection prevalent among the local population. The GIS mapping of LF cases shows a considerable prevalence of LF and marked variability by geographic site in Gampaha.

  8. Geographic information system (GIS) mapping of lymphatic filariasis endemic areas of Gampaha District, Sri Lanka based on epidemiological and entomological screening.

    PubMed

    Wijegunawardana, N D A D; Gunawardene, Y I N Silva; Manamperi, Aresha; Senarathne, H; Abeyewickreme, W

    2012-05-01

    The objective of this study was to develop a site directed geographic information system (GIS) map of lymphatic filariasis (LF) in Gampaha District, Sri Lanka as a guide for targeted control activities. Epidemiological and entomological screening of LF was carried out in nine pre-identified endemic areas in Gampaha District, using night blood screening and pool-screening PCR-ELISA. In total, 1,073 subjects (286 children, 787 adults) from 9 sites were examined. Positive cases were detected at 2 sites, with prevalence rates of 0.5% (Hekiththa) and 3.4% (Peliyagoda); the prevalence of microfilaria (mf) among adult Culex quinquefasciatus mosquitoes surveyed was 30%. The overall prevalence of mosquitoes with L1-L2 larvae of W. bancrofti ranged from 0% to 8.31% using dissection and point estimates of infection prevalence, and ranged from 0 to 32.4% using PCR-ELISA. The largest number of human cases was found at altitudes of 2.5-3.5 min highly populated areas, where transmission appears to have taken place. Questionnaires indicated that limited community awareness of LF may be a reason for the fairly static infection prevalent among the local population. The GIS mapping of LF cases shows a considerable prevalence of LF and marked variability by geographic site in Gampaha. PMID:23077834

  9. Sensitivity analysis of near-infrared functional lymphatic imaging

    NASA Astrophysics Data System (ADS)

    Weiler, Michael; Kassis, Timothy; Dixon, J. Brandon

    2012-06-01

    Near-infrared imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, yet the imaging capabilities of this approach have yet to be quantitatively characterized. We seek to quantify its capabilities as a diagnostic tool for lymphatic disease. Imaging is performed in a tissue phantom for sensitivity analysis and in hairless rats for in vivo testing. To demonstrate the efficacy of this imaging approach to quantifying immediate functional changes in lymphatics, we investigate the effects of a topically applied nitric oxide (NO) donor glyceryl trinitrate ointment. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being 150 μg/mL ICG and 60 g/L albumin. ICG fluorescence can be detected at a concentration of 150 μg/mL as deep as 6 mm with our system, but spatial resolution deteriorates below 3 mm, skewing measurements of vessel geometry. NO treatment slows lymphatic transport, which is reflected in increased transport time, reduced packet frequency, reduced packet velocity, and reduced effective contraction length. NIR imaging may be an alternative to invasive procedures measuring lymphatic function in vivo in real time.

  10. Lymphatics at the crossroads of angiogenesis and lymphangiogenesis

    PubMed Central

    Scavelli, Claudio; Weber, Elisabetta; Aglianò, Margherita; Cirulli, Teresa; Nico, Beatrice; Vacca, Angelo; Ribatti, Domenico

    2004-01-01

    The lymphatic system is implicated in interstitial fluid balance regulation, immune cell trafficking, oedema and cancer metastasis. However, the sequence of events that initiate and coordinate lymphatic vessel development (lymphangiogenesis) remains obscure. In effect, the understanding of physiological regulation of lymphatic vasculature has been overshadowed by the greater emphasis focused on angiogenesis, and delayed by a lack of specific markers, thereby limiting this field to no more than a descriptive characterization. Recently, new insights into lymphangiogenesis research have been due to the discovery of lymphatic-specific markers and growth factors of vascular endothelial growth factor (VEGF) family, such as VEGF-C and VEGF-D. Studies using transgenic mice overexpressing VEGF-C and VEGF-D have demonstrated a crucial role for these factors in tumour lymphangiogenesis. Knowledge of lymphatic development has now been redefined at the molecular level, providing an interesting target for innovative therapies. This review highlights the recent insights and advances into the field of lymphatic vascular research, outlining the most important aspects of the embryo development, structure, specific markers and methods applied for studying lymphangiogenesis. Finally, molecular mechanisms involved in the regulation of lymphangiogenesis are described. PMID:15198686

  11. Expansion of the lymphatic vasculature in cancer and inflammation: new opportunities for in vivo imaging and drug delivery.

    PubMed

    Proulx, Steven T; Luciani, Paola; Dieterich, Lothar C; Karaman, Sinem; Leroux, Jean-Christophe; Detmar, Michael

    2013-12-10

    Over the last 15 years, discovery of key growth factors and specific molecular markers for lymphatic vessels has enabled a new era of molecular research on the lymphatic vascular system. As a result, it has been found that lymphangiogenesis, the expansion of existing lymphatic vessels, plays an important role in tumor progression and in the control of chronic inflammation. At the same time, technical advancements have been made to improve the visualization of the lymphatic system. We have recently developed liposomal and polymer-based formulations of near-infrared lymphatic-specific imaging tracers for the non-invasive quantitative in vivo imaging of lymphatic vessel function. Using these tracers, a near-infrared stereomicroscope system allows imaging of initial and collecting lymphatic vessels with high spatial and temporal resolution in mice. In addition, we have developed a new method, using antibodies to a lymphatic specific marker and positron emission tomography, to sensitively detect lymphatic expansion in lymph nodes as the earliest sign of cancer metastasis. These imaging methods have great potential to provide non-invasive measures to assess the functionality of the lymphatic system and to assess the efficiency of lymphatic drug delivery.

  12. Immunohistochemical study of the lymphatic vessels in major salivary glands of the rat.

    PubMed

    Aiyama, Shigeo; Kikuchi, Kenichiro; Takada, Kiyomi; Ikeda, Rie; Sato, Sumie; Kuroki, Jyunya

    2011-02-01

    This study was designed to examine whether lymphatic vessels are present in the lobules of major salivary glands in the rat. Immunostaining with an antibody against podoplanin, a lymphatic endothelial cell marker, was performed on sections of the submandibular, sublingual and parotid glands. Light microscopy demonstrated podoplanin-positive lymphatic vessels around the interlobular ducts and the interlobular arteries and veins in the interlobular connective tissue in all of the major salivary glands. No podoplanin-positive lymphatic vessels were found in the lobules. Electron microscopy also demonstrated lymphatic endothelial cells showing podoplanin expression only in the interlobular connective tissue. These findings suggest that the lymphatic system of the rat major salivary glands originates in the interlobular connective tissue, and not in the lobules.

  13. Recent Advance in Lymph Dynamic Analysis in Lymphatics and Lymph Nodes

    PubMed Central

    2012-01-01

    Lymphatics are a unidirectional transport system that carries fluid from the interstitial space and back into the blood stream. Initial lymphatics take up not only fluid but also high-molecular-weight substances, such as plasma proteins and hyaluronan; immune cells, such as lymphocytes, macrophages, and dendritic cells; and colloidal particles, such as carbon particles, bacteria, and tattoo dye. Interstitially injected colloidal particles are known to accumulate in the regional lymph nodes. This phenomenon is applied to find sentinel lymph nodes in cancer patients. Lymph flow rate and composition are influenced by interstitial fluid, lymphatic pump activity, and intra-lymphatic pressure. Lymph composition is changed during its flow downstream. In this review, the main focus is on the mechanisms of lymph formation at the initial lymphatics and lymph transport through the collecting lymphatics and lymph nodes. (*English Translation of J Jpn Coll Angiol, 2008, 48: 113-123.) PMID:23555523

  14. Lymphatics in Neurological Disorders: A Neuro-Lympho-Vascular Component of Multiple Sclerosis and Alzheimer's Disease?

    PubMed

    Louveau, Antoine; Da Mesquita, Sandro; Kipnis, Jonathan

    2016-09-01

    Lymphatic vasculature drains interstitial fluids, which contain the tissue's waste products, and ensures immune surveillance of the tissues, allowing immune cell recirculation. Until recently, the CNS was considered to be devoid of a conventional lymphatic vasculature. The recent discovery in the meninges of a lymphatic network that drains the CNS calls into question classic models for the drainage of macromolecules and immune cells from the CNS. In the context of neurological disorders, the presence of a lymphatic system draining the CNS potentially offers a new player and a new avenue for therapy. In this review, we will attempt to integrate the known primary functions of the tissue lymphatic vasculature that exists in peripheral organs with the proposed function of meningeal lymphatic vessels in neurological disorders, specifically multiple sclerosis and Alzheimer's disease. We propose that these (and potentially other) neurological afflictions can be viewed as diseases with a neuro-lympho-vascular component and should be therapeutically targeted as such. PMID:27608759

  15. In vivo albumin labeling and lymphatic imaging.

    PubMed

    Wang, Yu; Lang, Lixin; Huang, Peng; Wang, Zhe; Jacobson, Orit; Kiesewetter, Dale O; Ali, Iqbal U; Teng, Gaojun; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    The ability to accurately and easily locate sentinel lymph nodes (LNs) with noninvasive imaging methods would assist in tumor staging and patient management. For this purpose, we developed a lymphatic imaging agent by mixing fluorine-18 aluminum fluoride-labeled NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid)-conjugated truncated Evans blue ((18)F-AlF-NEB) and Evans blue (EB) dye. After local injection, both (18)F-AlF-NEB and EB form complexes with endogenous albumin in the interstitial fluid and allow for visualizing the lymphatic system. Positron emission tomography (PET) and/or optical imaging of LNs was performed in three different animal models including a hind limb inflammation model, an orthotropic breast cancer model, and a metastatic breast cancer model. In all three models, the LNs can be distinguished clearly by the apparent blue color and strong fluorescence signal from EB as well as a high-intensity PET signal from (18)F-AlF-NEB. The lymphatic vessels between the LNs can also be optically visualized. The easy preparation, excellent PET and optical imaging quality, and biosafety suggest that this combination of (18)F-AlF-NEB and EB has great potential for clinical application to map sentinel LNs and provide intraoperative guidance. PMID:25535368

  16. In vivo albumin labeling and lymphatic imaging

    PubMed Central

    Wang, Yu; Lang, Lixin; Huang, Peng; Wang, Zhe; Jacobson, Orit; Kiesewetter, Dale O.; Ali, Iqbal U.; Teng, Gaojun; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    The ability to accurately and easily locate sentinel lymph nodes (LNs) with noninvasive imaging methods would assist in tumor staging and patient management. For this purpose, we developed a lymphatic imaging agent by mixing fluorine-18 aluminum fluoride-labeled NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid)-conjugated truncated Evans blue (18F-AlF-NEB) and Evans blue (EB) dye. After local injection, both 18F-AlF-NEB and EB form complexes with endogenous albumin in the interstitial fluid and allow for visualizing the lymphatic system. Positron emission tomography (PET) and/or optical imaging of LNs was performed in three different animal models including a hind limb inflammation model, an orthotropic breast cancer model, and a metastatic breast cancer model. In all three models, the LNs can be distinguished clearly by the apparent blue color and strong fluorescence signal from EB as well as a high-intensity PET signal from 18F-AlF-NEB. The lymphatic vessels between the LNs can also be optically visualized. The easy preparation, excellent PET and optical imaging quality, and biosafety suggest that this combination of 18F-AlF-NEB and EB has great potential for clinical application to map sentinel LNs and provide intraoperative guidance. PMID:25535368

  17. Coexistence of WiFi and WiMAX systems based on PS-request protocols.

    PubMed

    Kim, Jongwoo; Park, Suwon; Rhee, Seung Hyong; Choi, Yong-Hoon; Chung, Young-uk; Hwang, Ho Young

    2011-01-01

    We introduce both the coexistence zone within the WiMAX frame structure and a PS-Request protocol for the coexistence of WiFi and WiMAX systems sharing a frequency band. Because we know that the PS-Request protocol has drawbacks, we propose a revised PS-Request protocol to improve the performance. Two PS-Request protocols are based on the time division operation (TDO) of WiFi system and WiMAX system to avoid the mutual interference, and use the vestigial power management (PwrMgt) bit within the Frame Control field of the frames transmitted by a WiFi AP. The performance of the revised PS-Request protocol is evaluated by computer simulation, and compared to those of the cases without a coexistence protocol and to the original PS-Request protocol. PMID:22163721

  18. Coexistence of WiFi and WiMAX systems based on PS-request protocols.

    PubMed

    Kim, Jongwoo; Park, Suwon; Rhee, Seung Hyong; Choi, Yong-Hoon; Chung, Young-uk; Hwang, Ho Young

    2011-01-01

    We introduce both the coexistence zone within the WiMAX frame structure and a PS-Request protocol for the coexistence of WiFi and WiMAX systems sharing a frequency band. Because we know that the PS-Request protocol has drawbacks, we propose a revised PS-Request protocol to improve the performance. Two PS-Request protocols are based on the time division operation (TDO) of WiFi system and WiMAX system to avoid the mutual interference, and use the vestigial power management (PwrMgt) bit within the Frame Control field of the frames transmitted by a WiFi AP. The performance of the revised PS-Request protocol is evaluated by computer simulation, and compared to those of the cases without a coexistence protocol and to the original PS-Request protocol.

  19. A tale of two models: mouse and zebrafish as complementary models for lymphatic studies.

    PubMed

    Kim, Jun-Dae; Jin, Suk-Won

    2014-07-01

    Lymphatic vessels provide essential roles in maintaining fluid homeostasis and lipid absorption. Dysfunctions of the lymphatic vessels lead to debilitating pathological conditions, collectively known as lymphedema. In addition, lymphatic vessels are a critical moderator for the onset and progression of diverse human diseases including metastatic cancer and obesity. Despite their clinical importance, there is no currently effective pharmacological therapy to regulate functions of lymphatic vessels. Recent efforts to manipulate the Vascular Endothelial Growth Factor-C (VEGFC) pathway, which is arguably the most important signaling pathway regulating lymphatic endothelial cells, to alleviate lymphedema yielded largely mixed results, necessitating identification of new targetable signaling pathways for therapeutic intervention for lymphedema. Zebrafish, a relatively new model system to investigate lymphatic biology, appears to be an ideal model to identify novel therapeutic targets for lymphatic biology. In this review, we will provide an overview of our current understanding of the lymphatic vessels in vertebrates, and discuss zebrafish as a promising in vivo model to study lymphatic vessels.

  20. Contractile activity of lymphatic vessels is altered in the TNBS model of guinea pig ileitis.

    PubMed

    Wu, Theresa F; Carati, Colin J; Macnaughton, Wallace K; von der Weid, Pierre-Yves

    2006-10-01

    The ability of the lymphatic system to actively remove fluid from the interstitium is critical to the resolution of edema. The response of the lymphatics to inflammatory situations is poorly studied, so we examined mesenteric lymphatic contractile activity in the 2,4,6-trinitrobenzenesulfonic acid (TNBS) model of guinea pig ileitis, a well-accepted animal model of intestinal inflammation, by videomicroscopy in vivo and in vitro 1, 3, and 6 days after induction of ileitis. Lymphatic function (diameter, constriction frequency, amplitude of constrictions, and calculated stroke volume and lymph flow rate) of isolated vessels from TNBS-treated guinea pigs were impaired compared with sham-treated controls. The dysfunction was well correlated with the degree of inflammation, with differences reaching significance (P < 0.05) at the highest inflammation-induced damage observed at day 3. In vivo, significantly fewer lymphatics exhibited spontaneous constrictions in TNBS-treated than sham-treated animals. Cyclooxygenase (COX) metabolites were suggested to be involved in this lymphatic dysfunction, since application of nonselective COX inhibitor (10 microM indomethacin) or a combination of COX-1 and COX-2 inhibitors (1 microM SC-560 and 10 microM celecoxib) markedly increased constriction frequency or induced them in lymphatics from TNBS-treated animals in vivo and in vitro. The present results demonstrate that lymphatic contractile function is altered in TNBS-induced ileitis and suggest a role for prostanoids in the lymphatic dysfunction.

  1. A transgenic Prox1-Cre-tdTomato reporter mouse for lymphatic vessel research.

    PubMed

    Bianchi, Roberta; Teijeira, Alvaro; Proulx, Steven T; Christiansen, Ailsa J; Seidel, Catharina D; Rülicke, Thomas; Mäkinen, Taija; Hägerling, René; Halin, Cornelia; Detmar, Michael

    2015-01-01

    The lymphatic vascular system plays an active role in immune cell trafficking, inflammation and cancer spread. In order to provide an in vivo tool to improve our understanding of lymphatic vessel function in physiological and pathological conditions, we generated and characterized a tdTomato reporter mouse and crossed it with a mouse line expressing Cre recombinase under the control of the lymphatic specific promoter Prox1 in an inducible fashion. We found that the tdTomato fluorescent signal recapitulates the expression pattern of Prox1 in lymphatic vessels and other known Prox1-expressing organs. Importantly, tdTomato co-localized with the lymphatic markers Prox1, LYVE-1 and podoplanin as assessed by whole-mount immunofluorescence and FACS analysis. The tdTomato reporter was brighter than a previously established red fluorescent reporter line. We confirmed the applicability of this animal model to intravital microscopy of dendritic cell migration into and within lymphatic vessels, and to fluorescence-activated single cell analysis of lymphatic endothelial cells. Additionally, we were able to describe the early morphological changes of the lymphatic vasculature upon induction of skin inflammation. The Prox1-Cre-tdTomato reporter mouse thus shows great potential for lymphatic research.

  2. A closed-loop identification protocol for nonlinear dynamical systems.

    PubMed

    Feng, Xiao-jiang; Rabitz, Herschel; Turinici, Gabriel; Le Bris, Claude

    2006-06-29

    A previous work introduced an optimal identification (OI) technique for reliably extracting model parameters of biochemical reaction systems from tailored laboratory experiments. The notion of optimality enters through seeking an external control in the laboratory producing data that leads to minimum uncertainties in the identified parameter distributions. A number of algorithmic and operational improvements are introduced in this paper to OI, aiming to build a more practical and efficient closed-loop identification protocol/procedure (CLIP) for nonlinear dynamical systems. The improvements in CLIP include (a) inversion cost function modification to preferably search for the upper and lower boundaries of the parameter distributions consistent with the observed data, (b) dynamic search range updating of the unknown parameters to better exploit the information from the prior iterative experiments, (c) replacing the control genetic algorithm by the simplex method to enable better balance between operational cost and inversion quality, and (d) utilizing virtual sensitivity optimization techniques to further reduce the laboratory costs. The workings of CLIP utilizing these new algorithms are illustrated in indentifying a simulated tRNA proofreading model, and the results demonstrate enhanced performance of CLIP in terms of algorithmic reliability and efficiency. PMID:16789759

  3. LyP-1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics

    NASA Astrophysics Data System (ADS)

    Yan, Zhiqiang; Zhan, Changyou; Wen, Ziyi; Feng, Linglin; Wang, Fei; Liu, Yu; Yang, Xiangkun; Dong, Qing; Liu, Min; Lu, Weiyue

    2011-10-01

    Lymphatic metastasis can be greatly promoted by metastases growth and lymphangiogenesis in lymph nodes (LNs). LyP-1, a cyclic peptide, is able to specifically bind with tumor cells and tumor lymphatics in metastatic LNs. This work aimed to use LyP-1-conjugated liposomes (L-LS) loaded with doxorubicin (DOX) (L-LS/DOX) to suppress lymphatic metastasis by inhibiting both metastases and tumor lymphatics in LNs. L-LS were prepared and exhibited sizes around 90 nm and spherical morphology as characterized by transmission electron microscopy. The in vitro cellular studies showed that LyP-1 modification obviously increased liposome uptake by MDA-MB-435 tumor cells and enhanced the cytotoxicity of liposomal DOX. A popliteal and iliac LN metastases model was successfully established by subcutaneous inoculation of tumor cells to nude mice. The immunofluorescence staining analysis indicated that LyP-1 modification enabled specific binding of liposome with tumor lymphatics and enhanced the destroying effect of liposomal DOX on tumor lymphatics. The in vivo fluorescence imaging and pharmacodynamic studies showed that LyP-1 modification increased liposome uptake by metastatic LNs and that L-LS/DOX significantly decreased metastatic LN growth and LN metastasis rate. These results suggested that L-LS/DOX were an effective delivery system for suppressing lymphatic metastasis by simultaneously inhibiting LN metastases and tumor lymphatics.

  4. Protocol for Uniformly Measuring and Expressing the Performance of Energy Storage Systems

    SciTech Connect

    Conover, David R.; Crawford, Aladsair J.; Viswanathan, Vilayanur V.; Ferreira, Summer; Schoenwald, David

    2014-06-01

    The Protocol for Uniformly Measuring and Expressing the Performance of Energy Storage Systems (PNNL-22010) was first issued in November 2012 as a first step toward providing a foundational basis for developing an initial standard for the uniform measurement and expression of energy storage system (ESS) performance. Its subsequent use in the field and review by the protocol working group and most importantly the users’ subgroup and the thermal subgroup has led to the fundamental modifications reflected in this update of the 2012 Protocol. As an update of the 2012 Protocol, this document (the June 2014 Protocol) is intended to supersede its predecessor and be used as the basis for measuring and expressing ESS performance. The foreword provides general and specific details about what additions, revisions, and enhancements have been made to the 2012 Protocol and the rationale for them in arriving at the June 2014 Protocol.

  5. A New Technique to Map the Lymphatic Distribution and Alignment of the Penis.

    PubMed

    Long, Liu Yan; Qiang, Pan Fu; Ling, Tao; Wei, Zhang Yan; Long, Zhang Yu; Shan, Meng; Rong, Li Shi; Li, Li Hong

    2015-08-01

    The present study was to examine the distribution of lymphatic vessels in the penis of normal adult males, which could provide an anatomical basis for improvement of incisions in penile lengthening surgery, and may also help to prevent postoperative refractory edema. Thirteen normal adult male volunteers were recruited for this study. Contrast agent was injected subcutaneously in the foreskin of the penis, and after two minutes magnetic resonance lymphangiography (MRL) was performed. The acquired magnetic resonance images were analyzed to determine the changes in the number and diameter of lymphatic vessels in different parts of the penis. Maximum intensity projections (MIP) and materializes interactive medical image control system (MIMICS) were applied to analyze the overall distribution of lymphatic vessels in the penis. Magnetic resonance imaging (MRI) showed that the lymphatic vessels were in conspicuous contrast with surrounding tissues and could be clearly identified. Penile lymphatic vessels were clearly visible in the root of the penis. At the junction of the penis and the abdominal wall, all lymphatic vessels were found to be concentrated in the dorsal part of the penis. MIP two-dimensional reconstruction showed that the overall distribution of relatively large lymphatic vessels in the dorsal and ventral parts of the penis could be seen clearly on bilateral 45° position, but not inside the abdominal wall because some of lymphatic vessels were overlapped by other tissues in the abdomen. MIMICS three-dimensional reconstruction was able to reveal the overall spatial distribution of lymphatic vessels in the penis from any angle. The reconstruction results showed that there were 1-2 main lymphatic vessels on the root of dorsal penis, which coursed along the cavernous to the first physiological curvature of the penis. Lymphatic vessels merged on both sides of the ventral penis. At the root of the penis, lymphatic vessels gradually coursed to the dorsal surface

  6. Impaired lymphatic contraction associated with immunosuppression.

    PubMed

    Liao, Shan; Cheng, Gang; Conner, David A; Huang, Yuhui; Kucherlapati, Raju S; Munn, Lance L; Ruddle, Nancy H; Jain, Rakesh K; Fukumura, Dai; Padera, Timothy P

    2011-11-15

    To trigger an effective immune response, antigen and antigen-presenting cells travel to the lymph nodes via collecting lymphatic vessels. However, our understanding of the regulation of collecting lymphatic vessel function and lymph transport is limited. To dissect the molecular control of lymphatic function, we developed a unique mouse model that allows intravital imaging of autonomous lymphatic vessel contraction. Using this method, we demonstrated that endothelial nitric oxide synthase (eNOS) in lymphatic endothelial cells is required for robust lymphatic contractions under physiological conditions. By contrast, under inflammatory conditions, inducible NOS (iNOS)-expressing CD11b(+)Gr-1(+) cells attenuate lymphatic contraction. This inhibition of lymphatic contraction was associated with a reduction in the response to antigen in a model of immune-induced multiple sclerosis. These results suggest the suppression of lymphatic function by the CD11b(+)Gr-1(+) cells as a potential mechanism of self-protection from autoreactive responses during on-going inflammation. The central role for nitric oxide also suggests that other diseases such as cancer and infection may also mediate lymphatic contraction and thus immune response. Our unique method allows the study of lymphatic function and its molecular regulation during inflammation, lymphedema, and lymphatic metastasis.

  7. Protocol for Addressing Induced Seismicity Associated with Enhanced Geothermal Systems

    SciTech Connect

    Majer, Ernie; Nelson, James; Robertson-Tait, Ann; Savy, Jean; Wong, Ivan

    2012-01-01

    This Protocol is a living guidance document for geothermal developers, public officials, regulators and the general public that provides a set of general guidelines detailing useful steps to evaluate and manage the effects of induced seismicity related to EGS projects.

  8. Robotically assisted peritoneal mesometrial resection (PMMR) in endometrial cancer supported by ICG labeling of the compartmental lymphatic system.

    PubMed

    Kimmig, Rainer; Aktas, Bahriye; Buderath, Paul; Heubner, Martin

    2016-04-01

    •Peritoneal mesometrial resection is a compartment based radical hysterectomy in endometrial cancer•ICG staining of the lymph-vessel system facilitates identification of compartment borders•Fluorescence based HD-video documentation supports education in surgery of endometrial cancer. PMID:27331131

  9. Cryptanalysis and improvement of an improved two factor authentication protocol for telecare medical information systems.

    PubMed

    Chaudhry, Shehzad Ashraf; Naqvi, Husnain; Shon, Taeshik; Sher, Muhammad; Farash, Mohammad Sabzinejad

    2015-06-01

    Telecare medical information systems (TMIS) provides rapid and convenient health care services remotely. Efficient authentication is a prerequisite to guarantee the security and privacy of patients in TMIS. Authentication is used to verify the legality of the patients and TMIS server during remote access. Very recently Islam et al. (J. Med. Syst. 38(10):135, 2014) proposed a two factor authentication protocol for TMIS using elliptic curve cryptography (ECC) to improve Xu et al.'s (J. Med. Syst. 38(1):9994, 2014) protocol. They claimed their improved protocol to be efficient and provides all security requirements. However our analysis reveals that Islam et al.'s protocol suffers from user impersonation and server impersonation attacks. Furthermore we proposed an enhanced protocol. The proposed protocol while delivering all the virtues of Islam et al.'s protocol resists all known attacks. PMID:25912427

  10. Building a flexible protocol information system with ready for use' web-technology.

    PubMed

    Vissers, M C; Hasman, A

    1999-01-01

    This paper describes how web technology, currently available, can be used to build a fast and easy flexible protocol information system. The interface design and functionalities of the system were based on experiences with a previous version of a protocol information system (ProtoVIEW). A wide range of diagnostic or therapeutic protocols could be retrieved and viewed with ProtoVIEW. The Web-based version contains all functionalities of the non web-based version plus several new functionalities. The web version contains an X-ray viewer and a great deal of interactivity such as validation of electronic patient data forms. The most important additional function is the context sensitive protocol support that may lead to improved protocol adherence. Finally, the web-based version can be accessed from any working place since patient data and protocols are stored centrally.

  11. Emerging lymphatic imaging technologies for mouse and man

    PubMed Central

    Sevick-Muraca, Eva M.; Kwon, Sunkuk; Rasmussen, John C.

    2014-01-01

    The lymphatic circulatory system has diverse functions in lipid absorption, fluid homeostasis, and immune surveillance and responds dynamically when presented with infection, inflammation, altered hemodynamics, and cancer. Visualization of these dynamic processes in human disease and animal models of disease is key to understanding the contributory role of the lymphatic circulatory system in disease and to devising effective therapeutic strategies. Longitudinal, non-destructive, and repeated imaging is necessary to expand our understanding of disease progression and regression in basic science and clinical investigations. Herein we summarize recent advances in in vivo lymphatic imaging employing magnetic resonance, computed tomography, lymphoscintigraphy, and emerging optical techniques with respect to their contributory roles in both basic science and clinical research investigations. PMID:24590275

  12. Blood and lymphatic vessel formation.

    PubMed

    Bautch, Victoria L; Caron, Kathleen M

    2015-03-02

    Blood and lymphatic vessels deliver oxygen and nutrients, remove waste and CO2, and regulate interstitial pressure in tissues and organs. These vessels begin life early in embryogenesis using transcription factors and signaling pathways that regulate differentiation, morphogenesis, and proliferation. Here we describe how these vessels develop in the mouse embryo, and the signals that are important to their development.

  13. Model Checking a Byzantine-Fault-Tolerant Self-Stabilizing Protocol for Distributed Clock Synchronization Systems

    NASA Technical Reports Server (NTRS)

    Malekpour, Mahyar R.

    2007-01-01

    This report presents the mechanical verification of a simplified model of a rapid Byzantine-fault-tolerant self-stabilizing protocol for distributed clock synchronization systems. This protocol does not rely on any assumptions about the initial state of the system. This protocol tolerates bursts of transient failures, and deterministically converges within a time bound that is a linear function of the self-stabilization period. A simplified model of the protocol is verified using the Symbolic Model Verifier (SMV) [SMV]. The system under study consists of 4 nodes, where at most one of the nodes is assumed to be Byzantine faulty. The model checking effort is focused on verifying correctness of the simplified model of the protocol in the presence of a permanent Byzantine fault as well as confirmation of claims of determinism and linear convergence with respect to the self-stabilization period. Although model checking results of the simplified model of the protocol confirm the theoretical predictions, these results do not necessarily confirm that the protocol solves the general case of this problem. Modeling challenges of the protocol and the system are addressed. A number of abstractions are utilized in order to reduce the state space. Also, additional innovative state space reduction techniques are introduced that can be used in future verification efforts applied to this and other protocols.

  14. Role of lymphatic vessels in tumor immunity: passive conduits or active participants?

    PubMed

    Lund, Amanda W; Swartz, Melody A

    2010-09-01

    Research in lymphatic biology and cancer immunology may soon intersect as emerging evidence implicates the lymphatics in the progression of chronic inflammation and autoimmunity as well as in tumor metastasis and immune escape. Like the blood vasculature, the lymphatic system comprises a highly dynamic conduit system that regulates fluid homeostasis, antigen transport and immune cell trafficking, which all play important roles in the progression and resolution of inflammation, autoimmune diseases, and cancer. This review presents emerging evidence that lymphatic vessels are active modulators of immunity, perhaps fine-tuning the response to adjust the balance between peripheral tolerance and immunity. This suggests that the tumor-associated lymphatic vessels and draining lymph node may be important in tumor immunity which in turn governs metastasis.

  15. Imaging blood vessels and lymphatic vessels in the zebrafish.

    PubMed

    Jung, H M; Isogai, S; Kamei, M; Castranova, D; Gore, A V; Weinstein, B M

    2016-01-01

    Blood vessels supply tissues and organs with oxygen, nutrients, cellular, and humoral factors, while lymphatic vessels regulate tissue fluid homeostasis, immune trafficking, and dietary fat absorption. Understanding the mechanisms of vascular morphogenesis has become a subject of intense clinical interest because of the close association of both types of vessels with pathogenesis of a broad spectrum of human diseases. The zebrafish provides a powerful animal model to study vascular morphogenesis because of their small, accessible, and transparent embryos. These unique features of zebrafish embryos permit sophisticated high-resolution live imaging of even deeply localized vessels during embryonic development and even in adult tissues. In this chapter, we summarize various methods for blood and lymphatic vessel imaging in zebrafish, including nonvital resin injection-based or dye injection-based vessel visualization, and alkaline phosphatase staining. We also provide protocols for vital imaging of vessels using microangiography or transgenic fluorescent reporter zebrafish lines. PMID:27263409

  16. Protocol dependence of mechanical properties in granular systems.

    PubMed

    Inagaki, S; Otsuki, M; Sasa, S

    2011-11-01

    We study the protocol dependence of the mechanical properties of granular media by means of computer simulations. We control a protocol of realizing disk packings in a systematic manner. In 2D, by keeping material properties of the constituents identical, we carry out compaction with various strain rates. The disk packings exhibit the strain rate dependence of the critical packing fraction above which the pressure becomes non-zero. The observed behavior contrasts with the well-studied jamming transitions for frictionless disk packings. We also observe that the elastic moduli of the disk packings depend on the strain rate logarithmically. Our results suggest that there exists a time-dependent state variable to describe macroscopic material properties of disk packings, which depend on its protocol.

  17. Mechanosensitive β-catenin signaling regulates lymphatic vascular development.

    PubMed

    Cha, Boksik; Srinivasan, R Sathish

    2016-08-01

    The Wnt/β-catenin signaling is an evolutionarily conserved pathway that plays a pivotal role in embryonic development and adult homeostasis. However, we have limited information about the involvement of Wnt/β-catenin signaling in the lymphatic vascular system that regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood circulation. In this recent publication we report that canonical Wnt/β-catenin signaling is highly active and critical for the formation of lymphovenus valves (LVVs) and lymphatic valves (LVs). β-catenin directly associates with the regulatory elements of the lymphedema-associated transcription factor, FOXC2 and activates its expression in an oscillatory shear stress (OSS)-dependent manner. The phenotype of β-catenin null embryos was rescued by FOXC2 overexpression. These results suggest that Wnt/β-catenin signaling is a mechanotransducer that links fluid force with lymphatic vascular development. [BMB Reports 2016; 49(8): 403-404]. PMID:27418286

  18. Cell-based approach for 3D reconstruction of lymphatic capillaries in vitro reveals distinct functions of HGF and VEGF-C in lymphangiogenesis.

    PubMed

    Gibot, Laure; Galbraith, Todd; Kloos, Bryan; Das, Suvendu; Lacroix, Dan A; Auger, François A; Skobe, Mihaela

    2016-02-01

    Regeneration of lymphatic vessels is important for treatment of various disorders of lymphatic system and for restoration of lymphatic function after surgery. We have developed a method for generating a human 3D lymphatic vascular construct. In this system, human lymphatic endothelial cells, co-cultured with fibroblasts, spontaneously organized into a stable 3D lymphatic capillary network without the use of any exogenous factors. In vitro-generated lymphatic capillaries exhibited the major molecular and ultra-structural features of native, human lymphatic microvasculature: branches in the three dimensions, wide lumen, blind ends, overlapping borders, adherens and tight junctions, anchoring filaments, lack of mural cells, and poorly developed basement membrane. Furthermore, we show that fibroblast-derived VEGF-C and HGF cooperate in the formation of lymphatic vasculature by activating ERK1/2 signaling, and demonstrate distinct functions of HGF/c-Met and VEGF-C/VEGFR-3 in lymphangiogenesis. This lymphatic vascular construct is expected to facilitate studies of lymphangiogenesis in vitro and it holds promise as a strategy for regeneration of lymphatic vessels and treatment of lymphatic disorders in various conditions.

  19. A High-Salt Diet Differentially Modulates Mechanical Activity of Afferent and Efferent Collecting Lymphatics in Murine Iliac Lymph Nodes

    PubMed Central

    Mizuno, Risuke; Ono, Nobuyuki; Nishimoto, Mitsuhiro; Fujita, Toshiro

    2015-01-01

    Abstract Background: The lymphatic system contributes to fluid homeostasis in various tissues. Recent evidence suggests that lymphangiogenesis induced by a high-salt diet (HSD) is associated with blood pressure regulation. Lymph nodes, located along lymphatic pathways, are not only important secondary lymphoid tissues for cancer metastasis, inflammation, and immune responses, but are also important for fluid homeostasis. Afferent lymphatics collect lymph from the pre-nodal area and efferent lymphatics drain lymph out of the lymph nodes. However, the difference in mechanical activity between afferent and efferent lymphatics and the effect of a HSD on these vessels have not been shown. Methods and Results: Changes in mechanical activity of isolated afferent and efferent lymphatics in normal salt diet (NSD) and 4-week HSD mice in response to increases in intraluminal pressures from 3 to 7 cmH2O were measured using video-microscopy. The higher intramural pressure equivalently decreased pumping activity of afferent and efferent lymphatics in NSD mice. A HSD suppressed the amplitude, ejection fraction, and stroke volume of afferent lymphatics, leading to marked reductions in pumping activity. In contrast, the pumping activities of efferent lymphatics were resistant to a HSD and were preserved by enhancing the contraction frequency. Conclusions: A HSD differentially modulated the mechanical activity of afferent and efferent collecting lymphatics in murine iliac lymph nodes. PMID:26091404

  20. Components of the Lymphatic System

    MedlinePlus

    ... Cells, Tissues, & Membranes Cell Structure & Function Cell Structure Cell Function Body Tissues Epithelial Tissue Connective Tissue Muscle Tissue Nervous Tissue Membranes Review Quiz Skeletal ... capillary is composed of endothelium in which the simple squamous cells overlap to form a simple one-way valve. ...

  1. What Is the Lymphatic System?

    MedlinePlus

    ... Stage 3 Infection and Other Complications NLN Position Papers Lymphedema Awareness Campaign Education Kits Educational Videos What ... Patients (8) LymphLink Articles (175) FAQ's (6) Position Papers (9) LSAP Perspective (9) Become a member now » ...

  2. Lymphatic Vascular Response to Acute Inflammation

    PubMed Central

    Lachance, Pier-Anne; Hazen, Amy; Sevick-Muraca, Eva M.

    2013-01-01

    During acute inflammation, functioning lymphatics are believed to reduce edema and to provide a transiting route for immune cells, but the extent at which the dermal lymphatic remodeling impacts lymphatic transport or the factors regulating these changes remains unclear. Herein we quantify the increase in lymphatic endothelial cells (LECs) and examine the expression of pro-angiogenenic and lymphangiogenic factors during acute cutaneous hypersensitivity (CHS). We found that LECs actively proliferate during CHS but that this proliferation does not affect the lymphatic vessel density. Instead, lymphatic remodeling is accompanied by lymphatic vessel leakiness and lower ejection of lymph fluid, which is observed only in the proximal lymphatic vessel draining the inflamed area. LECs and the immune cells release growth factors and cytokines during inflammation, which impact the lymphatic microenvironment and function. We identified that FGF-2, PLGF-2, HGF, EGF, and KC/CXCL17 are differentially expressed within tissues during acute CHS, but both VEGF-C and VEGF-D levels do not significantly change. Our results indicate that VEGF-C and VEGF-D are not the only players and other factors may be responsible for the LECs proliferation and altered lymphatic function in acute CHS. PMID:24086691

  3. Protocols development for security and privacy of radio frequency identification systems

    NASA Astrophysics Data System (ADS)

    Sabbagha, Fatin

    There are benefits to adopting radio frequency identification (RFID) technology, although there are methods of attack that can compromise the system. This research determined how that may happen and what possible solutions can keep that from happening. Protocols were developed to implement better security. In addition, new topologies were developed to handle the problems of the key management. Previously proposed protocols focused on providing mutual authentication and privacy between readers and tags. However, those protocols are still vulnerable to be attacked. These protocols were analyzed and the disadvantages shown for each one. Previous works assumed that the channels between readers and the servers were secure. In the proposed protocols, a compromised reader is considered along with how to prevent tags from being read by that reader. The new protocols provide mutual authentication between readers and tags and, at the same time, remove the compromised reader from the system. Three protocols are proposed. In the first protocol, a mutual authentication is achieved and a compromised reader is not allowed in the network. In the second protocol, the number of times a reader contacts the server is reduced. The third protocol provides authentication and privacy between tags and readers using a trusted third party. The developed topology is implemented using python language and simulates work to check the efficiency regarding the processing time. The three protocols are implemented by writing codes in C language and then compiling them in MSP430. IAR Embedded workbench is used, which is an integrated development environment with the C/C++ compiler to generate a faster code and to debug the microcontroller. In summary, the goal of this research is to find solutions for the problems on previously proposed protocols, handle a compromised reader, and solve key management problems.

  4. 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.

  5. Communication protocol in chassis detecting wireless transmission system based on WiFi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In chassis detecting wireless transmission system, the wireless network communication protocol plays a key role in the information exchange and synchronization between the host and chassis PDA. This paper presents a wireless network transmission protocol based on TCP/IP which makes the rules of info...

  6. A network identity authentication protocol of bank account system based on fingerprint identification and mixed encryption

    NASA Astrophysics Data System (ADS)

    Zhu, Lijuan; Liu, Jingao

    2013-07-01

    This paper describes a network identity authentication protocol of bank account system based on fingerprint identification and mixed encryption. This protocol can provide every bank user a safe and effective way to manage his own bank account, and also can effectively prevent the hacker attacks and bank clerk crime, so that it is absolute to guarantee the legitimate rights and interests of bank users.

  7. Development of a Decision Support System to Predict Physicians' Rehabilitation Protocols for Patients with Knee Osteoarthritis

    ERIC Educational Resources Information Center

    Hawamdeh, Ziad M.; Alshraideh, Mohammad A.; Al-Ajlouni, Jihad M.; Salah, Imad K.; Holm, Margo B.; Otom, Ali H.

    2012-01-01

    To design a medical decision support system (MDSS) that would accurately predict the rehabilitation protocols prescribed by the physicians for patients with knee osteoarthritis (OA) using only their demographic and clinical characteristics. The demographic and clinical variables for 170 patients receiving one of three treatment protocols for knee…

  8. A Secure RFID Tag Authentication Protocol with Privacy Preserving in Telecare Medicine Information System.

    PubMed

    Li, Chun-Ta; Weng, Chi-Yao; Lee, Cheng-Chi

    2015-08-01

    Radio Frequency Identification (RFID) based solutions are widely used for providing many healthcare applications include patient monitoring, object traceability, drug administration system and telecare medicine information system (TMIS) etc. In order to reduce malpractices and ensure patient privacy, in 2015, Srivastava et al. proposed a hash based RFID tag authentication protocol in TMIS. Their protocol uses lightweight hash operation and synchronized secret value shared between back-end server and tag, which is more secure and efficient than other related RFID authentication protocols. Unfortunately, in this paper, we demonstrate that Srivastava et al.'s tag authentication protocol has a serious security problem in that an adversary may use the stolen/lost reader to connect to the medical back-end server that store information associated with tagged objects and this privacy damage causing the adversary could reveal medical data obtained from stolen/lost readers in a malicious way. Therefore, we propose a secure and efficient RFID tag authentication protocol to overcome security flaws and improve the system efficiency. Compared with Srivastava et al.'s protocol, the proposed protocol not only inherits the advantages of Srivastava et al.'s authentication protocol for TMIS but also provides better security with high system efficiency. PMID:26084587

  9. A Secure RFID Tag Authentication Protocol with Privacy Preserving in Telecare Medicine Information System.

    PubMed

    Li, Chun-Ta; Weng, Chi-Yao; Lee, Cheng-Chi

    2015-08-01

    Radio Frequency Identification (RFID) based solutions are widely used for providing many healthcare applications include patient monitoring, object traceability, drug administration system and telecare medicine information system (TMIS) etc. In order to reduce malpractices and ensure patient privacy, in 2015, Srivastava et al. proposed a hash based RFID tag authentication protocol in TMIS. Their protocol uses lightweight hash operation and synchronized secret value shared between back-end server and tag, which is more secure and efficient than other related RFID authentication protocols. Unfortunately, in this paper, we demonstrate that Srivastava et al.'s tag authentication protocol has a serious security problem in that an adversary may use the stolen/lost reader to connect to the medical back-end server that store information associated with tagged objects and this privacy damage causing the adversary could reveal medical data obtained from stolen/lost readers in a malicious way. Therefore, we propose a secure and efficient RFID tag authentication protocol to overcome security flaws and improve the system efficiency. Compared with Srivastava et al.'s protocol, the proposed protocol not only inherits the advantages of Srivastava et al.'s authentication protocol for TMIS but also provides better security with high system efficiency.

  10. Multivalent Vaccine for Lymphatic Filariasis

    PubMed Central

    Samykutty, Abhilash; Dakshinamoorthy, Gajalakshmi; Kalyanasundaram, Ramaswamy

    2011-01-01

    Lymphatic filariasis is a mosquito borne parasitic infection that cause severe economic burden in several parts of the world. Currently there is no vaccine available to prevent this infection in human. Multidrug therapy is effective, however, requires annual treatment and there is significant concern of drug resistance. In this manuscript we describe development of a multivalent DNA based vaccine comprising BmALT-2 and BmHSP antigens of lymphatic filariasis. Challenge experiments using third stage infective larvae of Brugia malayi in a mouse model suggested that nearly 90% protection can be achieved using the multivalent formulation in a DNA prime protein boost approach. The vaccination regimen induced significant IgG antibody responses and ELISPOT analysis for secreted cytokines from the spleen cells of vaccinated animals showed that these cells produce significant amount of IL-4. Results from this study thus show that a multivalent vaccine formulation of BmALT-2 and BmHSP is an excellent vaccine for lymphatic filariasis and significant protection can be achieved against a challenge infection with B. malayi in a mouse model. PMID:21709765

  11. Multivalent Vaccine for Lymphatic Filariasis.

    PubMed

    Samykutty, Abhilash; Dakshinamoorthy, Gajalakshmi; Kalyanasundaram, Ramaswamy

    2010-01-01

    Lymphatic filariasis is a mosquito borne parasitic infection that cause severe economic burden in several parts of the world. Currently there is no vaccine available to prevent this infection in human. Multidrug therapy is effective, however, requires annual treatment and there is significant concern of drug resistance. In this manuscript we describe development of a multivalent DNA based vaccine comprising BmALT-2 and BmHSP antigens of lymphatic filariasis. Challenge experiments using third stage infective larvae of Brugia malayi in a mouse model suggested that nearly 90% protection can be achieved using the multivalent formulation in a DNA prime protein boost approach. The vaccination regimen induced significant IgG antibody responses and ELISPOT analysis for secreted cytokines from the spleen cells of vaccinated animals showed that these cells produce significant amount of IL-4. Results from this study thus show that a multivalent vaccine formulation of BmALT-2 and BmHSP is an excellent vaccine for lymphatic filariasis and significant protection can be achieved against a challenge infection with B. malayi in a mouse model.

  12. Lymphatic Imaging: Focus on Imaging Probes

    PubMed Central

    Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    In view of the importance of sentinel lymph nodes (SLNs) in tumor staging and patient management, sensitive and accurate imaging of SLNs has been intensively explored. Along with the advance of the imaging technology, various contrast agents have been developed for lymphatic imaging. In this review, the lymph node imaging agents were summarized into three groups: tumor targeting agents, lymphatic targeting agents and lymphatic mapping agents. Tumor targeting agents are used to detect metastatic tumor tissue within LNs, lymphatic targeting agents aim to visualize lymphatic vessels and lymphangionesis, while lymphatic mapping agents are mainly for SLN detection during surgery after local administration. Coupled with various signal emitters, these imaging agents work with single or multiple imaging modalities to provide a valuable way to evaluate the location and metastatic status of SLNs. PMID:25897334

  13. Lymphatic function in the liver after hepatic venous pressure elevation.

    PubMed

    Elk, J R; Drake, R E; Williams, J P; Gabel, J C; Laine, G A

    1988-05-01

    The liver lymphatic system plays an important role in removing excess fluid from the hepatic tissue. A complete analysis of the liver lymphatic system would be difficult. However, we used a simple circuit-analysis technique to represent the intrahepatic portion of the lymph system as a single pressure source (PL) pushing lymph through a single resistance (RL). Liver lymphatic vessels were cannulated in nine halothane-anesthetized dogs. The lymphatic vessel outflow pressure (PO) was varied by raising the outflow end of the cannula. Lymph flow from the cannula (QL) decreased linearly with PO, and we calculated RL as -delta PO/delta QL and PL as the extrapolated PO at which QL = 0. At base line, PL = 8.5 +/- 2.9 cmH2O, and RL = 0.05 +/- 0.03 cmH2O.min/microliter. After we increased inferior vena caval pressure from 5.8 +/- 2.7 to 15.2 +/- 2.5 cmH2O, PL increased significantly to 13.7 +/- 3.4 cmH2O, and RL decreased to 0.02 +/- 0.02 cmH2O.min/microliter (P less than 0.05). The results indicate that increases in QL occur because the effective pressure pushing lymph from the liver (PL) increases, and the effective resistance of the intrahepatic lymph vessels (RL) decreases.

  14. The discovery of the synovial lymphatic stomata and lymphatic reabsorption in knee effusion.

    PubMed

    Ping, Zepeng; Jiang, Tingting; Wang, Chong; Chen, Zhongyi; Chen, Zhongliang; Wang, Jiaxiong; Wang, Li; Wang, Beibei; Xu, Dandan; Liu, Changming; Li, Zhongjie; Li, Ji-Cheng

    2015-06-01

    To illustrate the mechanism of lymphatic reabsorption in knee joint effusion. The current investigation employed transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques to reveal the ultrastructure of the knee synovial membrane in New Zealand rabbits and human. Ultrastructural changes of the synovial lymphatic stomata were observed by using trypan blue absorption and sodium hydroxide (NaOH) digestion methods, and the animal models of synovitis. New Zealand rabbits and human synovial membranes were composed of two types of synovial cells: type A and type B. No lymphatic stomata were found among type A synovial cells, whereas lymphatic stomata with the diameters ranging 0.74-3.26 µm were found in type B synovial cells, and some stomata were closed. After the NaOH digestion, a number of sieve pores, similar to lymphatic stomata in size and shape, were observed in the dense fibrous connective tissue underneath the type B synovial cells. After injecting trypan blue into the rabbit knee joint cavity, absorption of trypan blue through the lymphatic stomata was observed, suggesting the absorption function of the synovial lymphatic stomata. In the rabbit knee joint synovitis models, the synovial lymphatic stomata diameter enlarged. Some macrophages migrated from the lymphatic stomata, indicating that the synovial lymphatic stomata were involved in the joint effusion absorption and inflammatory response. Our study is the first to report the existence of synovial lymphatic stomata in the New Zealand rabbits and human knee joints. Lymphatic stomata may have an important role in the reabsorption of joint effusion.

  15. Acute neonatal presentation of a lymphatic malformation

    PubMed Central

    Tang, Chee Yan; Wijnen, M; Sambeeck van, S J; Halbertsma, F J J

    2013-01-01

    Oropharyngeal lymphatic malformations usually present with a mass either at birth or in the first 2 years of life. Rarely, lymphatic malformations present with extremely progressive respiratory problems shortly after birth, and usually occur in cases which have remained undetected in the absence of antenatal ultrasound. We report the case of a newborn that required tracheostomy and gastrostomy due to a rapidly expansive lymphatic malformation. MRI showed multilocular microcystic lymphatic malformation. Intralesional bleomycin injections proved to be successful in this patient. A short review of epidemiology, clinical manifestation and treatment is given. PMID:23907961

  16. Evaluating Management Information Systems, A Protocol for Automated Peer Review Systems

    PubMed Central

    Black, Gordon C.

    1980-01-01

    This paper discusses key issues in evaluating an automated Peer Review System. Included are the conceptual base, design, steps in planning structural components, operation parameters, criteria, costs and a detailed outline or protocol for use in the evaluation. At the heart of the Peer Review System is the criteria utilized for measuring quality. Criteria evaluation should embrace, as a minimum, appropriateness, validity and reliability, and completemess or comprehensiveness of content. Such an evaluation is not complete without determining the impact (clinical outcome) of the service system or the patient and the population served.

  17. Microneedles for the Noninvasive Structural and Functional Assessment of Dermal Lymphatic Vessels.

    PubMed

    Brambilla, Davide; Proulx, Steven T; Marschalkova, Patrizia; Detmar, Michael; Leroux, Jean-Christophe

    2016-02-24

    The medical and scientific communities' interest in the lymphatic system has been growing rapidly in recent years. It has become evident that the lymphatic system is much more than simply a homeostasis controller and that it plays key roles in several pathological conditions. This work describes the identification of the optimal combination of poly(N-vinylpyrrolidone) and a near-infrared dye (indocyanine green) for the manufacturing of soluble microneedles and their application to the imaging of the lymphatic system. Upon application to the skin, the microneedle-bearing indocyanine green is delivered in the dermal layer, where the lymphatic vessels are abundant. The draining lymphatics can then be visualized and the clearance kinetics from the administration site simply determined using a near-infrared camera. This painless functional "tattooing" procedure can be used for quantitative assessment of the dermal lymphatic function in several dermal conditions and treatment-response evaluations. The two components of these microneedles are extensively used in routine medical care, potentially leading to rapid clinical translation. Moreover, this procedure may have a significant impact on preclinical lymphatic studies.

  18. A hash based mutual RFID tag authentication protocol in telecare medicine information system.

    PubMed

    Srivastava, Keerti; Awasthi, Amit K; Kaul, Sonam D; Mittal, R C

    2015-01-01

    Radio Frequency Identification (RFID) is a technology which has multidimensional applications to reduce the complexity of today life. Everywhere, like access control, transportation, real-time inventory, asset management and automated payment systems etc., RFID has its enormous use. Recently, this technology is opening its wings in healthcare environments, where potential applications include patient monitoring, object traceability and drug administration systems etc. In this paper, we propose a secure RFID-based protocol for the medical sector. This protocol is based on hash operation with synchronized secret. The protocol is safe against active and passive attacks such as forgery, traceability, replay and de-synchronization attack. PMID:25491577

  19. A hash based mutual RFID tag authentication protocol in telecare medicine information system.

    PubMed

    Srivastava, Keerti; Awasthi, Amit K; Kaul, Sonam D; Mittal, R C

    2015-01-01

    Radio Frequency Identification (RFID) is a technology which has multidimensional applications to reduce the complexity of today life. Everywhere, like access control, transportation, real-time inventory, asset management and automated payment systems etc., RFID has its enormous use. Recently, this technology is opening its wings in healthcare environments, where potential applications include patient monitoring, object traceability and drug administration systems etc. In this paper, we propose a secure RFID-based protocol for the medical sector. This protocol is based on hash operation with synchronized secret. The protocol is safe against active and passive attacks such as forgery, traceability, replay and de-synchronization attack.

  20. Lymphatic vessels in the development of tissue and organ rejection.

    PubMed

    Hos, Deniz; Cursiefen, Claus

    2014-01-01

    The lymphatic vascular system-amongst other tasks-is critically involved in the regulation of adaptive immune responses as it provides an important route for APC trafficking to secondary lymphatic organs. In this context, the cornea, which is the transparent and physiologically avascular "windscreen" of the eye, has served as an excellent in vivo model to study the role of the blood and lymphatic vasculature in mediating allogenic immune responses after transplantation. Especially the mouse model of high-risk corneal transplantation, where corneal avascularity is abolished by a severe inflammatory stimulus prior to keratoplasty, allows for comparison to other transplantations performed in primarily vascularized tissues and solid organs. Using this model, we recently demonstrated that especially lymphatic vessels, but not blood vessels, define the high-risk status of vascularized corneas and that anti(lymph)angiogenic treatment significantly promotes corneal allograft survival. Since evidence for lymphangiogenesis and its potential association with graft rejection is nowadays also present in solid organ transplantation, studies are currently addressing the potential benefits of anti(lymph)angiogenic treatment as a novel therapeutic concept also in solid organ grafting with promising initial results.

  1. Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis

    PubMed Central

    Connor, Alicia L.; Kelley, Philip M.; Tempero, Richard M.

    2015-01-01

    Post natal inflammatory lymphangiogenesis presumably requires precise regulatory processes to properly assemble proliferating lymphatic endothelial cells (LECs). The specific mechanisms that regulate the assembly of LECs during new lymphatic vessel synthesis are unclear. Dynamic endothelial shuffling and rearrangement has been proposed as a mechanism of blood vessel growth. We developed genetic lineage tracing strategies using an inductive transgenic technology to track the fate of entire tandem dimer tomato positive (tdT) lymphatic vessels or small, in some cases clonal, populations of LECs. We coupled this platform with a suture induced mouse model of corneal lymphangiogenesis and used different analytic microscopy techniques including serial live imaging to study the spatial properties of proliferating tdT+ LEC progenies. LEC precursors and their progeny expanded from the corneal limbal lymphatic vessel and were assembled contiguously to comprise a subunit within a new lymphatic vessel. VE-cadherin blockade induced morphologic abnormalities in newly synthesized lymphatic vessels, but did not disrupt the tdT+ lymphatic endothelial lineage assembly. Analysis of this static and dynamic data based largely on direct in vivo observations supports a model of lymphatic endothelial lineage assemblage during corneal inflammatory lymphangiogenesis. PMID:26658452

  2. Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis.

    PubMed

    Connor, Alicia L; Kelley, Philip M; Tempero, Richard M

    2016-03-01

    Postnatal inflammatory lymphangiogenesis presumably requires precise regulatory processes to properly assemble proliferating lymphatic endothelial cells (LECs). The specific mechanisms that regulate the assembly of LECs during new lymphatic vessel synthesis are unclear. Dynamic endothelial shuffling and rearrangement has been proposed as a mechanism of blood vessel growth. We developed genetic lineage-tracing strategies using an inductive transgenic technology to track the fate of entire tandem dimer tomato-positive (tdT) lymphatic vessels or small, in some cases clonal, populations of LECs. We coupled this platform with a suture-induced mouse model of corneal lymphangiogenesis and used different analytic microscopy techniques including serial live imaging to study the spatial properties of proliferating tdT(+) LEC progenies. LEC precursors and their progeny expanded from the corneal limbal lymphatic vessel and were assembled contiguously to comprise a subunit within a new lymphatic vessel. VE-cadherin blockade induced morphologic abnormalities in newly synthesized lymphatic vessels, but did not disrupt the tdT(+) lymphatic endothelial lineage assembly. Analysis of this static and dynamic data based largely on direct in vivo observations supports a model of lymphatic endothelial lineage assemblage during corneal inflammatory lymphangiogenesis. PMID:26658452

  3. Temporal Space Lymphatic Malformation in a 15-Year-Old Adolescent: An Extraordinary Case.

    PubMed

    Igoumenakis, Dimosthenis; Logothetis, Ioannis; Barmpagadaki, Alina; Ieromonachou, Panayotis; Mastorakis, George

    2016-07-01

    Lymphatic malformations-previously called lymphangiomas or cystic hygromas-are regarded as non-malignant primary disorders of the lymphatic system. They appear predominantly in infants and children, with 90 % of cases being diagnosed by the age of 2 years. Also, they constitute an infrequent entity, accounting for 5 % of all benign tumors in infants and children. In adults they are extremely rare. In the present article we present an extraordinary case of a lymphatic malformation that ensued in the temporal area of a 15-year old adolescent.

  4. Temporal Space Lymphatic Malformation in a 15-Year-Old Adolescent: An Extraordinary Case.

    PubMed

    Igoumenakis, Dimosthenis; Logothetis, Ioannis; Barmpagadaki, Alina; Ieromonachou, Panayotis; Mastorakis, George

    2016-07-01

    Lymphatic malformations-previously called lymphangiomas or cystic hygromas-are regarded as non-malignant primary disorders of the lymphatic system. They appear predominantly in infants and children, with 90 % of cases being diagnosed by the age of 2 years. Also, they constitute an infrequent entity, accounting for 5 % of all benign tumors in infants and children. In adults they are extremely rare. In the present article we present an extraordinary case of a lymphatic malformation that ensued in the temporal area of a 15-year old adolescent. PMID:27408452

  5. Byzantine-fault tolerant self-stabilizing protocol for distributed clock synchronization systems

    NASA Technical Reports Server (NTRS)

    Malekpour, Mahyar R. (Inventor)

    2010-01-01

    A rapid Byzantine self-stabilizing clock synchronization protocol that self-stabilizes from any state, tolerates bursts of transient failures, and deterministically converges within a linear convergence time with respect to the self-stabilization period. Upon self-stabilization, all good clocks proceed synchronously. The Byzantine self-stabilizing clock synchronization protocol does not rely on any assumptions about the initial state of the clocks. Furthermore, there is neither a central clock nor an externally generated pulse system. The protocol converges deterministically, is scalable, and self-stabilizes in a short amount of time. The convergence time is linear with respect to the self-stabilization period.

  6. In vivo visualization and quantification of collecting lymphatic vessel contractility using near-infrared imaging

    PubMed Central

    Chong, Chloé; Scholkmann, Felix; Bachmann, Samia B.; Luciani, Paola; Leroux, Jean-Christophe; Detmar, Michael; Proulx, Steven T.

    2016-01-01

    Techniques to image lymphatic vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome measures for collecting lymphatic vessel function are sorely needed. In this study, we aimed to develop a method to visualize and quantify collecting lymphatic vessel function in mice, and to establish an in vivo system for evaluation of contractile agonists and antagonists using near-infrared fluorescence imaging. The flank collecting lymphatic vessel in mice was exposed using a surgical technique and a near-infrared tracer was infused into the inguinal lymph node. Collecting lymphatic vessel contractility and valve function could be easily visualized after the infusion. A diameter tracking method was established and the diameter of the vessel was found to closely correlate to near-infrared fluorescence signal. Phasic contractility measures of frequency and amplitude were established using an automated algorithm. The methods were validated by tracking the vessel response to topical application of a contractile agonist, prostaglandin F2α, and by demonstrating the potential of the technique for non-invasive evaluation of modifiers of lymphatic function. These new methods will enable high-resolution imaging and quantification of collecting lymphatic vessel function in animal models and may have future clinical applications. PMID:26960708

  7. Utilization of Internet Protocol-Based Voice Systems in Remote Payload Operations

    NASA Technical Reports Server (NTRS)

    Best, Susan; Nichols, Kelvin; Bradford, Robert

    2003-01-01

    This viewgraph presentation provides an overview of a proposed voice communication system for use in remote payload operations performed on the International Space Station. The system, Internet Voice Distribution System (IVoDS), would make use of existing Internet protocols, and offer a number of advantages over the system currently in use. Topics covered include: system description and operation, system software and hardware, system architecture, project status, and technology transfer applications.

  8. Expression of Lymphatic Markers in the Adult Rat Spinal Cord

    PubMed Central

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A.; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  9. Expression of Lymphatic Markers in the Adult Rat Spinal Cord.

    PubMed

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  10. The Use of Efficient Broadcast Protocols in Asynchronous Distributed Systems. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Schmuck, Frank Bernhard

    1988-01-01

    Reliable broadcast protocols are important tools in distributed and fault-tolerant programming. They are useful for sharing information and for maintaining replicated data in a distributed system. However, a wide range of such protocols has been proposed. These protocols differ in their fault tolerance and delivery ordering characteristics. There is a tradeoff between the cost of a broadcast protocol and how much ordering it provides. It is, therefore, desirable to employ protocols that support only a low degree of ordering whenever possible. This dissertation presents techniques for deciding how strongly ordered a protocol is necessary to solve a given application problem. It is shown that there are two distinct classes of application problems: problems that can be solved with efficient, asynchronous protocols, and problems that require global ordering. The concept of a linearization function that maps partially ordered sets of events to totally ordered histories is introduced. How to construct an asynchronous implementation that solves a given problem if a linearization function for it can be found is shown. It is proved that in general the question of whether a problem has an asynchronous solution is undecidable. Hence there exists no general algorithm that would automatically construct a suitable linearization function for a given problem. Therefore, an important subclass of problems that have certain commutativity properties are considered. Techniques for constructing asynchronous implementations for this class are presented. These techniques are useful for constructing efficient asynchronous implementations for a broad range of practical problems.

  11. A simple, effective media access protocol system for integrated, high data rate networks

    NASA Technical Reports Server (NTRS)

    Foudriat, E. C.; Maly, K.; Overstreet, C. M.; Khanna, S.; Zhang, L.

    1992-01-01

    The operation and performance of a dual media access protocol for integrated, gigabit networks are described. Unlike other dual protocols, each protocol supports a different class of traffic. The Carrier Sensed Multiple Access-Ring Network (CSMA/RN) protocol and the Circulating Reservation Packet (CRP) protocol support asynchronous and synchronous traffic, respectively. The two protocols operate with minimal impact upon each other. Performance information demonstrates that they support a complete range of integrated traffic loads, do not require call setup/termination or a special node for synchronous traffic control, and provide effective pre-use and recovery. The CRP also provides guaranteed access and fairness control for the asynchronous system. The paper demonstrates that the CSMA-CRP system fulfills many of the requirements for gigabit LAN-MAN networks most effectively and simply. To accomplish this, CSMA-CRP features are compared against similar ring and bus systems, such as Cambridge Fast Ring, Metaring, Cyclic Reservation Multiple Access, and Distributed Dual Queue Data Bus (DQDB).

  12. Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow.

    PubMed

    Datar, Sanjeev A; Johnson, Eric G; Oishi, Peter E; Johengen, Michael; Tang, Eric; Aramburo, Angela; Barton, Jubilee; Kuo, Hsuan-Chang; Bennett, Stephen; Xoinis, Konstantine; Reel, Bhupinder; Kalkan, Gokhan; Sajti, Eniko; Osorio, Oscar; Raff, Gary W; Matthay, Michael A; Fineman, Jeffrey R

    2012-03-15

    Abnormalities of the lymphatic circulation are well recognized in patients with congenital heart defects. However, it is not known how the associated abnormal blood flow patterns, such as increased pulmonary blood flow (PBF), might affect pulmonary lymphatic function and structure. Using well-established ovine models of acute and chronic increases in PBF, we cannulated the efferent lymphatic duct of the caudal mediastinal node and collected and analyzed lymph effluent from the lungs of lambs with acutely increased PBF (n = 6), chronically increased PBF (n = 6), and age-matched normal lambs (n = 8). When normalized to PBF, we found that lymph flow was unchanged following acute increases in PBF but decreased following chronic increases in PBF. The lymph:plasma protein ratio decreased with both acute and chronic increases in PBF. Lymph bioavailable nitric oxide increased following acute increases in PBF but decreased following chronic increases in PBF. In addition, we found perturbations in the transit kinetics of contrast material through the pleural lymphatics of lambs with chronic increases in PBF. Finally, there were structural changes in the pulmonary lymphatic system in lambs with chronic increases in PBF: lymphatics from these lambs were larger and more dilated, and there were alterations in the expression of vascular endothelial growth factor-C, lymphatic vessel endothelial hyaluronan receptor-1, and Angiopoietin-2, proteins known to be important for lymphatic growth, development, and remodeling. Taken together these data suggest that chronic increases in PBF lead to both functional and structural aberrations of lung lymphatics. These findings have important therapeutic implications that warrant further study.

  13. Nitric Oxide Regulates The Lymphatic Reactivity Following Hemorrhagic Shock Through Atp-Sensitive Potassium Channel.

    PubMed

    Zhang, Li-Min; Qin, Li-Peng; Zhang, Yu-Ping; Zhao, Zi-Gang; Niu, Chun-Yu

    2016-06-01

    Lymphatic reactivity has been shown to exhibit a biphasic change following hemorrhagic shock, and nitric oxide (NO) is involved in this process. However, the precise mechanism responsible for NO regulation of the lymphatic reactivity along with the progression of hemorrhagic shock is unclear. Therefore, the present study was to investigate how NO participates in regulating the shock-induced biphasic changes in lymphatic reactivity and its underlying mechanisms. First, the expressions or contents of inducible NO synthase, nitrite plus nitrate, and elements of cAMP-PKA-KATP and cGMP-PKG-KATP pathway in thoracic ducts tissue were assessed. The results revealed that levels of nitrite plus nitrate, cAMP, cyclic guanosine monophosphate (cGMP), p-PKA, and p-PKG were increased gradually along with the process of shock. Second, the roles of cAMP-PKA-KATP and cGMP-PKG-KATP in NO regulating lymphatic response to gradient substance P were evaluated with an isolated lymphatic perfusion system. The results showed that the NOS substrate (L-Arg), PKA donor (8-Br-cAMP) decreased the reactivity of shock 0.5 h-lymphatics, and that the PKA inhibitor (H-89) and KATP inhibitor (glibenclamide) restrained the effects of L-Arg while glibenclamide abolished the effects of 8-Br-cAMP. Meanwhile, NOS antagonist (L-NAME), protein kinase G (PKG) inhibitor (KT-5823), and soluble guanylate cyclase inhibitor (ODQ) increased the reactivity of shock 2 h-lymphatics, whereas KATP opener (pinacidil) inhibited these elevated effects induced by either L-NAME, ODQ, or KT-5823. Taken together, these results indicate that NO regulation of lymphatic reactivity during shock involves both cAMP-PKA-KATP and cGMP-PKG-KATP pathways. These findings have potential significance for the treatment of hemorrhagic shock through regulating lymphatic reactivity. PMID:26796572

  14. Conserved signaling through vascular endothelial growth (VEGF) receptor family members in murine lymphatic endothelial cells.

    PubMed

    Coso, Sanja; Zeng, Yiping; Sooraj, Dhanya; Williams, Elizabeth D

    2011-10-15

    Lymphatic vessels guide interstitial fluid, modulate immune responses by regulating leukocyte and antigen trafficking to lymph nodes, and in a cancer setting enable tumor cells to track to regional lymph nodes. The aim of the study was to determine whether primary murine lymphatic endothelial cells (mLECs) show conserved vascular endothelial growth factor (VEGF) signaling pathways with human LECs (hLECs). LECs were successfully isolated from murine dermis and prostate. Similar to hLECs, vascular endothelial growth factor (VEGF) family ligands activated MAPK and pAkt intracellular signaling pathways in mLECs. We describe a robust protocol for isolation of mLECs which, by harnessing the power of transgenic and knockout mouse models, will be a useful tool to study how LEC phenotype contributes to alterations in lymphatic vessel formation and function.

  15. Label-free optical imaging of lymphatic vessels within tissue beds in vivo

    PubMed Central

    Yousefi, Siavash; Zhi, Zhongwei; Wang, Ruikang K.

    2015-01-01

    Lymphatic vessels are a part of circulatory system in vertebrates that maintain tissue fluid homeostasis and drain excess fluid and large cells that cannot easily find their way back into venous system. Due to the lack of non-invasive monitoring tools, lymphatic vessels are known as forgotten circulation. However, lymphatic system plays an important role in diseases such as cancer and inflammatory conditions. In this paper, we start to briefly review the current existing methods for imaging lymphatic vessels, mostly involving dye/targeting cell injection. We then show the capability of optical coherence tomography (OCT) for label-free non-invasive in vivo imaging of lymph vessels and nodes. One of the advantages of using OCT over other imaging modalities is its ability to assess label-free blood flow perfusion that can be simultaneously observed along with lymphatic vessels for imaging the microcirculatory system within tissue beds. Imaging the microcirculatory system including blood and lymphatic vessels can be utilized for imaging and better understanding pathologic mechanisms and treatment technique development in some critical diseases such as inflammation, malignant cancer angiogenesis and metastasis. PMID:25642129

  16. An Efficient Two-Tier Causal Protocol for Mobile Distributed Systems

    PubMed Central

    Dominguez, Eduardo Lopez; Pomares Hernandez, Saul E.; Gomez, Gustavo Rodriguez; Medina, Maria Auxilio

    2013-01-01

    Causal ordering is a useful tool for mobile distributed systems (MDS) to reduce the non-determinism induced by three main aspects: host mobility, asynchronous execution, and unpredictable communication delays. Several causal protocols for MDS exist. Most of them, in order to reduce the overhead and the computational cost over wireless channels and mobile hosts (MH), ensure causal ordering at and according to the causal view of the Base Stations. Nevertheless, these protocols introduce certain disadvantage, such as unnecessary inhibition at the delivery of messages. In this paper, we present an efficient causal protocol for groupware that satisfies the MDS's constraints, avoiding unnecessary inhibitions and ensuring the causal delivery based on the view of the MHs. One interesting aspect of our protocol is that it dynamically adapts the causal information attached to each message based on the number of messages with immediate dependency relation, and this is not directly proportional to the number of MHs. PMID:23585828

  17. Visualisation of blood and lymphatic vessels with increasing exposure time of the detector

    NASA Astrophysics Data System (ADS)

    Kalchenko, V. V.; Kuznetsov, Yu L.; Meglinski, I. V.

    2013-07-01

    We describe the laser speckle contrast method for simultaneous noninvasive imaging of blood and lymphatic vessels of living organisms, based on increasing detector exposure time. In contrast to standard methods of fluorescent angiography, this technique of vascular bed imaging and lymphatic and blood vessel demarcation does not employ toxic fluorescent markers. The method is particularly promising with respect to the physiology of the cardiovascular system under in vivo conditions.

  18. Visualisation of blood and lymphatic vessels with increasing exposure time of the detector

    SciTech Connect

    Kalchenko, V V; Kuznetsov, Yu L; Meglinski, I V

    2013-07-31

    We describe the laser speckle contrast method for simultaneous noninvasive imaging of blood and lymphatic vessels of living organisms, based on increasing detector exposure time. In contrast to standard methods of fluorescent angiography, this technique of vascular bed imaging and lymphatic and blood vessel demarcation does not employ toxic fluorescent markers. The method is particularly promising with respect to the physiology of the cardiovascular system under in vivo conditions. (laser applications in biology and medicine)

  19. Communications protocol

    NASA Technical Reports Server (NTRS)

    Zhou, Xiaoming (Inventor); Baras, John S. (Inventor)

    2010-01-01

    The present invention relates to an improved communications protocol which increases the efficiency of transmission in return channels on a multi-channel slotted Alohas system by incorporating advanced error correction algorithms, selective retransmission protocols and the use of reserved channels to satisfy the retransmission requests.

  20. Mouse exo utero development system: protocol and troubleshooting.

    PubMed

    Yamada, Makiko; Hatta, Toshihisa; Otani, Hiroki

    2008-12-01

    The exo utero development system allows us to manipulate or operate on live embryos of mice or rats at mid- to late gestation stages, from late organogenetic to histogenetic periods, and keep them alive in situ until the analysis of their effects at a desired time point. We can examine the effects of injecting bioactive molecules or cells into targeted parts of a live embryo, destroying specific embryonic regions, or performing fetal surgery. This system is far simpler and more time- and cost-effective for in vivo functional analyses than establishing genetically modified mouse lines and provides a fine-tuned experimental design for developmental scientists. To promote use of the mouse exo utero development system, we elaborate on the technical procedures, discuss critical points for troubleshooting the system, and illustrate some apparatuses essential for fetal microinjection.

  1. Secure Data Network System (SDNS) network, transport, and message security protocols

    NASA Astrophysics Data System (ADS)

    Dinkel, C.

    1990-03-01

    The Secure Data Network System (SDNS) project, implements computer to computer communications security for distributed applications. The internationally accepted Open Systems Interconnection (OSI) computer networking architecture provides the framework for SDNS. SDNS uses the layering principles of OSI to implement secure data transfers between computer nodes of local area and wide area networks. Four security protocol documents developed by the National Security Agency (NSA) as output from the SDNS project are included. SDN.301 provides the framework for security at layer 3 of the OSI Model. Cryptographic techniques to provide data protection for transport connections or for connectionless-mode transmission are described in SDN.401. Specifications for message security service and protocol are contained in SDN.701. Directory System Specifications for Message Security Protocol are covered in SDN.702.

  2. Cryptanalysis and improvement of authentication and key agreement protocols for telecare medicine information systems.

    PubMed

    Islam, S K Hafizul; Khan, Muhammad Khurram

    2014-10-01

    Recently, many authentication protocols have been presented using smartcard for the telecare medicine information system (TMIS). In 2014, Xu et al. put forward a two-factor mutual authentication with key agreement protocol using elliptic curve cryptography (ECC). However, the authors have proved that the protocol is not appropriate for practical use as it has many problems (1) it fails to achieve strong authentication in login and authentication phases; (2) it fails to update the password correctly in the password change phase; (3) it fails to provide the revocation of lost/stolen smartcard; and (4) it fails to protect the strong replay attack. We then devised an anonymous and provably secure two-factor authentication protocol based on ECC. Our protocol is analyzed with the random oracle model and demonstrated to be formally secured against the hardness assumption of computational Diffie-Hellman problem. The performance evaluation demonstrated that our protocol outperforms from the perspective of security, functionality and computation costs over other existing designs. PMID:25190590

  3. Exploring local immune responses to vaccines using efferent lymphatic cannulation.

    PubMed

    Mahakapuge, Thilini An; Every, Alison L; Scheerlinck, Jean-Pierre Y

    2015-04-01

    The early stages of the induction of a primary immune response to a vaccine can shape the overall quality of the immune memory generated and hence affect the success of the vaccine. This early interaction between a vaccine and the immune system occurs first at the site of vaccination and can be explored using afferent cannulation. Subsequently, the vaccine and adjuvant activates the local draining lymph node. These interactions can be studied in real time in vivo using efferent lymphatic duct cannulation in large animal models and are the subject of this review. Depending on how the vaccine is delivered, the draining lymph nodes of different organs can be accessed, facilitating the testing of tissue-specific vaccinations. The efferent lymphatic cannulation model provides an avenue to study the effect of both adjuvants and antigen on the local immune system, and hence opens a pathway toward developing more effective ways of inducing immunity.

  4. A real-time VLC to UART protocol conversion system

    NASA Astrophysics Data System (ADS)

    Deng, Jian-zhi; Yao, Meng; Cheng, Xiao-hui; Deng, Zhuo-hong

    2016-07-01

    A real-time visible light communication (VLC) to universal asynchronous receiver/transmitter (UART) conversion system is made up of a transmitter with a light emitting diode (LED) and a receiver with a photodiode (PD), by which a VLC system is connected to traditional communication modes, and the data are transferred by wireless visible light. UART packets are converted to light packets by the modulation of a 10 kHz on-off-keying (OOK) light signal, and the data losses in the transportation are avoided by the protection of a data buffer mechanism. The experimental results reveal that the real-time VLC to UART conversion system can provide a real-time VLC transmission way for two UART devices in not less than 10 m at a baud rate not less than 19 200 Bd with stable ambient lighting at the same time.

  5. [A universal verification and protocol system for teletherapy].

    PubMed

    Brasching, H P; Franz, H; Geyer, P; Lehmann, D; Lorenz, J; Röthig, H; Theilig, B; Voigtmann, L

    1990-01-01

    To increase the quality of radiotherapy a verify and record system (VPS) was developed for teletherapy equipments, that takes control of manually adjusted irradiation parameters and of recording all relevant data of radiotherapy. The VPS can be adapted to special wishes of the user and it lends itself to application on different irradiation equipments. In the represented paper especially the extent of efficiency of the system is shown which is characterized by high operating comfort, flexible reacting to exceptional cases and by high date and operating security. The testing phase on an accelerator model has been brought to a close, actually the system is installed to an electron linear accelerator "Neptun 10p" and led to clinical trial. PMID:2277832

  6. A Byzantine-Fault Tolerant Self-Stabilizing Protocol for Distributed Clock Synchronization Systems

    NASA Technical Reports Server (NTRS)

    Malekpour, Mahyar R.

    2006-01-01

    Embedded distributed systems have become an integral part of safety-critical computing applications, necessitating system designs that incorporate fault tolerant clock synchronization in order to achieve ultra-reliable assurance levels. Many efficient clock synchronization protocols do not, however, address Byzantine failures, and most protocols that do tolerate Byzantine failures do not self-stabilize. Of the Byzantine self-stabilizing clock synchronization algorithms that exist in the literature, they are based on either unjustifiably strong assumptions about initial synchrony of the nodes or on the existence of a common pulse at the nodes. The Byzantine self-stabilizing clock synchronization protocol presented here does not rely on any assumptions about the initial state of the clocks. Furthermore, there is neither a central clock nor an externally generated pulse system. The proposed protocol converges deterministically, is scalable, and self-stabilizes in a short amount of time. The convergence time is linear with respect to the self-stabilization period. Proofs of the correctness of the protocol as well as the results of formal verification efforts are reported.

  7. Joint Polar Satellite System (JPSS) Common Ground System (CGS) Use of Space Link Extension (SLE) Protocol

    NASA Astrophysics Data System (ADS)

    Jamilkowski, M. L.; Cordier, G. R.; Johnson, L. M.; Tillery, C. J.

    2014-12-01

    NOAA & NASA are acquiring the next-generation civilian operational weather satellite -- Joint Polar Satellite System (JPSS). Contributing the afternoon orbit & ground system (GS) to replace current NOAA POES Satellites, its sensors will collect meteorological, oceanographic, climatological & solar-geophysical data. The JPSS Common Ground System (CGS), consisting of Command, Control & Communications (C3) and Interface Data Processing (IDP) segments, is developed by Raytheon. CGS now flies the Suomi National Polar-orbiting Partnership (S-NPP) satellite, transferring data between ground facilities, processing them into Environmental Data Records for NOAA & DoD weather centers, and expanding to support JPSS-1 in 2017. CGS Block 2.0 (B2.0) is the recent CDR-approved design to support both the current S-NPP and upcoming JPSS-1 missions. In B2.0, many important improvements were made to evolve CGS C3. One of those improvements is the addition of SLE services. The CCSDS SLE Protocol standard facilitates and significantly improves GS-to-Data Center communications. The CGS SLE architecture provides data reliability and resource scheduling and is scalable to support added missions. The JPSS CGS is a mature, tested solution for supporting operational weather forecasting for civil, military, and international partners as well as climate research. It features a flexible design that handles order-of-magnitude increases in data over legacy satellite ground systems and meets demanding science accuracy needs. The JPSS CGS is expandable to support additional ground station service providers with or without the deployment of additional JPSS ground hardware by using standard SLE Transfer Service protocol and offers opportunities to reduce costs and improve information Integration across missions. The Raytheon-built JPSS CGS provides the full common ground capability, from design and development through operations & sustainment. These features lay the foundation for the CGS future

  8. Visualisation and stereological assessment of blood and lymphatic vessels.

    PubMed

    Lokmic, Zerina; Mitchell, Geraldine M

    2011-06-01

    The physiological processes involved in tissue development and regeneration also include the parallel formation of blood and lymphatic vessel circulations which involves their growth, maturation and remodelling. Both vascular systems are also frequently involved in the development and progression of pathological conditions in tissues and organs. The blood vascular system circulates oxygenated blood and nutrients at appropriate physiological levels for tissue survival, and efficiently removes all waste products including carbon dioxide. This continuous network consists of the heart, aorta, arteries, arterioles, capillaries, post-capillary venules, venules, veins and vena cava. This system exists in an interstitial environment together with the lymphatic vascular system, including lymph nodes, which aids maintenance of body fluid balance and immune surveillance. To understand the process of vascular development, vascular network stability, remodelling and/or regression in any research model under any experimental conditions, it is necessary to clearly and unequivocally identify and quantify all elements of the vascular network. By utilising stereological methods in combination with cellular markers for different vascular cell components, it is possible to estimate parameters such as surface density and surface area of blood vessels, length density and length of blood vessels as well as absolute vascular volume. This review examines the current strategies used to visualise blood vessels and lymphatic vessels in two- and three-dimensions and the basic principles of vascular stereology used to quantify vascular network parameters.

  9. Pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis in tumor lymphangiogenesis and lymphatic metastasis.

    PubMed

    Wang, Jingwen; Huang, Yuhong; Zhang, Jun; Wei, Yuanyi; Mahoud, Salma; Bakheet, Ahmed Musa Hago; Wang, Li; Zhou, Shuting; Tang, Jianwu

    2016-10-01

    Precondition for tumor lymphatic metastasis is that tumor cells induce formation of original and newborn lymphatic vessels and invade surrounding lymphatic vessels in tumor stroma, while some pathway-related molecules play an important role in mechanisms associated with proliferation and migration of lymphatic endothelial cells (LECs) and tumor cells. In lymphangiogenesis and lymphatic metastasis, the pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, such as Furin-like enzyme, CNTN1, Prox1, LYVE-1, Podoplanin, SOX18, SDF1 and CXCR4, are direct constitutors as a portion of VEGFC/D-VEGFR3/NRP2 axis, and their biological activities rely on this ligand-receptor system. These axis-related signal molecules could gradually produce waterfall-like cascading effects, mediate differentiation and maturation of LECs, remodel original and neonatal lymphatic vessels, as well as ultimately promote tumor cell chemotaxis, migration, invasion and metastasis to lymphoid tracts. This review summarizes the structure and function features of pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, the expression changes of these molecules in different anatomic organs or histopathologic types or development stages of various tumors, the characteristics of transduction, implementation, integration of signal networks, the interactive effects on biological behaviors between tumor cells and lymphatic endothelial cells, and their molecular mechanisms and significances in tumor lymphangiogenesis and lymphatic metastasis.

  10. Identification of Vascular Lineage-Specific Genes by Transcriptional Profiling of Isolated Blood Vascular and Lymphatic Endothelial Cells

    PubMed Central

    Hirakawa, Satoshi; Hong, Young-Kwon; Harvey, Natasha; Schacht, Vivien; Matsuda, Kant; Libermann, Towia; Detmar, Michael

    2003-01-01

    In mammals, the lymphatic vascular system develops by budding of lymphatic progenitor endothelial cells from embryonic veins to form a distinct network of draining vessels with important functions in the immune response and in cancer metastasis. However, the lineage-specific molecular characteristics of blood vascular versus lymphatic endothelium have remained poorly defined. We isolated lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BVECs) by immunomagnetic isolation directly from human skin. Cultured LECs but not BVECs expressed the lymphatic markers Prox1 and LYVE-1 and formed LYVE-1-positive vascular tubes after implantation in vivo. Transcriptional profiling studies revealed increased expression of several extracellular matrix and adhesion molecules in BVECs, including versican, collagens, laminin, and N-cadherin, and of the growth factor receptors endoglin and vascular endothelial growth factor receptor-1/Flt-1. Differential immunostains of human skin confirmed the blood vessel-specific expression of these genes. During embryonic development, endoglin expression was gradually down-regulated on lymphatic endothelium whereas vascular endothelial growth factor receptor-1 was absent from lymphatics. We also identified several genes with specific expression in LECs. These results demonstrate that some lineage-specific genes are only expressed during distinct developmental stages and they identify new molecular markers for blood vascular and lymphatic endothelium with important implications for future studies of vascular development and function. PMID:12547715

  11. Topographic study on nerve-associated lymphatic vessels in the murine craniofacial region by immunohistochemistry and electron microscopy.

    PubMed

    Furukawa, Masahide; Shimoda, Hiroshi; Kajiwara, Tooru; Kato, Seiji; Yanagisawa, Shigetaka

    2008-12-01

    The distribution and fine structure of lymphatic vessels associated with nerves was studied by immunohistochemistry in the murine craniofacial region. The tissue sections and blocks were immunostained for LYVE-1, protein gene product 9.5, CD34 and aquaporin-1 to demonstrate the lymphatic vessels, nerves, blood vessels and water channel protein, respectively. Transmission electron microscopic examination was also performed to investigate the relationship between the lymphatics and nerves. In the nasal area, the lymphatics were found in dura mater on the cribriform plate and beneath the nasal mucosa, this supposedly supplying the cerebrospinal fluid drainage route along the olfactory nerves. The proximal portions of the cranial nerves were equipped with the lymphatics in the epineurium. In the distal portions of the nerves, the lymphatics were distributed in close proximity of the perineural sheath, and thus might contribute to maintenance of microenvironment suitable for the nerves by an absorptive activity of the lymphatic endothelial cells. The present findings suggest that the lymphatic system associated with the cranial nerves provides the pathway for transport of cerebrospinal fluid, tissue fluid, and free cells involved in immune response and tumor metastasis in the craniofacial region.

  12. Altered lymphatic function and architecture in salt-induced hypertension assessed by near-infrared fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Kwon, Sunkuk; Agollah, Germaine D.; Chan, Wenyaw; Sevick-Muraca, Eva M.

    2012-08-01

    The lymphatic system plays an important role in maintaining the fluid homeostasis between the blood vascular and interstitial tissue compartment and there is recent evidence that its transport capabilities may regulate blood pressure in salt-induced hypertension. Yet, there is little known how the lymphatic contractile function and architecture responds to dietary salt-intake. Thus, we longitudinally characterized lymphatic contractile function and vessel remodeling noninvasively using dynamic near-infrared fluorescence imaging in animal models of salt-induced hypertension. The lymphatics of mice and rats were imaged following intradermal injection of indocyanine green to the ear tip or the base of the tail before and during two weeks of either a high salt diet (HSD) or normal chow. Our noninvasive imaging data demonstrated dilated lymphatic vessels in the skin of mice and rats on a HSD as compared to their baseline levels. In addition, our dynamic imaging results showed increased lymphatic contraction frequency in HSD-fed mice and rats. Lymphatic contractile function and vessel remodeling occurs in response to salt-induced hypertension suggesting a possible role for the lymphatics in the regulation of vascular blood pressure.

  13. Pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis in tumor lymphangiogenesis and lymphatic metastasis.

    PubMed

    Wang, Jingwen; Huang, Yuhong; Zhang, Jun; Wei, Yuanyi; Mahoud, Salma; Bakheet, Ahmed Musa Hago; Wang, Li; Zhou, Shuting; Tang, Jianwu

    2016-10-01

    Precondition for tumor lymphatic metastasis is that tumor cells induce formation of original and newborn lymphatic vessels and invade surrounding lymphatic vessels in tumor stroma, while some pathway-related molecules play an important role in mechanisms associated with proliferation and migration of lymphatic endothelial cells (LECs) and tumor cells. In lymphangiogenesis and lymphatic metastasis, the pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, such as Furin-like enzyme, CNTN1, Prox1, LYVE-1, Podoplanin, SOX18, SDF1 and CXCR4, are direct constitutors as a portion of VEGFC/D-VEGFR3/NRP2 axis, and their biological activities rely on this ligand-receptor system. These axis-related signal molecules could gradually produce waterfall-like cascading effects, mediate differentiation and maturation of LECs, remodel original and neonatal lymphatic vessels, as well as ultimately promote tumor cell chemotaxis, migration, invasion and metastasis to lymphoid tracts. This review summarizes the structure and function features of pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, the expression changes of these molecules in different anatomic organs or histopathologic types or development stages of various tumors, the characteristics of transduction, implementation, integration of signal networks, the interactive effects on biological behaviors between tumor cells and lymphatic endothelial cells, and their molecular mechanisms and significances in tumor lymphangiogenesis and lymphatic metastasis. PMID:27527412

  14. CT demonstration of perirenal lymphatic cysts.

    PubMed

    De Maeyer, P; Baert, A L; Usewils, R; Wynants, P; De Pauw, A

    1982-01-01

    A case of perirenal lymphatic cysts demonstrated by computed tomography is reported. These lymphatic cysts, a histological subtype of lymphangiomata, are clearly visible as collections with clear fluid-type density surrounding both kidneys. The retroperitoneal localization of this rarity has been reported in the radiological literature, whereas, to our knowledge, the radiological demonstration of the perirenal localization has not. CT provides a unique method for direct radiological visualization of the cyst.

  15. Colonic insult impairs lymph flow, increases cellular content of the lymph, alters local lymphatic micro-environment and leads to sustained inflammation in the rat ileum

    PubMed Central

    Cromer, Walter; Wang, Wei; Zawieja, Scott D.; von der Weid, Pierre-Yves; Newell Rogers, M. Karen; Zawieja, David C.

    2015-01-01

    Background Lymphatic dysfunction has been linked to inflammation since the 1930’s. Lymphatic function in the gut and mesentery is grossly underexplored in models of IBD despite the use of lymphatic occlusion in early models of IBD. Activation of the innate and adaptive immune system is a hallmark of TNBS-induced inflammation and is linked to disruption of the intrinsic lymph pump. Recent identification of crosstalk between lymphatic vessel resident immune cells and regulation of lymphatic vessel contractility underscore the importance of the timing of lymphatic dysfunction during tissue inflammation in response to TNBS. Methods To evaluate lymphatic function in TNBS induced inflammation, lymph was collected and flow measured from mesenteric lymphatics. Cellularity and cytokine profile of the lymph was also measured. Histopathology was performed to determine severity of injury and immunofluorescent staining of the mesentery was done to evaluate changes in the population of immune cells that reside near and on gastro-intestinal collecting lymphatics. Results Lymph transport fell 24hrs after TNBS administration and began recovering at 72hrs. Significant reduction of lymph flow preceded significant increase in histopathological score and occurred simultaneously with increased MPO activity. These changes were preceded by increased MHCII+ cells surrounding mesenteric lymphatics leading to an altered lymphatic environment that would favor dysfunction. Conclusions Alterations in environmental factors that effect lymphatic function occur before the development of gross GI inflammation. Reduced lymphatic function in TNBS-mediated inflammation is likely an early factor in the development of injury and that recovery of function is associated with resolution of inflammation. PMID:25939039

  16. Platelets: Covert Regulators of Lymphatic Development

    PubMed Central

    Bertozzi, Cara C.; Hess, Paul R.; Kahn, Mark L.

    2010-01-01

    The field of platelet biology has rapidly expanded beyond the classical role of platelets in preventing blood loss and orchestrating clot formation. Despite the lack of transcriptional ability of these anuclear cell fragments, platelet function is now thought to encompass such diverse contexts as tissue repair, immune activation, primary tumor formation, and metastasis. Recent studies from multiple groups have turned the spotlight on an exciting new role for platelets in the formation of lymphatic vessels during embryonic development. Genetic experiments demonstrate that Podoplanin, a transmembrane protein expressed on lymphatic endothelial cells, engages the platelet CLEC-2 receptor when exposed to blood, leading to SYK-SLP-76-dependent platelet activation. When components of this pathway are disrupted, aberrant vascular connections form, resulting in blood-lymphatic mixing. Furthermore, platelet-null embryos manifest identical blood-lymphatic mixing. The identification of platelets as the critical cell type mediating blood-lymphatic vascular separation raises new questions in our understanding of lymphatic development and platelet biology. PMID:21071706

  17. Connexins in lymphatic vessel physiology and disease.

    PubMed

    Meens, Merlijn J; Sabine, Amélie; Petrova, Tatiana V; Kwak, Brenda R

    2014-04-17

    Connexins are transmembrane proteins that form gap junction- and hemi-channels. Once inserted into the membrane, hemi-channels (connexons) allow for diffusion of ions and small molecules (<1 kDa) between the extracellular space and the cytosol. Gap junction channels allow diffusion of similar molecules between the cytoplasms of adjacent cells. The expression and function of connexins in blood vessels has been intensely studied in the last few decades. In contrast, only a few studies paid attention to lymphatic vessels; convincing in vivo data with respect to expression patterns of lymphatic connexins and their functional roles have only recently begun to emerge. Interestingly, mutations in connexin genes have been linked to diseases of lymphatic vasculature, most notably primary and secondary lymphedema. This review summarizes the available data regarding lymphatic connexins. More specifically it addresses (i) early studies aimed at presence of gap junction-like structures in lymphatic vessels, (ii) more recent studies focusing on lymphatic connexins using genetically engineered mice, and (iii) results of clinical studies that have reported lymphedema-linked mutations in connexin genes.

  18. Optimization of monoclonal antibody delivery via the lymphatics: the dose dependence

    SciTech Connect

    Steller, M.A.; Parker, R.J.; Covell, D.G.; Holton, O.D. 3d.; Keenan, A.M.; Sieber, S.M.; Weinstein, J.N.

    1986-04-01

    After interstitial injection in mice, antibody molecules enter local lymphatic vessels, flow with the lymph to regional lymph nodes, and bind to target antigens there. Compared with i.v. administration, delivery via the lymphatics provides a more efficient means for localizing antibody in lymph nodes. An IgG2a (36-7-5) directed against the murine class I major histocompatibility antigen H-2Kk has proved useful for studying the pharmacology of lymphatic delivery. At very low doses, most of the antibody remains at the injection site in Kk-positive animals. As the dose is progressively increased, most effective labeling occurs first in nodes proximal to the injection site and then in the next group of nodes along the lymphatic chain. At higher doses, antibody overflows the lymphatic system and enters the blood-stream via the thoracic duct and other lymphatic-venous connections. Once in the blood, antibody is rapidly cleared, apparently by binding to Kk-bearing cells. These findings indicate that the single-pass distribution of monoclonal antibodies in the lymphatics can be strongly dose dependent, a principle which may be of clinical significance in the improvement of immunolymphoscintigraphic imaging, especially with antibodies directed against normal and malignant lymphoid cells. Monoclonal antibodies directed against normal cell types in the lymph node may be useful for assessing the integrity of lymphatic chains by immunolymphoscintigraphy or, more speculatively, for altering the status of regional immune function. The results presented here indicate that a low or intermediate antibody dose may optimize the signal:noise ratio for imaging. In Kk-negative animals, the percentage of dose taken up in the major organs was essentially independent of the dose administered; there was no evidence for saturable sites of nonspecific binding.

  19. Lymphoedema: Pathophysiology and management in resource-poor settings - relevance for lymphatic filariasis control programmes

    PubMed Central

    Vaqas, Babar; Ryan, Terence J

    2003-01-01

    Low cost reduction of morbidity in lymphoedema is an essential goal in the management of lymphatic filariasis. This review emphasises the role of movement and elevation, and refers to the literature on the effects of these on the venous and lymphatic system. The patient with lymphoedema becomes increasingly immobile and the affected limb is often in a permanently dependent position causing venous hypertension and resultant overloading of the failing lymphatics. The evidence that breathing exercises are important for reducing venous hypertension and inducing lymphatic flow is discussed. The contribution of a damaged epidermis to lymphatic failure is emphasised. Loss of barrier function encourages penetration of bacteria and stimulates repair mechanisms that generate cytokines, which, in turn lead to inflammation. Management programmes that improve the health of the epidermis play a part in reducing lymphatic load. In taking morbidity management of lymphoedema into the general health services there are benefits in promoting skin hygiene and self-help regimes that can ameliorate many diseases along with lymphoedema. PMID:12685942

  20. Absence of lymphatic vessels in human dental pulp: a morphological study.

    PubMed

    Gerli, Renato; Secciani, Ilaria; Sozio, Francesca; Rossi, Antonella; Weber, Elisabetta; Lorenzini, Guido

    2010-04-01

    Few and controversial data are available in the literature regarding the presence of lymphatic vessels in the human dental pulp. The present study was designed to examine morphologically the existence of a lymph drainage system in human dental pulp. Human dental pulp and skin sections were immunohistochemically stained with specific antibodies for lymphatic endothelium (D2-40, LYVE-1, VEGFR-3 [vascular endothelial growth factor receptor-3], and Prox-1), with the pan-endothelial markers CD31 and von Willebrand factor (vWF), and with the blood-specific marker CD34. Several blood vessels were identified in human pulps and skin. Lymphatic vessels were found in all human skin samples but in none of the pulps examined. Western blotting performed on human dermis and on pulps treated with collagenase (to remove odontoblasts) confirmed these results. Transmission electron microscopy indicated that vessels which, by light microscopy, appeared to be initial lymphatic vessels had no anchoring filaments or discontinuous basement membrane, both of which are typical ultrastructural characteristics of lymphatic vessels. These results suggest that under normal conditions human dental pulp does not contain true lymphatic vessels. The various theories about dental pulp interstitial fluid circulation should be revised accordingly.

  1. Diphtheria toxin–mediated ablation of lymphatic endothelial cells results in progressive lymphedema

    PubMed Central

    Gardenier, Jason C.; Hespe, Geoffrey E.; Kataru, Raghu P.; Savetsky, Ira L.; Torrisi, Jeremy S.; Nores, Gabriela D. García; Dayan, Joseph J.; Chang, David; Zampell, Jamie; Martínez-Corral, Inés; Ortega, Sagrario; Mehrara, Babak J.

    2016-01-01

    Development of novel treatments for lymphedema has been limited by the fact that the pathophysiology of this disease is poorly understood. It remains unknown, for example, why limb swelling resulting from surgical injury resolves initially, but recurs in some cases months or years later. Finding answers for these basic questions has been hampered by the lack of adequate animal models. In the current study, we used Cre-lox mice that expressed the human diphtheria toxin receptor (DTR) driven by a lymphatic-specific promoter in order to noninvasively ablate the lymphatic system of the hind limb. Animals treated in this manner developed lymphedema that was indistinguishable from clinical lymphedema temporally, radiographically, and histologically. Using this model and clinical biopsy specimens, we show that the initial resolution of edema after injury is dependent on the formation of collateral capillary lymphatics and that this process is regulated by M2-polarized macrophages. In addition, we show that despite these initial improvements in lymphatic function, persistent accumulation of CD4+ cells inhibits lymphangiogenesis and promotes sclerosis of collecting lymphatics, resulting in late onset of edema and fibrosis. Our findings therefore provide strong evidence that inflammatory changes after lymphatic injury play a key role in the pathophysiology of lymphedema.

  2. Diphtheria toxin–mediated ablation of lymphatic endothelial cells results in progressive lymphedema

    PubMed Central

    Gardenier, Jason C.; Hespe, Geoffrey E.; Kataru, Raghu P.; Savetsky, Ira L.; Torrisi, Jeremy S.; Nores, Gabriela D. García; Dayan, Joseph J.; Chang, David; Zampell, Jamie; Martínez-Corral, Inés; Ortega, Sagrario; Mehrara, Babak J.

    2016-01-01

    Development of novel treatments for lymphedema has been limited by the fact that the pathophysiology of this disease is poorly understood. It remains unknown, for example, why limb swelling resulting from surgical injury resolves initially, but recurs in some cases months or years later. Finding answers for these basic questions has been hampered by the lack of adequate animal models. In the current study, we used Cre-lox mice that expressed the human diphtheria toxin receptor (DTR) driven by a lymphatic-specific promoter in order to noninvasively ablate the lymphatic system of the hind limb. Animals treated in this manner developed lymphedema that was indistinguishable from clinical lymphedema temporally, radiographically, and histologically. Using this model and clinical biopsy specimens, we show that the initial resolution of edema after injury is dependent on the formation of collateral capillary lymphatics and that this process is regulated by M2-polarized macrophages. In addition, we show that despite these initial improvements in lymphatic function, persistent accumulation of CD4+ cells inhibits lymphangiogenesis and promotes sclerosis of collecting lymphatics, resulting in late onset of edema and fibrosis. Our findings therefore provide strong evidence that inflammatory changes after lymphatic injury play a key role in the pathophysiology of lymphedema. PMID:27699240

  3. Students' Attitudes toward a Group Coursework Protocol and Peer Assessment System

    ERIC Educational Resources Information Center

    Moraes, Caroline; Michaelidou, Nina; Canning, Louise

    2016-01-01

    This paper addresses a knowledge gap by presenting an empirical investigation of a group coursework protocol and peer assessment system (GCP&PAS) used in a UK university to support postgraduate marketing students in their assessed group activities. The aim of the research was to examine students' understanding of the GCP&PAS and their…

  4. Implementation of the Commonwealth Teacher Recruitment Protocol: Considering the Education Systems and Context

    ERIC Educational Resources Information Center

    Ochs, Kimberley

    2007-01-01

    The Commonwealth Teacher Recruitment Protocol (CTRP), adopted by Commonwealth member states in 2004, "aims to balance the rights of teachers to migrate internationally, on a temporary or permanent basis, against the need to protect the integrity of national education systems, and to prevent the exploitation of the scarce human resources of poorer…

  5. A Locality-Aware Cooperative Cache Management Protocol to Improve Network File System Performance

    SciTech Connect

    Jiang, Song; Petrini, Fabrizio; Ding, Xiaoning; Zhang, Xiaodong

    2006-10-10

    In a distributed environment the utilization of file buffer caches in different clients may vary greatly. Cooperative caching is used to increase cache utilization by coordinating the usage of distributed caches. Existing cooperative caching protocols mainly address organizational issues, paying little attention to exploiting locality of file access patterns. We propose a locality-aware cooperative caching protocol, called LAC, that is based on analysis and manipulation of data block reuse distance to effectively predict cache utilization and the probability of data reuse. Using a dynamically controlled synchronization technique, we make local information consistently comparable among clients. The system is highly scalable in the sense that global coordination is achieved without centralized control.

  6. Automated Static Culture System Cell Module Mixing Protocol and Computational Fluid Dynamics Analysis

    NASA Technical Reports Server (NTRS)

    Kleis, Stanley J.; Truong, Tuan; Goodwin, Thomas J,

    2004-01-01

    This report is a documentation of a fluid dynamic analysis of the proposed Automated Static Culture System (ASCS) cell module mixing protocol. The report consists of a review of some basic fluid dynamics principles appropriate for the mixing of a patch of high oxygen content media into the surrounding media which is initially depleted of oxygen, followed by a computational fluid dynamics (CFD) study of this process for the proposed protocol over a range of the governing parameters. The time histories of oxygen concentration distributions and mechanical shear levels generated are used to characterize the mixing process for different parameter values.

  7. Fast equilibration protocol for million atom systems of highly entangled linear polyethylene chains

    NASA Astrophysics Data System (ADS)

    Sliozberg, Yelena R.; Kröger, Martin; Chantawansri, Tanya L.

    2016-04-01

    Equilibrated systems of entangled polymer melts cannot be produced using direct brute force equilibration due to the slow reptation dynamics exhibited by high molecular weight chains. Instead, these dense systems are produced using computational techniques such as Monte Carlo-Molecular Dynamics hybrid algorithms, though the use of soft potentials has also shown promise mainly for coarse-grained polymeric systems. Through the use of soft-potentials, the melt can be equilibrated via molecular dynamics at intermediate and long length scales prior to switching to a Lennard-Jones potential. We will outline two different equilibration protocols, which use various degrees of information to produce the starting configurations. In one protocol, we use only the equilibrium bond angle, bond length, and target density during the construction of the simulation cell, where the information is obtained from available experimental data and extracted from the force field without performing any prior simulation. In the second protocol, we moreover utilize the equilibrium radial distribution function and dihedral angle distribution. This information can be obtained from experimental data or from a simulation of short unentangled chains. Both methods can be used to prepare equilibrated and highly entangled systems, but the second protocol is much more computationally efficient. These systems can be strictly monodisperse or optionally polydisperse depending on the starting chain distribution. Our protocols, which utilize a soft-core harmonic potential, will be applied for the first time to equilibrate a million particle system of polyethylene chains consisting of 1000 united atoms at various temperatures. Calculations of structural and entanglement properties demonstrate that this method can be used as an alternative towards the generation of entangled equilibrium structures.

  8. Network, system, and status software enhancements for the autonomously managed electrical power system breadboard. Volume 2: Protocol specification

    NASA Technical Reports Server (NTRS)

    Mckee, James W.

    1990-01-01

    This volume (2 of 4) contains the specification, structured flow charts, and code listing for the protocol. The purpose of an autonomous power system on a spacecraft is to relieve humans from having to continuously monitor and control the generation, storage, and distribution of power in the craft. This implies that algorithms will have been developed to monitor and control the power system. The power system will contain computers on which the algorithms run. There should be one control computer system that makes the high level decisions and sends commands to and receive data from the other distributed computers. This will require a communications network and an efficient protocol by which the computers will communicate. One of the major requirements on the protocol is that it be real time because of the need to control the power elements.

  9. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

    PubMed Central

    Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

    2016-01-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

  10. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis.

    PubMed

    Lerner, Thomas R; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R G; Borel, Sophie; Diedrich, Collin R; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M; Wilkinson, Robert J; Griffiths, Gareth; Gutierrez, Maximiliano G

    2016-03-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes.

  11. [Immunologic significance of lymphatic drainage of the brain].

    PubMed

    Weller, R O; Phillips, M J; Kida, S; Zhang, E T

    1997-04-01

    Despite the evidence for immunological reactions in the human CNS, in viral encephalitis and in multiple sclerosis, connections between the brain and the immune system are poorly understood. In rodents, tracers injected into the interstitial fluid of the brain drain to the cervical lymph nodes by perivascular pathways in the brain and nasal lymphatics. Similar pathways could serve as lymphatics in the human brain. In the present study, we test the hypothesis that lymphatic drainage of the brain and cervical lymph nodes play a key role in T-cell mediated immunity of the brain. Experimental allergic encephalomyelitis (EAE) was induced in Lewis rats by the injection of guinea pig spinal cord homogenate in complete Freund's adjuvant into the foot pads. This resulted in paralysis of the hind limbs and infiltration of lymphocytes and microglial activation centred mainly on the spinal cord; little inflammation was seen in the cerebrum. When a brain wound, in the form of cryolesion, was inflicted on one cerebral hemisphere, 8 days after the induction of EAE, there was a 6-fold enhancement of EAE lesions in the brain. This enhancement was reduced by 40% cervical lymphadenectomy at the time of the cryolesion. These results suggest that cervical lymph nodes play a pivotal role in cerebral EAE and may be a major source of brain-directed lymphocytes. If similar mechanisms apply in man, study of cervical lymphocytes and their manipulation could open new therapeutic avenues for the treatment of multiple sclerosis.

  12. The Predigest Project of TCP/IP Protocol Communication System Based on DSP Technology and Ethernet

    NASA Astrophysics Data System (ADS)

    hong-you, Wang; san-ping, Zhao

    The paper introduce a predigest project of TCP/IP based on DSP CMOS chip TMS320F2407 and Ethernet interface. The system design the Network Interface Controller using TMS320F2407and TRL8019AS,it simplify TCP/IP, achieve simple protocol stack in DSP, and achieve Data transmission by software program. The experiment indicated that, the communication system constructed by TMS320F2407andTRL8019AS is low cast, simple and reliable.

  13. On-Farm Welfare Assessment Protocol for Adult Dairy Goats in Intensive Production Systems

    PubMed Central

    Battini, Monica; Stilwell, George; Vieira, Ana; Barbieri, Sara; Canali, Elisabetta; Mattiello, Silvana

    2015-01-01

    Simple Summary The Animal Welfare Indicators (AWIN) project developed a practical welfare assessment protocol for lactating dairy goats in intensive husbandry systems, using animal-based indicators that cover the whole multidimensional concept of animal welfare. The strict collaboration between scientists and stakeholders resulted in an easy-to-use protocol that provides farmers or veterinarians with comprehensive but clear feedback on the welfare status of the herd in less than three hours. The protocol, which highlights key points and motivates farmers to achieve improvements, has received much attention from interested parties. Abstract Within the European AWIN project, a protocol for assessing dairy goats’ welfare on the farm was developed. Starting from a literature review, a prototype including animal-based indicators covering four welfare principles and 12 welfare criteria was set up. The prototype was tested in 60 farms for validity, reliability, and feasibility. After testing the prototype, a two-level assessment protocol was proposed in order to increase acceptability among stakeholders. The first level offers a more general overview of the welfare status, based on group assessment of a few indicators (e.g., hair coat condition, latency to the first contact test, severe lameness, Qualitative Behavior Assessment), with no or minimal handling of goats and short assessment time required. The second level starts if welfare problems are encountered in the first level and adds a comprehensive and detailed individual evaluation (e.g., Body Condition Score, udder asymmetry, overgrown claws), supported by an effective sampling strategy. The assessment can be carried out using the AWIN Goat app. The app results in a clear visual output, which provides positive feedback on welfare conditions in comparison with a benchmark of a reference population. The protocol may be a valuable tool for both veterinarians and technicians and a self-assessment instrument for

  14. Development of a decision support system to predict physicians' rehabilitation protocols for patients with knee osteoarthritis.

    PubMed

    Hawamdeh, Ziad M; Alshraideh, Mohammad A; Al-Ajlouni, Jihad M; Salah, Imad K; Holm, Margo B; Otom, Ali H

    2012-09-01

    To design a medical decision support system (MDSS) that would accurately predict the rehabilitation protocols prescribed by the physicians for patients with knee osteoarthritis (OA) using only their demographic and clinical characteristics. The demographic and clinical variables for 170 patients receiving one of three treatment protocols for knee OA were entered into the MDSS. Demographic variables in the model were age and sex. Clinical variables entered into the model were height, weight, BMI, affected side, severity of knee OA, and severity of pain. All patients in the study received one of three treatment protocols for patients with knee OA: (a) hot packs, followed by electrotherapy and exercise, (b) ice packs, followed by ultrasound and exercise and (c) exercise alone. The resilient back propagation artificial neural network algorithm was used, with a ten-fold cross-validation. It was estimated that the MDSS is able to accurately predict the treatment prescribed by the physician for 87% of the patients. We developed an artificial neural network-based decision support system that can viably aid physicians in determining which treatment protocol would best match the anthropometric and clinical characteristics of patients with knee OA. PMID:22508428

  15. Characterization of modems and error correcting protocols using a scintillation playback system

    NASA Astrophysics Data System (ADS)

    Rabinovich, William S.; Mahon, Rita; Ferraro, Mike S.; Murphy, James L.; Moore, Christopher I.

    2016-03-01

    The performance of free space optical (FSO) communication systems is strongly affected by optical scintillation. Scintillation fades can cause errors when the power on a detector falls below its noise floor, while surges can overload a detector. The very long time scale of scintillation compared to a typical bit in an FSO link means that error-correcting protocols designed for fiber optic links are inappropriate for FSO links. Comparing the performance effects of different components, such as photodetectors, or protocols, such as forward error correction, in the field is difficult because conditions are constantly changing. On the other hand, laboratory-based turbulence simulators, often using hot plates and fans, do not really simulate the effects of long-range propagation through the atmosphere. We have investigated a different approach. Scintillation has been measured during field tests using FSO terminals by sending a continuous wave beam through the atmosphere. A high dynamic range photodetector was digitized at a 10 KHz rate and files of the intensity variations were saved. Many hours of scintillation data under different environmental conditions and at different sites have been combined into a library of data. A fiber-optic based scintillation playback system was then used in the laboratory to test modems and protocols with the recorded files. This allowed comparisons using the same atmospheric conditions allowing optimization of such parameters as detector dynamic range. It also allowed comparison and optimization of different error correcting protocols.

  16. Peri-articular Lymphatics and “Bi” Theory of Chinese Medicine in the Pathogenesis and Treatment of Arthritis*

    PubMed Central

    Qian-qian, LIANG; Qi, SHI; Wood, Ronald W.; Lian-ping, XING; Yong-jun, WANG

    2016-01-01

    Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most common joint diseases, and they have characterization of synovial inflammation and cartilage destruction, associated with the accumulation of numerous catabolic mediators and inflammatory cells in the synovial space and surrounding soft tissues. How these factors are cleared and if the “clearance” process contributes to pathogenesis of arthritis are not known. Recently, we found the existence of the peri-articular lymphatic system in mouse joints. The blockade of lymphangiogenesis and lymphatic draining function accelerates while stimulation of lymphatic function attenuates the severity of joint tissue lesions in mouse models of RA and OA. More importantly, we noticed the similarity between the dysfunction of lymphatic drainage in arthritic joints and “Bi” theory of Chinese medicine (CM), and demonstrated that several Bi disease-treated herbal drugs directly affect the function of lymphatic endothelial cells. Here we review the advances about the interactions between joint inflammation and changes in the peri-articular lymphatic system and discuss our view of linking “Bi” theory of CM to lymphatic dysfunction in arthritis. PMID:26432788

  17. Near-infrared fluorescence imaging of lymphatics in head and neck lymphedema

    NASA Astrophysics Data System (ADS)

    Tan, I.-Chih; Maus, Erik A.; Rasmussen, John C.; Marshall, Milton V.; Fife, Caroline E.; Smith, Latisha A.; Sevick-Muraca, Eva M.

    2011-03-01

    Treatment of lymphatic disease is complicated and controversial, due in part to the limited understanding of the lymphatic system. Lymphedema (LE) is a frequent complication after surgical resection and radiation treatment in cancer survivors, and is especially debilitating in regions where treatment options are limited. Although some extremity LE can be effectively treated with manual lymphatic drainage (MLD) therapy or compression devices to direct proximal lymph transport, head and neck LE is more challenging, due to complicated geometry and complex lymphatic structure in head and neck region. Herein, we describe the compassionate use of an investigatory technique of near-infrared (NIR) fluorescence imaging to understand the lymphatic anatomy and function, and to help direct MLD in a patient with head and neck LE. Immediately after 9 intradermal injections of 25 μg indocyanine green each around the face and neck region, NIR fluorescence images were collected using a custom-built imaging system with diffused excitation light illumination. These images were then used to direct MLD therapy. In addition, 3-dimensional (3D) surface profilometry was used to monitor response to therapy. NIR fluorescence images of functioning lymphatic vessels and abnormal structures were obtained. Precise geometries of facial structures were obtained using 3D profilometry, and detection of small changes in edema between therapy sessions was achieved. NIR fluorescence imaging provides a mapping of lymphatic architecture to direct MLD therapy and thus improve treatment efficacy in the head and neck LE, while 3D profilometry allowed longitudinal assessment of edema to evaluate the efficacy of therapy.

  18. An improved authenticated key agreement protocol for telecare medicine information system.

    PubMed

    Liu, Wenhao; Xie, Qi; Wang, Shengbao; Hu, Bin

    2016-01-01

    In telecare medicine information systems (TMIS), identity authentication of patients plays an important role and has been widely studied in the research field. Generally, it is realized by an authenticated key agreement protocol, and many such protocols were proposed in the literature. Recently, Zhang et al. pointed out that Islam et al.'s protocol suffers from the following security weaknesses: (1) Any legal but malicious patient can reveal other user's identity; (2) An attacker can launch off-line password guessing attack and the impersonation attack if the patient's identity is compromised. Zhang et al. also proposed an improved authenticated key agreement scheme with privacy protection for TMIS. However, in this paper, we point out that Zhang et al.'s scheme cannot resist off-line password guessing attack, and it fails to provide the revocation of lost/stolen smartcard. In order to overcome these weaknesses, we propose an improved protocol, the security and authentication of which can be proven using applied pi calculus based formal verification tool ProVerif.

  19. An improved authenticated key agreement protocol for telecare medicine information system.

    PubMed

    Liu, Wenhao; Xie, Qi; Wang, Shengbao; Hu, Bin

    2016-01-01

    In telecare medicine information systems (TMIS), identity authentication of patients plays an important role and has been widely studied in the research field. Generally, it is realized by an authenticated key agreement protocol, and many such protocols were proposed in the literature. Recently, Zhang et al. pointed out that Islam et al.'s protocol suffers from the following security weaknesses: (1) Any legal but malicious patient can reveal other user's identity; (2) An attacker can launch off-line password guessing attack and the impersonation attack if the patient's identity is compromised. Zhang et al. also proposed an improved authenticated key agreement scheme with privacy protection for TMIS. However, in this paper, we point out that Zhang et al.'s scheme cannot resist off-line password guessing attack, and it fails to provide the revocation of lost/stolen smartcard. In order to overcome these weaknesses, we propose an improved protocol, the security and authentication of which can be proven using applied pi calculus based formal verification tool ProVerif. PMID:27218005

  20. An expert system to advise astronauts during experiments: The protocol manager module

    NASA Technical Reports Server (NTRS)

    Haymann-Haber, Guido; Colombano, Silvano P.; Groleau, Nicolas; Rosenthal, Don; Szolovits, Peter; Young, Laurence R.

    1990-01-01

    Perhaps the scarcest resource for manned flight experiments - on Spacelab or on the Space Station Freedom - will continue to be crew time. To maximize the efficiency of the crew and to make use of their abilities to work as scientist collaborators as well as equipment operators, normally requires more training in a wide variety of disciplines than is practical. The successful application of on-board expert systems, as envisioned by the Principal Investigator in a Box program, should alleviate the training bottleneck and provide the astronaut with the guidance and coaching needed to permit him or her to operate an experiment according to the desires and knowledge of the PI, despite changes in conditions. The Protocol Manager module of the system is discussed. The Protocol Manager receives experiment data that has been summarized and categorized by the other modules. The Protocol Manager acts on the data in real-time, by employing expert system techniques. Its recommendations are based on heuristics provided by the Principal Investigator in charge of the experiment. This prototype was developed on a Macintosh II by employing CLIPS, a forward-chaining rule-based system, and HyperCard as an object-oriented user interface builder.

  1. Test Protocol for Room-to-Room Distribution of Outside Air by Residential Ventilation Systems

    SciTech Connect

    Barley, C. D.; Anderson, R.; Hendron, B.; Hancock, E.

    2007-12-01

    This test and analysis protocol has been developed as a practical approach for measuring outside air distribution in homes. It has been used successfully in field tests and has led to significant insights on ventilation design issues. Performance advantages of more sophisticated ventilation systems over simpler, less-costly designs have been verified, and specific problems, such as airflow short-circuiting, have been identified.

  2. Characterization of internodal collecting lymphatic vessel function after surgical removal of an axillary lymph node in mice.

    PubMed

    Kwon, Sunkuk; Price, Roger E

    2016-04-01

    Secondary lymphedema is an acquired lymphatic disorder, which occurs because of damage to the lymphatic system from surgery and/or radiation therapy for cancer treatment. However, it remains unknown how post-nodal collecting lymphatic vessels (CLVs) draining to the surgical wound area change in response to lymphadenectomy. We investigated functional and architectural changes of inguinal-to-axillary internodal CLVs (ICLVs) in mice after a single axillary LN (ALN) dissection using near-infrared fluorescence imaging. Our data showed no lymph flow in the ICLVs draining from the inguinal LN (ILN) at 2 days post-surgery. External compression enabled visualization of a small segment of contractile fluorescent ICLVs, but not all the way to the axillary region. At day 6, abnormal lymphatic drainage patterns, including lateral and retrograde lymph flow via vessels branching off the ICLVs were observed, which started to disappear beginning 9 days after surgery. The administration of vascular endothelial growth factor (VEGF)-C into the wound increased resolution of altered lymphatic drainage. Lymphatic drainage from the base of the tail to the ILN did not significantly change over time. These results demonstrate that lymph flow in the CLVs is dramatically affected by a LN dissection and long-term interruption of lymph flow might cause CLV dysfunction and thus contribute to chronic lymphatic disorders. PMID:27446639

  3. Effects of dynamic shear and transmural pressure on wall shear stress sensitivity in collecting lymphatic vessels.

    PubMed

    Kornuta, Jeffrey A; Nepiyushchikh, Zhanna; Gasheva, Olga Y; Mukherjee, Anish; Zawieja, David C; Dixon, J Brandon

    2015-11-01

    Given the known mechanosensitivity of the lymphatic vasculature, we sought to investigate the effects of dynamic wall shear stress (WSS) on collecting lymphatic vessels while controlling for transmural pressure. Using a previously developed ex vivo lymphatic perfusion system (ELPS) capable of independently controlling both transaxial pressure gradient and average transmural pressure on an isolated lymphatic vessel, we imposed a multitude of flow conditions on rat thoracic ducts, while controlling for transmural pressure and measuring diameter changes. By gradually increasing the imposed flow through a vessel, we determined the WSS at which the vessel first shows sign of contraction inhibition, defining this point as the shear stress sensitivity of the vessel. The shear stress threshold that triggered a contractile response was significantly greater at a transmural pressure of 5 cmH2O (0.97 dyne/cm(2)) than at 3 cmH2O (0.64 dyne/cm(2)). While contraction frequency was reduced when a steady WSS was applied, this inhibition was reversed when the applied WSS oscillated, even though the mean wall shear stresses between the conditions were not significantly different. When the applied oscillatory WSS was large enough, flow itself synchronized the lymphatic contractions to the exact frequency of the applied waveform. Both transmural pressure and the rate of change of WSS have significant impacts on the contractile response of lymphatic vessels to flow. Specifically, time-varying shear stress can alter the inhibition of phasic contraction frequency and even coordinate contractions, providing evidence that dynamic shear could play an important role in the contractile function of collecting lymphatic vessels.

  4. Lymphangiogenesis, Lymphatic Endothelial Cells and Lymphatic Metastasis in Head and Neck Cancer — A Review of Mechanisms

    PubMed Central

    Zhang, Zhuang; Helman, Joseph I; Li, Long-jiang

    2010-01-01

    Lymphatic metastasis is a continuous and complicated process. The detailed mechanisms of lymphatic metastasis are still not very clear, despite considerable research efforts in recent years. Previously, it was commonly accepted that there were no lymphatic vessels in the primary tumor. However, recent studies have demonstrated that lymphatic vessels are detectable in certain types of cancer, and more and more evidence has shown that cancer cells invade into local lymph nodes mainly via peritumoral lymphatic vessels. Moreover, activated endothelial cells may also be important, having an influence on lymphatic metastasis of cancer cells. This article, based on recent research findings, provides an in-depth discussion of the relationship between lymphangiogenesis, tumor-derived lymphatic endothelial cells and lymphatic metastasis in head and neck cancer. PMID:20690413

  5. Cerebral Lipiodol Embolism after Lymphatic Embolization for Plastic Bronchitis

    PubMed Central

    Kirschen, Matthew P.; Dori, Yoav; Itkin, Maxim; Licht, Daniel J.; Ichord, Rebecca; Vossough, Arastoo

    2016-01-01

    An adolescent with plastic bronchitis due to congenital heart disease had altered mental status after an interventional lymphatic procedure in which lipiodol contrast was used. Neuroimaging revealed cerebral lipiodol embolization due to direct shunting between lymphatic channels and pulmonary veins. Cerebral lipiodol embolization is a potential neurologic morbidity associated with interventional lymphatic procedures. PMID:27297208

  6. Anatomic and Functional Evaluation of Central Lymphatics With Noninvasive Magnetic Resonance Lymphangiography

    PubMed Central

    Kim, Eun Young; Hwang, Hye Sun; Lee, Ho Yun; Cho, Jong Ho; Kim, Hong Kwan; Lee, Kyung Soo; Shim, Young Mog; Zo, Jaeil

    2016-01-01

    Abstract Accurate assessment of the lymphatic system has been limited due to the lack of optimal diagnostic methods. Recently, we adopted noncontrast magnetic resonance (MR) lymphangiography to evaluate the central lymphatic channel. We aimed to investigate the feasibility and the clinical usefulness of noninvasive MR lymphangiography for determining lymphatic disease. Ten patients (age range 42–72 years) with suspected chylothorax (n = 7) or lymphangioma (n = 3) who underwent MR lymphangiography were included in this prospective study. The thoracic duct was evaluated using coronal and axial images of heavily T2-weighted sequences, and reconstructed maximum intensity projection. Two radiologists documented visualization of the thoracic duct from the level of the diaphragm to the thoracic duct outlet, and also an area of dispersion around the chyloma or direct continuity between the thoracic duct and mediastinal cystic mass. The entire thoracic duct was successfully delineated in all patients. Lymphangiographic findings played a critical role in identifying leakage sites in cases of postoperative chylothorax, and contributed to differential diagnosis and confirmation of continuity with the thoracic duct in cases of lymphangioma, and also in diagnosing Gorham disease, which is a rare disorder. In patients who underwent surgery, intraoperative findings were matched with lymphangiographic imaging findings. Nonenhanced MR lymphangiography is a safe and effective method for imaging the central lymphatic system, and can contribute to differential diagnosis and appropriate preoperative evaluation of pathologic lymphatic problems. PMID:27015184

  7. Anatomic and Functional Evaluation of Central Lymphatics With Noninvasive Magnetic Resonance Lymphangiography.

    PubMed

    Kim, Eun Young; Hwang, Hye Sun; Lee, Ho Yun; Cho, Jong Ho; Kim, Hong Kwan; Lee, Kyung Soo; Shim, Young Mog; Zo, Jaeil

    2016-03-01

    Accurate assessment of the lymphatic system has been limited due to the lack of optimal diagnostic methods. Recently, we adopted noncontrast magnetic resonance (MR) lymphangiography to evaluate the central lymphatic channel. We aimed to investigate the feasibility and the clinical usefulness of noninvasive MR lymphangiography for determining lymphatic disease.Ten patients (age range 42-72 years) with suspected chylothorax (n = 7) or lymphangioma (n = 3) who underwent MR lymphangiography were included in this prospective study. The thoracic duct was evaluated using coronal and axial images of heavily T2-weighted sequences, and reconstructed maximum intensity projection. Two radiologists documented visualization of the thoracic duct from the level of the diaphragm to the thoracic duct outlet, and also an area of dispersion around the chyloma or direct continuity between the thoracic duct and mediastinal cystic mass.The entire thoracic duct was successfully delineated in all patients. Lymphangiographic findings played a critical role in identifying leakage sites in cases of postoperative chylothorax, and contributed to differential diagnosis and confirmation of continuity with the thoracic duct in cases of lymphangioma, and also in diagnosing Gorham disease, which is a rare disorder. In patients who underwent surgery, intraoperative findings were matched with lymphangiographic imaging findings.Nonenhanced MR lymphangiography is a safe and effective method for imaging the central lymphatic system, and can contribute to differential diagnosis and appropriate preoperative evaluation of pathologic lymphatic problems. PMID:27015184

  8. Distributed robust finite-time nonlinear consensus protocols for multi-agent systems

    NASA Astrophysics Data System (ADS)

    Zuo, Zongyu; Tie, Lin

    2016-04-01

    This paper investigates the robust finite-time consensus problem of multi-agent systems in networks with undirected topology. Global nonlinear consensus protocols augmented with a variable structure are constructed with the aid of Lyapunov functions for each single-integrator agent dynamics in the presence of external disturbances. In particular, it is shown that the finite settling time of the proposed general framework for robust consensus design is upper bounded for any initial condition. This makes it possible for network consensus problems to design and estimate the convergence time offline for a multi-agent team with a given undirected information flow. Finally, simulation results are presented to demonstrate the performance and effectiveness of our finite-time protocols.

  9. Development of the Diabetes Technology Society Blood Glucose Monitor System Surveillance Protocol

    PubMed Central

    Klonoff, David C.; Lias, Courtney; Beck, Stayce; Parkes, Joan Lee; Kovatchev, Boris; Vigersky, Robert A.; Arreaza-Rubin, Guillermo; Burk, Robert D.; Kowalski, Aaron; Little, Randie; Nichols, James; Petersen, Matt; Rawlings, Kelly; Sacks, David B.; Sampson, Eric; Scott, Steve; Seley, Jane Jeffrie; Slingerland, Robbert; Vesper, Hubert W.

    2015-01-01

    Background: Inaccurate blood glucsoe monitoring systems (BGMSs) can lead to adverse health effects. The Diabetes Technology Society (DTS) Surveillance Program for cleared BGMSs is intended to protect people with diabetes from inaccurate, unreliable BGMS products that are currently on the market in the United States. The Surveillance Program will provide an independent assessment of the analytical performance of cleared BGMSs. Methods: The DTS BGMS Surveillance Program Steering Committee included experts in glucose monitoring, surveillance testing, and regulatory science. Over one year, the committee engaged in meetings and teleconferences aiming to describe how to conduct BGMS surveillance studies in a scientifically sound manner that is in compliance with good clinical practice and all relevant regulations. Results: A clinical surveillance protocol was created that contains performance targets and analytical accuracy-testing studies with marketed BGMS products conducted by qualified clinical and laboratory sites. This protocol entitled “Protocol for the Diabetes Technology Society Blood Glucose Monitor System Surveillance Program” is attached as supplementary material. Conclusion: This program is needed because currently once a BGMS product has been cleared for use by the FDA, no systematic postmarket Surveillance Program exists that can monitor analytical performance and detect potential problems. This protocol will allow identification of inaccurate and unreliable BGMSs currently available on the US market. The DTS Surveillance Program will provide BGMS manufacturers a benchmark to understand the postmarket analytical performance of their products. Furthermore, patients, health care professionals, payers, and regulatory agencies will be able to use the results of the study to make informed decisions to, respectively, select, prescribe, finance, and regulate BGMSs on the market. PMID:26481642

  10. Label-free 3D imaging of microstructure, blood, and lymphatic vessels within tissue beds in vivo.

    PubMed

    Zhi, Zhongwei; Jung, Yeongri; Wang, Ruikang K

    2012-03-01

    This Letter reports the use of an ultrahigh resolution optical microangiography (OMAG) system for simultaneous 3D imaging of microstructure and lymphatic and blood vessels without the use of an exogenous contrast agent. An automatic algorithm is developed to segment the lymphatic vessels from the microstructural images based on the fact that the lymph fluid is optically transparent. An OMAG system is developed that utilizes a broadband supercontinuum light source, providing an axial resolution of 2.3 μm and lateral resolution of 5.8 μm, capable of resolving the capillary vasculature and lymphatic vessels innervating microcirculatory tissue beds. Experimental demonstration is performed by showing detailed 3D lymphatic and blood vessel maps, coupled with morphology, within mouse ears in vivo.

  11. Label-free 3D imaging of microstructure, blood and lymphatic vessels within tissue beds in vivo

    PubMed Central

    Zhi, Zhongwei; Jung, Yeongri; Wang, Ruikang K.

    2014-01-01

    This letter reports the use of an ultrahigh resolution optical microangiography (OMAG) system for simultaneous 3D imaging of microstructure, lymphatic and blood vessels without the use of exogenous contrast agent. An automatic algorithm is developed to segment the lymphatic vessels from the microstructural images, based on the fact that the lymph fluid is optically transparent. The OMAG system is developed that utilizes a broadband supercontinuum light source, providing an axial resolution of 2.3 μm and lateral resolution of 5.8 μm, capable of resolving the capillary vasculature and lymphatic vessels innervating microcirculatory tissue beds. Experimental demonstration is performed by showing detailed 3D lymphatic and blood vessel maps, coupled with morphology, within mouse ears in vivo. PMID:22378402

  12. Lymphatic Muscle Cells in Rat Mesenteric Lymphatic Vessels of Various Ages

    PubMed Central

    Bridenbaugh, Eric A.; Nizamutdinova, Irina Tsoy; Jupiter, Daniel; Nagai, Takashi; Thangaswamy, Sangeetha; Chatterjee, Victor

    2013-01-01

    Abstract Background Recent studies on aging-associated changes in mesenteric lymph flow in situ demonstrated predominance of the severe negative chronotropic effect of aging on the contractility of aged mesenteric lymphatic vessels (MLV). At the same time, contraction amplitude of the aged vessels was only slightly diminished by aging and can be rapidly stimulated within 5–15 minutes. However, the detailed quantitative evaluation of potential aging-associated changes in muscle cells investiture in MLV has never been performed. Methods and Results In this study we, for the first time, performed detailed evaluation of muscle cells investiture in MLV in reference to the position of lymphatic valve in different zones of lymphangion within various age groups (3-mo, 9-mo and 24-mo Fischer-344 rats). Using visual and quantitative analyses of the images of MLV immunohistochemically labeled for actin, we confirmed that the zones located close upstream (pre-valve zones) and above lymphatic valves (valve zones) possess the lowest investiture of lymphatic muscle cells. Most of the high muscle cells investiture zones exist downstream to the lymphatic valve (post-valve zones). The muscle cells investiture of these zones is not affected by aging, while pre-valve and valve zones demonstrate significant aging-associated decrease in muscle cells investiture. Conclusions The low muscle cells investiture zones in lymphatic vessels consist of predominantly longitudinally oriented muscle cells which are positioned in pre-valve and valve zones and connect adjacent lymphangions. These cells may provide important functional impact on the biomechanics of the lymphatic valve gating and electrical coupling between lymphangions, while their aging-associated changes may delimit adaptive reserves of aged lymphatic vessels. PMID:23531183

  13. Lymphatic Leak Complicating Central Venous Catheter Insertion

    SciTech Connect

    Barnacle, Alex M. Kleidon, Tricia M.

    2005-12-15

    Many of the risks associated with central venous access are well recognized. We report a case of inadvertent lymphatic disruption during the insertion of a tunneled central venous catheter in a patient with raised left and right atrial pressures and severe pulmonary hypertension, which led to significant hemodynamic instability. To our knowledge, this rare complication is previously unreported.

  14. VEGFR signaling during lymphatic vascular development: From progenitor cells to functional vessels.

    PubMed

    Secker, Genevieve A; Harvey, Natasha L

    2015-03-01

    Lymphatic vessels are an integral component of the cardiovascular system, serving important roles in fluid homeostasis, lipid absorption, and immune cell trafficking. Defining the mechanisms by which the lymphatic vasculature is constructed and remodeled into a functional vascular network not only provides answers to fascinating biological questions, but is fundamental to understanding how lymphatic vessel growth and development goes awry in human pathologies. While long recognized as dysfunctional in lymphedema and exploited as a route of tumor metastasis, recent work has highlighted important roles for lymphatic vessels in modulating immune responses, regulating salt-sensitive hypertension and important for lung inflation at birth. Substantial progress in our understanding of the signaling pathways important for development and morphogenesis of the lymphatic vasculature has been made in recent years. Here, we review advances in our knowledge of the best characterized of these signaling pathways, that involving the vascular endothelial growth factor (VEGF) family members VEGF-C and VEGF-D, together with their receptors VEGFR2 and VEGFR3. Recent work has defined multiple levels at which signal transduction by means of this key axis is regulated; these include control of ligand processing and bioavailability, modulation of receptor activation by interacting proteins, and regulation of receptor endocytosis and trafficking.

  15. Development of Blood and Lymphatic Endothelial Cells in Embryonic and Fetal Human Skin.

    PubMed

    Schuster, Christopher; Mildner, Michael; Botta, Albert; Nemec, Lucas; Rogojanu, Radu; Beer, Lucian; Fiala, Christian; Eppel, Wolfgang; Bauer, Wolfgang; Petzelbauer, Peter; Elbe-Bürger, Adelheid

    2015-09-01

    Blood and lymphatic vessels provide nutrients for the skin and fulfill important homeostatic functions, such as the regulation of immunologic processes. In this study, we investigated the development of blood and lymphatic endothelial cells in prenatal human skin in situ using multicolor immunofluorescence and analyzed angiogenic molecules by protein arrays of lysates and cell culture supernatants. We found that at 8 to 10 weeks of estimated gestational age, CD144(+) vessels predominantly express the venous endothelial cell marker PAL-E, whereas CD144(+)PAL-E(-) vessels compatible with arteries only appear at the end of the first trimester. Lymphatic progenitor cells at 8 weeks of estimated gestational age express CD31, CD144, Prox1, and temporary PAL-E. At that developmental stage not all lymphatic progenitor cells express podoplanin or Lyve-1, which are acquired with advancing gestational age in a stepwise fashion. Already in second-trimester human skin, the phenotype of blood and lymphatic vessels roughly resembles the one in adult skin. The expression pattern of angiogenic molecules in lysates and cell culture supernatants of prenatal skin did not reveal the expected bent to proangiogenic molecules, indicating a complex regulation of angiogenesis during ontogeny. In summary, this study provides enticing new insights into the development and phenotypic characteristics of the vascular system in human prenatal skin.

  16. Isolation and characterization of lymphatic endothelial cells from human glossal lymphangioma.

    PubMed

    You, Lanying; Wu, Mingfu; Chen, Ying; Xu, Gang; Wei, Juncheng; Li, Qiong; Song, Anping; Zhao, Liangpin; Li, Shuang; Han, Zhiqiang; Zhou, Jianfeng; Lu, Yunpin; Wang, Shixuan; Ma, Ding; Meng, Li

    2010-01-01

    Abnormal lymphangiogenesis is associated with several diseases such as tumor metastasis and lymphangioma. Human lymphangioma originated from the transformation of lymphatic endothelium is a benign malformation of lymphatic vessels and its pathogenesis has up to date not been illuminated and its cell model has also not been established. An optimized method was used to isolate lymphatic endothelial cells from human glossal lymphangioma (GL-LECs) and GL-LECs were further primarily cultured and expanded. GL-LECs were of typical cobblestone appearance when they reached confluence. The weible-palade body was observed in the GL-LECs cytoplasm. Almost all GL-LECs were strongly positive for specific lymphatic markers FLT-4, LYVE-1 and prox-1 by immunocytochemistry. Furthermore, three-dimension tube-like capillaries of GL-LECs resembled the lymphatic system in vivo, and the GL-LECs spheroids sprouted radically out to form three-dimensional buds when embedded in the cultured BME. These results indicated that high purity GL-LECs were successfully isolated and expanded. They had the abilities of tube formation and differentiation in vitro, which provide a favorable cell model for further uncovering the pathogenesis of human lymphangiomas.

  17. Lymphatic drainage of the liver and its implications in the management of colorectal cancer liver metastases.

    PubMed

    Lupinacci, Renato Micelli; Paye, François; Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirolla; Herman, Paulo

    2014-12-01

    The liver is the most common site of distant metastases in patients with colorectal cancer. Surgery represents the mainstream for curative treatment of colorectal cancer liver metastases (CRCLM) with long-term survival up to 58 and 36 % at 5 and 10 years, respectively. Despite advances on diagnosis, staging and surgical strategies, 60-70 % of patients will develop recurrence of the disease even after R0 resection of CRCLM. Tumor staging, prognosis, and therapeutic approaches for cancer are most often based on the extent of involvement of regional lymph nodes (LNs) and, to a lesser extent, on the invasion of regional lymphatic vessels draining the primary tumor. For CRCLM, the presence of intra hepatic lymphatic and blood vascular dissemination has been associated with an increased risk of intra hepatic recurrence, poorer disease-free and overall survival after liver resection. Also, several studies have reviewed the role of surgery in the patient with concomitant CRCLM and liver pedicle LN metastasis. Although pedicle LN involvement is related to worst survival rates, it does not differentiate patients that will relapse from those that will not. This review aims to briefly describe the anatomy of the liver's lymphatic drainage, the incidence of intrahepatic lymphatic invasion and hilar lymph node involvement, as well as their clinical impact in CRCLM. A better understanding of the role of liver lymphatic metastasis might, in the near future, impact the strategy of systemic therapies after liver resection as for primary colorectal tumors.

  18. Role of RhoA in regulating the pump function of isolated lymphatics from hemorrhagic shock rats.

    PubMed

    Si, Yong-Hua; Niu, Chun-Yu; Zhao, Zi-Gang; Zhang, Li-Min; Zhang, Yu-Ping

    2013-07-01

    The aim of this present study was to examine changes in RhoA protein levels and the role in RhoA in lymphatic contractility and reactivity after hemorrhagic shock. Levels of RhoA and phospho-RhoA in lymphatic tissue isolated from hemorrhagic shock rats were measured, and the contractility and reactivity to substance P of lymphatics isolated from control rats and rats subjected to shock 0.5 and 2 h were determined with an isolated lymphatic perfusion system at a transmural pressure of 3 cmH2O. At the same time, lymphatics isolated from rats subjected to shock 0.5 and 2 h were incubated with agonists and antagonists of RhoA/Rho kinase signaling. Contractile frequency, end-diastolic and end-systolic diameter, and passive diameter were recorded and used to calculate lymphatic tonic index, contractile amplitude, and fractional pump flow. After stimulation with a gradient of substance P, the differences between the preadministration and postadministration values of contractile frequency, contractile amplitude, tonic index, and fractional pump flow were calculated to further assess lymphatic reactivity. RhoA protein levels were significantly increased at 0.5 h after shock but decreased at 2 and 3 h after shock; p-Rho levels were initially increased after shock and subsequently decreased. The contractility and reactivity of 0.5-h-shocked lymphatics were significantly reduced by the RhoA antagonist C3 transferase and the Rho kinase antagonist Y-27632. The RhoA agonist U-46619 increased the contractility and reactivity of 2-h-shocked lymphatics, whereas Y-27632 suppressed the effect of U-46619. Okadaic acid, an inhibitor of myosin light-chain phosphatase, had no effect on the contractility of 2-h-shocked lymphatics, but improved lymphatic reactivity. These results suggest that RhoA is involved in the modulation of lymphatic pump function during hemorrhagic shock and that its effects may be mediated by Rho kinase and MLCP.

  19. How size evaluation of lymph node is protocol dependent in MRI when using ultrasmall superparamagnetic iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Gharehaghaji, Nahideh; Oghabian, Mohammad Ali; Sarkar, Saeed; Darki, Fahimeh; Beitollahi, Ali

    2009-05-01

    In this study, the volume of susceptibility artifact was evaluated in T1 and T2-weighted spin echo (SE) and gradient echo (GRE) images at various parameters using registration and subtraction methods. In order to state an important misinterpretation problem in lymphography, it was demonstrated that a lymph node size may be enlarged approximately 10 times when a T2*-weighted GRE protocol is used. To overcome this problem a technical consideration using multisequence (GRE and SE) paradigm was suggested to ensure both lymph node detection and metastasis identification in lymphatic system. The paradigm was also extended by post-processing manipulation of the SE images using a registration and subtraction approach for detection of lymphatic lesions.

  20. Analysis of energy efficient routing protocols for implementation of a ubiquitous health system

    NASA Astrophysics Data System (ADS)

    Kwon, Jongwon; Park, Yongman; Koo, Sangjun; Ayurzana, Odgeral; Kim, Hiesik

    2007-12-01

    The innovative Ubiquitous-Health was born through convergence of medical service, with development of up to date information technologies and ubiquitous IT. The U-Health can be applied to a variety of special situations for managing functions of each medical center efficiently. This paper focuses on estimation of various routing protocols for implementation of U-health monitoring system. In order to facilitate wireless communication over the network, a routing protocol on the network layer is used to establish precise and efficient route between sensor nodes so that information acquired from sensors may be delivered in a timely manner. A route establishment should be considered to minimize overhead, data loss and power consumption because wireless networks for U-health are organized by a large number of sensor nodes which are small in size and have limited processing power, memory and battery life. In this paper a overview of wireless sensor network technologies commonly known is described as well as evaluation of three multi hop routing protocols which are flooding, gossiping and modified low energy adaptive clustering hierarchy(LEACH) for use with these networks using TOSSIM simulator. As a result of evaluation the integrated wireless sensor board was developed in particular. The board is embedded device based on AVR128 porting TinyOS. Also it employs bio sensor measures blood pressure, pulse frequency and ZigBee module for wireless communication. This paper accelerates the digital convergence age through continual research and development of technologies related the U-Health.

  1. Protocol for uniformly measuring and expressing the performance of energy storage systems.

    SciTech Connect

    Ferreira, Summer Kamal Rhodes; Rose, David Martin; Schoenwald, David A; Bray, Kathy; Conover, David; Kintner-Meyer, Michael; Viswanathan, Vilayanur

    2013-08-01

    The U.S. Department of Energys Energy Storage Systems (ESS) Program, through the support of Pacific Northwest National Laboratory (PNNL) and Sandia National Laboratories (SNL), facilitated the development of the protocol provided in this report. The focus of the protocol is to provide a uniform way of measuring, quantifying, and reporting the performance of ESSs in various applications; something that does not exist today and, as such, is hampering the consideration and use of this technology in the market. The availability of an application-specific protocol for use in measuring and expressing performance-related metrics of ESSs will allow technology developers, power-grid operators and other end-users to evaluate the performance of energy storage technologies on a uniform and comparable basis. This will help differentiate technologies and products for specific application(s) and provide transparency in how performance is measured. It also will assist utilities and other consumers of ESSs to make more informed decisions as they consider the potential application and use of ESSs, as well as form the basis for documentation that might be required to justify utility investment in such technologies.

  2. Protocol for Uniformly Measuring and Expressing the Performance of Energy Storage Systems

    SciTech Connect

    Bray, Kathryn L.; Conover, David R.; Kintner-Meyer, Michael CW; Viswanathan, Vijayganesh; Ferreira, Summer; Rose, David; Schoenwald, David

    2012-10-01

    The U.S. Department of Energy’s Energy Storage Systems (ESS) Program, through the support of Pacific Northwest National Laboratory (PNNL) and Sandia National Laboratories (SNL), facilitated the development of the protocol provided in this report. The focus of the protocol is to provide a uniform way of measuring, quantifying, and reporting the performance of EESs in various applications; something that does not exist today and, as such, is hampering the consideration and use of this technology in the market. The availability of an application-specific protocol for use in measuring and expressing performance-related metrics of ESSs will allow technology developers, power-grid operators and other end-users to evaluate the performance of energy storage technologies on a uniform and comparable basis. This will help differentiate technologies and products for specific application(s) and provide transparency in how performance is measured. It also will assist utilities and other consumers of ESSs make more informed decisions as they consider the potential application and use of ESSs, as well as form the basis for documentation that might be required to justify utility investment in such technologies.

  3. VehiHealth: An Emergency Routing Protocol for Vehicular Ad Hoc Network to Support Healthcare System.

    PubMed

    Bhoi, S K; Khilar, P M

    2016-03-01

    Survival of a patient depends on effective data communication in healthcare system. In this paper, an emergency routing protocol for Vehicular Ad hoc Network (VANET) is proposed to quickly forward the current patient status information from the ambulance to the hospital to provide pre-medical treatment. As the ambulance takes time to reach the hospital, ambulance doctor can provide sudden treatment to the patient in emergency by sending patient status information to the hospital through the vehicles using vehicular communication. Secondly, the experienced doctors respond to the information by quickly sending a treatment information to the ambulance. In this protocol, data is forwarded through that path which has less link breakage problem between the vehicles. This is done by calculating an intersection value I v a l u e for the neighboring intersections by using the current traffic information. Then the data is forwarded through that intersection which has minimum I v a l u e . Simulation results show VehiHealth performs better than P-GEDIR, GyTAR, A-STAR and GSR routing protocols in terms of average end-to-end delay, number of link breakage, path length, and average response time.

  4. Personalized Therapy for Generalized Lymphatic Anomaly/Gorham-Stout Disease With a Combination of Sunitinib and Taxol.

    PubMed

    Rössler, Jochen; Saueressig, Ulrich; Kayser, Gian; von Winterfeld, Moritz; Klement, Gianoula L

    2015-11-01

    The recently revised ISSVA classification approved in Melbourne in April 2014 recognizes generalized lymphatic anomaly and lymphatic malformation in Gorham-Stout disease. The 2 entities can overlap in presentation, as both are characterized by destructive lymphatic vessel invasion of the axial skeleton and surrounding soft tissues. At least at present, no standard therapeutic options exist, and due to the rarity of the disease, no clinical trials are available. We present 2 patients, 1 with generalized lymphatic anomaly and 1 with lymphatic malformation in Gorham-Stout disease, with severe exacerbation during puberty. The first child presented in florid pulmonary failure and pleural effusion, the other with severe pain due to bone destruction of the pelvis and inability to walk. Both were treated using individualized protocols. The manuscript describes the rationale for choosing sunitinib in combination with low-dose (metronomic) taxol. Both patients experienced clinical and radiologic response without major toxicities, suggesting that patients with rare conditions may benefit from individualized, molecularly based therapies.

  5. Personalized Therapy for Generalized Lymphatic Anomaly/Gorham-Stout Disease With a Combination of Sunitinib and Taxol

    PubMed Central

    Rössler, Jochen; Saueressig, Ulrich; Kayser, Gian; von Winterfeld, Moritz

    2015-01-01

    The recently revised ISSVA classification approved in Melbourne in April 2014 recognizes generalized lymphatic anomaly and lymphatic malformation in Gorham-Stout disease. The 2 entities can overlap in presentation, as both are characterized by destructive lymphatic vessel invasion of the axial skeleton and surrounding soft tissues. At least at present, no standard therapeutic options exist, and due to the rarity of the disease, no clinical trials are available. We present 2 patients, 1 with generalized lymphatic anomaly and 1 with lymphatic malformation in Gorham-Stout disease, with severe exacerbation during puberty. The first child presented in florid pulmonary failure and pleural effusion, the other with severe pain due to bone destruction of the pelvis and inability to walk. Both were treated using individualized protocols. The manuscript describes the rationale for choosing sunitinib in combination with low-dose (metronomic) taxol. Both patients experienced clinical and radiologic response without major toxicities, suggesting that patients with rare conditions may benefit from individualized, molecularly based therapies. PMID:26458155

  6. Personalized Therapy for Generalized Lymphatic Anomaly/Gorham-Stout Disease With a Combination of Sunitinib and Taxol.

    PubMed

    Rössler, Jochen; Saueressig, Ulrich; Kayser, Gian; von Winterfeld, Moritz; Klement, Gianoula L

    2015-11-01

    The recently revised ISSVA classification approved in Melbourne in April 2014 recognizes generalized lymphatic anomaly and lymphatic malformation in Gorham-Stout disease. The 2 entities can overlap in presentation, as both are characterized by destructive lymphatic vessel invasion of the axial skeleton and surrounding soft tissues. At least at present, no standard therapeutic options exist, and due to the rarity of the disease, no clinical trials are available. We present 2 patients, 1 with generalized lymphatic anomaly and 1 with lymphatic malformation in Gorham-Stout disease, with severe exacerbation during puberty. The first child presented in florid pulmonary failure and pleural effusion, the other with severe pain due to bone destruction of the pelvis and inability to walk. Both were treated using individualized protocols. The manuscript describes the rationale for choosing sunitinib in combination with low-dose (metronomic) taxol. Both patients experienced clinical and radiologic response without major toxicities, suggesting that patients with rare conditions may benefit from individualized, molecularly based therapies. PMID:26458155

  7. Pkd1 regulates lymphatic vascular morphogenesis during development.

    PubMed

    Coxam, Baptiste; Sabine, Amélie; Bower, Neil I; Smith, Kelly A; Pichol-Thievend, Cathy; Skoczylas, Renae; Astin, Jonathan W; Frampton, Emmanuelle; Jaquet, Muriel; Crosier, Philip S; Parton, Robert G; Harvey, Natasha L; Petrova, Tatiana V; Schulte-Merker, Stefan; Francois, Mathias; Hogan, Benjamin M

    2014-05-01

    Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by known signaling and transcriptional mechanisms. The ongoing elaboration of vessels to form a network is less well understood. This involves cell polarization, coordinated migration, adhesion, mixing, regression, and shape rearrangements. We identified a zebrafish mutant, lymphatic and cardiac defects 1 (lyc1), with reduced lymphatic vessel development. A mutation in polycystic kidney disease 1a was responsible for the phenotype. PKD1 is the most frequently mutated gene in autosomal dominant polycystic kidney disease (ADPKD). Initial lymphatic precursor sprouting is normal in lyc1 mutants, but ongoing migration fails. Loss of Pkd1 in mice has no effect on precursor sprouting but leads to failed morphogenesis of the subcutaneous lymphatic network. Individual lymphatic endothelial cells display defective polarity, elongation, and adherens junctions. This work identifies a highly selective and unexpected role for Pkd1 in lymphatic vessel morphogenesis during development.

  8. Developing a quality control protocol for diffusion imaging on a clinical MRI system.

    PubMed

    Delakis, Ioannis; Moore, Elizabeth M; Leach, Martin O; De Wilde, Janet P

    2004-04-21

    This work describes the development of a quality control protocol, which can be implemented to assess the accuracy, precision and reproducibility of the apparent diffusion coefficient (ADC) measurement on a clinical magnetic resonance imaging (MRI) system. The precision and accuracy of the ADC measurement are analysed with regard to MRI system noise, signal reproducibility and differences between nominal and effective b values. Two aqueous test-solutions of CuSO4 and sucrose are prepared for the quality control protocol. ADC measurement with the CuSO4 solution is more sensitive to differences between nominal and effective b values, on account of the solution's high ADC. ADC measurement with the sucrose solution is more sensitive to signal reproducibility due to the solution's low baseline signal intensity. The ADC of the test-solutions is measured on an MRI system at our centre with a sequence used for clinical studies using diffusion imaging. Two parameters, Q and R, are defined for the analysis of the quality control ADC values. The Q parameter is the ratio of the standard deviation of the quality control mean ADC values over time to the optimal standard deviation, as derived from the effect of thermal noise on the ADC measurement uncertainty. Analysis with the Q parameter indicates that signal reproducibility errors contribute to ADC variations on our MRI system when imaging with high b values (b > 500 mm s(-2)), whereas differences between nominal and effective b values have a greater impact on the ADC measurement when imaging with low b values (b < 500 mm s(-2)). The R parameter is defined as the ratio of the directional variation of the ADC quality control values to the uncertainty of the ADC measurement. Analysis with the R parameter shows that the effect of directional variation of the ADC measurement on our MRI system is more pronounced when imaging with low b values. The quality control protocol identified a systematic error, which introduced a small

  9. Microparticle image velocimetry approach to flow measurements in isolated contracting lymphatic vessels

    NASA Astrophysics Data System (ADS)

    Margaris, Konstantinos N.; Nepiyushchikh, Zhanna; Zawieja, David C.; Moore, James; Black, Richard A.

    2016-02-01

    We describe the development of an optical flow visualization method for resolving the flow velocity vector field in lymphatic vessels in vitro. The aim is to develop an experimental protocol for accurately estimating flow parameters, such as flow rate and shear stresses, with high spatial and temporal resolution. Previous studies in situ have relied on lymphocytes as tracers, but their low density resulted in a reduced spatial resolution whereas the assumption that the flow was fully developed in order to determine the flow parameters of interest may not be valid, especially in the vicinity of the valves, where the flow is undoubtedly more complex. To overcome these issues, we have applied the time-resolved microparticle image velocimetry (μ-PIV) technique, a well-established method that can provide increased spatial and temporal resolution that this transient flow demands. To that end, we have developed a custom light source, utilizing high-power light-emitting diodes, and associated control and image processing software. This paper reports the performance of the system and the results of a series of preliminary experiments performed on vessels isolated from rat mesenteries, demonstrating, for the first time, the successful application of the μ-PIV technique in these vessels.

  10. Microparticle image velocimetry approach to flow measurements in isolated contracting lymphatic vessels.

    PubMed

    Margaris, Konstantinos N; Nepiyushchikh, Zhanna; Zawieja, David C; Moore, James; Black, Richard A

    2016-02-01

    We describe the development of an optical flow visualization method for resolving the flow velocity vector field in lymphatic vessels in vitro. The aim is to develop an experimental protocol for accurately estimating flow parameters, such as flow rate and shear stresses, with high spatial and temporal resolution. Previous studies in situ have relied on lymphocytes as tracers, but their low density resulted in a reduced spatial resolution whereas the assumption that the flow was fully developed in order to determine the flow parameters of interest may not be valid, especially in the vicinity of the valves, where the flow is undoubtedly more complex. To overcome these issues, we have applied the time-resolved microparticle image velocimetry (μ -PIV) technique, a well-established method that can provide increased spatial and temporal resolution that this transient flow demands. To that end, we have developed a custom light source, utilizing high-power light-emitting diodes, and associated control and image processing software. This paper reports the performance of the system and the results of a series of preliminary experiments performed on vessels isolated from rat mesenteries, demonstrating, for the first time, the successful application of the μ -PIV technique in these vessels.

  11. Safety of methylene blue dye for lymphatic mapping in patients taking selective serotonin reuptake inhibitors.

    PubMed

    Shah-Khan, Miraj G; Lovely, Jenna; Degnim, Amy C

    2012-11-01

    Methylene blue dye has an important role in lymphatic mapping for sentinel lymph node surgery. A recent safety announcement from the US Food and Drug Administration warned physicians about possible serious central nervous system reactions in patients on serotonergic medications who received intravenous methylene blue for the identification of parathyroid glands. This report summarizes evidence from the Food and Drug Administration's announcement and methylene blue pharmacokinetics. The authors conclude that the use of methylene blue dye at low doses for lymphatic mapping likely carries very little risk for serotonin neurotoxicity, although breast surgeons should be aware of this potential complication in the event of mental status or neuromuscular changes in patients after lymphatic mapping.

  12. Analysis of Existing Privacy-Preserving Protocols in Domain Name System

    NASA Astrophysics Data System (ADS)

    Zhao, Fangming; Hori, Yoshiaki; Sakurai, Kouichi

    In a society preoccupied with gradual erosion of electronic privacy, loss of privacy in the current Domain Name System is an important issue worth considering. In this paper, we first review the DNS and some security & privacy threats to make average users begin to concern about the significance of privacy preservation in DNS protocols. Then, by an careful survey of four noise query generation based existing privacy protection approaches, we analyze some benefits and limitations of these proposals in terms of both related performance evaluation results and theoretic proofs. Finally, we point out some problems that still exist for research community's continuing efforts in the future.

  13. Systematic development and validation of sanitization protocols for a chromatographic system designed for biotherapeutics purification.

    PubMed

    Burgoyne, R F; Priest, M C; Roche, K L; Vella, G

    1993-01-01

    Production of protein therapeutics through the application of genetic engineering and biotechnology techniques requires comprehensive attention to good manufacturing practice and good laboratory practice (GMP/GLP) guidelines for product recovery and purification. Validated clean-in-place procedures are part of the master method and require analysis of microbial bioburden to assess the efficacy of cleaning protocols. This article describes the extensive microbial challenge of a chromatography system, the use of membrane filtration methods for high sensitivity microbial contamination measurement, and the effectiveness of sodium hydroxide and ethanol solutions in achieving multilog reduction of microbial contamination. PMID:8123748

  14. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides.

    PubMed

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-10-15

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nM) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P = 0.01, n = 7) and 2.7 ± 0.8-fold (P = 0.07, n = 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P = 0.005) and frequency (P = 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.

  15. Mesenchymal status of lymphatic endothelial cell: enlightening treatment of lymphatic malformation.

    PubMed

    Cai, Xu; Zhang, Wei; Chen, Gang; Li, Rui-Fang; Sun, Yan-Fang; Zhao, Yi-Fang

    2015-01-01

    In contrast to blood capillaries, lymphatic capillaries in peripheral tissues are composed of a single-cell layer of lymphatic endothelial cells (LECs) without a covering of mural cells. However, in lymphatic malformations, the enlarged lymphatic vessels were covered with mural cells. This study aimed to understand the molecular mechanism of differences between human dermal lymphatic endothelial cells (HDLECs) and human umbilical vein endothelial cells (HUVECs) and to determine the changes of LECs in the pathological condition of lymphatic malformation. Results showed that HDLECs exhibited lower expression of endothelial proteins, including VE-cadherin and CD31, than HUVECs; HDLECs also showed higher expression of mesenchymal proteins, including α-SMA, SM22α, calponin, and epithelial mesenchymal transition-related transcription factor Slug, than HUVECs. Likewise, HDLECs displayed higher permeability and weaker recruitment of SMCs than HUVECs; HDLECs also exhibited low PDGF-BB expression. TGF-β2 treatment and FGF2 depletion enhanced mesenchymal marker expression with increased permeability and reduced SMC recruitment. By contrast, Slug depletion in HDLECs enhanced VE-cadherin expression, inhibited α-SMA expression, decreased permeability, and enhanced PDGF-BB expression. These results suggested that HDLECs were in a mesenchymal status, which contributed to their functions and might determine their identities. Our data also revealed that miR143/145 was implicated in the mesenchymal status of HDLECs. In lymphatic malformations (LMs) treated with OK-432 sclerotherapy, immunohistochemistry results showed that Prox1 expression was reduced and mural cell investment was increased; these results indicated that LECs lost their mesenchymal status after OK-432 treatment was administered. The decreased mesenchymal status of LECs in LMs may induce dilated vessel constriction, which could be the mechanism of OK-432 sclerotherapy. PMID:26550134

  16. Sorting signals from protein NMR spectra: SPI, a Bayesian protocol for uncovering spin systems.

    PubMed

    Grishaev, Alexander; Llinás, Miguel

    2002-11-01

    Grouping of spectral peaks into J-connected spin systems is essential in the analysis of macromolecular NMR data as it provides the basis for disentangling chemical shift degeneracies. It is a mandatory step before resonance and NOESY cross-peak identities can be established. We have developed SPI, a computational protocol that scrutinizes peak lists from homo- and hetero-nuclear multidimensional NMR spectra and progressively assembles sets of resonances into consensus J- and/or NOE-connected spin systems. SPI estimates the likelihood of nuclear spin resonances appearing at defined frequencies given sets of cross-peaks measured from multi-dimensional experiments. It quantifies spin system matching probabilities via Bayesian inference. The protocol takes advantage of redundancies in the number of connectivities revealed by suites of diverse NMR experiments, systematically tracking the adequacy of each grouping hypothesis. SPI was tested on 2D homonuclear and 2D/3D(15)N-edited data recorded from two protein modules, the col 2 domain of matrix metalloproteinase-2 (MMP-2) and the kringle 2 domain of plasminogen, of 60 and 83 amino acid residues, respectively. For these protein domains SPI identifies approximately 95% unambiguous resonance frequencies, a relatively good performance vis-à-vis the reported 'manual' (interactive) analyses. Abbreviations and Acronyms: SPI, SPin Identification; BMRB, BioMagResBank (Madison, WI).

  17. Ultrasound Imaging System Implementation and Ignition Protocol for the Microgravity Smoldering Combustion (MSC) Experiments

    NASA Technical Reports Server (NTRS)

    Walther, David C.; Anthenien, Ralph A.; Roslon, Mark; Fernandez-Pello, A. Carlos; Urban, David L.

    1999-01-01

    The Microgravity Smoldering Combustion (MSC) experiment is a study of the smolder characteristics of porous combustible materials in a microgravity environment. The objective of the study is to provide a better understanding of the controlling mechanisms of smolder, both in microgravity and normal earth gravity. Experiments have been conducted aboard the NASA Space Shuttle in the Get Away Special Canister (GAS-CAN), an apparatus requiring completely remote operation. Future GAS-CAN experiments will utilize an ultrasound imaging system (UIS) which has been incorporated into the MSC experimental apparatus. Thermocouples are currently used to measure temperature and reaction front velocities. A less intrusive method is desirable, however, as smolder is a very weak reaction and it has been found that heat transfer along the thermocouple is sufficient to affect the smolder reaction. It is expected that the UIS system will eventually replace the existing array of thermocouples as a non-intrusive technique without compromising data acquisition. The UIS measures line of sight permeability, providing information about the reaction front position and extent. Additionally, the ignition sequence of the MSC experiments has been optimized from previous experiments to provide longer periods of self-supported smolder. An ignition protocol of a fixed power to the igniter for a fixed time is now implemented. This, rather than a controlled temperature profile ignition protocol at the igniter surface, along with the UIS system, will allow for better study of the effect of gravity on a smolder reaction.

  18. Closed system cell culture protocol using HYPERStack vessels with gas permeable material technology.

    PubMed

    Titus, Kim; Klimovich, Vitaly; Rothenberg, Mark; Pardo, Pilar; Tanner, Allison; Martin, Greg

    2010-11-29

    Large volume adherent cell culture is currently standardized on stacked plate cell growth products when microcarrier beads are not an optimal choice. HYPERStack vessels allow closed system scale up from the current stacked plate products and delivers >2.5X more cells in the same volumetric footprint. The HYPERStack vessels function via gas permeable material which allows gas exchange to occur, therefore eliminating the need for internal headspace within a vessel. The elimination of headspace allows the compartment where cell growth occurs to be minimized to reduce space, allowing more layers of cell growth surface area within the same volumetric footprint. For many applications such as cell therapy or vaccine production, a closed system is required for cell growth and harvesting. The HYPERStack vessel allows cell and reagent addition and removal via tubing from media bags or other methods. This protocol will explain the technology behind the gas permeable material used in the HYPERStack vessels, gas diffusion results to meet the metabolic needs of cells, closed system cell growth protocols, and various harvesting methods.

  19. Closed System Cell Culture Protocol Using HYPERStack Vessels with Gas Permeable Material Technology

    PubMed Central

    Rothenberg, Mark; Martin, Greg

    2010-01-01

    Large volume adherent cell culture is currently standardized on stacked plate cell growth products when microcarrier beads are not an optimal choice. HYPERStack vessels allow closed system scale up from the current stacked plate products and delivers >2.5X more cells in the same volumetric footprint. The HYPERStack vessels function via gas permeable material which allows gas exchange to occur, therefore eliminating the need for internal headspace within a vessel. The elimination of headspace allows the compartment where cell growth occurs to be minimized to reduce space, allowing more layers of cell growth surface area within the same volumetric footprint. For many applications such as cell therapy or vaccine production, a closed system is required for cell growth and harvesting. The HYPERStack vessel allows cell and reagent addition and removal via tubing from media bags or other methods. This protocol will explain the technology behind the gas permeable material used in the HYPERStack vessels, gas diffusion results to meet the metabolic needs of cells, closed system cell growth protocols, and various harvesting methods. PMID:21189467

  20. Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging.

    PubMed

    Nelson, Tyler S; Akin, Ryan E; Weiler, Michael J; Kassis, Timothy; Kornuta, Jeffrey A; Dixon, J Brandon

    2014-03-01

    The ability to quantify collecting vessel function in a minimally invasive fashion is crucial to the study of lymphatic physiology and the role of lymphatic pump function in disease progression. Therefore, we developed a highly sensitive, minimally invasive research platform for quantifying the pumping capacity of collecting lymphatic vessels in the rodent tail and forelimb. To achieve this, we have integrated a near-infrared lymphatic imaging system with a feedback-controlled pressure cuff to modulate lymph flow. After occluding lymphatic flow by inflating a pressure cuff on the limb or tail, we gradually deflate the cuff while imaging flow restoration proximal to the cuff. Using prescribed pressure applications and automated image processing of fluorescence intensity levels in the vessels, we were able to noninvasively quantify the effective pumping pressure (P(eff), pressure at which flow is restored after occlusion) and vessel emptying rate (rate of fluorescence clearance during flow occlusion) of lymphatics in the rat. To demonstrate the sensitivity of this system to changes in lymphatic function, a nitric oxide (NO) donor cream, glyceryl trinitrate ointment (GTNO), was applied to the tails. GTNO decreased P(eff) of the vessels by nearly 50% and the average emptying rate by more than 60%. We also demonstrate the suitability of this approach for acquiring measurements on the rat forelimb. Thus, this novel research platform provides the first minimally invasive measurements of P(eff) and emptying rate in rodents. This experimental platform holds strong potential for future in vivo studies that seek to evaluate changes in lymphatic health and disease.

  1. Trial of a proposed protocol for constancy control of digital mammography systems

    SciTech Connect

    Pedersen, Kristin; Landmark, Ingrid Dypvik

    2009-12-15

    Purpose: Evaluate the utility of tests in a proposed protocol for constancy control of digital mammography systems. Methods: The protocol contained tests for image acquisition, mechanical function and safety, monitors and printers, and viewing conditions. Nine sites with digital systems from four equipment manufacturers were recruited. Dedicated PMMA test objects and Excel spreadsheets were developed. Quantitative measurements were done on processed images for systems where these images were the ones most readily available. For daily assessment of the automatic exposure control system, a homogeneous PMMA phantom was exposed under clinical conditions. The mAs and signal to noise ratio (SNR) were recorded, the deviation from a target value calculated, and the resulting image inspected for artifacts. For thickness tracking, the signal difference to noise ratio obtained for three thicknesses was calculated. Detector uniformity was assessed through comparison of SNR values for regions of interest in the center and corners of an image of a homogeneous test object. Mechanical function and safety control included a compression test, a checklist for mechanical aspects, and control of field alignment. Monitor performance was evaluated by visual inspection of the AAPM TG 18 QC test image [E. Samei et al., ''Assessment of display performance for medical imaging systems,'' Task Group 18 (Madison, WI, April 2005)]. Results: For quantitative parameters, target values and tolerance limits were established. Test results exceeding the limits were registered. Most systems exhibited stable mAs values, indicating that the tolerance limit of {+-}10% was readily achievable. The SNR also showed little variation, indicating that the tolerance limit of {+-}20% was too wide. At one site, a defective grid caused artifacts that were visible in the test images. The monitor controls proved more difficult to implement due to both difficulties importing and displaying the test image, and the

  2. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure.

    PubMed

    Wiig, Helge; Schröder, Agnes; Neuhofer, Wolfgang; Jantsch, Jonathan; Kopp, Christoph; Karlsen, Tine V; Boschmann, Michael; Goss, Jennifer; Bry, Maija; Rakova, Natalia; Dahlmann, Anke; Brenner, Sven; Tenstad, Olav; Nurmi, Harri; Mervaala, Eero; Wagner, Hubertus; Beck, Franz-Xaver; Müller, Dominik N; Kerjaschki, Dontscho; Luft, Friedrich C; Harrison, David G; Alitalo, Kari; Titze, Jens

    2013-07-01

    The skin interstitium sequesters excess Na+ and Cl- in salt-sensitive hypertension. Mononuclear phagocyte system (MPS) cells are recruited to the skin, sense the hypertonic electrolyte accumulation in skin, and activate the tonicity-responsive enhancer-binding protein (TONEBP, also known as NFAT5) to initiate expression and secretion of VEGFC, which enhances electrolyte clearance via cutaneous lymph vessels and increases eNOS expression in blood vessels. It is unclear whether this local MPS response to osmotic stress is important to systemic blood pressure control. Herein, we show that deletion of TonEBP in mouse MPS cells prevents the VEGFC response to a high-salt diet (HSD) and increases blood pressure. Additionally, an antibody that blocks the lymph-endothelial VEGFC receptor, VEGFR3, selectively inhibited MPS-driven increases in cutaneous lymphatic capillary density, led to skin Cl- accumulation, and induced salt-sensitive hypertension. Mice overexpressing soluble VEGFR3 in epidermal keratinocytes exhibited hypoplastic cutaneous lymph capillaries and increased Na+, Cl-, and water retention in skin and salt-sensitive hypertension. Further, we found that HSD elevated skin osmolality above plasma levels. These results suggest that the skin contains a hypertonic interstitial fluid compartment in which MPS cells exert homeostatic and blood pressure-regulatory control by local organization of interstitial electrolyte clearance via TONEBP and VEGFC/VEGFR3-mediated modification of cutaneous lymphatic capillary function. PMID:23722907

  3. FLOSYS--a web-accessible workflow system for protocol-driven biomolecular sequence analysis.

    PubMed

    Badidi, E; Lang, B F; Burger, G

    2004-11-01

    FLOSYS is an interactive web-accessible bioinformatics workflow system designed to assist biologists in multi-step data analyses. FLOSYS allows the user to create complex analysis pathways (protocols) graphically, similar to drawing a flowchart: icons representing particular bioinformatics tools are dragged and dropped onto a canvas and lines connecting those icons are drawn to specify the relationships between the tools. In addition, FLOSYS permits to select input-data, execute the protocol and store the results in a personal workspace. The three-tier architecture of FLOSYS has been implemented in Java and uses a relational database system together with new technologies for distributed and web computing such as CORBA, RMI, JSP and JDBC. The prototype of FLOSYS, which is part of the bioinformatics workbench AnaBench, is accessible on-line at http://malawimonas.bcm.umontreal.ca: 8091/anabench. The entire package is available on request to academic groups who wish to have a customized local analysis environment for research or teaching.

  4. Utilization of Internet Protocol-Based Voice Systems in Remote Payload Operations

    NASA Technical Reports Server (NTRS)

    Chamberlain, jim; Bradford, Bob; Best, Susan; Nichols, Kelvin

    2002-01-01

    Due to limited crew availability to support science and the large number of experiments to be operated simultaneously, telescience is key to a successful International Space Station (ISS) science program. Crew, operations personnel at NASA centers, and researchers at universities and companies around the world must work closely together to per orm scientific experiments on-board ISS. The deployment of reliable high-speed Internet Protocol (IP)-based networks promises to greatly enhance telescience capabilities. These networks are now being used to cost-effectively extend the reach of remote mission support systems. They reduce the need for dedicated leased lines and travel while improving distributed workgroup collaboration capabilities. NASA has initiated use of Voice over Internet Protocol (VoIP) to supplement the existing mission voice communications system used by researchers at their remote sites. The Internet Voice Distribution System (IVoDS) connects remote researchers to mission support "loopsll or conferences via NASA networks and Internet 2. Researchers use NODS software on personal computers to talk with operations personnel at NASA centers. IVoDS also has the ;capability, if authorized, to allow researchers to communicate with the ISS crew during experiment operations. NODS was developed by Marshall Space Flight Center with contractors & Technology, First Virtual Communications, Lockheed-Martin, and VoIP Group. NODS is currently undergoing field-testing with full deployment for up to 50 simultaneous users expected in 2002. Research is being performed in parallel with IVoDS deployment for a next-generation system to qualitatively enhance communications among ISS operations personnel. In addition to the current voice capability, video and data/application-sharing capabilities are being investigated. IVoDS technology is also being considered for mission support systems for programs such as Space Launch Initiative and Homeland Defense.

  5. Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses

    PubMed Central

    Das, Suvendu; Sarrou, Eliana; Podgrabinska, Simona; Cassella, Melanie; Mungamuri, Sathish Kumar; Feirt, Nikki; Gordon, Ronald; Nagi, Chandandeep S.; Wang, Yarong; Entenberg, David; Condeelis, John

    2013-01-01

    Lymphatic vessels are thought to contribute to metastasis primarily by serving as a transportation system. It is widely believed that tumor cells enter lymph nodes passively by the flow of lymph. We demonstrate that lymph node lymphatic sinuses control tumor cell entry into the lymph node, which requires active tumor cell migration. In human and mouse tissues, CCL1 protein is detected in lymph node lymphatic sinuses but not in the peripheral lymphatics. CCR8, the receptor for CCL1, is strongly expressed by human malignant melanoma. Tumor cell migration to lymphatic endothelial cells (LECs) in vitro is inhibited by blocking CCR8 or CCL1, and recombinant CCL1 promotes migration of CCR8+ tumor cells. The proinflammatory mediators TNF, IL-1β, and LPS increase CCL1 production by LECs and tumor cell migration to LECs. In a mouse model, blocking CCR8 with the soluble antagonist or knockdown with shRNA significantly decreased lymph node metastasis. Notably, inhibition of CCR8 led to the arrest of tumor cells in the collecting lymphatic vessels at the junction with the lymph node subcapsular sinus. These data identify a novel function for CCL1–CCR8 in metastasis and lymph node LECs as a critical checkpoint for the entry of metastases into the lymph nodes. PMID:23878309

  6. Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development

    PubMed Central

    Lin, Fu-Jung; Chen, Xinpu; Qin, Jun; Hong, Young-Kwon; Tsai, Ming-Jer; Tsai, Sophia Y.

    2010-01-01

    The lymphatic system plays a key role in tissue fluid homeostasis. Lymphatic dysfunction contributes to the pathogenesis of many human diseases, including lymphedema and tumor metastasis. However, the mechanisms regulating lymphangiogenesis remain largely unknown. Here, we show that COUP-TFII (also known as Nr2f2), an orphan member of the nuclear receptor superfamily, mediates both developmental and pathological lymphangiogenesis in mice. Conditional ablation of COUP-TFII at an early embryonic stage resulted in failed formation of pre-lymphatic ECs (pre-LECs) and lymphatic vessels. COUP-TFII deficiency at a late developmental stage resulted in loss of LEC identity, gain of blood EC fate, and impaired lymphatic vessel sprouting. siRNA-mediated downregulation of COUP-TFII in cultured primary human LECs demonstrated that the maintenance of lymphatic identity and VEGF-C–induced lymphangiogenic activity, including cell proliferation and migration, are COUP-TFII–dependent and cell-autonomous processes. COUP-TFII enhanced the pro-lymphangiogenic actions of VEGF-C, at least in part by directly stimulating expression of neuropilin-2, a coreceptor for VEGF-C. In addition, COUP-TFII inactivation in a mammary gland mouse tumor model resulted in inhibition of tumor lymphangiogenesis, suggesting that COUP-TFII also regulates neo-lymphangiogenesis in the adult. Thus, COUP-TFII is a critical factor that controls lymphangiogenesis in embryonic development and tumorigenesis in adults. PMID:20364082

  7. Aberrant mural cell recruitment to lymphatic vessels and impaired lymphatic drainage in a murine model of pulmonary fibrosis.

    PubMed

    Meinecke, Anna-Katharina; Nagy, Nadine; Lago, Gabriela D'Amico; Kirmse, Santina; Klose, Ralph; Schrödter, Katrin; Zimmermann, Annika; Helfrich, Iris; Rundqvist, Helene; Theegarten, Dirk; Anhenn, Olaf; Orian-Rousseau, Véronique; Johnson, Randall S; Alitalo, Kari; Fischer, Jens W; Fandrey, Joachim; Stockmann, Christian

    2012-06-14

    Pulmonary fibrosis is a progressive disease with unknown etiology that is characterized by extensive remodeling of the lung parenchyma, ultimately resulting in respiratory failure. Lymphatic vessels have been implicated with the development of pulmonary fibrosis, but the role of the lymphatic vasculature in the pathogenesis of pulmonary fibrosis remains enigmatic. Here we show in a murine model of pulmonary fibrosis that lymphatic vessels exhibit ectopic mural coverage and that this occurs early during the disease. The abnormal lymphatic vascular patterning in fibrotic lungs was driven by expression of platelet-derived growth factor B (PDGF-B) in lymphatic endothelial cells and signaling through platelet-derived growth factor receptor (PDGFR)-β in associated mural cells. Because of impaired lymphatic drainage, aberrant mural cell coverage fostered the accumulation of fibrogenic molecules and the attraction of fibroblasts to the perilymphatic space. Pharmacologic inhibition of the PDGF-B/PDGFR-β signaling axis disrupted the association of mural cells and lymphatic vessels, improved lymphatic drainage of the lung, and prevented the attraction of fibroblasts to the perilymphatic space. Our results implicate aberrant mural cell recruitment to lymphatic vessels in the pathogenesis of pulmonary fibrosis and that the drainage capacity of pulmonary lymphatics is a critical mediator of fibroproliferative changes.

  8. An evaluation plan of bus architectures and protocols using the NASA Ames intelligent redundant actuation system

    NASA Technical Reports Server (NTRS)

    Defeo, P.; Chen, M.

    1987-01-01

    Means for evaluating data bus architectures and protocols for highly integrated flight control system applications are needed. Described are the criteria and plans to do this by using the NASA/Ames Intelligent Redundant Actuation System (IRAS) experimental set-up. Candidate bus architectures differ from one another in terms of: topology, access control, message transfer schemes, message characteristics, initialization. data flow control, transmission rates, fault tolerance, and time synchronization. The evaluation criteria are developed relative to these features. A preliminary, analytical evaluation of four candidate busses (MIL-STD-1553B, DATAC, Ethernet, and HSIS) is described. A bus must be exercised in a real-time environment to evaluate its dynamic characteristics. A plan for real-time evaluation of these four busses using a combination of hardware and simulation techniques is presented.

  9. Implementation of Quantum Plug and Play Protocol in a Trapped Ion System

    NASA Astrophysics Data System (ADS)

    Zhang, Kuan; Zhang, Xiang; Shen, Yangchao; Lu, Yao; Zhang, Shuaining; Ma, Jiajun; Kim, Kihwan; Gu, Mile; Thompson, Jayne; Vedral, Vlatko

    2016-05-01

    For the large-scale computer programing, it is important to modularize the program into many small parts, which are called as module. To integrate the modules in the program, all that we need to know is the relation between inputs and outputs not the specific details of the physical implementation. However, such modularity is generically impossible to be adapted in quantum computing. It was discussed with the example of deterministic quantum computing with one qubit (DQC1), which efficiently computes the trace of a unitary matrix U. The authors in Ref. pointed that if we compute | Tr(U) | instead of Tr(U) , the whole process can be modularized. We implement the proposed quantum plug and play protocol in the simplest situation in our trapped ion system. In the protocol, we begin with 1 pure control qubit and 2 completely mixed registers, which are swapped on a state of the control qubit. The | Tr(U) | is computed for any arbitrary unitary operation performed on the one of the register. This work was supported by the National Basic Research Program of China Grant 11CBA00300, 2011CBA00301, the National Natural Science Foundation of China Grant 11374178 and 11574002.

  10. Delivery of molecules to the lymph node via lymphatic vessels using ultrasound and nano/microbubbles.

    PubMed

    Kato, Shigeki; Shirai, Yuko; Kanzaki, Hiroyuki; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya

    2015-05-01

    Lymph node (LN) dissection is the primary option for head and neck cancer when imaging modalities and biopsy confirm metastasis to the sentinel LN. However, there are no effective alternative treatments to dissection for LN metastasis. Here, we describe a novel drug delivery system combining nano/microbubbles (NMBs) with ultrasound (US) that exhibits considerable potential for the delivery of exogenous molecules into LNs through the lymphatic vessels. A solution containing fluorophores (as a model of a therapeutic molecule) and NMBs was injected into the subiliac LNs of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of LNs (up to 13 mm in diameter, similar to human LNs). It was found that the NMBs were delivered to the entire area of the proper axillary LN (proper-ALN) via the lymphatic channels and that these were retained there for more than 8 min. Furthermore, exposure to US in the presence of NMBs enhanced the delivery of fluorophores into the lymphocytes near the lymphatic channels, compared with exposure to US in the absence of NMBs. It is proposed that a system using US and NMBs to deliver therapeutic drugs via lymphatic vessels can serve as a new treatment method for LN metastasis.

  11. Lymphatic route of transport and pharmacokinetics of Micrurus fulvius (coral snake) venom in sheep.

    PubMed

    Paniagua, D; Jiménez, L; Romero, C; Vergara, I; Calderón, A; Benard, M; Bernas, M J; Rilo, H; de Roodt, A; D' Suze, G; Witte, M H; Boyer, L; Alagón, A

    2012-12-01

    The contribution of the lymphatic system to the absorption and systemic bioavailability of Micrurus fulvius venom after subcutaneous (SC) administration was assessed using a central lymph-cannulated sheep model. Micrurus fulvius venom was administered either by intravenous bolus (IV) or subcutaneous injection (SC) in 12 sheep with and without thoracic duct cannulation and drainage. Venom concentration in serum and lymph was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) in samples collected over a 6-hour period and in tissues harvested at the end of the experiment. Pharmacokinetic parameters were determined by a non-compartmental analysis. In the lymphatic cannulated group, over the 6 hours after the venom was administered, 69% of administered dose was accounted for in blood (45%) and lymph (25%). Negligible levels of venom were detected in organs and urine implying that the steady state observed after SC administration is maintained by a slow absorption process. Comparison of kinetics of the thoracic duct cannulated and non-cannulated groups showed that lymphatic absorption contributed in an important way to maintenance of this steady state. These results show that the limiting process in the pharmacokinetics of Micrurus fulvius venom following SC administration is absorption, and that the lymphatic system plays a key role in this process.

  12. Lymphatic communication: Connexin junction, what’s your function?

    PubMed Central

    Kanady, John D.; Simon, Alexander M.

    2012-01-01

    Summary This article reviews recent findings on expression and function of connexin proteins - the structural subunits of gap junction intercellular channels in the lymphatic vasculature - both during development and in the mature lymphatic vessel. Highlighted in particular are recent mouse connexin knockout studies which show that connexins are crucial for normal lymphatic development. We discuss, in general terms, both channel-dependent as well as channel-independent functions of connexins and raise some of the many unanswered questions about the mechanism(s) of action and physiological roles of connexins in the lymphatic vasculature. PMID:22165579

  13. Rational Protocols

    NASA Astrophysics Data System (ADS)

    Cachin, Christian

    Security research continues to provide a plethora of new protocols and mechanisms; these solutions patch either existing vulnerabilities found in practical systems or solve hypothetical security problems in the sense that the problem is often conceived at the same time when the first solution is proposed. Yet only a very small fraction of this research is relevant to ordinary users in the sense that they are willing to actually deploy the technology.

  14. The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel.

    PubMed

    Aspelund, Aleksanteri; Tammela, Tuomas; Antila, Salli; Nurmi, Harri; Leppänen, Veli-Matti; Zarkada, Georgia; Stanczuk, Lukas; Francois, Mathias; Mäkinen, Taija; Saharinen, Pipsa; Immonen, Ilkka; Alitalo, Kari

    2014-09-01

    In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment.

  15. Near-Infrared Fluorescence Lymphatic Imaging to Reconsider Occlusion Pressure of Superficial Lymphatic Collectors in Upper Extremities of Healthy Volunteers

    PubMed Central

    Vandermeeren, Liesbeth; Vankerckhove, Sophie; Valsamis, Jean-Baptiste; Malloizel-Delaunay, Julie; Moraine, Jean-Jacques; Liebens, Fabienne

    2016-01-01

    Abstract Background: There are very little scientific data on occlusion pressure for superficial lymphatic collectors. Given its importance in determining the transport capacity of lymphatic vessels, it is crucial to know its value. The novel method of near-infrared fluorescence lymphatic imaging (NIRFLI) can be used to visualize lymphatic flow in real time. The goal of this study was to see if this method could be used to measure the lymphatic occlusion pressure. Methods: We observed and recorded lymph flow in the upper limb of healthy volunteers through a transparent cuff using near-infrared fluorescence lymphatic imaging. After obtaining a baseline of the lymph flow without pressure inside the cuff, the cuff was inflated by increments of 10 mm Hg starting at 30 mm Hg. A NIRFLI guided manual lymphatic drainage technique named “Fill & Flush Drainage Method” was performed during the measurement to promote lymph flow. Lymphatic occlusion pressure was determined by observing when lymph flow stopped under the cuff. Results: We measured the lymphatic occlusion pressure on 30 healthy volunteers (11 men and 19 women). Mean lymphatic occlusion pressure in the upper limb was 86 mm Hg (CI ±3.7 mm Hg, α = 0.5%). No significant differences were found between age groups (p = 0.18), gender (p = 0.12), or limb side (p = 0.85). Conclusions: NIRFLI, a transparent sphygmomanometer cuff and the “Fill and Flush” manual lymphatic drainage method were used to measure the lymphatic occlusion pressure in 30 healthy humans. That combination of these techniques allows the visualization of the lymph flow in real time, while ensuring the continuous filling of the lymph collectors during the measurement session, reducing false negative observations. The measured occlusion pressures are much higher than previously described in the medical literature. PMID:27167187

  16. Commercial Building Energy Asset Score System: Program Overview and Technical Protocol (Version 1.0)

    SciTech Connect

    Wang, Na; Gorrissen, Willy J.

    2013-01-11

    The U.S. Department of Energy (DOE) is developing a national voluntary energy asset score system that includes an energy asset score tool to help building owners evaluate their buildings with respect to the score system. The goal of the energy asset score system is to facilitate cost-effective investment in energy efficiency improvements of commercial buildings. The system will allow building owners and managers to compare their building infrastructure against peers and track building upgrade progress over time. The system can also help other building stakeholders (e.g., building operators, tenants, financiers, and appraisers) understand the relative efficiency of different buildings in a way that is independent from their operations and occupancy. This report outlines the technical protocol used to generate the energy asset score, explains the scoring methodology, and provides additional details regarding the energy asset score tool. This report also describes alternative methods that were considered prior to developing the current approach. Finally, this report describes a few features of the program where alternative approaches are still under evaluation.

  17. Voice over Internet Protocol (VoIP) Technology as a Global Learning Tool: Information Systems Success and Control Belief Perspectives

    ERIC Educational Resources Information Center

    Chen, Charlie C.; Vannoy, Sandra

    2013-01-01

    Voice over Internet Protocol- (VoIP) enabled online learning service providers struggling with high attrition rates and low customer loyalty issues despite VoIP's high degree of system fit for online global learning applications. Effective solutions to this prevalent problem rely on the understanding of system quality, information quality, and…

  18. Design of the Protocol Processor for the ROBUS-2 Communication System

    NASA Technical Reports Server (NTRS)

    Torres-Pomales, Wilfredo; Malekpour, Mahyar R.; Miner, Paul S.

    2005-01-01

    The ROBUS-2 Protocol Processor (RPP) is a custom-designed hardware component implementing the functionality of the ROBUS-2 fault-tolerant communication system. The Reliable Optical Bus (ROBUS) is the core communication system of the Scalable Processor-Independent Design for Enhanced Reliability (SPIDER), a general-purpose fault tolerant integrated modular architecture currently under development at NASA Langley Research Center. ROBUS is a time-division multiple access (TDMA) broadcast communication system with medium access control by means of time-indexed communication schedule. ROBUS-2 is a developmental version of the ROBUS providing guaranteed fault-tolerant services to the attached processing elements (PEs), in the presence of a bounded number of faults. These services include message broadcast (Byzantine Agreement), dynamic communication schedule update, time reference (clock synchronization), and distributed diagnosis (group membership). ROBUS also features fault-tolerant startup and restart capabilities. ROBUS-2 tolerates internal as well as PE faults, and incorporates a dynamic self-reconfiguration capability driven by the internal diagnostic system. ROBUS consists of RPPs connected to each other by a lower-level physical communication network. The RPP has a pipelined architecture and the design is parameterized in the behavioral and structural domains. The design of the RPP enables the bus to achieve a PE-message throughput that approaches the available bandwidth at the physical layer.

  19. The mesenteric lymph duct cannulated rat model: application to the assessment of intestinal lymphatic drug transport.

    PubMed

    Trevaskis, Natalie L; Hu, Luojuan; Caliph, Suzanne M; Han, Sifei; Porter, Christopher J H

    2015-03-06

    The intestinal lymphatic system plays key roles in fluid transport, lipid absorption and immune function. Lymph flows directly from the small intestine via a series of lymphatic vessels and nodes that converge at the superior mesenteric lymph duct. Cannulation of the mesenteric lymph duct thus enables the collection of mesenteric lymph flowing from the intestine. Mesenteric lymph consists of a cellular fraction of immune cells (99% lymphocytes), aqueous fraction (fluid, peptides and proteins such as cytokines and gut hormones) and lipoprotein fraction (lipids, lipophilic molecules and apo-proteins). The mesenteric lymph duct cannulation model can therefore be used to measure the concentration and rate of transport of a range of factors from the intestine via the lymphatic system. Changes to these factors in response to different challenges (e.g., diets, antigens, drugs) and in disease (e.g., inflammatory bowel disease, HIV, diabetes) can also be determined. An area of expanding interest is the role of lymphatic transport in the absorption of orally administered lipophilic drugs and prodrugs that associate with intestinal lipid absorption pathways. Here we describe, in detail, a mesenteric lymph duct cannulated rat model which enables evaluation of the rate and extent of lipid and drug transport via the lymphatic system for several hours following intestinal delivery. The method is easily adaptable to the measurement of other parameters in lymph. We provide detailed descriptions of the difficulties that may be encountered when establishing this complex surgical method, as well as representative data from failed and successful experiments to provide instruction on how to confirm experimental success and interpret the data obtained.

  20. New broadcasting protocols for video-on-demand systems in multicast environment

    NASA Astrophysics Data System (ADS)

    Feng, Jian; Poon, Wing-Fai; Lo, Kwok-Tung

    2002-09-01

    In this paper, two new broadcasting protocols are proposed for providing video-on-demand (VoD) services in multicast environment. The two protocols are developed by introducing a new first-segment delivery scheme for the skycraper and staggered protocols. With our approach, the first segment of a video is further divided into a number of small pieces so that customers can download the request data and start watching the video in a shorter time. The results show that the start-up latency for users is greatly reduced when using our new protocols.

  1. Monitoring of small lymphatics function under different impact on animal model by integrated optical imaging

    NASA Astrophysics Data System (ADS)

    Galanzha, Ekaterina I.; Tuchin, Valery V.; Chowdhury, Parimal; Zharov, Vladimir P.

    2004-08-01

    The digital transmission microscopy is very informative, noninvasive for vessels, simple and available method for studying and measuring lymph microvessels function in vivo. Rat mesentery can use as promising animal model of lymph microvessels in vivo. Such imaging system allowed visualizing the entire lymphangion (with input and output valves), its wall, lymphatic valves, lymph flow as well as single cells in flow; obtaining anew basic information on lymph microcirculation and quantitative data on lymphatic function including indexes of phasic contractions and valve function, the quantitative parameters of lymph-flow velocity. Rat mesentery is good model to create different types of lymphedemas in acute and chronic experiments. The obtained data revealed that significant edema started immediately after lymph node dissection in one-half of cases and was accompanied by lymphatic disturbances. The greatest degree of edema was found after 1 week. After 4 weeks, the degree of edema sometimes decreased, but functional lymphatic disturbances progressed. Nicotine had significant direct dose-dependent effect on microlymphatic function at the acute local application, but the same dose of this drug was not effect on microcirculation in chronic intoxication. Despite yielding interesting data, transmittance microscopy had some limitations when applied to microcirculation studies. The problems could be solved at the application of integrated measuring technique.

  2. Lymphatic drainage and CTV in pancreatic carcinoma.

    PubMed

    Morganti, Alessio G; Cellini, Numa; Mattiucci, Gian Carlo; Macchia, Gabriella; Smaniotto, Daniela; Luzi, Stefano; Balducci, Mario; Deodato, Francesco; Valentini, Vincenzo; Trodella, Lucio

    2003-01-01

    CTV definition in exclusive or adjuvant radiation therapy of pancreatic carcinoma is essentially based on the opinion of "expert" authors and on the knowledge of lymphatic pathways. The subject has been widely debated. Radiotherapy treatments of the entire upper abdomen (liver and pancreatic region), pancreas and lymph node stations, to volumes focused on macroscopic tumor only, have been proposed. Carcinoma of exocrine pancreas is characterized by the frequent, early appearance of metastasis via the lymphatic route. Most commonly involved lymph node stations include those of the celiac trunk, superior mesenteric, peripancreatic, lumboaortic lymph nodes, those of the hepatic portal (the latter in particular for pancreatic head tumors) and of the hilum of spleen (the latter in particular for pancreatic tail tumors). The possible multicentricity of pancreatic carcinoma, most likely due to intraductal spread, should lead to the inclusion in the CTV of the entire pancreatic parenchyma. This should be considered also for the frequent perineural intra- or extrapancreatic spread of pancreatic carcinoma present also in small tumors (T1). In extrapancreatic spread the retropancreatic adipose tissue should be included in the CTV at least at the GTV level. At the present state of knowledge, in the absence of pattern of failure analysis and of comparison of different treatment approaches, in terms of the definition of volumes of interest, CTV definitions which include lymphatic drainage stations, most part of pancreatic parenchyma and retropancreatic adipose tissue seem justified especially in treatments for cure. In palliation, the CTV may be limited to the GTV and the adipose tissue behind it. PMID:15018319

  3. Lymph transport in rat mesenteric lymphatics experiencing edemagenic stress

    PubMed Central

    Rahbar, Elaheh; Akl, Tony; Coté, Gerard L.; Moore, James E.; Zawieja, David C.

    2014-01-01

    Objective To assess lymphatic flow adaptations to edema, we evaluated lymph transport function in rat mesenteric lymphatics under normal and edemagenic conditions in situ. Methods Twelve rats were infused with saline (intravenous infusion, 0.2 ml/min/100g body weight) to induce edema. We intravitally measured mesenteric lymphatic diameter and contraction frequency, as well as immune cell velocity and density before, during and after infusion. Results A 10-fold increase in lymph velocity (0.1–1 mm/s) and a 6-fold increase in flow rate (0.1–0.6 μL/min), were observed post-infusion, respectively. There were also increases in contraction frequency and fractional pump flow 1-minute post-infusion. Time-averaged wall shear stress increased 10 fold post-infusion to nearly 1.5 dynes/cm2. Similarly, maximum shear stress rose from 5 dynes/cm2 to 40 dynes/cm2. Conclusions Lymphatic vessels adapted to edemagenic stress by increasing lymph transport. Specifically, the increases in lymphatic contraction frequency, lymph velocity, and shear stress were significant. Lymph pumping increased post-infusion, though changes in lymphatic diameter were not statistically significant. These results indicate that edemagenic conditions stimulate lymph transport via increases in lymphatic contraction frequency, lymph velocity and flow. These changes, consequently, resulted in large increases in wall shear stress, which could then activate NO pathways and modulate lymphatic transport function. PMID:24397756

  4. Consensus statement on the immunohistochemical detection of ocular lymphatic vessels.

    PubMed

    Schroedl, Falk; Kaser-Eichberger, Alexandra; Schlereth, Simona L; Bock, Felix; Regenfuss, Birgit; Reitsamer, Herbert A; Lutty, Gerard A; Maruyama, Kazuichi; Chen, Lu; Lütjen-Drecoll, Elke; Dana, Reza; Kerjaschki, Dontscho; Alitalo, Kari; De Stefano, Maria Egle; Junghans, Barbara M; Heindl, Ludwig M; Cursiefen, Claus

    2014-10-01

    There is currently considerable controversy about existence and classification of "lymphatic vessels" in the eye. Some of the confusion is certainly caused by inappropriate use (or nonuse) of the correct immunohistochemical markers. Many experts in the field expressed the need for a consensus statement, and, in this perspective, authors offer arguments and solutions to reliably continue with immunohistochemical ocular lymphatic research.

  5. Effects of LDL Receptor Modulation on Lymphatic Function

    PubMed Central

    Milasan, Andreea; Dallaire, François; Mayer, Gaétan; Martel, Catherine

    2016-01-01

    Atherosclerosis is driven by the accumulation of immune cells and cholesterol in the arterial wall. Although recent studies have shown that lymphatic vessels play an important role in macrophage reverse cholesterol transport, the specific underlying mechanisms of this physiological feature remain unknown. In the current report, we sought to better characterize the lymphatic dysfunction that is associated with atherosclerosis by studying the physiological and temporal origins of this impairment. First, we assessed that athero-protected Pcsk9−/− mice exhibited improved collecting lymphatic vessel function throughout age when compared to WT mice for up to six months, while displaying enhanced expression of LDLR on lymphatic endothelial cells. Lymphatic dysfunction was present before the atherosclerotic lesion formation in a mouse model that is predisposed to develop atherosclerosis (Ldlr−/−; hApoB100+/+). This dysfunction was presumably associated with a defect in the collecting lymphatic vessels in a non-specific cholesterol- but LDLR-dependent manner. Treatment with a selective VEGFR-3 agonist rescued this impairment observed early in the onset of this arterial disease. We suggest that LDLR modulation is associated with early atherosclerosis-related lymphatic dysfunction, and bring forth a pleiotropic role for PCSK9 in lymphatic function. Our study unveils new potential therapeutic targets for the prevention and treatment of atherosclerosis. PMID:27279328

  6. [Protocol and quality control for Chinese food and nutrition surveillance system in 1998 (1998 CFNSS)].

    PubMed

    He, W

    2000-09-01

    Establishment of Chinese Food and Nutrition Surveillance System is of great importance in providing information on food consumption behavior and nutrition status of the people which is essential for health, economic planning and agriculture development. Sampling of CFNSS is based on the 145 sites Disease Surveillance Point (DSP) System built by Ministry of Health, and in conjunction with the 600 sites Household Social Economic Survey System founded by State Statistics Bureau. According to indicator system developed by the Ministry of Health for stratification, strata of urban, general rural and less-developed rural were defined and 40 sites were randomly sampled as national sample. The CFNSS sample was the common sub-sample of DSP system and the SSB Household Survey System that makes sharing of information resources possible. The 40 sites are distributed in 26 Provinces/Municipalities/Autonomous Regions. All the sites information was collected on body weight and height of children under 6 years of age, and questionnaire covering the basic family information, feeding practice and disease, health conditions of the households were surveyed by interviews. Whole year food consumption data collected at the sampled households by SSB Urban Household Survey Team and Rural Household Survey Team in the previous year was provided. Comprehensive data analysis was done to formulate the information on the relationship of food, nutrition and health. The protocol, methodologies and principles for the survey are described. 5 sites of CFNSS were selected for quality evaluation on the anthropometric measurement and questionnaire interview. The body weight and length of 20 children of 3-5 years of age in each of 5 sites was measured again. The result showed that the completeness of questionnaires interview was 96%, the rate of logic error was zero. There was no significant difference between the results measured by supervisor and investigator and no significant error on repeated

  7. 9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration: Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema

    PubMed Central

    Choi, Inho; Lee, Sunju; Chung, Hee Kyoung; Lee, Yong Suk; Kim, Kyu Eui; Choi, Dongwon; Park, Eun Kyung; Yang, Dongyun; Ecoiffier, Tatiana; Monahan, John; Chen, Wen; Aguilar, Berenice; Lee, Ha Neul; Yoo, Jaehyuk; Koh, Chester J.; Chen, Lu; Wong, Alex K.; Hong, Young-Kwon

    2012-01-01

    Background The lymphatic system plays a key role in tissue fluid homeostasis and lymphatic dysfunction due to genetic defects or lymphatic vessel obstruction can cause lymphedema, disfiguring tissue swellings often associated with fibrosis and recurrent infections without available cures to date. In this study, retinoic acids (RAs) were determined to be a potent therapeutic agent that is immediately applicable to reduce secondary lymphedema. Methods and Results We report that RAs promote proliferation, migration and tube formation of cultured lymphatic endothelial cells (LECs) by activating FGF-receptor signaling. Moreover, RAs control the expression of cell-cycle checkpoint regulators such as p27Kip1, p57Kip2 and the aurora kinases through both an Akt-mediated non-genomic action and a transcription-dependent genomic action that is mediated by Prox1, a master regulator of lymphatic development. Moreover, 9-cisRA was found to activate in vivo lymphangiogenesis in animals based on mouse trachea, matrigel plug and cornea pocket assays. Finally, we demonstrate that 9-cisRA can provide a strong therapeutic efficacy in ameliorating the experimental mouse tail lymphedema by enhancing lymphatic vessel regeneration. Conclusions These in vitro and animal studies demonstrate that 9-cisRA potently activates lymphangiogenesis and promotes lymphatic regeneration in an experimental lymphedema model, presenting it as a promising novel therapeutic agent to treat human lymphedema patients. PMID:22275501

  8. The RTS2 protocol

    NASA Astrophysics Data System (ADS)

    Kubánek, Petr; Jelínek, Martin; French, John; Prouza, Michal; Vítek, Stanislav; Castro-Tirado, Alberto J.; Reglero, Victor

    2008-07-01

    Remote Telescope System 2nd version (RTS2) is an open source project aimed at developing a software environment to control a fully robotic observatory. RTS2 consists of various components, which communicate via an ASCII based protocol. As the protocol was from the beginning designed as an observatory control system, it provides some unique features, which are hard to find in the other communication systems. These features include advanced synchronisation mechanisms and strategies for setting variables. This presentation describes the protocol and its unique features. It also assesses protocol performance, and provides examples how the RTS2 library can be used to quickly build an observatory control system.

  9. Tissue contribution to the mechanical features of diaphragmatic initial lymphatics

    PubMed Central

    Moriondo, Andrea; Boschetti, Federica; Bianchin, Francesca; Lattanzio, Simone; Marcozzi, Cristiana; Negrini, Daniela

    2010-01-01

    The role of the mechanical properties of the initial lymphatic wall and of the surrounding tissue in supporting lymph formation and/or progression was studied in six anaesthetized, neuromuscularly blocked and mechanically ventilated rats. After mid-sternal thoracotomy, submesothelial initial lymphatics were identified on the pleural diaphragmatic surface through stereomicroscopy. An ‘in vivo’ lymphatic segment was prepared by securing two surgical threads around the vessel at a distance of ∼2.5 mm leaving the vessel in place. Two glass micropipettes were inserted into the lumen, one for intraluminar injections of 4.6 nl saline boluses and one for hydraulic pressure (Plymph) recording. The compliance of the vessel wall (Clymph) was calculated as the slope of the plot describing the change in segment volume as a function of the post-injection Plymph changes. Two superficial lymphatic vessel populations with a significantly different Clymph (6.7 ± 1.6 and 1.5 ± 0.4 nl mmHg−1 (mean ± s.e.m.), P < 0.001) were identified. In seven additional rats, the average elastic modulus of diaphragmatic tissue strips was determined by uniaxial tension tests to be 1.7 ± 0.3 MPa. Clymph calculated for an initial lymphatic completely surrounded by isotropic tissue was 0.068 nl mmHg−1, i.e. two orders of magnitude lower than in submesothelial lymphatics. Modelling of stress distribution in the lymphatic wall suggests that compliant vessels may act as reservoirs accommodating large absorbed fluid volumes, while lymphatics with stiffer walls serve to propel fluid through the lumen of the lymphatic vessel by taking advantage of the more efficient mechanical transmission of tissue stresses to the lymphatic lumen. PMID:20724369

  10. Lymphatic albumin clearance from psoriatic skin

    SciTech Connect

    Staberg, B.; Klemp, P.; Aasted, M.; Worm, A.M.; Lund, P.

    1983-12-01

    In nine patients with untreated psoriasis vulgaris, human serum albumin labelled with /sup 125/I or /sup 131/I was injected intradermally in symmetrically located involved and uninvolved skin. The activity of the depots was followed by external detection, and the arrival of labelled albumin in plasma was monitored. In involved psoriatic skin the local mean half-time (T1/2) for tracer disappearance was 20.8 +/- 8.2 (S.D.) hr and in clinically normal skin, 29.1 +/- 9.6 (S.D.) hr. The difference was significant (p less than 0.002). Accordingly, the tracer from involved skin reached higher plasma levels than the tracer from uninvolved skin. However, under slight lymphatic stasis the appearance rate of radiolabelled albumin in plasma from both tissues was minimal during 1 to 2 hours after the injection, indicating that a local direct transvascular drainage of plasma albumin from the interstitium of diseased and normal skin was negligible. We conclude that the previously demonstrated increased extravasation of plasma proteins in involved psoriatic skin is compensated by an increased lymphatic drainage of plasma proteins, and not by an increased local transvascular return.

  11. A Participatory Approach to Designing and Enhancing Integrated Health Information Technology Systems for Veterans: Protocol

    PubMed Central

    Nazi, Kim M; Chavez, Margeaux; Lind, Jason D; Antinori, Nicole; Gosline, Robert M; Martin, Tracey L

    2015-01-01

    Background The Department of Veterans Affairs (VA) has developed health information technologies (HIT) and resources to improve veteran access to health care programs and services, and to support a patient-centered approach to health care delivery. To improve VA HIT access and meaningful use by veterans, it is necessary to understand their preferences for interacting with various HIT resources to accomplish health management related tasks and to exchange information. Objective The objective of this paper was to describe a novel protocol for: (1) developing a HIT Digital Health Matrix Model; (2) conducting an Analytic Hierarchy Process called pairwise comparison to understand how and why veterans want to use electronic health resources to complete tasks related to health management; and (3) developing visual modeling simulations that depict veterans’ preferences for using VA HIT to manage their health conditions and exchange health information. Methods The study uses participatory research methods to understand how veterans prefer to use VA HIT to accomplish health management tasks within a given context, and how they would like to interact with HIT interfaces (eg, look, feel, and function) in the future. This study includes two rounds of veteran focus groups with self-administered surveys and visual modeling simulation techniques. This study will also convene an expert panel to assist in the development of a VA HIT Digital Health Matrix Model, so that both expert panel members and veteran participants can complete an Analytic Hierarchy Process, pairwise comparisons to evaluate and rank the applicability of electronic health resources for a series of health management tasks. Results This protocol describes the iterative, participatory, and patient-centered process for: (1) developing a VA HIT Digital Health Matrix Model that outlines current VA patient-facing platforms available to veterans, describing their features and relevant contexts for use; and (2

  12. ANALOG I/O MODULE TEST SYSTEM BASED ON EPICS CA PROTOCOL AND ACTIVEX CA INTERFACE

    SciTech Connect

    YENG,YHOFF,L.

    2003-10-13

    Analog input (ADC) and output (DAC) modules play a substantial role in device level control of accelerator and large experiment physics control system. In order to get the best performance some features of analog modules including linearity, accuracy, crosstalk, thermal drift and so on have to be evaluated during the preliminary design phase. Gain and offset error calibration and thermal drift compensation (if needed) may have to be done in the implementation phase as well. A natural technique for performing these tasks is to interface the analog VO modules and GPIB interface programmable test instruments with a computer, which can complete measurements or calibration automatically. A difficulty is that drivers of analog modules and test instruments usually work on totally different platforms (vxworks VS Windows). Developing new test routines and drivers for testing instruments under VxWorks (or any other RTOS) platform is not a good solution because such systems have relatively poor user interface and developing such software requires substantial effort. EPICS CA protocol and ActiveX CA interface provide another choice, a PC and LabVIEW based test system. Analog 110 module can be interfaced from LabVIEW test routines via ActiveX CA interface. Test instruments can be controlled via LabVIEW drivers, most of which are provided by instrument vendors or by National Instruments. Labview also provides extensive data analysis and process functions. Using these functions, users can generate powerful test routines very easily. Several applications built for Spallation Neutron Source (SNS) Beam Loss Monitor (BLM) system are described in this paper.

  13. Restriction fragment length polymorphism DNA analysis by the FBI Laboratory protocol using a simple, convenient hardware system.

    PubMed

    Lewis, M E; Kouri, R E; Latorra, D; Berka, K M; Lee, H C; Gaensslen, R E

    1990-09-01

    Restriction fragment length polymorphism analysis of human deoxyribonucleic acid (DNA) using two probes, pYNH24 and CMM101, was performed on the BIOS Timeframe system following the Federal Bureau of Investigation (FBI) Laboratory protocol and some variations of it. Comparable results were obtained by the different methods used.

  14. Reducing Tobacco Use among Youth: Community-Based Approaches. A Guideline for Prevention Practitioners. Prevention Enhancement Protocols System (PEPS) Series.

    ERIC Educational Resources Information Center

    Birch & Davis Associates, Inc., Silver Spring, MD.

    A substantial knowledge base exists on reduction of tobacco use by youth. Effective prevention in this area can have major health and economic benefits. Information from research and prevention practice, organized by means of the Prevention Enhancement Protocols System (PEPS), is provided in the form of guidelines and recommendations for planning…

  15. Rho Kinase Enhances Contractions of Rat Mesenteric Collecting Lymphatics

    PubMed Central

    Kurtz, Kristine H.; Souza-Smith, Flavia M.; Moor, Andrea N.; Breslin, Jerome W.

    2014-01-01

    The mechanisms that control phasic and tonic contractions of lymphatic vessels are poorly understood. We hypothesized that rho kinase ROCK, previously shown to increase calcium (Ca2+) sensitivity in vascular smooth muscle, enhances lymphatic contractile activity in a similar fashion. Contractions of isolated rat mesenteric lymphatic vessels were observed at a luminal pressure of 2 cm H2O in a 37°C bath. The expression of ROCK in isolated rat mesenteric lymphatic vessels was assessed by Western blotting and confocal microscopy. The role of ROCK in contractile function was tested using two specific yet structurally distinct inhibitors: H1152 (0.1–10 μM) and Y-27632 (0.5–50 μM). In addition, lymphatics were transfected with constitutively active (ca)-ROCK protein (2 μg/ml) to assess gain of contractile function. Vessel diameter and the concentration of intracellular free Ca2+ ([Ca2+]i) were simultaneously measured in a subset of isolated lymphatics loaded with the Ca2+-sensing dye fura-2. The results show expression of both the ROCK1 and ROCK2 isoforms in lymphatic vessels. Inhibition of ROCK increased lymphatic end diastolic diameter and end systolic diameter in a concentration-dependent manner. Significant reductions in lymphatic tone and contraction amplitude were observed after treatment 1–10 μM H1152 or 25–50 μM Y-27632. H1152 (10 μM) also significantly reduced contraction frequency. Transient increases in [Ca2+]i preceded each phasic contraction, however this pattern was disrupted by either 10 μM H1152 or 50 μM Y-27632 in the majority of lymphatics studied. The significant decrease in tone caused by H1152 or Y-27632 was not associated with a significant change in the basal [Ca2+]i between transients. Transfection with ca-ROCK protein enhanced lymphatic tone, but was not associated with a significant change in basal [Ca2+]i. Our data suggest that ROCK mediates normal tonic constriction and influences phasic contractions in lymphatics. We propose

  16. Rho kinase enhances contractions of rat mesenteric collecting lymphatics.

    PubMed

    Kurtz, Kristine H; Souza-Smith, Flavia M; Moor, Andrea N; Breslin, Jerome W

    2014-01-01

    The mechanisms that control phasic and tonic contractions of lymphatic vessels are poorly understood. We hypothesized that rho kinase ROCK, previously shown to increase calcium (Ca2+) sensitivity in vascular smooth muscle, enhances lymphatic contractile activity in a similar fashion. Contractions of isolated rat mesenteric lymphatic vessels were observed at a luminal pressure of 2 cm H2O in a 37°C bath. The expression of ROCK in isolated rat mesenteric lymphatic vessels was assessed by Western blotting and confocal microscopy. The role of ROCK in contractile function was tested using two specific yet structurally distinct inhibitors: H1152 (0.1-10 μM) and Y-27632 (0.5-50 μM). In addition, lymphatics were transfected with constitutively active (ca)-ROCK protein (2 μg/ml) to assess gain of contractile function. Vessel diameter and the concentration of intracellular free Ca2+ ([Ca2+]i) were simultaneously measured in a subset of isolated lymphatics loaded with the Ca2+-sensing dye fura-2. The results show expression of both the ROCK1 and ROCK2 isoforms in lymphatic vessels. Inhibition of ROCK increased lymphatic end diastolic diameter and end systolic diameter in a concentration-dependent manner. Significant reductions in lymphatic tone and contraction amplitude were observed after treatment 1-10 μM H1152 or 25-50 μM Y-27632. H1152 (10 μM) also significantly reduced contraction frequency. Transient increases in [Ca2+]i preceded each phasic contraction, however this pattern was disrupted by either 10 μM H1152 or 50 μM Y-27632 in the majority of lymphatics studied. The significant decrease in tone caused by H1152 or Y-27632 was not associated with a significant change in the basal [Ca2+]i between transients. Transfection with ca-ROCK protein enhanced lymphatic tone, but was not associated with a significant change in basal [Ca2+]i. Our data suggest that ROCK mediates normal tonic constriction and influences phasic contractions in lymphatics. We propose that

  17. The left-right Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine

    PubMed Central

    Mahadevan, Aparna; Welsh, Ian C.; Sivakumar, Aravind; Gludish, David W.; Shilvock, Abigail R.; Noden, Drew M.; Kurpios, Natasza A.

    2015-01-01

    SUMMARY The dorsal mesentery (DM) is the major conduit for blood and lymphatic vessels in the gut. The mechanisms underlying their morphogenesis are challenging to study and remain unknown. Here we show that arteriogenesis in the DM begins during gut rotation and proceeds strictly on the left side, dependent on the Pitx2 target gene Cxcl12. Although competent Cxcr4-positive angioblasts are present on the right, they fail to form vessels and progressively emigrate. Surprisingly, gut lymphatics also initiate in the left DM and arise only after – and dependent on – arteriogenesis, implicating arteries as drivers of gut lymphangiogenesis. Our data begin to unravel the origin of two distinct vascular systems and demonstrate how early L-R molecular asymmetries are translated into organ-specific vascular patterns. We propose a dual origin of gut lymphangiogenesis, where prior arterial growth is required to initiate local lymphatics that only subsequently connect to the vascular system. PMID:25482882

  18. Internet Protocol Display Sharing Solution for Mission Control Center Video System

    NASA Technical Reports Server (NTRS)

    Brown, Michael A.

    2009-01-01

    With the advent of broadcast television as a constant source of information throughout the NASA manned space flight Mission Control Center (MCC) at the Johnson Space Center (JSC), the current Video Transport System (VTS) characteristics provides the ability to visually enhance real-time applications as a broadcast channel that decision making flight controllers come to rely on, but can be difficult to maintain and costly. The Operations Technology Facility (OTF) of the Mission Operations Facility Division (MOFD) has been tasked to provide insight to new innovative technological solutions for the MCC environment focusing on alternative architectures for a VTS. New technology will be provided to enable sharing of all imagery from one specific computer display, better known as Display Sharing (DS), to other computer displays and display systems such as; large projector systems, flight control rooms, and back supporting rooms throughout the facilities and other offsite centers using IP networks. It has been stated that Internet Protocol (IP) applications are easily readied to substitute for the current visual architecture, but quality and speed may need to be forfeited for reducing cost and maintainability. Although the IP infrastructure can support many technologies, the simple task of sharing ones computer display can be rather clumsy and difficult to configure and manage to the many operators and products. The DS process shall invest in collectively automating the sharing of images while focusing on such characteristics as; managing bandwidth, encrypting security measures, synchronizing disconnections from loss of signal / loss of acquisitions, performance latency, and provide functions like, scalability, multi-sharing, ease of initial integration / sustained configuration, integration with video adjustments packages, collaborative tools, host / recipient controllability, and the utmost paramount priority, an enterprise solution that provides ownership to the whole

  19. Protocol: optimising hydroponic growth systems for nutritional and physiological analysis of Arabidopsis thaliana and other plants

    PubMed Central

    2013-01-01

    Background Hydroponic growth systems are a convenient platform for studying whole plant physiology. However, we found through trialling systems as they are described in the literature that our experiments were frequently confounded by factors that affected plant growth, including algal contamination and hypoxia. We also found the way in which the plants were grown made them poorly amenable to a number of common physiological assays. Results The drivers for the development of this hydroponic system were: 1) the exclusion of light from the growth solution; 2) to simplify the handling of individual plants, and 3) the growth of the plant to allow easy implementation of multiple assays. These aims were all met by the use of pierced lids of black microcentrifuge tubes. Seed was germinated on a lid filled with an agar-containing germination media immersed in the same solution. Following germination, the liquid growth media was exchanged with the experimental solution, and after 14-21 days seedlings were transferred to larger tanks with aerated solution where they remained until experimentation. We provide details of the protocol including composition of the basal growth solution, and separate solutions with altered calcium, magnesium, potassium or sodium supply whilst maintaining the activity of the majority of other ions. We demonstrate the adaptability of this system for: gas exchange measurement on single leaves and whole plants; qRT-PCR to probe the transcriptional response of roots or shoots to altered nutrient composition in the growth solution (we demonstrate this using high and low calcium supply); producing highly competent mesophyll protoplasts; and, accelerating the screening of Arabidopsis transformants. This system is also ideal for manipulating plants for micropipette techniques such as electrophysiology or SiCSA. Conclusions We present an optimised plant hydroponic culture system that can be quickly and cheaply constructed, and produces plants with similar

  20. Lymphatic vessels regulate immune microenvironments in human and murine melanoma.

    PubMed

    Lund, Amanda W; Wagner, Marek; Fankhauser, Manuel; Steinskog, Eli S; Broggi, Maria A; Spranger, Stefani; Gajewski, Thomas F; Alitalo, Kari; Eikesdal, Hans P; Wiig, Helge; Swartz, Melody A

    2016-09-01

    Lymphatic remodeling in tumor microenvironments correlates with progression and metastasis, and local lymphatic vessels play complex and poorly understood roles in tumor immunity. Tumor lymphangiogenesis is associated with increased immune suppression, yet lymphatic vessels are required for fluid drainage and immune cell trafficking to lymph nodes, where adaptive immune responses are mounted. Here, we examined the contribution of lymphatic drainage to tumor inflammation and immunity using a mouse model that lacks dermal lymphatic vessels (K14-VEGFR3-Ig mice). Melanomas implanted in these mice grew robustly, but exhibited drastically reduced cytokine expression and leukocyte infiltration compared with those implanted in control animals. In the absence of local immune suppression, transferred cytotoxic T cells more effectively controlled tumors in K14-VEGFR3-Ig mice than in control mice. Furthermore, gene expression analysis of human melanoma samples revealed that patient immune parameters are markedly stratified by levels of lymphatic markers. This work suggests that the establishment of tumor-associated inflammation and immunity critically depends on lymphatic vessel remodeling and drainage. Moreover, these results have implications for immunotherapies, the efficacies of which are regulated by the tumor immune microenvironment. PMID:27525437

  1. Pkd1 regulates lymphatic vascular morphogenesis during development

    PubMed Central

    Coxam, Baptiste; Sabine, Amélie; Bower, Neil I.; Smith, Kelly A.; Pichol-Thievend, Cathy; Skoczylas, Renae; Astin, Jonathan W.; Frampton, Emmanuelle; Jaquet, Muriel; Crosier, Philip S.; Parton, Robert G.; Harvey, Natasha L.; Petrova, Tatiana V.; Schulte-Merker, Stefan; Francois, Mathias; Hogan, Benjamin M.

    2016-01-01

    Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by well-studied signaling and transcriptional mechanisms. Less well understood is the ongoing elaboration of vessels to form a network. This involves cell polarisation, coordinated migration, adhesion, mixing, regression and cell shape rearrangements. We identified a zebrafish mutant, lymphatic and cardiac defects 1 (lyc1), with reduced lymphatic vessel development. We found a mutation in polycystic kidney disease 1a to be responsible for the phenotype. PKD1 is the most frequently mutated gene in autosomal dominant polycystic kidney disease (ADPKD). Initial sprouting of lymphatic precursors is normal in lyc1 mutants, but ongoing migration fails. Loss of Pkd1 in mice also has no effect on sprouting of precursors but leads to failed morphogenesis of the subcutaneous lymphatic network. Individual lymphatic endothelial cells display defective polarity, elongation and adherens junctions. This work identifies a highly selective and unexpected role for Pkd1 in lymphatic vessel morphogenesis during development. PMID:24767999

  2. Itching for answers: how histamine relaxes lymphatic vessels.

    PubMed

    Scallan, Joshua P; Davis, Michael J

    2014-10-01

    In the current issue of Microcirculation, studies by Kurtz et al. and Nizamutdinova et al. together provide new evidence supporting a role for histamine as an endothelial-derived molecule that inhibits lymphatic muscle contraction. In particular, Nizamutdinova et al. show that the effects of flow-induced shear stress on lymphatic endothelium are mediated by both nitric oxide and histamine, since only blockade of both prevents contraction strength and frequency from being altered by flow. Separately, Kurtz et al. used confocal microscopy to determine a preferential expression of histamine receptors on the lymphatic endothelium and demonstrated that histamine applied to spontaneously contracting collecting lymphatics inhibits contractions. Previous studies disagreed on whether histamine stimulates or inhibits lymphatic contractions, but also used differing concentrations, species, and preparations. Together these new reports shed light on how histamine acts within the lymphatic vasculature, but also raise important questions about the cell type on which histamine exerts its effects and the signaling pathways involved. This editorial briefly discusses the contribution of each study and its relevance to lymphatic biology.

  3. Online colour training system for dental students: a comprehensive assessment of different training protocols.

    PubMed

    Liu, M; Chen, L; Liu, X; Yang, Y; Zheng, M; Tan, J

    2015-04-01

    The purpose of this study was to evaluate the training effect and to determine the optimal training protocol for a recently developed online colour training system. Seventy students participated in the evaluation. They first completed a baseline test with shade guides (SGT) and the training system (TST), and then trained with one of the three system training methods (Basic colour training for group E1, Vitapan Classical for E2, and Vitapan 3D-Master for E3) or shade guides (group C1) for 4 days. The control group (C2) received no training. The same test was performed after training and they finally completed a questionnaire. The correct matches after training increased in three experimental groups and group C1. Among experimental groups, the greatest improvement of correct matching number was achieved by group E3 (4·00 ± 1·88 in SGT, 4·29 ± 2·73 in TST), followed by E2 (2·29 ± 2·73 in SGT, 3·50 ± 3·03 in TST) and E1 (2·00 ± 2·60 in SGT, 1·93 ± 2·96 in TST). The difference between E3 and E1 was statistically significant (P = 0·036 in SGT, 0·026 in TST). The total average training time was shorter in group E2 (15·39 ± 4·22 min) and E3 (17·63 ± 5·22 min), with no significant difference between them. Subjective evaluations revealed that self-confidence in colour matching were improved greater in group C1 and E3. In conclusion, all tested sections of the system effectively improved students' colour-matching ability. Among system training methods, Vitapan 3D-Master showed the best performance; it enabled greater shade-matching improvement, it saved time and was superior in subjective evaluations.

  4. Autoimmune antibodies in chronic lymphatic leukaemia.

    PubMed

    Lewis, C M; Pegrum, G D

    1978-01-01

    In chronic lymphocytic leukaemia a factor in patients' serum enhances the in vitro viability of the abnormal cells and this has been identified as an antibody. The activity of this factor can be removed by interaction with anti-immunoglobulin and by ammonium sulphate precipitation with a degree of saturation in excess of 46%. Cohn fractionation and chromatography with A-50 Sephadex show that the factor is not a complex but an immunoglobulin. No activity is removed after reaction of sera with 2-mercapto-ethanol and di-thiothreitol. The evidence therefore suggests that a gamma-G immunoglobulin is involved. Concentrated washings from the leukaemic cells behave in exactly the same way as patients' sera and activity is retained in the same fraction during precipitation and purification procedure. The extensive cross-reactivity of the sera suggests a common chronic lymphatic leukaemic antibody and it is considered that an active autoimmune response may be an integral part of the disease.

  5. Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer

    PubMed Central

    Lund, Amanda W.; Medler, Terry R.; Leachman, Sancy A.; Coussens, Lisa M.

    2015-01-01

    Skin is a highly ordered immune organ that coordinates rapid responses to external insult while maintaining self-tolerance. In healthy tissue, lymphatic vessels drain fluid and coordinate local immune responses; however, environmental factors induce lymphatic vessel dysfunction, leading to lymph stasis and perturbed regional immunity. These same environmental factors drive the formation of local malignancies, which are also influenced by local inflammation. Herein, we discuss clinical and experimental evidence supporting the tenet that lymphatic vessels participate in regulation of cutaneous inflammation and immunity, are important contributors to malignancy and potential biomarkers and targets for immunotherapy. PMID:26552413

  6. Laparoscopic excision of a retroperitoneal lymphatic malformation in a newborn.

    PubMed

    Solari, Valeria; Mullassery, Dhanya; Lansdale, Nick; Jesudason, Edwin C

    2011-02-01

    Abdominal lymphatic malformations may be challenging to eradicate. Retroperitoneal lesions may more difficult to resect than mesenteric ones; however, the latter may predispose to intestinal volvulus, leading to calls for their prompt excision. Such lesions identified perinatally may pose particular challenges: in one case, respiratory failure caused by abdominal distension required emergency drainage followed by later laparoscopic excision; laparoscopy has also been used promptly to diagnose and resect neonatal mesenteric lymphatic malformations with their inherent volvulus risk. We illustrate that even if neonatal laparoscopy identifies a retroperitoneal rather than mesenteric lymphatic malformation, curative endosurgical excision remains feasible.

  7. Potential Projective Material on the Rorschach: Comparing Comprehensive System Protocols to Their Modeled R-Optimized Administration Counterparts.

    PubMed

    Pianowski, Giselle; Meyer, Gregory J; Villemor-Amaral, Anna Elisa de

    2016-01-01

    Exner ( 1989 ) and Weiner ( 2003 ) identified 3 types of Rorschach codes that are most likely to contain personally relevant projective material: Distortions, Movement, and Embellishments. We examine how often these types of codes occur in normative data and whether their frequency changes for the 1st, 2nd, 3rd, 4th, or last response to a card. We also examine the impact on these variables of the Rorschach Performance Assessment System's (R-PAS) statistical modeling procedures that convert the distribution of responses (R) from Comprehensive System (CS) administered protocols to match the distribution of R found in protocols obtained using R-optimized administration guidelines. In 2 normative reference databases, the results indicated that about 40% of responses (M = 39.25) have 1 type of code, 15% have 2 types, and 1.5% have all 3 types, with frequencies not changing by response number. In addition, there were no mean differences in the original CS and R-optimized modeled records (M Cohen's d = -0.04 in both databases). When considered alongside findings showing minimal differences between the protocols of people randomly assigned to CS or R-optimized administration, the data suggest R-optimized administration should not alter the extent to which potential projective material is present in a Rorschach protocol. PMID:26963932

  8. Validation protocol of analytical procedures for quantification of drugs in polymeric systems for parenteral administration: dexamethasone phosphate disodium microparticles.

    PubMed

    Martín-Sabroso, Cristina; Tavares-Fernandes, Daniel Filipe; Espada-García, Juan Ignacio; Torres-Suárez, Ana Isabel

    2013-12-15

    In this work a protocol to validate analytical procedures for the quantification of drug substances formulated in polymeric systems that comprise both drug entrapped into the polymeric matrix (assay:content test) and drug released from the systems (assay:dissolution test) is developed. This protocol is applied to the validation two isocratic HPLC analytical procedures for the analysis of dexamethasone phosphate disodium microparticles for parenteral administration. Preparation of authentic samples and artificially "spiked" and "unspiked" samples is described. Specificity (ability to quantify dexamethasone phosphate disodium in presence of constituents of the dissolution medium and other microparticle constituents), linearity, accuracy and precision are evaluated, in the range from 10 to 50 μg mL(-1) in the assay:content test procedure and from 0.25 to 10 μg mL(-1) in the assay:dissolution test procedure. The robustness of the analytical method to extract drug from microparticles is also assessed. The validation protocol developed allows us to conclude that both analytical methods are suitable for their intended purpose, but the lack of proportionality of the assay:dissolution analytical method should be taken into account. The validation protocol designed in this work could be applied to the validation of any analytical procedure for the quantification of drugs formulated in controlled release polymeric microparticles.

  9. Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters.

    PubMed

    Yousefi, Siavash; Qin, Jia; Zhi, Zhongwei; Wang, Ruikang K

    2013-08-01

    Lymphatic vessels are a part of the circulatory system that collect plasma and other substances that have leaked from the capillaries into interstitial fluid (lymph) and transport lymph back to the circulatory system. Since lymph is transparent, lymphatic vessels appear as dark hallow vessel-like regions in optical coherence tomography (OCT) cross sectional images. We propose an automatic method to segment lymphatic vessel lumen from OCT structural cross sections using eigenvalues of Hessian filters. Compared to the existing method based on intensity threshold, Hessian filters are more selective on vessel shape and less sensitive to intensity variations and noise. Using this segmentation technique along with optical micro-angiography allows label-free noninvasive simultaneous visualization of blood and lymphatic vessels in vivo. Lymphatic vessels play an important role in cancer, immune system response, inflammatory disease, wound healing and tissue regeneration. Development of imaging techniques and visualization tools for lymphatic vessels is valuable in understanding the mechanisms and studying therapeutic methods in related disease and tissue response.

  10. Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters

    NASA Astrophysics Data System (ADS)

    Yousefi, Siavash; Qin, Jia; Zhi, Zhongwei; Wang, Ruikang K.

    2013-08-01

    Lymphatic vessels are a part of the circulatory system that collect plasma and other substances that have leaked from the capillaries into interstitial fluid (lymph) and transport lymph back to the circulatory system. Since lymph is transparent, lymphatic vessels appear as dark hallow vessel-like regions in optical coherence tomography (OCT) cross sectional images. We propose an automatic method to segment lymphatic vessel lumen from OCT structural cross sections using eigenvalues of Hessian filters. Compared to the existing method based on intensity threshold, Hessian filters are more selective on vessel shape and less sensitive to intensity variations and noise. Using this segmentation technique along with optical micro-angiography allows label-free noninvasive simultaneous visualization of blood and lymphatic vessels in vivo. Lymphatic vessels play an important role in cancer, immune system response, inflammatory disease, wound healing and tissue regeneration. Development of imaging techniques and visualization tools for lymphatic vessels is valuable in understanding the mechanisms and studying therapeutic methods in related disease and tissue response.

  11. Label-free optical lymphangiography: development of an automatic segmentation method applied to optical coherence tomography to visualize lymphatic vessels using Hessian filters.

    PubMed

    Yousefi, Siavash; Qin, Jia; Zhi, Zhongwei; Wang, Ruikang K

    2013-08-01

    Lymphatic vessels are a part of the circulatory system that collect plasma and other substances that have leaked from the capillaries into interstitial fluid (lymph) and transport lymph back to the circulatory system. Since lymph is transparent, lymphatic vessels appear as dark hallow vessel-like regions in optical coherence tomography (OCT) cross sectional images. We propose an automatic method to segment lymphatic vessel lumen from OCT structural cross sections using eigenvalues of Hessian filters. Compared to the existing method based on intensity threshold, Hessian filters are more selective on vessel shape and less sensitive to intensity variations and noise. Using this segmentation technique along with optical micro-angiography allows label-free noninvasive simultaneous visualization of blood and lymphatic vessels in vivo. Lymphatic vessels play an important role in cancer, immune system response, inflammatory disease, wound healing and tissue regeneration. Development of imaging techniques and visualization tools for lymphatic vessels is valuable in understanding the mechanisms and studying therapeutic methods in related disease and tissue response. PMID:23922124

  12. Intraoperative blood glucose management: impact of a real-time decision support system on adherence to institutional protocol.

    PubMed

    Nair, Bala G; Grunzweig, Katherine; Peterson, Gene N; Horibe, Mayumi; Neradilek, Moni B; Newman, Shu-Fang; Van Norman, Gail; Schwid, Howard A; Hao, Wei; Hirsch, Irl B; Patchen Dellinger, E

    2016-06-01

    Poor perioperative glycemic management can lead to negative surgical outcome. Improved compliance to glucose control protocol could lead to better glucose management. An Anesthesia Information Management System based decision support system-Smart Anesthesia Manager™ (SAM) was used to generate real-time reminders to the anesthesia providers to closely adhere to our institutional glucose management protocol. Compliance to hourly glucose measurements and correct insulin dose adjustments was compared for the baseline period (12 months) without SAM and the intervention period (12 months) with SAM decision support. Additionally, glucose management parameters were compared for the baseline and intervention periods. A total of 1587 cases during baseline and 1997 cases during intervention met the criteria for glucose management (diabetic patients or non-diabetic patients with glucose level >140 mg/dL). Among the intervention cases anesthesia providers chose to use SAM reminders 48.7 % of the time primarily for patients who had diabetes, higher HbA1C or body mass index, while disabling the system for the remaining cases. Compliance to hourly glucose measurement and correct insulin doses increased significantly during the intervention period when compared with the baseline (from 52.6 to 71.2 % and from 13.5 to 24.4 %, respectively). In spite of improved compliance to institutional protocol, the mean glucose levels and other glycemic management parameters did not show significant improvement with SAM reminders. Real-time electronic reminders improved intraoperative compliance to institutional glucose management protocol though glycemic parameters did not improve even when there was greater compliance to the protocol. PMID:26067402

  13. Predictive lymphatic mapping: a method for mapping lymphatic channels in patients with advanced unilateral lymphedema using indocyanine green lymphography.

    PubMed

    Mihara, Makoto; Seki, Yukio; Hara, Hisako; Iida, Takuya; Oka, Aiko; Kikuchi, Kazuki; Narushima, Mitsunaga; Haragi, Makiko; Furniss, Dominic; Hin-Lun, Lawrence; Mitsui, Kito; Murai, Noriyuki; Koshima, Isao

    2014-01-01

    In severe lymphedema, indocyanine green lymphography cannot be used to map lymphatic channels before lymphaticovenular anastomosis (LVA) because linear lymphatics cannot be detected in a severely affected leg. Here, we describe a new method, which we refer to as predictive lymphatic mapping, to predict the location of lymphatics for anastomosis in unilateral lymphedema, thereby improving surgical accuracy and efficiency. The approach consists of marking anatomical landmarks and joining selected landmarks with fixed lines. The distance from these fixed lines to lymphatic channels mapped by indocyanine green lymphography in the unaffected leg is then measured, scaled up based on the difference in circumference between the legs, and transposed to the affected leg. To date, we have used this method in 5 cases of unilateral or asymmetric lymphedema of the lower extremities. In no cases have we failed to find a lymphatic channel suitable for LVA within a 2-cm incision. These results suggest that predictive lymphatic mapping is a useful additional tool for surgeons performing LVA under local anesthesia, which will help to improve the accuracy of incisions and the efficiency of surgery.

  14. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia.

    PubMed

    Lukacs, Viktor; Mathur, Jayanti; Mao, Rong; Bayrak-Toydemir, Pinar; Procter, Melinda; Cahalan, Stuart M; Kim, Helen J; Bandell, Michael; Longo, Nicola; Day, Ronald W; Stevenson, David A; Patapoutian, Ardem; Krock, Bryan L

    2015-01-01

    Piezo1 ion channels are mediators of mechanotransduction in several cell types including the vascular endothelium, renal tubular cells and erythrocytes. Gain-of-function mutations in PIEZO1 cause an autosomal dominant haemolytic anaemia in humans called dehydrated hereditary stomatocytosis. However, the phenotypic consequence of PIEZO1 loss of function in humans has not previously been documented. Here we discover a novel role of this channel in the lymphatic system. Through whole-exome sequencing, we identify biallelic mutations in PIEZO1 (a splicing variant leading to early truncation and a non-synonymous missense variant) in a pair of siblings affected with persistent lymphoedema caused by congenital lymphatic dysplasia. Analysis of patients' erythrocytes as well as studies in a heterologous system reveal greatly attenuated PIEZO1 function in affected alleles. Our results delineate a novel clinical category of PIEZO1-associated hereditary lymphoedema. PMID:26387913

  15. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia

    PubMed Central

    Lukacs, Viktor; Mathur, Jayanti; Mao, Rong; Bayrak-Toydemir, Pinar; Procter, Melinda; Cahalan, Stuart M.; Kim, Helen J.; Bandell, Michael; Longo, Nicola; Day, Ronald W.; Stevenson, David A.; Patapoutian, Ardem; Krock, Bryan L.

    2015-01-01

    Piezo1 ion channels are mediators of mechanotransduction in several cell types including the vascular endothelium, renal tubular cells and erythrocytes. Gain-of-function mutations in PIEZO1 cause an autosomal dominant haemolytic anaemia in humans called dehydrated hereditary stomatocytosis. However, the phenotypic consequence of PIEZO1 loss of function in humans has not previously been documented. Here we discover a novel role of this channel in the lymphatic system. Through whole-exome sequencing, we identify biallelic mutations in PIEZO1 (a splicing variant leading to early truncation and a non-synonymous missense variant) in a pair of siblings affected with persistent lymphoedema caused by congenital lymphatic dysplasia. Analysis of patients' erythrocytes as well as studies in a heterologous system reveal greatly attenuated PIEZO1 function in affected alleles. Our results delineate a novel clinical category of PIEZO1-associated hereditary lymphoedema. PMID:26387913

  16. A Space Based Internet Protocol System for Sub-Orbital Tracking and Control

    NASA Technical Reports Server (NTRS)

    Bull, Barton; Grant, Charles; Morgan, Dwayne; Streich, Ron; Bauer, Frank (Technical Monitor)

    2001-01-01

    Personnel from the Goddard Space Flight Center Wallops Flight Facility (GSFC/WFF) in Virginia are responsible for the overall management of the NASA Sounding Rocket Program. Payloads are generally in support of NASA's Space Science Enterprise's missions and return a variety of scientific data as well as providing a reasonably economical means of conducting engineering tests for instruments and devices used on satellites and other spacecraft. The fifteen types of sounding rockets used by NASA can carry payloads of various weights to altitudes from 50 km to more than 1,300 km. Launch activities are conducted not only from established missile ranges, but also from remote locations worldwide requiring mobile tracking and command equipment to be transported and set up at considerable expense. The advent of low earth orbit (LEO) commercial communications satellites provides an opportunity to dramatically reduce tracking and control costs of launch vehicles and Unpiloted Aerial Vehicles (UAVs) by reducing or eliminating this ground infrastructure. Additionally, since data transmission is by packetized Internet Protocol (IP), data can be received and commands initiated from practically any location. A low cost Commercial Off The Shelf (COTS) system is currently under development for sounding rockets which also has application to UAVs and scientific balloons. Due to relatively low data rate (9600 baud) currently available, the system will first be used to provide GPS data for tracking and vehicle recovery. Range safety requirements for launch vehicles usually stipulate at least two independent tracking sources. Most sounding rockets flown by NASA now carry GPS receivers that output position data via the payload telemetry system to the ground station. The Flight Modem can be configured as a completely separate link thereby eliminating requirement for tracking radar. The system architecture which integrates antennas, GPS receiver, commercial satellite packet data modem, and a

  17. A Space Based Internet Protocol System for Launch Vehicle Tracking and Control

    NASA Technical Reports Server (NTRS)

    Bull, Barton; Grant, Charles; Morgan, Dwayne; Streich, Ron; Bauer, Frank (Technical Monitor)

    2001-01-01

    Personnel from the Goddard Space Flight Center Wallops Flight Facility (GSFC/WFF) in Virginia are responsible for the overall management of the NASA Sounding Rocket and Scientific Balloon Programs. Payloads are generally in support of NASA's Space Science Enterprise's missions and return a variety of scientific data as well as providing a reasonably economical means of conducting engineering tests for instruments and devices used on satellites and other spacecraft. Sounding rockets used by NASA can carry payloads of various weights to altitudes from 50 km to more than 1,300 km. Scientific balloons can carry a payload weighing as much as 3,630 Kg to an altitude of 42 km. Launch activities for both are conducted not only from established ranges, but also from remote locations worldwide requiring mobile tracking and command equipment to be transported and set up at considerable expense. The advent of low earth orbit (LEO) commercial communications satellites provides an opportunity to dramatically reduce tracking and control costs of these launch vehicles and Unpiloted Aerial Vehicles (UAVs) by reducing or eliminating this ground infrastructure. Additionally, since data transmission is by packetized Internet Protocol (IP), data can be received and commands initiated from practically any location. A low cost Commercial Off The Shelf (COTS) system is currently under development for sounding rockets that also has application to UAVs and scientific balloons. Due to relatively low data rate (9600 baud) currently available, the system will first be used to provide GPS data for tracking and vehicle recovery. Range safety requirements for launch vehicles usually stipulate at least two independent tracking sources. Most sounding rockets flown by NASA now carry GP receivers that output position data via the payload telemetry system to the ground station. The Flight Modem can be configured as a completely separate link thereby eliminating the requirement for tracking radar. The

  18. Translymphatic chemotherapy by intrapleural placement of gelatin sponge containing biodegradable Paclitaxel colloids controls lymphatic metastasis in lung cancer.

    PubMed

    Liu, Jiang; Meisner, Dale; Kwong, Elizabeth; Wu, Xiao Y; Johnston, Michael R

    2009-02-01

    As a means of treating lymphatic metastasis from lung cancer, the pharmacokinetics and therapeutic effects of an intrapleural (ipl) implantable drug delivery system consisting of a gelatin sponge impregnated with polylactide-co-glycolide paclitaxel (PLGA-PTX) microspheres were studied. PLGA-PTX with 7% (w/w) drug loading were incorporated into gelatin matrix. The pharmacokinetics were studied in rats with one of the following regimens: (a) Taxol 8 mg/kg by i.v. injection; (b) Taxol 8 mg/kg ipl; (c) PLGA-PTX (100 mg/kg) ipl; (d) sponge containing PLGA-PTX (100 mg/kg) ipl. PTX concentrations in lymph node and plasma were determined by liquid chromatography mass spectrometry, and the area under the curve (AUC) was calculated. Therapeutic efficacy was assessed in an orthotopic lung cancer model with tumor resection 14 days following tumor implantation. Animals were randomized to ipl placement of PLGA-PTX sponge, placebo sponge, or no treatment. Lymph node metastases were examined at 32 d. The results show that the mediastinal lymph node AUC was significantly higher with ipl. placement of PLGA-PTX sponge compared with i.v. and ipl administration of Taxol. This represents 100- to 400-fold increase of lymphatic drug exposure compared with i.v. dosing. Peak plasma concentration was significantly reduced in the PLGA-PTX sponge group compared with i.v. dosing. PLGA-PTX particles were microscopically identified in lymphatic tissue and resulted in an 80% reduction of lymphatic metastasis compared with controls. Translymphatic-targeted drug delivery significantly decreases lymphatic metastasis in an orthotopic lung cancer model. This effect may be attributable to the improved distribution of PTX to the lymphatic system.

  19. The Orphan Adhesion G Protein-coupled Receptor GPR97 Regulates Migration of Lymphatic Endothelial Cells via the Small GTPases RhoA and Cdc42*

    PubMed Central

    Valtcheva, Nadejda; Primorac, Adriana; Jurisic, Giorgia; Hollmén, Maija; Detmar, Michael

    2013-01-01

    The important role of the lymphatic vascular system in pathological conditions such as inflammation and cancer has been increasingly recognized, but its potential as a pharmacological target is poorly exploited. Our study aimed at the identification and molecular characterization of lymphatic-specific G protein-coupled receptors (GPCRs) to assess new targets for pharmacological manipulation of the lymphatic vascular system. We used a TaqMan quantitative RT-PCR-based low density array to determine the GPCR expression profiles of ex vivo isolated intestinal mouse lymphatic (LECs) and blood vascular endothelial cells (BECs). GPR97, an orphan adhesion GPCR of unknown function, was the most highly and specifically expressed GPCR in mouse lymphatic endothelium. Using siRNA silencing, we found that GPR97-deficient primary human LECs displayed increased adhesion and collective cell migration, whereas single cell migration was decreased as compared with nontargeting siRNA-transfected control LECs. Loss of GPR97 shifted the ratio of active Cdc42 and RhoA and initiated cytoskeletal rearrangements, including F-actin redistribution, paxillin and PAK4 phosphorylation, and β1-integrin activation. Our data suggest a possible role of GPR97 in lymphatic remodeling and furthermore provide the first insights into the biological functions of GPR97. PMID:24178298

  20. Morphological and Molecular Characterization of Human Dermal Lymphatic Collectors

    PubMed Central

    Buttler, Kerstin; Ströbel, Philipp; Becker, Jürgen; Aung, Thiha; Felmerer, Gunther; Wilting, Jörg

    2016-01-01

    Millions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE1). We show and confirm differences between initial and collecting lymphatics concerning the markers ESAM1, D2-40 and LYVE-1. Our transmission electron microscopic studies reveal two types of smooth muscle cells (SMCs) in the media of the collectors with dark and light cytoplasm. We observed vasa vasorum in the media of the largest collectors, as well as interstitial Cajal-like cells, which are highly ramified cells with long processes, caveolae, and lacking a basal lamina. They are in close contact with SMCs, which possess multiple caveolae at the contact sites. Immunohistologically we identified such cells with antibodies against vimentin and PDGFRα, but not CD34 and cKIT. With Next Generation Sequencing we searched for highly expressed genes in the media of lymphatic collectors, and found therapeutic targets, suitable for acceleration of lymphatic contractility, such as neuropeptide Y receptors 1, and 5; tachykinin receptors 1, and 2; purinergic receptors P2RX1, and 6, P2RY12, 13, and 14; 5-hydroxytryptamine receptors HTR2B, and 3C; and adrenoceptors α2A,B,C. Our studies represent the first comprehensive characterization of human epifascial lymphatic collectors, as a prerequisite for diagnosis and therapy. PMID:27764183

  1. Substance Abuse Treatment For Adults in the Criminal Justice System. Treatment Improvement Protocol (TIP) Series 44

    ERIC Educational Resources Information Center

    Bartlett, Catalina; Dinsmore, Janet; Gilbert, J. Max; Kornblum, Annette; Latham, Joyce; Oliff, Helen; Paisner, Susan; Sutton, David

    2005-01-01

    This Treatment Improvement Protocol (TIP) provides guidelines for counselors and criminal justice personnel who treat offenders with substance use disorders. TIPs are best-practice guidelines that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts in the…

  2. RESPONSE PROTOCOL TOOLBOX: PLANNING FOR AND RESPONDING TO CONTAMINATION THREATS TO DRINKING WATER SYSTEMS

    EPA Science Inventory

    EPA's Office of Research and Development and Office of Water/Water Security Division have jointly developed a Response Protocol Toolbox (RPTB) to address the complex, multi-faceted challenges of a water utility's planning and response to intentional contamination of drinking wate...

  3. Antiedema effects of Siberian ginseng in humans and its molecular mechanism of lymphatic vascular function in vitro.

    PubMed

    Fukada, Kaedeko; Kajiya-Sawane, Mika; Matsumoto, Yuko; Hasegawa, Tatsuya; Fukaya, Yukitaka; Kajiya, Kentaro

    2016-07-01

    The lymphatic system in the skin plays a major role in tissue fluid homeostasis, in the afferent phase of the immune response, and in tumor metastasis. Although lymphangiogenic factors involved in embryonic development and the metastatic spread of tumor cells have been well studied, little is known about small-molecule compounds that activate lymphatic function, especially under physiological conditions. We hypothesized that the identification of a lymphatic-activating compound could provide a method for improving edema. Here, we show that Siberian ginseng (Eleutherococcus senticosus) and its component eleutheroside E induce phosphorylation of the endothelial-specific receptor Tie2 in vitro. The activation of Tie2 on lymphatic endothelial cells (LECs) is known to stabilize lymphatic vessels, so we examined the effects of Siberian ginseng on LECs. We found that Siberian ginseng induces the migration and cord formation of LECs. Permeability assays demonstrated that it stabilizes LECs by promoting the intercellular localization of vascular endothelial cadherin, which is an endothelium-specific cell-cell adhesion molecule involved in endothelial barrier function, and it induces the phosphorylation of endothelial nitric oxide synthase by LECs. These effects appear to be mediated by the activation of Tie2 in LECs. Finally, we investigated whether the consumption of Siberian ginseng powder improves edema in a 2-way, randomized, crossover study in 50 healthy female volunteers. Edema of the lower limbs was significantly attenuated at 2 and 4hours after ingestion as compared with the control group. Thus, we demonstrate that Siberian ginseng exerts its potent antiedema activity mainly by promoting lymphatic function. PMID:27333960

  4. Quantum dots trace lymphatic drainage from the mouse eye

    NASA Astrophysics Data System (ADS)

    Tam, Alex L. C.; Gupta, Neeru; Zhang, Zhexue; Yücel, Yeni H.

    2011-10-01

    Glaucoma is a leading cause of blindness in the world, often associated with elevated eye pressure. Currently, all glaucoma treatments aim to lower eye pressure by improving fluid exit from the eye. We recently reported the presence of lymphatics in the human eye. The lymphatic circulation is known to drain fluid from organ tissues and, as such, lymphatics may also play a role in draining fluid from the eye. We investigated whether lymphatic drainage from the eye is present in mice by visualizing the trajectory of quantum dots once injected into the eye. Whole-body hyperspectral fluorescence imaging was performed in 17 live mice. In vivo imaging was conducted prior to injection, and 5, 20, 40 and 70 min, and 2, 6 and 24 h after injection. A quantum dot signal was observed in the left neck region at 6 h after tracer injection into the eye. Examination of immunofluorescence-labelled sections using confocal microscopy showed the presence of a quantum dot signal in the left submandibular lymph node. This is the first direct evidence of lymphatic drainage from the mouse eye. The use of quantum dots to image this lymphatic pathway in vivo is a novel tool to stimulate new treatments to reduce eye pressure and prevent blindness from glaucoma.

  5. FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature.

    PubMed

    Sabine, Amélie; Bovay, Esther; Demir, Cansaran Saygili; Kimura, Wataru; Jaquet, Muriel; Agalarov, Yan; Zangger, Nadine; Scallan, Joshua P; Graber, Werner; Gulpinar, Elgin; Kwak, Brenda R; Mäkinen, Taija; Martinez-Corral, Inés; Ortega, Sagrario; Delorenzi, Mauro; Kiefer, Friedemann; Davis, Michael J; Djonov, Valentin; Miura, Naoyuki; Petrova, Tatiana V

    2015-10-01

    Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC2-dependent quiescence was mediated by the Hippo pathway transcriptional coactivator TAZ and, ultimately, led to cell death. In murine models, inducible deletion of Foxc2 within the lymphatic vasculature led to cell-cell junction defects, regression of valves, and focal vascular lumen collapse, which triggered generalized lymphatic vascular dysfunction and lethality. Together, our work describes a fundamental mechanism by which FOXC2 and oscillatory shear stress maintain lymphatic endothelial cell quiescence through intercellular junction and cytoskeleton stabilization and provides an essential link between biomechanical forces and endothelial cell identity that is necessary for postnatal vessel homeostasis. As FOXC2 is mutated in lymphedema-distichiasis syndrome, our data also underscore the role of impaired mechanotransduction in the pathology of this hereditary human disease.

  6. Lymphatic function is required prenatally for lung inflation at birth

    PubMed Central

    Jakus, Zoltán; Gleghorn, Jason P.; Enis, David R.; Sen, Aslihan; Chia, Stephanie; Liu, Xi; Rawnsley, David R.; Yang, Yiqing; Hess, Paul R.; Zou, Zhiying; Yang, Jisheng; Guttentag, Susan H.; Nelson, Celeste M.

    2014-01-01

    Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants. PMID:24733830

  7. FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature

    PubMed Central

    Sabine, Amélie; Bovay, Esther; Demir, Cansaran Saygili; Kimura, Wataru; Jaquet, Muriel; Agalarov, Yan; Zangger, Nadine; Scallan, Joshua P.; Graber, Werner; Gulpinar, Elgin; Kwak, Brenda R.; Mäkinen, Taija; Martinez-Corral, Inés; Ortega, Sagrario; Delorenzi, Mauro; Kiefer, Friedemann; Davis, Michael J.; Djonov, Valentin; Miura, Naoyuki; Petrova, Tatiana V.

    2015-01-01

    Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC2-dependent quiescence was mediated by the Hippo pathway transcriptional coactivator TAZ and, ultimately, led to cell death. In murine models, inducible deletion of Foxc2 within the lymphatic vasculature led to cell-cell junction defects, regression of valves, and focal vascular lumen collapse, which triggered generalized lymphatic vascular dysfunction and lethality. Together, our work describes a fundamental mechanism by which FOXC2 and oscillatory shear stress maintain lymphatic endothelial cell quiescence through intercellular junction and cytoskeleton stabilization and provides an essential link between biomechanical forces and endothelial cell identity that is necessary for postnatal vessel homeostasis. As FOXC2 is mutated in lymphedema-distichiasis syndrome, our data also underscore the role of impaired mechanotransduction in the pathology of this hereditary human disease. PMID:26389677

  8. Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

    PubMed

    Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

    2016-04-01

    The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

  9. Mechanotransduction activates canonical Wnt/β-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves.

    PubMed

    Cha, Boksik; Geng, Xin; Mahamud, Md Riaj; Fu, Jianxin; Mukherjee, Anish; Kim, Yeunhee; Jho, Eek-Hoon; Kim, Tae Hoon; Kahn, Mark L; Xia, Lijun; Dixon, J Brandon; Chen, Hong; Srinivasan, R Sathish

    2016-06-15

    Lymphatic vasculature regulates fluid homeostasis by returning interstitial fluid to blood circulation. Lymphatic endothelial cells (LECs) are the building blocks of the entire lymphatic vasculature. LECs originate as a homogeneous population of cells predominantly from the embryonic veins and undergo stepwise morphogenesis to become the lymphatic capillaries, collecting vessels or valves. The molecular mechanisms underlying the morphogenesis of the lymphatic vasculature remain to be fully understood. Here we show that canonical Wnt/β-catenin signaling is necessary for lymphatic vascular morphogenesis. Lymphatic vascular-specific ablation of β-catenin in mice prevents the formation of lymphatic and lymphovenous valves. Additionally, lymphatic vessel patterning is defective in these mice, with abnormal recruitment of mural cells. We found that oscillatory shear stress (OSS), which promotes lymphatic vessel maturation, triggers Wnt/β-catenin signaling in LECs. In turn, Wnt/β-catenin signaling controls the expression of several molecules, including the lymphedema-associated transcription factor FOXC2. Importantly, FOXC2 completely rescues the lymphatic vessel patterning defects in mice lacking β-catenin. Thus, our work reveals that mechanical stimulation is a critical regulator of lymphatic vascular development via activation of Wnt/β-catenin signaling and, in turn, FOXC2.

  10. Mechanotransduction activates canonical Wnt/β-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves

    PubMed Central

    Cha, Boksik; Geng, Xin; Mahamud, Md. Riaj; Fu, Jianxin; Mukherjee, Anish; Kim, Yeunhee; Jho, Eek-hoon; Kim, Tae Hoon; Kahn, Mark L.; Xia, Lijun; Dixon, J. Brandon; Chen, Hong; Srinivasan, R. Sathish

    2016-01-01

    Lymphatic vasculature regulates fluid homeostasis by returning interstitial fluid to blood circulation. Lymphatic endothelial cells (LECs) are the building blocks of the entire lymphatic vasculature. LECs originate as a homogeneous population of cells predominantly from the embryonic veins and undergo stepwise morphogenesis to become the lymphatic capillaries, collecting vessels or valves. The molecular mechanisms underlying the morphogenesis of the lymphatic vasculature remain to be fully understood. Here we show that canonical Wnt/β-catenin signaling is necessary for lymphatic vascular morphogenesis. Lymphatic vascular-specific ablation of β-catenin in mice prevents the formation of lymphatic and lymphovenous valves. Additionally, lymphatic vessel patterning is defective in these mice, with abnormal recruitment of mural cells. We found that oscillatory shear stress (OSS), which promotes lymphatic vessel maturation, triggers Wnt/β-catenin signaling in LECs. In turn, Wnt/β-catenin signaling controls the expression of several molecules, including the lymphedema-associated transcription factor FOXC2. Importantly, FOXC2 completely rescues the lymphatic vessel patterning defects in mice lacking β-catenin. Thus, our work reveals that mechanical stimulation is a critical regulator of lymphatic vascular development via activation of Wnt/β-catenin signaling and, in turn, FOXC2. PMID:27313318

  11. Manual lymphatic drainage and therapeutic ultrasound in liposuction and lipoabdominoplasty post-operative period

    PubMed Central

    Masson, Igor F. B.; de Oliveira, Bruna D. A.; Machado, Aline Fernanda Perez; Farcic, Thiago Saikali; Júnior, Ivaldo Esteves; Baldan, Cristiano Schiavinato

    2014-01-01

    Background: Physiotherapy in the plastic surgery post-operative (PO) is essential to provide means for an adequate and fast recovery as it restores function through the use of physiotherapeutic procedures. Aim: The aim of the following study is to verify the effects of the association between the manual lymphatic drainage and the therapeutic ultrasound on pain, oedema and the tissue fibrosis in liposuction and lipoabdominoplasty PO. Design: This is a clinical trial prospective. Materials and Methods: Eighteen women aged between 18 and 60 years participated in this study, in the late PO period following lipoabdominoplasty or liposuction in the abdomen, flanks and lower trunk, which showed tissue fibrosis of the flanks and abdomen regions. They were divided into two groups: Liposuction group and lipoabdominoplasty group. A total of twelve sessions of therapeutic ultrasound followed by the manual lymphatic drainage were performed. The patients were assessed with regard to pain, oedema and tissue fibrosis in different moments: Initial assessment, during assessment and final assessment through the application of the protocol of evaluation of cysts fibrosis levels. Statistical Analysis: The test of equality for two proportions and the confidence interval test for mean to evaluate the distribution of variables. The significance level adopted for statistical tests was 5% (P < 0.05). Results: There was a statistically significant reduction of pain, swelling and tissue fibrosis in both groups. Conclusion: the association between manual lymphatic drainage and the therapeutic ultrasound reduced the swelling and the tissue fibrosis and made pain disappear in liposuction and lipoabdominoplasty PO period. PMID:24987208

  12. ZEA-TDMA: design and system level implementation of a TDMA protocol for anonymous wireless networks

    NASA Astrophysics Data System (ADS)

    Banerjee, Debasmit; Dong, Bo; Biswas, Subir

    2013-05-01

    Wireless sensor network used in military applications may be deployed in hostile environments, where privacy and security is of primary concern. This can lead to the formation of a trust-based sub-network among mutually-trusting nodes. However, designing a TDMA MAC protocol is very challenging in situations where such multiple sub-networks coexist, since TDMA protocols require node identity information for slot assignments. This paper introduces a novel distributed TDMA MAC protocol, ZEA-TDMA (Zero Exposure Anonymous TDMA), for anonymous wireless networks. ZEA-TDMA achieves slot allocation with strict anonymity constraints, i.e. without nodes having to exchange any identity revealing information. By using just the relative time of arrival of packets and a novel technique of wireless collision-detection and resolution for fixed packetsizes, ZEA-TDMA is able to achieve MAC slot-allocation which is described as follows. Initially, a newly joined node listens to its one-hop neighborhood channel usage and creates a slot allocation table based on its own relative time, and finally, selects a slot that is collision free within its one-hop neighborhood. The selected slot can however cause hidden collisions with a two-hop neighbor of the node. These collisions are resolved by a common neighbor of the colliding nodes, which first detects the collision, and then resolve them using an interrupt packet. ZEA-TDMA provides the following features: a) it is a TDMA protocol ideally suited for highly secure or strictly anonymous environments b) it can be used in heterogeneous environments where devices use different packet structures c) it does not require network time-synchronization, and d) it is insensitive to channel errors. We have implemented ZEA-TDMA on the MICA2 hardware platform running TinyOS and evaluated the protocol functionality and performance on a MICA2 test-bed.

  13. Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging.

    PubMed

    Vergara, Irene; Castillo, Erick Y; Romero-Piña, Mario E; Torres-Viquez, Itzel; Paniagua, Dayanira; Boyer, Leslie V; Alagón, Alejandro; Medina, Luis Alberto

    2016-04-01

    The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx). The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA) and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%-78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50) and PLA₂ activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-(67)Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with (67)Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-(67)Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-(67)Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming. PMID:27023607

  14. Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging

    PubMed Central

    Vergara, Irene; Castillo, Erick Y.; Romero-Piña, Mario E.; Torres-Viquez, Itzel; Paniagua, Dayanira; Boyer, Leslie V.; Alagón, Alejandro; Medina, Luis Alberto

    2016-01-01

    The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx). The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA) and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%–78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50) and PLA2 activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-67Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with 67Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-67Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-67Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming. PMID:27023607

  15. Quantum cryptography: Theoretical protocols for quantum key distribution and tests of selected commercial QKD systems in commercial fiber networks

    NASA Astrophysics Data System (ADS)

    Jacak, Monika; Jacak, Janusz; Jóźwiak, Piotr; Jóźwiak, Ireneusz

    2016-06-01

    The overview of the current status of quantum cryptography is given in regard to quantum key distribution (QKD) protocols, implemented both on nonentangled and entangled flying qubits. Two commercial R&D platforms of QKD systems are described (the Clavis II platform by idQuantique implemented on nonentangled photons and the EPR S405 Quelle platform by AIT based on entangled photons) and tested for feasibility of their usage in commercial TELECOM fiber metropolitan networks. The comparison of systems efficiency, stability and resistivity against noise and hacker attacks is given with some suggestion toward system improvement, along with assessment of two models of QKD.

  16. Reliable broadcast protocols

    NASA Technical Reports Server (NTRS)

    Joseph, T. A.; Birman, Kenneth P.

    1989-01-01

    A number of broadcast protocols that are reliable subject to a variety of ordering and delivery guarantees are considered. Developing applications that are distributed over a number of sites and/or must tolerate the failures of some of them becomes a considerably simpler task when such protocols are available for communication. Without such protocols the kinds of distributed applications that can reasonably be built will have a very limited scope. As the trend towards distribution and decentralization continues, it will not be surprising if reliable broadcast protocols have the same role in distributed operating systems of the future that message passing mechanisms have in the operating systems of today. On the other hand, the problems of engineering such a system remain large. For example, deciding which protocol is the most appropriate to use in a certain situation or how to balance the latency-communication-storage costs is not an easy question.

  17. The Memory System Engaged During Acquisition Determines the Effectiveness of Different Extinction Protocols.

    PubMed

    Goodman, Jarid; Packard, Mark G

    2015-01-01

    Previous research indicates that extinction of rodent maze behavior may occur without explicit performance of the previously acquired response. In latent extinction, confining an animal to a previously rewarded goal location without reinforcement is typically sufficient to produce extinction of maze learning. However, previous studies have not determined whether latent extinction may be successfully employed to extinguish all types of memory acquired in the maze, or whether only specific types of memory may be vulnerable to latent extinction. The present study examined whether latent extinction may be effective across two plus-maze tasks that depend on anatomically distinct neural systems. Adult male Long-Evans rats were trained in a hippocampus-dependent place learning task (Experiment 1), in which animals were trained to approach a consistent spatial location for food reward. A separate group of rats were trained in a dorsolateral striatum-dependent response learning task (Experiment 2), in which animals were trained to make a consistent egocentric body-turn response for food reward. Following training, animals received response extinction or latent extinction. For response extinction, animals were given the opportunity to execute the original running approach response toward the empty food cup. For latent extinction, animals were confined to the original goal locations with the empty food cup, thus preventing them from making the original running approach response. Results indicate that, relative to no extinction, latent extinction was effective at extinguishing memory in the place learning task, but remained ineffective in the response learning task. In contrast, typical response extinction remained very effective at extinguishing memory in both place and response learning tasks. The present findings confirm that extinction of maze learning may occur with or without overt performance of the previously acquired response, but that the effectiveness of latent

  18. The Memory System Engaged During Acquisition Determines the Effectiveness of Different Extinction Protocols

    PubMed Central

    Goodman, Jarid; Packard, Mark G.

    2015-01-01

    Previous research indicates that extinction of rodent maze behavior may occur without explicit performance of the previously acquired response. In latent extinction, confining an animal to a previously rewarded goal location without reinforcement is typically sufficient to produce extinction of maze learning. However, previous studies have not determined whether latent extinction may be successfully employed to extinguish all types of memory acquired in the maze, or whether only specific types of memory may be vulnerable to latent extinction. The present study examined whether latent extinction may be effective across two plus-maze tasks that depend on anatomically distinct neural systems. Adult male Long-Evans rats were trained in a hippocampus-dependent place learning task (Experiment 1), in which animals were trained to approach a consistent spatial location for food reward. A separate group of rats were trained in a dorsolateral striatum-dependent response learning task (Experiment 2), in which animals were trained to make a consistent egocentric body-turn response for food reward. Following training, animals received response extinction or latent extinction. For response extinction, animals were given the opportunity to execute the original running approach response toward the empty food cup. For latent extinction, animals were confined to the original goal locations with the empty food cup, thus preventing them from making the original running approach response. Results indicate that, relative to no extinction, latent extinction was effective at extinguishing memory in the place learning task, but remained ineffective in the response learning task. In contrast, typical response extinction remained very effective at extinguishing memory in both place and response learning tasks. The present findings confirm that extinction of maze learning may occur with or without overt performance of the previously acquired response, but that the effectiveness of latent

  19. Computer-assisted machine-to-human protocols for authentication of a RAM-based embedded system

    NASA Astrophysics Data System (ADS)

    Idrissa, Abdourhamane; Aubert, Alain; Fournel, Thierry

    2012-06-01

    Mobile readers used for optical identification of manufactured products can be tampered in different ways: with hardware Trojan or by powering up with fake configuration data. How a human verifier can authenticate the reader to be handled for goods verification? In this paper, two cryptographic protocols are proposed to achieve the verification of a RAM-based system through a trusted auxiliary machine. Such a system is assumed to be composed of a RAM memory and a secure block (in practice a FPGA or a configurable microcontroller). The system is connected to an input/output interface and contains a Non Volatile Memory where the configuration data are stored. Here, except the secure block, all the blocks are exposed to attacks. At the registration stage of the first protocol, the MAC of both the secret and the configuration data, denoted M0 is computed by the mobile device without saving it then transmitted to the user in a secure environment. At the verification stage, the reader which is challenged with nonces sendsMACs / HMACs of both nonces and MAC M0 (to be recomputed), keyed with the secret. These responses are verified by the user through a trusted auxiliary MAC computer unit. Here the verifier does not need to tract a (long) list of challenge / response pairs. This makes the protocol tractable for a human verifier as its participation in the authentication process is increased. In counterpart the secret has to be shared with the auxiliary unit. This constraint is relaxed in a second protocol directly derived from Fiat-Shamir's scheme.

  20. Protocols for clinical tests on Parkinson disease affected persons and comparison with healthy people with a quantitative method of a new system Daphne.

    PubMed

    Rovetta, A

    2002-01-01

    This paper deals with Daphne, a portable equipment for the evaluation of the state of health in Parkinson disease. The protocols have been developed, according to the design, to the characteristics, to the performances of the system. Tests on patients and healthy persons are presented, as application of protocols.

  1. Tie1 is required for lymphatic valve and collecting vessel development

    PubMed Central

    Qu, Xianghu; Zhou, Bin; Baldwin, H. Scott

    2015-01-01

    Tie1 is a receptor tyrosine kinase with broad expression in embryonic endothelium. Reduction of Tie1 levels in mouse embryos with a hypomorphic Tie1 allele resulted in abnormal lymphatic patterning and architecture, decreased lymphatic draining efficiency, and ultimately, embryonic demise. Here we report that Tie1 is present uniformly throughout the lymphatics and from late embryonic/early postnatal stages, becomes more restricted to lymphatic valve regions. To investigate later events of lymphatic development, we employed Cre-loxP recombination utilizing a floxed Tie1 allele and an Nfatc1Cre line, to provide loxP excision predominantly in lymphatic endothelium and developing valves. Interestingly, unlike the early prenatal defects previously described by ubiquitous endothelial deletion, excision of Tie1 with Nfatc1Cre resulted in abnormal lymphatic defects in postnatal mice and was characterized by agenesis of lymphatic valves and a deficiency of collecting lymphatic vessels. Attenuation of Tie1 signaling in lymphatic endothelium prevented initiation of lymphatic valve specification by Prox1 high expression lymphatic endothelial cells that is associated with the onset of turbulent flow in the lymphatic circulation. Our findings reveal a fundamental role for Tie signaling during lymphatic vessel remodeling and valve morphogenesis and implicate it as a candidate gene involved in primary lymphedema. PMID:25576926

  2. Mechanisms of VIP-induced inhibition of the lymphatic vessel pump.

    PubMed

    von der Weid, Pierre-Yves; Rehal, Sonia; Dyrda, Peter; Lee, Stewart; Mathias, Ryan; Rahman, Mozibur; Roizes, Simon; Imtiaz, Mohammad S

    2012-06-01

    Lymphatic vessels serve as a route by which interstitial fluid, protein and other macromolecules are returned to the blood circulation and immune cells and antigens gain access to lymph nodes. Lymph flow is an active process promoted by rhythmical contraction-relaxation events occurring in the collecting lymphatic vessels. This lymphatic pumping is an intrinsic property of the lymphatic muscles in the vessel wall and consequent to action potentials. Compromised lymphatic pumping may affect lymph and immune cell transport, an action which could be particularly detrimental during inflammation. Importantly, many inflammatory mediators alter lymphatic pumping. Vasoactive intestinal peptide (VIP) is a neuro- and immuno-modulator thought to be released by nerve terminals and immune cells in close proximity to lymphatic vessels. We demonstrated the presence of the peptide in lymphatic vessels and in the lymph and examined the effects of VIP on mesenteric collecting lymphatic vessels of the guinea pig using pharmacological bioassays, intracellular microelectrode electrophysiology, immunofluorescence and quantitative real-time PCR. We showed that VIP alters lymphatic pumping by decreasing the frequency of lymphatic contractions and hyperpolarizing the lymphatic muscle membrane potential in a concentration-dependent manner. Our data further suggest that these effects are mainly mediated by stimulation of the VIP receptor VPAC2 located on the lymphatic muscle and the downstream involvement of protein kinase A (PKA) and ATP-sensitive K⁺ (KATP) channels. Inhibition of lymphatic pumping by VIP may compromise lymph drainage, oedema resolution and immune cell trafficking to the draining lymph nodes.

  3. Tie1 is required for lymphatic valve and collecting vessel development.

    PubMed

    Qu, Xianghu; Zhou, Bin; Scott Baldwin, H

    2015-03-01

    Tie1 is a receptor tyrosine kinase with broad expression in embryonic endothelium. Reduction of Tie1 levels in mouse embryos with a hypomorphic Tie1 allele resulted in abnormal lymphatic patterning and architecture, decreased lymphatic draining efficiency, and ultimately, embryonic demise. Here we report that Tie1 is present uniformly throughout the lymphatics and from late embryonic/early postnatal stages, becomes more restricted to lymphatic valve regions. To investigate later events of lymphatic development, we employed Cre-loxP recombination utilizing a floxed Tie1 allele and an Nfatc1Cre line, to provide loxP excision predominantly in lymphatic endothelium and developing valves. Interestingly, unlike the early prenatal defects previously described by ubiquitous endothelial deletion, excision of Tie1 with Nfatc1Cre resulted in abnormal lymphatic defects in postnatal mice and was characterized by agenesis of lymphatic valves and a deficiency of collecting lymphatic vessels. Attenuation of Tie1 signaling in lymphatic endothelium prevented initiation of lymphatic valve specification by Prox1 high expression lymphatic endothelial cells that is associated with the onset of turbulent flow in the lymphatic circulation. Our findings reveal a fundamental role for Tie1 signaling during lymphatic vessel remodeling and valve morphogenesis and implicate it as a candidate gene involved in primary lymphedema.

  4. Localization and proliferation of lymphatic vessels in the tympanic membrane in normal state and regeneration

    SciTech Connect

    Miyashita, Takenori; Burford, James L.; Hong, Young-Kwon; Gevorgyan, Haykanush; Lam, Lisa; Mori, Nozomu; Peti-Peterdi, Janos

    2013-10-25

    Highlights: •We newly developed the whole-mount imaging method of the tympanic membrane. •Lymphatic vessel loops were localized around the malleus handle and annulus tympanicus. •In regeneration, abundant lymphatic vessels were observed in the pars tensa. •Site-specific lymphatic vessels may play an important role in the tympanic membrane. -- Abstract: We clarified the localization of lymphatic vessels in the tympanic membrane and proliferation of lymphatic vessels during regeneration after perforation of the tympanic membrane by using whole-mount imaging of the tympanic membrane of Prox1 GFP mice. In the pars tensa, lymphatic vessel loops surrounded the malleus handle and annulus tympanicus. Apart from these locations, lymphatic vessel loops were not observed in the pars tensa in the normal tympanic membrane. Lymphatic vessel loops surrounding the malleus handle were connected to the lymphatic vessel loops in the pars flaccida and around the tensor tympani muscle. Many lymphatic vessel loops were detected in the pars flaccida. After perforation of the tympanic membrane, abundant lymphatic regeneration was observed in the pars tensa, and these regenerated lymphatic vessels extended from the lymphatic vessels surrounding the malleus at day 7. These results suggest that site-specific lymphatic vessels play an important role in the tympanic membrane.

  5. Biplane interventional pediatric system with cone-beam CT: dose and image quality characterization for the default protocols.

    PubMed

    Corredoira, Eva; Vañó, Eliseo; Alejo, Luis; Ubeda, Carlos; Gutiérrez-Larraya, Federico; Garayoa, Julia

    2016-07-08

    The aim of this study was to assess image quality and radiation dose of a biplane angiographic system with cone-beam CT (CBCT) capability tuned for pediatric cardiac procedures. The results of this study can be used to explore dose reduction techniques. For pulsed fluoroscopy and cine modes, polymethyl methacrylate phantoms of various thicknesses and a Leeds TOR 18-FG test object were employed. Various fields of view (FOV) were selected. For CBCT, the study employed head and body dose phantoms, Catphan 504, and an anthropomorphic cardiology phantom. The study also compared two 3D rotational angiography protocols. The entrance surface air kerma per frame increases by a factor of 3-12 when comparing cine and fluoroscopy frames. The biggest difference in the signal-to- noise ratio between fluoroscopy and cine modes occurs at FOV 32 cm because fluoroscopy is acquired at a 1440 × 1440 pixel matrix size and in unbinned mode, whereas cine is acquired at 720 × 720 pixels and in binned mode. The high-contrast spatial resolution of cine is better than that of fluoroscopy, except for FOV 32 cm, because fluoroscopy mode with 32 cm FOV is unbinned. Acquiring CBCT series with a 16 cm head phantom using the standard dose protocol results in a threefold dose increase compared with the low-dose protocol. Although the amount of noise present in the images acquired with the low-dose protocol is much higher than that obtained with the standard mode, the images present better spatial resolution. A 1 mm diameter rod with 250 Hounsfield units can be distinguished in reconstructed images with an 8 mm slice width. Pediatric-specific protocols provide lower doses while maintaining sufficient image quality. The system offers a novel 3D imaging mode. The acquisition of CBCT images results in increased doses administered to the patients, but also provides further diagnostic information contained in the volumetric images. The assessed CBCT protocols provide images that are noisy, but with

  6. Biplane interventional pediatric system with cone-beam CT: dose and image quality characterization for the default protocols.

    PubMed

    Corredoira, Eva; Vañó, Eliseo; Alejo, Luis; Ubeda, Carlos; Gutiérrez-Larraya, Federico; Garayoa, Julia

    2016-01-01

    The aim of this study was to assess image quality and radiation dose of a biplane angiographic system with cone-beam CT (CBCT) capability tuned for pediatric cardiac procedures. The results of this study can be used to explore dose reduction techniques. For pulsed fluoroscopy and cine modes, polymethyl methacrylate phantoms of various thicknesses and a Leeds TOR 18-FG test object were employed. Various fields of view (FOV) were selected. For CBCT, the study employed head and body dose phantoms, Catphan 504, and an anthropomorphic cardiology phantom. The study also compared two 3D rotational angiography protocols. The entrance surface air kerma per frame increases by a factor of 3-12 when comparing cine and fluoroscopy frames. The biggest difference in the signal-to- noise ratio between fluoroscopy and cine modes occurs at FOV 32 cm because fluoroscopy is acquired at a 1440 × 1440 pixel matrix size and in unbinned mode, whereas cine is acquired at 720 × 720 pixels and in binned mode. The high-contrast spatial resolution of cine is better than that of fluoroscopy, except for FOV 32 cm, because fluoroscopy mode with 32 cm FOV is unbinned. Acquiring CBCT series with a 16 cm head phantom using the standard dose protocol results in a threefold dose increase compared with the low-dose protocol. Although the amount of noise present in the images acquired with the low-dose protocol is much higher than that obtained with the standard mode, the images present better spatial resolution. A 1 mm diameter rod with 250 Hounsfield units can be distinguished in reconstructed images with an 8 mm slice width. Pediatric-specific protocols provide lower doses while maintaining sufficient image quality. The system offers a novel 3D imaging mode. The acquisition of CBCT images results in increased doses administered to the patients, but also provides further diagnostic information contained in the volumetric images. The assessed CBCT protocols provide images that are noisy, but with

  7. Lymphatic filariasis: Treatment, control and elimination.

    PubMed

    Ottesen, Eric A

    2006-01-01

    Lymphatic filariasis (LF) is a disease not just treatable or controllable; it is a disease that can be eliminated. Indeed, LF is currently the target of a major global initiative to do just that; a few visionaries of the past 50 years did hypothesize that LF elimination was feasible. However, for most of the scientific and global health communities, the elimination of such a broadly disseminated, mosquito-borne disease has seemed highly unlikely. During the past decade, however, both the treatment strategies and the control strategies for LF have undergone profound paradigm shifts-all because of a rapid increase in knowledge and understanding of LF that derived directly from a series of remarkable achievements by the scientific and medical research communities. As a result, a public health dimension with a focus on affected populations, now supplements the earlier, predominantly patient-oriented clinical approach to LF. The early uncertainties, then the essential steps leading to this change in outlook are outlined below, followed by descriptions of the new strategy for LF elimination, the Global Programme created to attain this goal and the successes achieved to date.

  8. An architecture and protocol for communications satellite constellations regarded as multi-agent systems

    NASA Technical Reports Server (NTRS)

    Lindley, Craig A.

    1995-01-01

    This paper presents an architecture for satellites regarded as intercommunicating agents. The architecture is based upon a postmodern paradigm of artificial intelligence in which represented knowledge is regarded as text, inference procedures are regarded as social discourse and decision making conventions and the semantics of representations are grounded in the situated behaviour and activity of agents. A particular protocol is described for agent participation in distributed search and retrieval operations conducted as joint activities.

  9. [The prognostic value of evaluation of minimal residual disease using technique of flow cytofluorometry during application of therapy of chronic lymphatic leukemia].

    PubMed

    Kisilichina, D G; Lugovskaia, C A; Naumova, E V; Pochtar', M E; Nikitin, E A; Dolgov, V V

    2014-11-01

    The achievement of molecular remission is associated with increasing of survival of patients with chronic lymphatic leukemia. The important direction of research is seeking of parameters applicable to forecast of response to therapy. The purpose of the study was evaluating prognostic significance of indicator of minimal residual disease detected by technique of flow cytofluorometry of peripheral blood of patients with chronic lymphatic leukemia during therapy application. The sampling included 112 patients with chronic lymphatic leukemia aged from 43 to 82 years. All patients were given treatment consisted of 6 courses of immune chemotherapy combined with fludarabine with cyclophosphan and rituximab. The samples of peripheral blood were analyzed after 3 courses during therapy and after 6 courses after completion of treatment. The cells were analyzed using 5 and 6 color flow cytometry for the purpose of detection of immune phenotype associated with chronic lymphatic leukemia. The evaluation of minimal residual disease was implemented according international standardized protocol (Rawstron A.C. et al. 2007; 21 (5): 956-64). The minimal residual disease negative status was reached in 87 (78%) patients during evaluation of response after 6th course of treatment. The implementation of indicators of residual disease after 3 courses with fludarabine, cyclophosphan and rituximab permitted to sort out two groups of patients with chronic lymphatic leukemia i.e 67 patients with low (< 0.12%) level of minimal residual disease and 45 patients with high (> 0.12%) level of tumor cells. The rate of molecular remission after completion of treatment. in the given groups consisted 100% and 44% correspondingly. The study demonstrates possibilities of early immune phenotype evaluation of minimal residual disease to forecast differences in response to treatment in patients with chronic lymphatic leukemia that makes it possible to avoid undesirable toxicity of therapy or to choose method

  10. The lymphatic phenotype in Turner syndrome: an evaluation of nineteen patients and literature review.

    PubMed

    Atton, Giles; Gordon, Kristiana; Brice, Glen; Keeley, Vaughan; Riches, Katie; Ostergaard, Pia; Mortimer, Peter; Mansour, Sahar

    2015-12-01

    Turner syndrome is a complex disorder caused by an absent or abnormal sex chromosome. It affects 1/2000-1/3000 live-born females. Congenital lymphoedema of the hands, feet and neck region (present in over 60% of patients) is a common and key diagnostic indicator, although is poorly described in the literature. The aim of this study was to analyse the medical records of a cohort of 19 Turner syndrome patients attending three specialist primary lymphoedema clinics, to elucidate the key features of the lymphatic phenotype and provide vital insights into its diagnosis, natural history and management. The majority of patients presented at birth with four-limb lymphoedema, which often resolved in early childhood, but frequently recurred in later life. The swelling was confined to the legs and hands with no facial or genital swelling. There was only one case of suspected systemic involvement (intestinal lymphangiectasia). The lymphoscintigraphy results suggest that the lymphatic phenotype of Turner syndrome may be due to a failure of initial lymphatic (capillary) function.

  11. Low-cost microcontroller platform for studying lymphatic biomechanics in vitro

    PubMed Central

    Kornuta, Jeffrey A.; Nipper, Matthew E.; Dixon, J. Brandon

    2012-01-01

    The pumping innate to collecting lymphatic vessels routinely exposes the endothelium to oscillatory wall shear stress and other dynamic forces. However, studying the mechanical sensitivity of the lymphatic endothelium remains a difficult task due to limitations of commercial or custom systems to apply a variety of time-varying stresses in vitro. Current biomechanical in vitro testing devices are very expensive, limited in capability, or highly complex; rendering them largely inaccessible to the endothelial cell biology community. To address these short-comings, the authors propose a reliable, low-cost platform for augmenting the capabilities of commercially available pumps to produce a wide variety of flow rate waveforms. In particular, the Arduino Uno, a microcontroller development board, is used to provide open-loop control of a digital peristaltic pump using precisely-timed serial commands. In addition, the flexibility of this platform is further demonstrated through its support of a custom-built cell-straining device capable of producing oscillatory strains with varying amplitudes and frequencies. Hence, this microcontroller development board is shown to be an inexpensive, precise, and easy-to-use tool for supplementing in vitro assays to quantify the effects of biomechanical forces on lymphatic endothelial cells. PMID:23178036

  12. Low-cost microcontroller platform for studying lymphatic biomechanics in vitro.

    PubMed

    Kornuta, Jeffrey A; Nipper, Matthew E; Dixon, J Brandon

    2013-01-01

    The pumping innate to collecting lymphatic vessels routinely exposes the endothelium to oscillatory wall shear stress and other dynamic forces. However, studying the mechanical sensitivity of the lymphatic endothelium remains a difficult task due to limitations of commercial or custom systems to apply a variety of time-varying stresses in vitro. Current biomechanical in vitro testing devices are very expensive, limited in capability, or highly complex; rendering them largely inaccessible to the endothelial cell biology community. To address these shortcomings, the authors propose a reliable, low-cost platform for augmenting the capabilities of commercially available pumps to produce a wide variety of flow rate waveforms. In particular, the Arduino Uno, a microcontroller development board, is used to provide open-loop control of a digital peristaltic pump using precisely timed serial commands. In addition, the flexibility of this platform is further demonstrated through its support of a custom-built cell-straining device capable of producing oscillatory strains with varying amplitudes and frequencies. Hence, this microcontroller development board is shown to be an inexpensive, precise, and easy-to-use tool for supplementing in vitro assays to quantify the effects of biomechanical forces on lymphatic endothelial cells.

  13. The lymphatic phenotype in Turner Syndrome: an evaluation of nineteen patients and literature review

    PubMed Central

    Atton, Giles; Gordon, Kristiana; Brice, Glen; Keeley, Vaughan; Riches, Katie; Ostergaard, Pia; Mortimer, Peter; Mansour, Sahar

    2015-01-01

    Turner Syndrome is a complex disorder caused by an absent or abnormal sex chromosome. It affects 1/2000-1/3000 live-born females. Congenital lymphoedema of the hands, feet and neck region (present in over 60% of patients) is a common and key diagnostic indicator, though is poorly described in the literature. The aim of this study was to analyse the medical records of a cohort of 19 Turner Syndrome patients attending three specialist primary lymphoedema clinics, to elucidate the key features of the lymphatic phenotype and provide vital insights into its diagnosis, natural history and management. The majority of patients presented at birth with 4-limb lymphoedema, which often resolved in early childhood, but frequently recurred in later life. The swelling was confined to the legs and hands with no facial or genital swelling. There was only one case of suspected systemic involvement (intestinal lymphangiectasia). The lymphoscintigraphy results suggest that the lymphatic phenotype of Turner Syndrome may be due to a failure of initial lymphatic (capillary) function. PMID:25804399

  14. An in vitro model of the tumor-lymphatic microenvironment with simultaneous transendothelial and luminal flows reveals mechanisms of flow enhanced invasion.

    PubMed

    Pisano, M; Triacca, V; Barbee, K A; Swartz, M A

    2015-05-01

    The most common cancers, including breast and skin, disseminate initially through the lymphatic system, yet the mechanisms by which tumor cells home towards, enter and interact with the lymphatic endothelium remain poorly understood. Transmural and luminal flows are important biophysical cues of the lymphatic microenvironment that can affect adhesion molecules, growth factors and chemokine expression as well as matrix remodeling, among others. Although microfluidic models are suitable for in vitro reconstruction of highly complex biological systems, the difficult assembly and operation of these systems often only allows a limited throughput. Here we present and characterize a novel flow chamber which recapitulates the lymphatic capillary microenvironment by coupling a standard Boyden chamber setup with a micro-channel and a controlled fluidic environment. The inclusion of luminal and transmural flow renders the model more biologically relevant, combining standard 3D culture techniques with advanced control of mechanical forces that are naturally present within the lymphatic microenvironment. The system can be monitored in real-time, allowing continuous quantification of different parameters of interest, such as cell intravasation and detachment from the endothelium, under varied biomechanical conditions. Moreover, the easy setup permits a medium-high throughput, thereby enabling downstream quantitative analyses. Using this model, we examined the kinetics of tumor cell (MDA-MB-231) invasion and transmigration dynamics across lymphatic endothelium under varying flow conditions. We found that luminal flow indirectly upregulates tumor cell transmigration rate via its effect on lymphatic endothelial cells. Moreover, we showed that the addition of transmural flow further increases intravasation, suggesting that distinct flow-mediated mechanisms regulate tumor cell invasion. PMID:25896438

  15. Uptake of a web-based oncology protocol system: how do cancer clinicians use eviQ cancer treatments online?

    PubMed Central

    2013-01-01

    Background The use of computerized systems to support evidence-based practice is commonplace in contemporary medicine. Despite the prolific use of electronic support systems there has been relatively little research on the uptake of web-based systems in the oncology setting. Our objective was to examine the uptake of a web-based oncology protocol system (http://www.eviq.org.au) by Australian cancer clinicians. Methods We used web-logfiles and Google Analytics to examine the characteristics of eviQ registrants from October 2009-December 2011 and patterns of use by cancer clinicians during a typical month. Results As of December 2011, there were 16,037 registrants; 85% of whom were Australian health care professionals. During a typical month 87% of webhits occurred in standard clinical hours (08:00 to 18:00 weekdays). Raw webhits were proportional to the size of clinician groups: nurses (47% of Australian registrants), followed by doctors (20%), and pharmacists (14%). However, pharmacists had up to three times the webhit rate of other clinical groups. Clinicians spent five times longer viewing chemotherapy protocol pages than other content and the protocols viewed reflect the most common cancers: lung, breast and colorectal. Conclusions Our results demonstrate eviQ is used by a range of health professionals involved in cancer treatment at the point-of-care. Continued monitoring of electronic decision support systems is vital to understanding how they are used in clinical practice and their impact on processes of care and patient outcomes. PMID:23497080

  16. The Schlemm’s canal is a VEGF-C/VEGFR-3–responsive lymphatic-like vessel

    PubMed Central

    Aspelund, Aleksanteri; Tammela, Tuomas; Antila, Salli; Nurmi, Harri; Leppänen, Veli-Matti; Zarkada, Georgia; Stanczuk, Lukas; Francois, Mathias; Mäkinen, Taija; Saharinen, Pipsa; Immonen, Ilkka; Alitalo, Kari

    2014-01-01

    In glaucoma, aqueous outflow into the Schlemm’s canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment. PMID:25061878

  17. Noninvasive real-time fluorescence imaging of the lymphatic uptake of BSA-IRDye 680 conjugate administered subcutaneously in mice.

    PubMed

    Wu, Fang; Bhansali, Suraj G; Tamhane, Mitalee; Kumar, Rajiv; Vathy, Lisa A; Ding, Hong; Yong, Ken-Tye; Bergey, Earl J; Prasad, Paras N; Morris, Marilyn E

    2012-05-01

    The goal of our studies was to determine lymphatic uptake of bovine serum albumin (BSA) using real-time noninvasive fluorescence imaging. BSA labeled with near-infrared dye (IRDye) 680 was used as a model protein-dye conjugate. The conjugation of BSA with IRDye 680 was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Size-exclusion high-performance liquid chromatography and SDS-PAGE demonstrated that the IRDye 680-labeled BSA conjugate in the lymph node (LN) homogenate samples was stable at physiological temperature (37°C) for at least 5 days. Whole-body noninvasive optical imaging of hairless SKH-1 mice was performed after subcutaneous (s.c.) injection (dose = 0.1 mg/kg) into the front footpad. Noninvasive fluorescence imaging demonstrated that BSA-IRDye 680 conjugates were dynamically taken up by the lymphatic system, accumulated in the axillary LNs and then cleared, indicating that lymphatic transport plays a role in the absorption of BSA. Ex vivo tissue imaging of LN homogenates provided confirmatory data with respect to the uptake of fluorescent-labeled BSA determined by in vivo imaging. Noninvasive real-time imaging of LNs provides a novel tool for evaluating uptake and accumulation of fluorescent-labeled proteins by the lymphatic system after s.c. injection in a mouse model.

  18. [Scintigraphic study of the lymphatic drainage of the anterior chamber of the mouse eye and its pathophysiological implications].

    PubMed

    Guignier, B; Bourahla, K; Bekaert, V; Brasse, D; Gaucher, D; Speeg-Schatz, C; Bourcier, T

    2013-12-01

    For many years, the intraocular lymphatic system and particularly the drainage of the aqueous humor by this system have been considered non-existant. Our study is the first to demonstrate, in a dynamic in vivo fashion, the existence of lymphatic drainage in the mouse eye. This has become possible with lymphoscintigraphy with nano-molecules of rhenium sulphide, marked by technetium-99m and injected into the anterior chamber of the mouse eye. Readings were taken using an experimental gamma camera specially built for the small animal. The hypothesis of a "uveolymphatic" drainage pathway within the ciliary body, contributing to aqueous outflow, has recently been highlighted by new improvements in microbiology (discovery of lymphatic endothelial-specific markers) and imaging. This new pathway may lead to many prospects: the development of techniques for visualization and quantification of this in vivo lymphatic flow may help to increase our understanding of the physiopathology and perhaps treatment of chronic glaucoma as well as neoplastic conditions. PMID:24099697

  19. Robust iterative learning protocols for finite-time consensus of multi-agent systems with interval uncertain topologies

    NASA Astrophysics Data System (ADS)

    Meng, Deyuan; Jia, Yingmin; Du, Junping

    2015-04-01

    This paper is devoted to the robust finite-time output consensus problems of multi-agent systems under directed graphs, where all agents and their communication topologies are subject to interval uncertainties. Distributed protocols are constructed by using iterative learning control (ILC) algorithms, where information is exchanged only at the end of one iteration and learning is used to update the control inputs after each iteration. It is proved that under ILC-based protocols, the finite-time consensus can be achieved with an increasing number of iterations if the communication network of agents is guaranteed to have a spanning tree. Moreover, if the information of any desired terminal output is available to a portion (not necessarily all) of the agents, then the consensus output that all agents finally reach can be enabled to be the desired terminal output. It is also proved that for all ILC-based protocols, gain selections can be provided in terms of bound values, and consensus conditions can be developed associated with bound matrices. Simulation results are given to demonstrate the effectiveness of our theoretical results.

  20. Some physics and system issues in the security analysis of quantum key distribution protocols

    NASA Astrophysics Data System (ADS)

    Yuen, Horace P.

    2014-10-01

    In this paper, we review a number of issues on the security of quantum key distribution (QKD) protocols that bear directly on the relevant physics or mathematical representation of the QKD cryptosystem. It is shown that the cryptosystem representation itself may miss out many possible attacks, which are not accounted for in the security analysis and proofs. Hence, the final security claims drawn from such analysis are not reliable, apart from foundational issues about the security criteria that are discussed elsewhere. The cases of continuous-variable QKD and multi-photon sources are elaborated upon.

  1. Lymphatic vessels in the developing diaphragm of the rat.

    PubMed

    Poggi, P; Marchetti, C; Calligaro, A; Casasco, A; Scelsi, R

    1991-01-01

    Diaphragms of fetal, neonatal and young albino rats have been observed both under light and electron microscopes to examine the presence and distribution of lymphatic vessels and their morphological features. In fetal diaphragms of between 18 and 22 days of gestation, no normal lymphatic vessels can be seen; only after birth, specifically in neonatal and 2-day-old rats, small lymphatic vessels appear; they are in close proximity to the blood vessels in the inner areas of the muscle. As the rats get older, lymphatic vessels are also observed in the subserosa where an abundant connective tissue is present. The fine structure of diaphragmatic lymphatic vessels is different at different ages. In neonatal rats of up to 2 days, the endothelial wall is very thin and often holed. The relationships between contiguous endothelial cells are characterized by simple end-to-end or overlapping structures. The basement membrane is virtually absent. Within the first week of life, the endothelial wall becomes more complex; along the wall, complex interdigitations between two contiguous endothelial cells often touch. A discontinuous basement membrane and collagen and elastic fibers surround the vessels. In the older rats (from 14 to 25 to 140 days), next to the complex interdigitations which characterize the junction between two contiguous endothelial cells, cellular flaps interdigitate forming a channel which opens out either to the exterior or the interior of the vessel. Dense bundles of elastic and collagen fibers are closely apposed to the endothelial wall.

  2. FOXC2 and FLT4 Gene Variants in Lymphatic Filariasis.

    PubMed

    Sheik, Yasmeen; Qureshi, Sameera Fatima; Mohhammed, Basheeruddin; Nallari, Pratibha

    2015-06-01

    Lymphatic filariasis is the leading cause of secondary lymphedema wherein lymph transport is impaired due to lymphatic damage. FLT4 signaling and transcription factors such as FOXC2 play an important role in this type of lymphangiogenesis process induced by filarial parasites. The present study aims to assess the association of FLT4 and FOXC2 genes in lymphatic development/remodeling in lymphatic filariasis. A total of 118 lymphatic filariasis patients and 100 non-endemic and 50 endemic healthy subjects were enrolled for the present study. Allele-specific PCR and PCR-RFLP were adopted for the genotyping, and screening of FLT4 and FOXC2 genes was carried out by PCR-SSCP, followed by in-silico and statistical analysis. A novel variation (G357A SNP) was identified on FOXC2 gene screening that may have an effect on codon usage frequency during translational process. In FLT4, A3123G mutation was found in 3.39% of the case subjects but the functional role of this mutation, along with subject's clinical presentations and patient's age, emphasize its pathogenic role in lymphedema development. Two of the subjects exhibit compound heterozygosity (A3123G FLT4 mutation and G357A SNP of FOXC2 gene). As these two genes share a common pathway, we hypothesise a synergistic interaction of these two SNPs in inhibiting the downstream signaling resulting in lymphedema progression.

  3. Elimination of Lymphatic Filariasis in The Gambia

    PubMed Central

    Rebollo, Maria P.; Sambou, Sana Malang; Thomas, Brent; Biritwum, Nana-Kwadwo; Jaye, Momodou C.; Kelly-Hope, Louise; Escalada, Alba Gonzalez; Molyneux, David H.; Bockarie, Moses J.

    2015-01-01

    Background The prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission. Methodology/Principal Finding We present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997–2013), and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT) test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6–7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts. Conclusions We conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF. PMID

  4. Pump function curve shape for a model lymphatic vessel.

    PubMed

    Bertram, C D; Macaskill, C; Moore, J E

    2016-07-01

    The transport capacity of a contractile segment of lymphatic vessel is defined by its pump function curve relating mean flow-rate and adverse pressure difference. Numerous system characteristics affect curve shape and the magnitude of the generated flow-rates and pressures. Some cannot be varied experimentally, but their separate and interacting effects can be systematically revealed numerically. This paper explores variations in the rate of change of active tension and the form of the relation between active tension and muscle length, factors not known from experiment to functional precision. Whether the pump function curve bends toward or away from the origin depends partly on the curvature of the passive pressure-diameter relation near zero transmural pressure, but rather more on the form of the relation between active tension and muscle length. A pump function curve bending away from the origin defines a well-performing pump by maximum steady output power. This behaviour is favoured by a length/active-tension relationship which sustains tension at smaller lengths. Such a relationship also favours high peak mechanical efficiency, defined as output power divided by the input power obtained from the lymphangion diameter changes and active-tension time-course. The results highlight the need to pin down experimentally the form of the length/active-tension relationship. PMID:27185045

  5. A Time-Slotted On-Demand Routing Protocol for Mobile Ad Hoc Unmanned Vehicle Systems

    SciTech Connect

    Hope Forsmann; Robert Hiromoto; John Svoboda

    2007-04-01

    The popularity of UAVs has increased dramatically because of their successful deployment in military operations, their ability to preserve human life, and the continual improvements in wireless communication that serves to increase their capabilities. We believe the usefulness of UAVs would be dramatically increased if formation flight were added to the list of capabilities. Currently, sustained formation flight with a cluster of UAVs has only been achieved with two nodes by the Multi-UAV Testbed at the Massachusetts Institute of Technology. (Park, 2004) Formation flight is a complex operation requiring the ability to adjust the flight patterns on the fly and correct for wind gusts, terrain, and differences in node equipment. All of which increases the amount of inner node communication. Since one of the problems with MANET communication is network congestion, we believe a first step towards formation flight can be made through improved inner node communication. We have investigated current communication routing protocols and developed an altered hybrid routing protocol in order to provide communication with less network congestion.

  6. Lymphatic-targeted therapy following neoadjuvant chemotherapy: a promising strategy for lymph node-positive breast cancer treatment.

    PubMed

    Chen, Jianghao; Yao, Qing; Wang, Hui; Wang, Bo; Zhang, Juliang; Wang, Ting; Lv, Yonggang; Han, Zenghui; Wang, Ling

    2015-07-01

    Neoadjuvant chemotherapy has been increasingly used to downstage breast cancer prior to surgery recently. However, in some cases, it was observed that despite sufficient regression of primary tumors, the metastatic lymph nodes remained nonresponsive. In this study, we applied lymphatic-targeted strategy to evaluate its efficacy and safety for patients presenting refractory nodes following systemic chemotherapy. A total of 318 breast cancer patients were demonstrated with lymph node metastasis by needle biopsy and given neoadjuvant chemotherapy. Two cycles later, 72 patients were observed with responsive tumors but stable nodes, 42 of which received a subcutaneous injection of lymphatic-targeted pegylated liposomal doxorubicin during the third cycle, while the remaining 30 patients were continued with former neoadjuvant therapeutic pattern and regarded as the control. Lymphatic-targeted treatment substantially increased both clinical and pathological node response rate [62 % (26/42) vs. 13 % (4/30) and 12 % (5/42) vs. 0 (0/30), respectively], and induced a higher apoptosis level of metastatic cells (median, 41 vs. 6 %), compared with the control. Moreover, a higher disease-free survival was observed after a median follow-up of 4 years (69 vs. 56 %). Inflammatory reaction surrounding injection sites was the most common side effect. Lymphatic chemotherapy has reliable efficacy and well-tolerated toxicity for breast cancer patients presenting refractory lymph nodes following neoadjuvant chemotherapy.

  7. Evaluation of a realtime, remote monitoring telemedicine system using the Bluetooth protocol and a mobile phone network.

    PubMed

    Jasemian, Yousef; Arendt-Nielsen, Lars

    2005-01-01

    A generic, realtime wireless telemedicine system has been developed that uses the Bluetooth protocol and the general packet radio service for mobile phones. The system was tested on 10 healthy volunteers, by continuous monitoring of their electrocardiograms (ECGs). Under realistic conditions, the system had 96.5% uptime, a data throughput of 3.3 kbit/s, a mean packet error rate of 8.5x10(-3) packet/s and a mean packet loss rate of 8.2x10(-3) packet/s. During 24 h testing, the total average downtime was 66 min and 90% of the periods of downtime were of only 1-3 min duration. Less than 10% of the ECGs were of unacceptable quality. Thus, the generic telemedicine system showed high reliability and performance, and the design may provide a foundation for realtime monitoring in clinical practice, for example in cardiology.

  8. Lymphatic Filariasis (Elephantiasis) Elimination: A public health success and development opportunity

    PubMed Central

    Molyneux, David

    2003-01-01

    action documented in this paper requires and deserves further support to bring to fruition elimination of lymphatic filariasis as a public health problem and health benefits to poor people. A future free of lymphatic filariasis will reduce poverty and bring better health to poor people, prevent disability, strengthen health systems and build partnerships. PMID:13129436

  9. The Lymphatic Endothelial mCLCA1 Antibody Induces Proliferation and Growth of Lymph Node Lymphatic Sinuses.

    PubMed

    Jordan-Williams, Kimberly L; Ramanujam, Neela; Farr, Andrew G; Ruddell, Alanna

    2016-01-01

    Lymphocyte- and leukocyte-mediated lymph node (LN) lymphatic sinus growth (lymphangiogenesis) is involved in immune responses and in diseases including cancer and arthritis. We previously discovered a 10.1.1 Ab that recognizes the lymphatic endothelial cell (LEC) surface protein mCLCA1, which is an interacting partner for LFA1 and Mac-1 that mediates lymphocyte adhesion to LECs. Here, we show that 10.1.1 Ab treatment specifically induces LEC proliferation, and influences migration and adhesion in vitro. Functional testing by injection of mice with 10.1.1 Ab but not control hamster Abs identified rapid induction of LN LEC proliferation and extensive lymphangiogenesis within 23 h. BrdU pulse-chase analysis demonstrated incorporation of proliferating LYVE-1-positive LEC into the growing medullary lymphatic sinuses. The 10.1.1 Ab-induced LN remodeling involved coordinate increases in LECs and also blood endothelial cells, fibroblastic reticular cells, and double negative stroma, as is observed during the LN response to inflammation. 10.1.1 Ab-induced lymphangiogenesis was restricted to LNs, as mCLCA1-expressing lymphatic vessels of the jejunum and dermis were unaffected by 23 h 10.1.1 Ab treatment. These findings demonstrate that 10.1.1 Ab rapidly and specifically induces proliferation and growth of LN lymphatic sinuses and stroma, suggesting a key role of mCLCA1 in coordinating LN remodeling during immune responses. PMID:27224029

  10. The Lymphatic Endothelial mCLCA1 Antibody Induces Proliferation and Growth of Lymph Node Lymphatic Sinuses

    PubMed Central

    Jordan-Williams, Kimberly L.; Ramanujam, Neela; Farr, Andrew G.

    2016-01-01

    Lymphocyte- and leukocyte-mediated lymph node (LN) lymphatic sinus growth (lymphangiogenesis) is involved in immune responses and in diseases including cancer and arthritis. We previously discovered a 10.1.1 Ab that recognizes the lymphatic endothelial cell (LEC) surface protein mCLCA1, which is an interacting partner for LFA1 and Mac-1 that mediates lymphocyte adhesion to LECs. Here, we show that 10.1.1 Ab treatment specifically induces LEC proliferation, and influences migration and adhesion in vitro. Functional testing by injection of mice with 10.1.1 Ab but not control hamster Abs identified rapid induction of LN LEC proliferation and extensive lymphangiogenesis within 23 h. BrdU pulse-chase analysis demonstrated incorporation of proliferating LYVE-1-positive LEC into the growing medullary lymphatic sinuses. The 10.1.1 Ab-induced LN remodeling involved coordinate increases in LECs and also blood endothelial cells, fibroblastic reticular cells, and double negative stroma, as is observed during the LN response to inflammation. 10.1.1 Ab-induced lymphangiogenesis was restricted to LNs, as mCLCA1-expressing lymphatic vessels of the jejunum and dermis were unaffected by 23 h 10.1.1 Ab treatment. These findings demonstrate that 10.1.1 Ab rapidly and specifically induces proliferation and growth of LN lymphatic sinuses and stroma, suggesting a key role of mCLCA1 in coordinating LN remodeling during immune responses. PMID:27224029

  11. Search for lymphatic drainage of the monkey orbit

    SciTech Connect

    McGetrick, J.J.; Wilson, D.G.; Dortzbach, R.K.; Kaufman, P.L.; Lemke, B.N.

    1989-02-01

    Colloid solutions of technetium Tc-99m and india ink injected into the retrobulbar space of the cynomolgus monkey outside the extraocular muscle cone were removed from the orbit by the lymphatic vessels of the conjunctiva and eyelids and were then concentrated within the lymph nodes that drained the conjunctival and eyelid areas. Colloid solutions injected into the retrobulbar space inside the extraocular muscle cone did not reach the conjunctiva and did not collect in any lymph nodes over a 24-hour period. Within the orbit, the injected colloids spread along the planes of the connective-tissue septa. No lymphatic vessels were identified within the orbits posterior to the conjunctiva. Small amounts of india ink left the posterior orbit and ultimately entered the contralateral orbit. This posterior pathway did not lead to lymphatic vessels or lymph nodes and therefore does not appear to represent a prelymphatic pathway.

  12. Epidemiology, health systems and stakeholders in rheumatic heart disease in Africa: a systematic review protocol

    PubMed Central

    Moloi, Annesinah Hlengiwe; Watkins, David; Engel, Mark E; Mall, Sumaya; Zühlke, Liesl

    2016-01-01

    Introduction Rheumatic heart disease (RHD) is a chronic disease affecting the heart valves, secondary to group A streptococcal infection (GAS) and subsequent acute rheumatic fever (ARF). However, RHD cure and preventative measures are inextricably linked with socioeconomic development, as the disease mainly affects children and young adults living in poverty. In order to address RHD, public health officials and health policymakers require up-to-date knowledge on the epidemiology of GAS, ARF and RHD, as well as the existing enablers and gaps in delivery of evidence-based care for these conditions. We propose to conduct a systematic review to assess the literature comprehensively, synthesising all existing quantitative and qualitative data relating to RHD in Africa. Methods and analysis We plan to conduct a comprehensive literature search using a number of databases and reference lists of relevant articles published from January 1995 to December 2015. Two evaluators will independently review and extract data from each article. Additionally, we will assess overall study quality and risk of bias, using the Newcastle-Ottawa Scale and the Critical Appraisal Skills Programme criteria for quantitative and qualitative studies, respectively. We will meta-analyse estimates of prevalence, incidence, case fatality and mortality for each of the conditions separately for each country. Qualitative meta-analysis will be conducted for facilitators and barriers in RHD health access. Lastly, we will create a list of key stakeholders. This protocol is registered in the PROSPERO International Prospective Register of systematic reviews, registration number CRD42016032852. Ethics and dissemination The information provided by this review will inform and assist relevant stakeholders in identifying key areas of intervention, and designing and implementing evidence-based programmes and policies at the local and regional level. With slight modifications (ie, to the country terms in the search

  13. [Simultaneous occurrence of hemophilia A and acute lymphatic leukemia].

    PubMed

    Schmid, L; Schafroth, U; Osterwalder, B; Senn, H J

    1987-11-14

    In this paper the case of a man with haemophilia A is presented. At the age of 18 years an acute lymphatic leukaemia was observed. The case report demonstrates that even in the presence of a severe plasmatic coagulopathy an acute lymphatic leukaemia can be successfully treated with intensive chemotherapy, if the monitoring of the coagulation values and the substitution of antihaemophilic globulin and thrombocytes are guaranteed. Only 4 cases of haemophilia and acute leukaemia in the same patient are described in the literature. So we believe that the association of these two rare disorders is merely accidental.

  14. Renal peripelvic lymphatic cysts (lymphangiomas) associated with generalized lymphangiomatosis.

    PubMed

    Younathan, C M; Kaude, J V

    1992-01-01

    Renal peripelvic lymphatic cysts (lymphangiomas) are usually seen as an isolated finding. They appear as multiple mass lesions with low attenuation on computed tomography (CT), and show no contrast enhancement. We present a case of renal peripelvic lymphatic cysts associated with generalized lymphangiomatosis, and examined with magnetic resonance imaging (MRI), CT, and lymphangiography. Multiplanar MRI demonstrated the extent of disease, including retroperitoneal lesions. The lesions had low-signal intensity on T1-weighted and high-signal intensity on T2-weighted images. The diagnosis of generalized lymphangiomatosis was verified by renal sinus cyst puncture, lymphangiography, and tissue biopsy.

  15. Lack of functioning intratumoral lymphatics in colon and pancreas cancer tissue.

    PubMed

    Olszewski, Waldemar L; Stanczyk, Marek; Gewartowska, Magdalena; Domaszewska-Szostek, Anna; Durlik, Marek

    2012-09-01

    There are controversial views as to whether intratumoral or peritumoral lymphatics play a dominant role in the metastatic process. Most clinical observations originate from studies of colon cancer. Colon contains mucosa and submucosa rich in lymphatics and with high lymph formation rate. This seems to be a prerequisite for easy metastasis of cancer cells to regional lymph nodes. However, there are other tissues as pancreas with a rudimentary lymphatic network where cancer metastasis formation is as intensive as in colon cancer. This contradicts the common notion that intratumor lymphatics play major role in metastases. We visualized interstitial space and lymphatics in the central and peripheral regions of colon and pancreas tumors using the color stereoscopic lymphography and simultaneously immunohistochemical performed stainings specific for lymphatic and blood endothelial cells. The density of open and compressed lymphatic and blood vessels was measured in the tumor core and edge. There were very few lymphatics in the colon and pancreas tumor core but numerous minor fluid "lakes" with no visible connection to the peritumoral lymphatics. Lining of "lakes" did not express molecular markers specific for lymphatic endothelial cells. Dense connective tissue surrounding tumor foci did not contain lymphatics. Peritumoral lymphatics were irregularly distributed in both types of tumor and only sporadically contained cells that might be tumor cells. Similar lymphoscintigraphic and histological pictures were seen in colon and pancreas cancer despite of different structure of both tissues. This suggests a uniform reaction of tissues to the growing cancer irrespective of the affected organ.

  16. Enzyme-histochemical study on postnatal development of rat stomach lymphatic vessels.

    PubMed

    Ji, R C; Kato, S

    1997-07-01

    Postnatal development of rat gastric lymphatics was studied by an enzyme-histochemical method to elucidate the morphological changes of lymphatics and their relationship to maturation and function, especially in the glandular portion. The significant features of 5'-Nase-positive lymphatics in distribution and structure were examined in different stages (within 24 hr, 4-21 days, and 2 months). Lymphatics in the greater curvature and anterior wall grew much slower than those in the lesser curvature and posterior wall of the stomach in newborn and infant rats. Lymphatic islands isolated from the primary lymphatic networks in the submucosa and subserosa underwent a morphological change during this early period. This is considered one of the basic steps in lymphatic development. Occurrence of lymphatic networks in the deep lamina propria indicates that development in the gastric wall is well characterized from Day 10. With further growth and modification of lymphatics, the networks in the different layers formed an extensive communication network and many lymphatic valves were found in the submucosa and subserosa. Pinocytotic vesicles, open junctions, and intraendothelial channels were frequently detected in the mucosal and submucosal lymphatic networks of the corpus-antrum and antrum-duodenum divisional zones in the adult rats. These findings suggest that developing lymphatics in the rat stomach may represent rapidly growing tissue not only with high 5'-Nase activity but also with high adaptability for future physiological demands.

  17. Finding an optimal method for imaging lymphatic vessels of the upper limb.

    PubMed

    O'Mahony, Susan; Rose, Sarah L; Chilvers, Alison J; Ballinger, James R; Solanki, Chandra K; Barber, Robert W; Mortimer, Peter S; Purushotham, Arnie D; Peters, A Michael

    2004-04-01

    Lymphoscintigraphy involves interstitial injection of radiolabelled particulate materials or radioproteins. Although several variations in the technique have been described, their place in clinical practice remains controversial. Traditional diagnostic criteria are based primarily on lymph node appearances but in situations such as breast cancer, where lymph nodes may have been excised, these criteria are of limited use. In these circumstances, lymphatic vessel morphology takes on greater importance as a clinical endpoint, so a method that gives good definition of lymphatic vessels would be useful. In patients with breast cancer, for example, such a method, used before and after lymph node resection, may assist in predicting the development of breast cancer-related lymphoedema. The aim of this study was to optimise a method for the visualisation of lymphatic vessels. Subcutaneous (sc) and intradermal (id) injection sites were compared, and technetium-99m nanocolloid, a particulate material, was compared with (99m)Tc-human immunoglobulin (HIG), which is a soluble macromolecule. Twelve normal volunteers were each studied on two occasions. In three subjects, id (99m)Tc-HIG was compared with sc (99m)Tc-HIG, in three id (99m)Tc-nanocolloid was compared with sc (99m)Tc-nanocolloid, in three id (99m)Tc-HIG was compared with id (99m)Tc-nanocolloid and in three sc (99m)Tc-HIG was compared with sc (99m)Tc-nanocolloid. Endpoints were quality of lymphatic vessel definition, the time after injection at which vessels were most clearly visualised, the rate constant of depot disappearance ( k) and the systemic blood accumulation rate as measured by gamma camera imaging over the liver or cardiac blood pool. Excellent definition of lymphatic vessels was obtained following id injection of either radiopharmaceutical, an injection route that was clearly superior to sc. Differences between radiopharmaceuticals were less clear, although after id injection, (99m)Tc-HIG gave images that

  18. Anatomy and physiology of lymphatic drainage of the breast from the perspective of sentinel node biopsy.

    PubMed

    Tanis, P J; Nieweg, O E; Valdés Olmos, R A; Kroon, B B

    2001-03-01

    Knowledge of the anatomy and physiology of the lymphatic system is helpful when considering a particular sentinel node biopsy technique. The delicate balance between internal and external pressures in a lymphatic channel can be influenced by the injection volume and by massage in a negative or positive way. The narrow openings in the interendothelial junctions determine the speed of clearance of particles with a certain size, and this has implications for the timing of lymphoscintigraphy and surgery. Tracer uptake and lymph flow are highly variable and depend on a number of factors, some of which are beyond our control. The lymphatic anatomy is not completely understood despite numerous studies since the end of the 18th century. Several topics have been elucidated in more recent studies and through experience with sentinel node biopsy. First, although axillary drainage is the principal lymphatic path of the breast, any drainage pattern from any quadrant of the breast can occur. Second, most lymph from the breast flows to the nodal basins with a direct course, not passing through the subareolar plexus. Another relevant point is that gentle massage encourages lymph flow and facilitates sentinel node detection. What problems do we still face in clinical practice? The optimum size and number of labeled colloid particles remain to be established. The optimum volume of the tracer also remains to be determined. But the main controversy concerns the injection site. Although the intradermal injection technique has attractive practical features, there is currently insufficient certainty that drainage of tracer injected anywhere in or underneath the skin of the breast reflects drainage from the cancer. Connections between collecting lymphatic vessels from the tumor site and the collecting vessels from the skin and subdermal lymphatics can explain the concordance between intraparenchymal and superficial injections in most patients. To determine the technique that yields the

  19. Improvement of Electrical Stimulation Protocol for Simultaneous Measurement of Extracellular Potential with On-Chip Multi-Electrode Array System

    NASA Astrophysics Data System (ADS)

    Kaneko, Tomoyuki; Nomura, Fumimasa; Hattori, Akihiro; Yasuda, Kenji

    2012-06-01

    Cardiotoxicity testing with a multi-electrode array (MEA) system requires the stable beating of cardiomyocytes for the measurement of the field potential duration (FPD), because different spontaneous beating rates cause different responses of FPD prolongation induced by drugs, and the beating rate change effected by drugs complicates the FPD prolongation assessment. We have developed an on-chip MEA system with electrical stimulation for the measurement of the FPD during the stable beating of human embryonic stem (ES) cell-derived cardiomyocyte clusters. Using a conventional bipolar stimulation protocol, we observed such large artifacts in electrical stimulation that we could not estimate the FPD quantitatively. Therefore, we improved the stimulation protocol by using sequential rectangular pulses in which the positive and negative stimulation voltages and number of pulses could be changed flexibly. The balanced voltages and number of pulses for sequential rectangular pulses enabled the recording of small negative artifacts only, which hardly affected the FPD measurement of human-ES-cell-derived cardiomyocyte clusters. These conditions of electrical stimulation are expected to find applications for the control of constant beating for cardiotoxicity testing.

  20. Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement.

    PubMed

    Hawighorst, H; Knapstein, P G; Weikel, W; Knopp, M V; Zuna, I; Knof, A; Brix, G; Schaeffer, U; Wilkens, C; Schoenberg, S O; Essig, M; Vaupel, P; van Kaick, G

    1997-11-01

    Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25-72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement. Pharmacokinetic MRI-derived parameters (A and k21) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k21 compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic

  1. A common framework for greenhouse gas assessment protocols in temperate agroforestry systems: Connecting via GRACEnet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agroforestry systems offer many ecosystem benefits, but such systems have previously been marginalized in temperate environments due to overriding economic goals and perceived management complexity. In view of adaptation to a changing climate, agroforestry systems offer advantages that require quan...

  2. Application of State Biological Assessment Protocols to the Lower Missouri River: are any Lotic Systems Non-Wadeable ?

    NASA Astrophysics Data System (ADS)

    Poulton, B. C.

    2005-05-01

    Benthic ecologists have suggested that the biological condition of large rivers could be successfully evaluated with modifications of small stream bioassessments. The lower Missouri system contains a unique fauna with rare, large-river macroinvertebrate species that are difficult to sample and more poorly known ecologically. As part of an evaluation of 27 indicator metrics and their ability to detect cumulative stressors, an 812 km section of the lower Missouri was sampled with three methods in two key habitats. Among these, rock revetments were sampled with a D-frame kick net using the state of Missouri's biological assessment protocol developed for coarse substrate in riffles of wadeable streams. A total of 62 species of macroinvertebrates were collected, as compared to 72 species from artificial substrates deployed at the same locations. Ranges in values for the four core metrics included in the Missouri protocol (total taxa richness 24-42, EPT taxa richness 9-18, Missouri Biotic Index 5.89-6.33, Shannon-Wiener Index 1.60-2.77) were more comparable to data from perennial 4th and 5th order streams than the values from artificial substrate data. However, proposed biocriteria for wadeable streams in Missouri could not identify impairment levels among sites, and no longitudinal response gradient was apparent until an additional 8 metrics were included in the site scores. Utilization of semi-quantitative kick net protocols in large rivers can yield data comparable to wadeable streams if sampling is performed under specific conditions related to hydrology and insect colonization dynamics.

  3. Glacial ice cores: A model system for developing extraterrestrial decontamination protocols

    NASA Astrophysics Data System (ADS)

    Christner, Brent C.; Mikucki, Jill A.; Foreman, Christine M.; Denson, Jackie; Priscu, John C.

    2005-04-01

    Evidence gathered from spacecraft orbiting Mars has shown that water ice exists at both poles and may form a large subsurface reservoir at lower latitudes. The recent exploration of the martian surface by unmanned landers and surface rovers, and the planned missions to eventually return samples to Earth have raised concerns regarding both forward and back contamination. Methods to search for life in these icy environments and adequate protocols to prevent contamination can be tested with earthly analogues. Studies of ice cores on Earth have established past climate changes and geological events, both globally and regionally, but only recently have these results been correlated with the biological materials (i.e., plant fragments, seeds, pollen grains, fungal spores, and microorganisms) that are entrapped and preserved within the ice. The inclusion of biology into ice coring research brings with it a whole new approach towards decontamination. Our investigations on ice from the Vostok core (Antarctica) have shown that the outer portion of the cores have up to 3 and 2 orders of magnitude higher bacterial density and dissolved organic carbon (DOC) than the inner portion of the cores, respectively, as a result of drilling and handling. The extreme gradients that exist between the outer and inner portion of these samples make contamination a very relevant aspect of geomicrobiological investigations with ice cores, particularly when the actual numbers of ambient bacterial cells are low. To address this issue and the inherent concern it raises for the integrity of future investigations with ice core materials from terrestrial and extraterrestrial environments, we employed a procedure to monitor the decontamination process in which ice core surfaces are painted with a solution containing a tracer microorganism, plasmid DNA, and fluorescent dye before sampling. Using this approach, a simple and direct method is proposed to verify the authenticity of geomicrobiological

  4. Improved computer-assisted analysis of the global lymphatic network in human cervical tissues.

    PubMed

    Balsat, Cédric; Signolle, Nicolas; Goffin, Frédéric; Delbecque, Katty; Plancoulaine, Benoit; Sauthier, Philippe; Samouëlian, Vanessa; Béliard, Aude; Munaut, Carine; Foidart, Jean-Michel; Blacher, Silvia; Noël, Agnès; Kridelka, Frédéric

    2014-06-01

    Lymphatic dissemination is a key event in cervical cancer progression and related tumor lymphatic markers are viewed as promising prognostic factor of nodal extension. However, validating such parameters requires an objective characterization of the lymphatic vasculature. Here, we performed a global analysis of the lymphatic network using a new computerized method applied on whole uterine cervical digital images. Sixty-eight cases of cervical neoplasia (12 CIN3, 10 FIGO stage 1A and 46 stage IB1) and 10 cases of normal cervical tissue were reacted with antibodies raised against D2-40, D2-40/p16 and D2-40/Ki67. Immunostained structures were automatically detected on whole slides. The lymphatic vessel density (D2-40), proliferating lymphatic vessel density (D2-40/ki67) and spatial lymphatic distribution in respect to the adjacent epithelium were assessed from normal cervix to early cervical cancer and correlated with lymphovascular space invasion and lymph node status. Prominent lymphatic vessel density and proliferating lymphatic vessel density are detected under the transformation zone of benign cervix and no further increase is noted during cancer progression. Notably, a shift of lymphatic vessel distribution toward the neoplastic edges is detected. In IB1 cervical cancer, although intra- and peritumoral lymphatic vessel density are neither correlated with lymphovascular space invasion nor with lymph node metastasis, a specific spatial distribution with more lymphatic vessels in the vicinity of tumor edges is predictive of lymphatic dissemination. Herein, we provide a new computerized method suitable for an innovative detailed analysis of the lymphatic network. We show that the transformation zone of the benign cervix acts as a baseline lymphangiogenic niche before the initiation of neoplastic process. During cancer progression, this specific microenvironment is maintained with lymphatic vessels even in closer vicinity to tumor cells. PMID:24309324

  5. Multisession Anodal tDCS Protocol Improves Motor System Function in an Aging Population

    PubMed Central

    Dumel, G.; Bourassa, M.-E.; Desjardins, M.; Voarino, N.; Charlebois-Plante, C.; Doyon, J.; De Beaumont, Louis

    2016-01-01

    Objectives. The primary objective of this study was to investigate the effects of five consecutive, daily 20-minute sessions of M1 a-tDCS on motor learning in healthy, cognitively intact, aging adults. Design. A total of 23 participants (51 to 69 years old) performed five consecutive, daily 20-minute sessions of a serial reaction time task (SRT task) concomitant with either anodal (n = 12) or sham (n = 11) M1 a-tDCS. Results. We found a significant group × training sessions interaction, indicating that whereas aging adults in the sham group exhibited little-to-no sequence-specific learning improvements beyond the first day of training, reproducible improvements in the ability to learn new motor sequences over 5 consecutive sessions were the net result in age-equivalent participants from the M1 a-tDCS group. A significant main effect of group on sequence-specific learning revealed greater motor learning for the M1 a-tDCS group when the five learning sessions were averaged. Conclusion. These findings raise into prominence the utility of multisession anodal TDCS protocols in combination with motor training to help prevent/alleviate age-associated motor function decline. PMID:26881118

  6. Protocols for assessing radiofrequency interactions with gold nanoparticles and biological systems for non-invasive hyperthermia cancer therapy.

    PubMed

    Corr, Stuart J; Cisneros, Brandon T; Green, Leila; Raoof, Mustafa; Curley, Steven A

    2013-08-28

    Cancer therapies which are less toxic and invasive than their existing counterparts are highly desirable. The use of RF electric-fields that penetrate deep into the body, causing minimal toxicity, are currently being studied as a viable means of non-invasive cancer therapy. It is envisioned that the interactions of RF energy with internalized nanoparticles (NPs) can liberate heat which can then cause overheating (hyperthermia) of the cell, ultimately ending in cell necrosis. In the case of non-biological systems, we present detailed protocols relating to quantifying the heat liberated by highly-concentrated NP colloids. For biological systems, in the case of in vitro experiments, we describe the techniques and conditions which must be adhered to in order to effectively expose cancer cells to RF energy without bulk media heating artifacts significantly obscuring the data. Finally, we give a detailed methodology for in vivo mouse models with ectopic hepatic cancer tumors.

  7. Toward a protocol for quantifying the greenhouse gas balance and identifying mitigation options in smallholder farming systems

    NASA Astrophysics Data System (ADS)

    Rosenstock, T. S.; Rufino, M. C.; Butterbach-Bahl, K.; Wollenberg, E.

    2013-06-01

    GHG budgets for developing economies. This dearth of information constrains the capacity to transition to low-carbon agricultural development, opportunities for smallholders to capitalize on carbon markets, and the negotiating position of developing countries in global climate policy discourse. Concerns over the poor state of information, in terms of data availability and representation, have fueled appeals for new approaches to quantifying GHG emissions and removals from smallholder agriculture, for both existing conditions and mitigation interventions (Berry and Ryan 2013, Olander et al 2013). Considering the dependence of quantification approaches on data and the current data deficit for smallholder systems, it is clear that in situ measurements must be a core part of initial and future strategies to improve GHG inventories and develop mitigation measures for smallholder agriculture. Once more data are available, especially for farming systems of high priority (e.g., those identified through global and regional rankings of emission hotspots or mitigation leverage points), better cumulative estimates and targeted actions will become possible. Greenhouse gas measurements in agriculture are expensive, time consuming, and error prone. These challenges are exacerbated by the heterogeneity of smallholder systems and landscapes and the diversity of methods used. Concerns over methodological rigor, measurement costs, and the diversity of approaches, coupled with the demand for robust information suggest it is germane for the scientific community to establish standards of measurements—'a protocol'—for quantifying GHG emissions from smallholder agriculture. A standard protocol for use by scientists and development organizations will help generate consistent, comparable, and reliable data on emissions baselines and allow rigorous comparisons of mitigation options. Besides enhancing data utility, a protocol serves as a benchmark for non-experts to easily assess data

  8. Intestinal and peri-tumoral lymphatic endothelial cells are resistant to radiation-induced apoptosis

    SciTech Connect

    Sung, Hoon Ki; Morisada, Tohru; Cho, Chung-Hyun; Oike, Yuichi; Lee, Jayhun; Sung, Eon Ki; Chung, Jae Hoon; Suda, Toshio; Koh, Gou Young . E-mail: gykoh@kaist.ac.kr

    2006-06-30

    Radiation therapy is a widely used cancer treatment, but it is unable to completely block cancer metastasis. The lymphatic vasculature serves as the primary route for metastatic spread, but little is known about how lymphatic endothelial cells respond to radiation. Here, we show that lymphatic endothelial cells in the small intestine and peri-tumor areas are highly resistant to radiation injury, while blood vessel endothelial cells in the small intestine are relatively sensitive. Our results suggest the need for alternative therapeutic modalities that can block lymphatic endothelial cell survival, and thus disrupt the integrity of lymphatic vessels in peri-tumor areas.

  9. The Socioeconomic Impact of Lymphatic Filariasis in Tropical Countries

    ERIC Educational Resources Information Center

    Nwoke, Bertram Ekejiuba Bright; Nwoke, Eunice Anyalewechi; Dozie, Ikechukwu Nosike Simplicius

    2007-01-01

    Lymphatic filariasis (LF) is an endemic parasitic disease and a major cause of acute and chronic morbidity and incapacitation with devastating public health and socio-economic consequences. It exacerbates poor conditions of afflicted persons and endemic communities through reduced or lost labour supply and productivity. Stigmatisation and…

  10. Monitoring contractile dermal lymphatic activity following uniaxial mechanical loading.

    PubMed

    Gray, R J; Worsley, P R; Voegeli, D; Bader, D L

    2016-09-01

    It is proposed that direct mechanical loading can impair dermal lymphatic function, contributing to the causal pathway of pressure ulcers. The present study aims to investigate the effects of loading on human dermal lymphatic vessels. Ten participants were recruited with ages ranging from 24 to 61 years. Participants had intradermal Indocyanine Green injections administrated between left finger digits. Fluorescence was imaged for 5min sequences with an infra-red camera prior to lymph vessel loading, immediately after axial loading (60mmHg) and following a recovery period. Image processing was employed to defined transient lymph packets and compare lymph function between each test phase. The results revealed that between 1-8 transient events (median=4) occurred at baseline, with a median velocity of 8.1mm/sec (range 4.1-20.1mm/sec). Immediately post-loading, there was a significant (p<0.05) reduction in velocity (median=6.4, range 2.2-13.5mm/sec), although the number of transient lymph packages varied between participants. During the recovery period the number (range 1-7) and velocity (recovery median=9.6mm/sec) of transient packets were largely restored to basal values. The present study revealed that some individuals present with impaired dermal lymphatic function immediately after uniaxial mechanical loading. More research is needed to investigate the effects of pressure and shear on lymphatic vessel patency. PMID:27245749

  11. Dermal lymphatic dilation in a mouse model of alopecia areata.

    PubMed

    Sundberg, John P; Pratt, C Herbert; Silva, Kathleen A; Kennedy, Victoria E; Stearns, Timothy M; Sundberg, Beth A; King, Lloyd E; HogenEsch, Harm

    2016-04-01

    Mouse models of various types of inflammatory skin disease are often accompanied by increased dermal angiogenesis. The C3H/HeJ inbred strain spontaneously develops alopecia areata (AA), a cell mediated autoimmune disorder that can be controllably expanded using full thickness skin grafts to young unaffected mice. This provides a reproducible and progressive model for AA in which the vascularization of the skin can be examined. Mice receiving skin grafts from AA or normal mice were evaluated at 5, 10, 15, and 20 weeks after engraftment. Lymphatics are often overlooked as they are small slit-like structures above the hair follicle that resemble artifact-like separation of collagen bundles with some fixatives. Lymphatics are easily detected using lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) by immunohistochemistry to label their endothelial cells. Using LYVE1, there were no changes in distribution or numbers of lymphatics although they were more prominent (dilated) in the mice with AA. Lyve1 transcripts were not significantly upregulated except at 10 weeks after skin grafting when clinical signs of AA first become apparent. Other genes involved with vascular growth and dilation or movement of immune cells were dysregulated, mostly upregulated. These findings emphasize aspects of AA not commonly considered and provide potential targets for therapeutic intervention.

  12. Dermal lymphatic dilation in a mouse model of alopecia areata.

    PubMed

    Sundberg, John P; Pratt, C Herbert; Silva, Kathleen A; Kennedy, Victoria E; Stearns, Timothy M; Sundberg, Beth A; King, Lloyd E; HogenEsch, Harm

    2016-04-01

    Mouse models of various types of inflammatory skin disease are often accompanied by increased dermal angiogenesis. The C3H/HeJ inbred strain spontaneously develops alopecia areata (AA), a cell mediated autoimmune disorder that can be controllably expanded using full thickness skin grafts to young unaffected mice. This provides a reproducible and progressive model for AA in which the vascularization of the skin can be examined. Mice receiving skin grafts from AA or normal mice were evaluated at 5, 10, 15, and 20 weeks after engraftment. Lymphatics are often overlooked as they are small slit-like structures above the hair follicle that resemble artifact-like separation of collagen bundles with some fixatives. Lymphatics are easily detected using lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) by immunohistochemistry to label their endothelial cells. Using LYVE1, there were no changes in distribution or numbers of lymphatics although they were more prominent (dilated) in the mice with AA. Lyve1 transcripts were not significantly upregulated except at 10 weeks after skin grafting when clinical signs of AA first become apparent. Other genes involved with vascular growth and dilation or movement of immune cells were dysregulated, mostly upregulated. These findings emphasize aspects of AA not commonly considered and provide potential targets for therapeutic intervention. PMID:26960166

  13. Population Dynamics P System (PDP) Models: A Standardized Protocol for Describing and Applying Novel Bio-Inspired Computing Tools

    PubMed Central

    Colomer, Maria Àngels; Margalida, Antoni; Pérez-Jiménez, Mario J.

    2013-01-01

    Today, the volume of data and knowledge of processes necessitates more complex models that integrate all available information. This handicap has been solved thanks to the technological advances in both software and hardware. Computational tools available today have allowed developing a new family of models, known as computational models. The description of these models is difficult as they can not be expressed analytically, and it is therefore necessary to create protocols that serve as guidelines for future users. The Population Dynamics P systems models (PDP) are a novel and effective computational tool to model complex problems, are characterized by the ability to work in parallel (simultaneously interrelating different processes), are modular and have a high computational efficiency. However, the difficulty of describing these models therefore requires a protocol to unify the presentation and the steps to follow. We use two case studies to demonstrate the use and implementation of these computational models for population dynamics and ecological process studies, discussing briefly their potential applicability to simulate complex ecosystem dynamics. PMID:23593284

  14. Population Dynamics P system (PDP) models: a standardized protocol for describing and applying novel bio-inspired computing tools.

    PubMed

    Colomer, Maria Àngels; Margalida, Antoni; Pérez-Jiménez, Mario J

    2013-01-01

    Today, the volume of data and knowledge of processes necessitates more complex models that integrate all available information. This handicap has been solved thanks to the technological advances in both software and hardware. Computational tools available today have allowed developing a new family of models, known as computational models. The description of these models is difficult as they can not be expressed analytically, and it is therefore necessary to create protocols that serve as guidelines for future users. The Population Dynamics P systems models (PDP) are a novel and effective computational tool to model complex problems, are characterized by the ability to work in parallel (simultaneously interrelating different processes), are modular and have a high computational efficiency. However, the difficulty of describing these models therefore requires a protocol to unify the presentation and the steps to follow. We use two case studies to demonstrate the use and implementation of these computational models for population dynamics and ecological process studies, discussing briefly their potential applicability to simulate complex ecosystem dynamics.

  15. Podoplanin-Fc reduces lymphatic vessel formation in vitro and in vivo and causes disseminated intravascular coagulation when transgenically expressed in the skin.

    PubMed

    Cueni, Leah N; Chen, Lu; Zhang, Hui; Marino, Daniela; Huggenberger, Reto; Alitalo, Annamari; Bianchi, Roberta; Detmar, Michael

    2010-11-18

    Podoplanin is a small transmembrane protein required for development and function of the lymphatic vascular system. To investigate the effects of interfering with its function, we produced an Fc fusion protein of its ectodomain. We found that podoplanin-Fc inhibited several functions of cultured lymphatic endothelial cells and also specifically suppressed lymphatic vessel growth, but not blood vessel growth, in mouse embryoid bodies in vitro and in mouse corneas in vivo. Using a keratin 14 expression cassette, we created transgenic mice that overexpressed podoplanin-Fc in the skin. No obvious outward phenotype was identified in these mice, but surprisingly, podoplanin-Fc-although produced specifically in the skin-entered the blood circulation and induced disseminated intravascular coagulation,