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Sample records for protocols lymphatic system

  1. Who discovered the lymphatic system.

    PubMed

    Chikly, B

    1997-12-01

    The 17th century saw several emerging and almost simultaneous discoveries in the field of lymphology by Asselli, Pecquet, Bartholin and possibly Joliffe. However, Olof Rudbeck (1630-1708) of Sweden, a true scientific genius, who mastered botany, chemistry, physics, mathematics, astronomy, music, drawing, architecture and engineering, and became the Rector of the Faculty of Upsala, was probably the first anatomist to consider correctly the lymphatic circulation as an integrated system of the whole body. PMID:9476250

  2. Modelling the lymphatic system: challenges and opportunities

    PubMed Central

    Margaris, K. N.; Black, R. A.

    2012-01-01

    The lymphatic system is a vital part of the circulatory and immune systems, and plays an important role in homeostasis by controlling extracellular fluid volume and in combating infection. Nevertheless, there is a notable disparity in terms of research effort expended in relation to the treatment of lymphatic diseases in contrast to the cardiovascular system. While similarities to the cardiovascular system exist, there are considerable differences in their anatomy and physiology. This review outlines some of the challenges and opportunities for those engaged in modelling biological systems. The study of the lymphatic system is still in its infancy, the vast majority of the models presented in the literature to date having been developed since 2003. The number of distinct models and their variants are few in number, and only one effort has been made thus far to study the entire lymphatic network; elements of the lymphatic system such as the nodes, which act as pumps and reservoirs, have not been addressed by mathematical models. Clearly, more work will be necessary in combination with experimental verification in order to progress and update the knowledge on the function of the lymphatic system. As our knowledge and understanding of its function increase, new and more effective treatments of lymphatic diseases are bound to emerge. PMID:22237677

  3. The lymphatic system. Some surgical considerations.

    PubMed

    Glenn, W W

    1981-08-01

    This article on the lymphatics was undertaken for three reasons: The first is to recount the story of the rediscovery of these vessels in the 17th century and briefly review the subsequent events leading up to our present knowledge of the lymphatic system. The second is to emphasize the role of the lymphatics in maintaining extracellular fluid balance, in the removal of protein, fat, and other substances of large molecular size from the tissue spaces, and in the circulation of the lymphocytes from their germinal centers and storage depots to all parts of the body via lymphaticovenous connections. The third reason is to suggest that the responsibility for maintaining the transport function of the lymphatics properly belongs to the vascular surgeon. PMID:7020649

  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. PMID:26863922

  5. Breast cancer metastasis and the lymphatic system

    PubMed Central

    RAHMAN, MUNAZZAH; MOHAMMED, SULMA

    2015-01-01

    Breast cancer remains the leading cause of cancer mortality worldwide, despite a significant decline in death rates due to early detection. The majority of cancer mortalities are due to the metastasis of tumor cells to other organs. Metastasis or tumor cell dissemination occurs via the hematogenous and lymphatic systems. For many carcinomas, the dissemination of tumor cells via lymphatic drainage of the tumor is the most common metastatic route. Such lymphatic drainage collects at the regional lymph nodes and the dissection and pathological examination of these nodes for lodged cancer cells is the gold standard procedure to detect metastasis. The present report provides an overview of the lymphatic system and its clinical significance as a prognostic factor, in addition to the interactions between the primary tumor and its microenvironment, and the influence of genomic subtypes on the resulting organ-specific pattern of tumor cell dissemination. It also examines the seemingly protracted asymptomatic period, during which the disseminated cells remain dormant, leading to the manifestation of metastasis decades after the successful treatment of the primary tumor. PMID:26622656

  6. 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. PMID:26980792

  7. 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

  8. 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

  9. 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. PMID:26009246

  10. 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 ...

  11. 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. ...

  12. 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. PMID:26030524

  13. Structural and functional features of central nervous system lymphatics

    PubMed Central

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

    2015-01-01

    One of the characteristics of the CNS is the lack of a classical lymphatic drainage system. Although it is now accepted that the CNS undergoes constant immune surveillance that takes place within the meningeal compartment1–3, the mechanisms governing the entrance and exit of immune cells from the CNS remain poorly understood4–6. 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 CSF, 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 CNS. The discovery of the CNS lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and shed new light on the etiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction. PMID:26030524

  14. 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

  15. Lymphatic system: a vital link between metabolic syndrome and inflammation.

    PubMed

    Chakraborty, Sanjukta; Zawieja, Scott; Wang, Wei; Zawieja, David C; Muthuchamy, Mariappan

    2010-10-01

    Metabolic syndrome is defined by a cluster of different metabolic risk factors that include overall and central obesity, elevated fasting glucose levels, dyslipidemia, hypertension, and intimal atherogenesis. Metabolic syndrome leads to increased risk for the development of type 2 diabetes and cardiovascular disease (e.g., heart disease and stroke). The exacerbated progression of metabolic syndrome to cardiovascular disease has lead to intense study of the physiological ramifications of metabolic syndrome on the blood vasculature. These studies have particularly focused on the signaling and architectural alterations that manifest in hypertension and atherosclerosis. However, despite the overlap of metabolic syndrome pathology with lymphatic function, tangent effects on the lymphatic system have not been extensively documented. In this review, we discuss the current status of metabolic syndrome and provide evidence for, and the remaining challenges in studying, the connections among the lymphatic system, lipid transport, obesity, insulin resistance, and general inflammation. PMID:20961312

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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. PMID:26471369

  2. 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. PMID:26572785

  3. 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

  4. Drug delivery to the lymphatic system: importance in future cancer diagnosis and therapies

    PubMed Central

    Xie, Yumei; Bagby, Taryn R; Cohen, MS

    2011-01-01

    Cancer is the second leading cause of death in the US. Currently, protocols for cancer treatment include surgery to remove diseased and suspect tissues, focused radiation, systemic chemotherapy, immunotherapy and their combinations. With conventional chemotherapy, it is almost impossible to deliver anticancer drugs specifically to the tumor cells without damaging healthy organs or tissues. Over the past several decades, efforts have been made to improve drug delivery technologies that target anticancer drugs specifically to tumor cells. It has been known for over four decades that the lymphatics are the first site of metastasis for most solid cancers; however, few efforts have been made to localize chemotherapies to lymphatic tissues. Trials of several systemic targeted drug delivery systems based on nanoparticles containing chemotherapeutic agents (e.g., liposomal doxorubicin) have shown similar antitumor activity but better patient tolerance compared with conventional formulations. Animal studies have demonstrated that nanoparticles made of natural or synthetic polymers and liposomal carriers have higher accumulation in the lymph nodes and surrounding lymphatics compared to conventional intravenous therapies. This combination has the potential to both reduce nonspecific organ toxicities and increase the chemotherapeutic dose to the most likely sites of locoregional cancer metastasis. PMID:19563270

  5. Imaging Lymphatic System in Breast Cancer Patients with Magnetic Resonance Lymphangiography

    PubMed Central

    Lu, Qing; Hua, Jia; Kassir, Mohammad M.; Delproposto, Zachary; Dai, Yongming; Sun, Jingyi; Haacke, Mark; Hu, Jiani

    2013-01-01

    Objective To investigate the feasibility of gadolinium (Gd) contrast-enhanced magnetic resonance lymphangiography (MRL) in breast cancer patients within a typical clinical setting, and to establish a Gd-MRL protocol and identify potential MRL biomarkers for differentiating metastatic from non-metastatic lymph nodes. Materials and Methods 32 patients with unilateral breast cancer were enrolled and divided into 4 groups of 8 patients. Groups I, II, and III received 1.0, 0.5, and 0.3 ml of intradermal contrast; group IV received two 0.5 ml doses of intradermal contrast. MRL images were acquired on a 3.0 T system and evaluated independently by two radiologists for the number and size of enhancing lymph nodes, lymph node contrast uptake kinetics, lymph vessel size, and contrast enhancement patterns within lymph nodes. Results Group III patients had a statistically significant decrease in the total number of enhancing axillary lymph nodes and lymphatic vessels compared to all other groups. While group IV patients had a statistically significant faster time to reach the maximum peak enhancement over group I and II (by 3 minutes), there was no other statistically significant difference between imaging results between groups I, II, and IV. 27 out of 128 lymphatic vessels (21%) showed dilatation, and all patients with dilated lymphatic vessels were pathologically proven to have metastases. Using the pattern of enhancement defects as the sole criterion for identifying metastatic lymph nodes during Gd-MRL interpretation, and using histopathology as the gold standard, the sensitivity and specificity were estimated to be 86% and 95%, respectively. Conclusion Gd-MRL can adequately depict the lymphatic system, can define sentinel lymph nodes, and has the potential to differentiate between metastatic and non-metastatic lymph nodes in breast cancer patients. PMID:23861979

  6. 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 ( ...

  7. 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

  8. 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

  9. 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. PMID:26077718

  10. Lymphatics and the breast

    MedlinePlus Videos and Cool Tools

    ... a very worrisome role in the spread of breast cancer. Components of the lymphatic system called lymph ... extensive network of lymphatic vessels in every woman’s breast tissue, which is important in regulating the local ...

  11. Artificial Lymphatic Drainage Systems for Vascularized Microfluidic Scaffolds

    PubMed Central

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

    2012-01-01

    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 mg/mL to 30 mg/mL and scaffold hydraulic conductivity decreased by a factor of twenty. 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 by 0.9 cm2) 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

  12. 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

  13. 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

  14. Afferent lymphatic cannulation as a model system to study innate immune responses to infection and vaccination.

    PubMed

    Neeland, Melanie R; Meeusen, Els N T; de Veer, Michael J

    2014-03-15

    The afferent lymphatics consist of the cells and immunomodulatory signals that are involved in the early response to peripheral stimuli. Examination of this compartment in both homeostatic and stimulatory conditions permits the analysis of the innate biological pathways responsible for the generation of an adaptive immune response in the lymph node. Afferent lymphatic cannulation is therefore an ideal model system to study cellular migration and antigen dispersal kinetics during infection and vaccination. Utilisation of these lymphatic cannulation models has demonstrated the ability to both increase current understanding of infectious diseases, vaccine delivery systems and has the potential to target effector cells and molecules that may be used as novel therapeutic or vaccine targets. PMID:23369582

  15. 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

  16. 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

  17. 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.

  18. Vegfr3-CreER (T2) mouse, a new genetic tool for targeting the lymphatic system.

    PubMed

    Martinez-Corral, Ines; Stanczuk, Lukas; Frye, Maike; Ulvmar, Maria Helena; Diéguez-Hurtado, Rodrigo; Olmeda, David; Makinen, Taija; Ortega, Sagrario

    2016-07-01

    The lymphatic system is essential in many physiological and pathological processes. Still, much remains to be known about the molecular mechanisms that control its development and function and how to modulate them therapeutically. The study of these mechanisms will benefit from better controlled genetic mouse models targeting specifically lymphatic endothelial cells. Among the genes expressed predominantly in lymphatic endothelium, Vegfr3 was the first one identified and is still considered to be one of the best lymphatic markers and a key regulator of the lymphatic system. Here, we report the generation of a Vegfr3-CreER (T2) knockin mouse by gene targeting in embryonic stem cells. This mouse expresses the tamoxifen-inducible CreER(T2) recombinase under the endogenous transcriptional control of the Vegfr3 gene without altering its physiological expression or regulation. The Vegfr3-CreER (T2) allele drives efficient recombination of floxed sequences upon tamoxifen administration specifically in Vegfr3-expressing cells, both in vitro, in primary lymphatic endothelial cells, and in vivo, at different stages of mouse embryonic development and postnatal life. Thus, our Vegfr3-CreER (T2) mouse constitutes a new powerful genetic tool for lineage tracing analysis and for conditional gene manipulation in the lymphatic endothelium that will contribute to improve our current understanding of this system. PMID:26993803

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

    PubMed

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

    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. PMID:23224192

  20. 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.

  1. 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

  2. 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. PMID:25636584

  3. Self-Emulsifying Drug Delivery System for Enhancing Bioavailability and Lymphatic Delivery of Tacrolimus.

    PubMed

    Cho, Hea-Young; Choi, Ji-Hoon; Oh, In-Joon; Lee, Yong-Bok

    2015-02-01

    A self-emulsifying drug delivery system (SEDDS) containing tacrolimus has been developed to enhance the bioavailability and lymphatic delivery of tacrolimus. Solubility tests, combination tests, and phase diagrams were constructed for different sorts and ratios of oils, surfactants, and cosurfactants to identify optimal formulation. Optimized SEDDS was assessed for droplet size, zeta potential, stability in various media, and in vitro release. The tacrolimus-loaded SEDDS and commercial capsule (Prograf®) were orally administered (5 mg/kg) to rats. Whole blood, and mesenteric and axillary lymph node samples were taken and the concentrations of tacrolimus were measured to evaluate pharmacokinetic characteristics and the lymphatic delivery effects. The optimized SEDDS droplets were approximately 40 nm in size and stable enough to endure gastric pH environments. The release rate of tacrolimus from SEDDS was significantly higher than that from the commercial capsule. The bioavailability of tacrolimus in SEDDS after oral administration was significantly improved versus that of Prograf®. The lymphatic targeting efficiency of the prepared SEDDS formulation showed significantly greater than that of Prograf®. Our research indicates that prepared SEDDS can be an alternative to the conventional oral formulation of tacrolimus. Furthermore, SEDDS should be explored as a potential drug carrier for other lipophilic drugs. PMID:26353739

  4. 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

  5. Lymphatics and the breast

    MedlinePlus Videos and Cool Tools

    ... very worrisome role in the spread of breast cancer. Components of the lymphatic system called lymph nodes ... may result in the formation of a secondary cancer mass in a different location of the body. ...

  6. 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

  7. 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

  8. 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

  9. The lymphatic vasculature in disease.

    PubMed

    Alitalo, Kari

    2011-01-01

    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. PMID:22064427

  10. 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 ...

  11. 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

  12. 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

  13. OCULAR LYMPHATICS: STATE-OF-THE-ART REVIEW

    PubMed Central

    Chen, L.

    2015-01-01

    Research involving the lymphatic system has experienced an exponential progression during the past decade largely because of advancement of modern technology and discovery of several lymphatic specific molecules. The eye provides an excellent site for lymphatic studies due to its accessible location and the unique feature of tissue heterogeneity – while some tissues are lymphatic-rich, others are lymphatic-free or -inducible. This review provides an update on our current understanding of ocular lymphatics and possible associated eye diseases. PMID:19725271

  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. PMID:27522506

  15. 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

  16. 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. PMID:25961925

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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. PMID:25324429

  5. 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.

  6. Optimal protocols for slowly driven quantum systems.

    PubMed

    Zulkowski, Patrick R; DeWeese, Michael R

    2015-09-01

    The design of efficient quantum information processing will rely on optimal nonequilibrium transitions of driven quantum systems. Building on a recently developed geometric framework for computing optimal protocols for classical systems driven in finite time, we construct a general framework for optimizing the average information entropy for driven quantum systems. Geodesics on the parameter manifold endowed with a positive semidefinite metric correspond to protocols that minimize the average information entropy production in finite time. We use this framework to explicitly compute the optimal entropy production for a simple two-state quantum system coupled to a heat bath of bosonic oscillators, which has applications to quantum annealing. PMID:26465432

  7. 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

  8. A three-drug nanoscale drug delivery system designed for preferential lymphatic uptake for the treatment of metastatic melanoma.

    PubMed

    Doddapaneni, Bhuvana S; Kyryachenko, Sergiy; Chagani, Sharmeen E; Alany, Raid G; Rao, Deepa A; Indra, Arup K; Alani, Adam W G

    2015-12-28

    Metastatic melanoma has a high mortality rate due to lymphatic progression of the disease. Current treatment is surgery followed by radiation and intravenous chemotherapy. However, drawbacks for current chemotherapeutics lie in the fact that they develop resistance and do not achieve therapeutic concentrations in the lymphatic system. We hypothesize that a three-drug nanoscale drug delivery system, tailored for lymphatic uptake, administered subcutaneously, will have decreased drug resistance and therefore offer better therapeutic outcomes. We prepared and characterized nanoparticles (NPs) with docetaxel, everolimus, and LY294002 in polyethyleneglycol-block-poly(ε-caprolactone) (PEG-PCL) polymer with different charge distributions by modifying the ratio of anionic and neutral end groups on the PEG block. These NPs are similarly sized (~48 nm), with neutral, partially charged, or fully charged surface. The NPs are able to load ~2mg/mL of each drug and are stable for 24h. The NPs are assessed for safety and efficacy in two transgenic metastatic melanoma mouse models. All the NPs were safe in both models based on general appearance, weight changes, death, and blood biochemical analyses. The partially charged NPs are most effective in decreasing the number of melanocytes at both the proximal (sentinel) lymph node (LN) and the distal LN from the injection site. The neutral NPs are efficacious at the proximal LN, while the fully charged NPs have no effect on either LNs. Thus, our data indicates that the NP surface charge and lymphatic efficacy are closely tied to each other and the partially charged NPs have the highest potential in treating metastatic melanoma. PMID:26578440

  9. 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.

  10. [Lymphatic endothelium in certain conditions].

    PubMed

    Nimaev, V V; Liubasrskiĭ, M S; Shevela, A I

    2013-01-01

    Presented herein is a review of the literature data concerning the structural and functional peculiarities of the endothelium of the lymphatic and blood vessels. The authors consider the current state of the art of the problem regarding dysfunction of lymphatic endothelium dysfunctions developing in various diseases, as well as in the process of ontogenesis, pointing out an important role of impaired processes of lymphangiogenesis, underlying the development of diseases of the lymphatic system. The authors also assess administration of quercetine in treatment for chronic venous insufficiency, followed by suggesting a possible mechanism of its positive action consisting ina decrease in the oedema at early stages of lymphoedema. PMID:23901429

  11. Applying QCVV protocols to real physical systems

    NASA Astrophysics Data System (ADS)

    Magesan, Easwar

    As experimental systems move closer to realizing small-scale quantum computers with high fidelity operations, errors become harder to detect and diagnose. Verification and validation protocols are becoming increasingly important for detecting and understanding the precise nature of these errors. I will outline various methods and protocols currently used to deal with errors in experimental systems. I will also discuss recent advances in implementing high fidelity operations which will help to understand some of the tools that are still needed on the road to realizing larger scale quantum systems. Work partially supported by ARO under Contract W911NF-14-1-0124.

  12. Gastrointestinal Lymphatics in Health and Disease

    PubMed Central

    Alexander, J.S.; Ganta, Vijay C.; Jordan, P.A.; Witte, Marlys H.

    2010-01-01

    Lymphatics perform essential transport and immune cell regulatory functions to maintain homeostasis in the gastrointestinal (GI) system. Although blood and lymphatic vessels function as parallel and integrated systems, our understanding of lymphatic structure, regulation and functioning lags far behind that of the blood vascular system. This chapter reviews lymphatic flow, differences in lymphangiogenic and hemangiogenic factors, lymphatic fate determinants and structural features, and examines how altered molecular signaling influences lymphatic function in organs of the GI system. Innate errors in lymphatic development frequently disturb GI functioning and physiology. Expansion of lymphatics, a prominent feature of GI inflammation, may also play an important role in tissue restitution following injury. Destruction or dysregulation of lymphatics, following injury, surgery or chronic inflammation also appears to exacerbate GI disease activity and morbidity. Understanding the physiological roles played by GI lymphatics is essential to elucidating their underlying contributions to forms of congenital and acquired forms of GI pathology, and will provide novel approaches for treatment of these conditions. PMID:20022228

  13. Network protocols for mobile robot systems

    NASA Astrophysics Data System (ADS)

    Gage, Douglas W.

    1998-01-01

    Communications and communications protocols will play an important role in mobile robot systems able to address real world applications. A poorly integrated 'stack' of communications protocols, or protocols which are poorly matched to the functional and performance characteristics of the underlying physical communications links, can greatly reduce the effectiveness of an otherwise well implemented robotic or networked sensors system. The proliferation of Internet-like networks in military as well as civilian domains has motivated research to address some of the performance limitations TCP suffers when using RF and other media with long bandwidth-delay, dynamic connectivity, and error-prone links. Beyond these performance issues, however, TCP is poorly matched to the requirements of mobile robot and other quasi-autonomous systems: it is oriented to providing a continuous data stream, rather than discrete messages, and the canonical 'socket' interface conceals short losses of communications connectivity, but simply gives up and forces the application layer software to deal with longer losses. For the multipurpose security and surveillance mission platform project, a software applique is being developed that will run on top of user datagram protocol to provide a reliable message-based transport service. In addition, a session layer protocol is planned to support the effective transfer of control of multiple platforms among multiple stations.

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

    PubMed Central

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

    2013-01-01

    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. PMID:24101508

  15. Dual origin of avian lymphatics.

    PubMed

    Wilting, Jörg; Aref, Yama; Huang, Ruijin; Tomarev, Stanislav I; Schweigerer, Lothar; Christ, Bodo; Valasek, Petr; Papoutsi, Maria

    2006-04-01

    The earliest signs of the lymphatic vascular system are the lymph sacs, which develop adjacent to specific embryonic veins. It has been suggested that sprouts from the lymph sacs form the complete lymphatic vascular system. We have studied the origin of the jugular lymph sacs (JLS), the dermal lymphatics and the lymph hearts of avian embryos. In day 6.5 embryos, the JLS is an endothelial-lined sinusoidal structure. The lymphatic endothelial cells (LECs) stain (in the quail) positive for QH1 antibody and soybean agglutinin. As early as day 4, the anlagen of the JLS can be recognized by their Prox1 expression. Prox1 is found in the jugular section of the cardinal veins, and in scattered cells located in the dermatomes along the cranio-caudal axis and in the splanchnopleura. In the quail, such cells are positive for Prox1 and QH1. In the jugular region, the veins co-express the angiopoietin receptor Tie2. Quail-chick-chimera studies show that the peripheral parts of the JLS form by integration of cells from the paraxial mesoderm. Intra-venous application of DiI-conjugated acetylated low-density lipoprotein into day 4 embryos suggests a venous origin of the deep parts of the JLS. Superficial lymphatics are directly derived from the dermatomes, as shown by dermatome grafting. The lymph hearts in the lumbo-sacral region develop from a plexus of Prox1-positive lymphatic capillaries. Both LECs and muscle cells of the lymph hearts are of somitic origin. In sum, avian lymphatics are of dual origin. The deep parts of the lymph sacs are derived from adjacent veins, the superficial parts of the JLS and the dermal lymphatics from local lymphangioblasts. PMID:16457798

  16. The role of the lymphatic system in inflammatory-erosive arthritis.

    PubMed

    Bouta, Echoe M; Li, Jie; Ju, Yawen; Brown, Edward B; Ritchlin, Christopher T; Xing, Lianping; Schwarz, Edward M

    2015-02-01

    Rheumatoid arthritis (RA) is a prevalent inflammatory joint disease with enigmatic flares, which causes swelling, pain, and irreversible connective tissue damage. Recently, it has been demonstrated in murine models of RA that the popliteal lymph node (PLN) is a biomarker of arthritic flare, as it "expands" in size and contrast enhancement during a prolonged asymptomatic phase, prior to when it "collapses" with accelerated synovitis and joint erosion. This PLN collapse is associated with adjacent knee flare, decreases in PLN volume and contrast enhancement, lymphatic pulse and pumping pressure, and an increase in PLN pressure. Currently, it is known that PLN collapse is accompanied by a translocation of B cells from the follicles to the sinuses, effectively clogging the lymphatic sinuses of the PLN, and that B cell depletion therapy ameliorates arthritic flare by eliminating these B cells and restoring passive lymphatic flow from inflamed joints. Here we review the technological advances that have launched this area of research, describe future directions to help elucidate the potential mechanism of PLN collapse, and speculate on clinical translation towards new diagnostics and therapies for RA. PMID:25598390

  17. [Lymphoscintigraphic exploration in the limbs lymphatic disease].

    PubMed

    Baulieu, Françoise; Lorette, Gérard; Baulieu, Jean-Louis; Vaillant, Loïc

    2010-12-01

    Lymphoscintigraphy is based upon the physiological transport of small radioactive particles injected into interstitium toward lymphatic vessels and nodes. Lymphoscintigraphy directly investigates lymphatic system while other methods (ultrasounds, CT, MRI) investigate tissular consequences of lymphatic disease. The scintigraphic procedure has to be standardized in order to be reproducible. Lymphatic vessels, lymphatic nodes and interstitium are systematically analysed. Interpretation is visual and qualitative. Multiple abnormalities can be observed. However, none of them can consistently differentiate between primary and secondary lymphedema. Differential diagnosis is usually obtained by taking together clinical and lymphoscintigraphic data. By providing informations about lymphatic component and physiopathology of edema, lymphoscintigraphy contributes to the management of lymphedema. Hybrid imaging is a new imaging modality of edema. Recently used, it combines functional (scintigraphy) and anatomical (CT) data and seems to be able to provide further informations. PMID:20863652

  18. 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

  19. Hepatic lymphatics: anatomy and related diseases.

    PubMed

    Pupulim, Lawrence F; Vilgrain, Valérie; Ronot, Maxime; Becker, Christoph D; Breguet, Romain; Terraz, Sylvain

    2015-08-01

    The liver normally produces a large amount of lymph. It is estimated that between 25% and 50% of the lymph received by the thoracic duct comes from the liver. In normal conditions, hepatic lymphatics are not depicted on cross-sectional imaging. They are divided in lymphatics of deep system (lymphatics following the hepatic veins and the portal tract) and those of superficial system (convex surface and inferior surface). A variety of diseases may affect hepatic lymphatics and in general they manifest as lymphedema, lymphatic mass, or cystic lesions. Abnormal distended lymphatics are especially seen in periportal spaces as linear hypoattenuations on CT or strong linear hyperintensities on heavily T2-weighted MR imaging. Lymphatic tumor spread as in lymphoma and lymphangitic carcinomatosis manifests as periportal masses and regional lymph node enlargement. Lymphatic disruption after trauma or surgery is depicted as perihepatic fluid collections of lymph (lymphocele). Lymphatic malformation such as lymphangioma is seen on imaging as cystic spaces of variable size. PMID:25579171

  20. 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

  1. [Lymphatic malformations in the head and neck area].

    PubMed

    Wiegand, S; Werner, J A

    2016-02-01

    Lymphatic malformations are congenital malformations of the lymphatic system. They are mainly located in the head and neck area, and grow proportional to the patients' body growth. Depending on the morphology, it can be distinguished between macrocystic, microcystic and mixed lymphatic malformations. Due to their infiltrative growth, microcystic lymphatic malformations are particularly difficult to treat. Therapeutic approaches include conventional surgical resection, laser therapy, sclerotherapy and systemic drug therapies. PMID:26820157

  2. 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

  3. Lymphatic anatomy and biomechanics

    PubMed Central

    Negrini, Daniela; Moriondo, Andrea

    2011-01-01

    Abstract 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. PMID:21486777

  4. 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. PMID:26710573

  5. 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.

  6. 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.

  7. 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.

  8. 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 ...

  9. Advanced orbiting systems test-bedding and protocol verification

    NASA Technical Reports Server (NTRS)

    Noles, James; De Gree, Melvin

    1989-01-01

    The Consultative Committee for Space Data Systems (CCSDS) has begun the development of a set of protocol recommendations for Advanced Orbiting Systems (SOS). The AOS validation program and formal definition of AOS protocols are reviewed, and the configuration control of the AOS formal specifications is summarized. Independent implementations of the AOS protocols by NASA and ESA are discussed, and cross-support/interoperability tests which will allow the space agencies of various countries to share AOS communication facilities are addressed.

  10. MDA—Lymphatic Filariasis

    PubMed Central

    2014-01-01

    Lymphatic filariasis is one of the neglected tropical diseases. It is estimated that 120 million people are currently infected in 73 countries where filariasis is endemic. Lymphatic filariasis is a leading cause of chronic disability worldwide, including of 15 million people who have lymphoedema (elephantiasis) and 25 million men who have hydrocoele. PMID:25425947

  11. [Involvement of the lymphatic system in primary non-lymphogenic edema of the leg. Studies with 2-compartment lymphoscintigraphy].

    PubMed

    Bräutigam, P; Vanscheidt, W; Földi, E; Krause, T; Moser, E

    1997-08-01

    Two-compartment lymphoscintigraphy was developed to examine the sub- and epifascial lymphatics of the leg. Digital images were evaluated visually and semiquantitatively by calculating the uptake of activity within the lymph nodes. The data from patient groups with four different types of leg edema were compared with those of the control group to prove the involvement of the lymphatics in the non-lymphatic edema. The cyclic idiopathic edema demonstrated an accelerated transport of the lymph consistent with a high volume insufficiency. In phlebedema the high volume insufficiency was epifascially so distinct, that it could be detected scintigraphically. In post thrombotic syndrome the transport of the lymph was reduced dramatically corresponding to a safety valve insufficiency. Epifascially however, an accelerated lymph flow was observed due to compensatory mechanisms. The lipedema did not show any scintigraphic abnormalities. These results show that two-compartment lymphoscintigraphy can detect alterations in lymphatic function secondary to non-lymphogenic leg edema. The lymphatic function is changed according to the underlying pathophysiology which may be facilitate the differential diagnosis of such a leg edema. PMID:9378636

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Emerging trends in the pathophysiology of lymphatic contractile function

    PubMed Central

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

    2015-01-01

    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. PMID:25617600

  18. Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis

    PubMed Central

    Lahdenranta, Johanna; Hagendoorn, Jeroen; Padera, Timothy P.; Hoshida, Tohru; Nelson, Gregory; Kashiwagi, Satoshi; Jain, Rakesh K.; Fukumura, Dai

    2009-01-01

    Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vafscular endothelial growth factor (VEGF)-C and -D were identified. However, the mechanistic understanding of lymphatic metastasis is still in infancy. Nitric oxide (NO) plays a crucial role in regulating blood vessel growth and function as well as lymphatic vessel function. NOS expression correlates with lymphatic metastasis. However, causal relationship between NOS and lymphatic metastasis has not been documented. To this end, we first show that both VEGF receptor-2 and -3 stimulation activate eNOS in lymphatic endothelial cells and that NO donors induce proliferation and/or survival of cultured lymphatic endothelial cells in a dose dependent manner. We find that an NOS inhibitor L-NMMA blocked regeneration of lymphatic vessels. Using intravital microscopy that allows us to visualize the steps of lymphatic metastasis, we show that genetic deletion of eNOS as well as NOS blockade attenuates peritumor lymphatic hyperplasia of VEGF-C-overexpressing T241 fibrosarcomas and decreases the delivery of metastatic tumor cells to the draining lymph nodes. Genetic deletion of eNOS in the host also leads to a decrease in T241 tumor cell dissemination to the lymph nodes and macroscopic lymph node metastasis of B16F10 melanoma. These findings indicate that eNOS mediates VEGF-C induced lymphangiogenesis and, consequently, plays a critical role in lymphatic metastasis. Our findings explain the correlation between NOS and lymphatic metastasis seen in a number of human tumors and open the door for potential therapies exploiting NO signaling to treat diseases of the lymphatic system. PMID:19318557

  19. Genetics of lymphatic anomalies

    PubMed Central

    Brouillard, Pascal; Boon, Laurence; Vikkula, Miikka

    2014-01-01

    Lymphatic anomalies include a variety of developmental and/or functional defects affecting the lymphatic vessels: sporadic and familial forms of primary lymphedema, secondary lymphedema, chylothorax and chylous ascites, lymphatic malformations, and overgrowth syndromes with a lymphatic component. Germline mutations have been identified in at least 20 genes that encode proteins acting around VEGFR-3 signaling but also downstream of other tyrosine kinase receptors. These mutations exert their effects via the RAS/MAPK and the PI3K/AKT pathways and explain more than a quarter of the incidence of primary lymphedema, mostly of inherited forms. More common forms may also result from multigenic effects or post-zygotic mutations. Most of the corresponding murine knockouts are homozygous lethal, while heterozygotes are healthy, which suggests differences in human and murine physiology and the influence of other factors. PMID:24590274

  20. 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).

  1. VEGF Pathways in the Lymphatics of Healthy and Diseased Heart.

    PubMed

    Dashkevich, Alexey; Hagl, Christian; Beyersdorf, Friedhelm; Nykänen, Antti I; Lemström, Karl B

    2016-01-01

    Cardiac lymphatic system is a rare focus of the modern cardiovascular research. Nevertheless, the growing body of evidence is depicting lymphatic endothelium as an important functional unit in healthy and diseased myocardium. Since the discovery of angiogenic VEGF-A in 1983 and lymphangiogenic VEGF-C in 1997, an increasing amount of knowledge has accumulated on the essential roles of VEGF ligands and receptors in physiological and pathological angiogenesis and lymphangiogenesis. Tissue adaptation to several stimuli such as hypoxia, pathogen invasion, degenerative process and inflammation often involves coordinated changes in both blood and lymphatic vessels. As lymphatic vessels are involved in the initiation and resolution of inflammation and regulation of tissue edema, VEGF family members may have important roles in myocardial lymphatics in healthy and in cardiac disease. We will review the properties of VEGF ligands and receptors concentrating on their lymphatic vessel effects first in normal myocardium and then in cardiac disease. PMID:26190445

  2. 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

  3. 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

  4. Tissue-engineered lymphatic graft for the treatment of lymphedema

    PubMed Central

    Kanapathy, Muholan; Patel, Nikhil M.; Kalaskar, Deepak M.; Mosahebi, Afshin; Mehrara, Babak J.; Seifalian, Alexander M.

    2015-01-01

    Background Lymphedema is a chronic debilitating condition and curative treatment is yet to be found. Tissue engineering approach, which combines cellular components, scaffold, and molecular signals hold great potential in the treatment of secondary lymphedema with the advent of lymphatic graft to reconstruct damaged collecting lymphatic vessel. This review highlights the ideal characteristics of lymphatic graft, the limitation and challenges faced, and the approaches in developing tissue-engineered lymphatic graft. Methods Literature on tissue engineering of lymphatic system and lymphatic tissue biology was reviewed. Results The prime challenge in the design and manufacturing of this graft is producing endothelialized conduit with intraluminal valves. Suitable scaffold material is needed to ensure stability and functionality of the construct. Endothelialization of the construct can be enhanced via biofunctionalization and nanotopography, which mimics extracellular matrix. Nanocomposite polymers with improved performance over existing biomaterials are likely to benefit the development of lymphatic graft. Conclusions With the in-depth understanding of tissue engineering, nanotechnology, and improved knowledge on the biology of lymphatic regeneration, the aspiration to develop successful lymphatic graft is well achievable. PMID:25248852

  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. 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

  7. 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

  8. 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

  9. 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 ( ...

  10. Electric current-induced lymphatic activation.

    PubMed

    Kajiya, Kentaro; Matsumoto-Okazaki, Yuko; Sawane, Mika; Fukada, Kaedeko; Takasugi, Yuya; Akai, Tomonori; Saito, Naoki; Mori, Yuichiro

    2014-12-01

    The lymphatic system in skin plays important roles in drainage of wastes and in the afferent phase of immune response. We previously showed that activation of vascular endothelial growth factor receptor (VEGFR), specifically the VEGFC/VEGFR-3 pathway, attenuates oedema and inflammation by promoting lymphangiogenesis, suggesting a protective role of lymphatic vessels against skin inflammation. However, it remains unknown how physical stimuli promote lymphatic function. Here, we show that lymphatic endothelial cells (LECs) are activated by direct-current (DC) electrical stimulation, which induced extension of actin filaments of LECs, increased calcium influx into LECs, and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK). An inhibitor of focal adhesion kinase, which plays a role in cellular adhesion and motility, diminished the DC-induced extension of F-actin and abrogated p38 phosphorylation. Time-lapse imaging revealed that pulsed-DC stimulation promoted proliferation and migration of LECs. Overall, these results indicate that electro-stimulation activates lymphatic function by activating p38 MAPK. PMID:25308203

  11. Assessment of lymphatic contractile function following manual lymphatic drainage using near-infrared fluorescence imaging

    PubMed Central

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

    2011-01-01

    Objective To investigate the feasibility of assessing the efficacy of manual lymphatic drainage (MLD), a method for lymphedema (LE) management, using near-infrared (NIR) fluorescence imaging. Design Exploratory pilot study. Setting Primary care unit. Intervention Indocyanine green of 25 μg in 0.1 cc each was injected intradermally in bilateral arms or legs of subjects. Diffused excitation light illuminated the limbs and NIR fluorescence images were collected using custom-built imaging systems. The subjects received MLD therapy, and imaging was performed pre- and post- therapy. Participants Ten subjects (age 18 – 68) diagnosed with Grade I or II LE and 12 normal control subjects (age 22 – 59). Main outcome measures Apparent lymph velocities and the periods between lymphatic propulsion events were computed from fluorescence images. The data collected pre- and post- MLD were compared and evaluated for differences. Results By comparing the pre- MLD lymphatic contractile function against post- MLD lymphatic function, our results show that the average apparent lymph velocity increased in both the symptomatic (+23%) and asymptomatic (+25%) limbs of LE subjects and in the control limbs (+28%) of normal subjects. The average lymphatic propulsion period decreased in the symptomatic (−9%) and asymptomatic (−20%) limbs of LE subjects, as well as in the control limbs (−23%). Conclusions We demonstrated that NIR fluorescence imaging could be used to quantify immediate benefits of lymphatic contractile function following MLD. PMID:21530723

  12. Lymphatic Function Regulates Contact Hypersensitivity Dermatitis in Obesity.

    PubMed

    Savetsky, Ira L; Albano, Nicholas J; Cuzzone, Daniel A; Gardenier, Jason C; Torrisi, Jeremy S; García Nores, Gabriela D; Nitti, Matthew D; Hespe, Geoffrey E; Nelson, Tyler S; Kataru, Raghu P; Dixon, J Brandon; Mehrara, Babak J

    2015-11-01

    Obesity is a major risk factor for inflammatory dermatologic diseases, including atopic dermatitis and psoriasis. In addition, recent studies have shown that obesity impairs lymphatic function. As the lymphatic system is a critical regulator of inflammatory reactions, we tested the hypothesis that obesity-induced lymphatic dysfunction is a key regulator of cutaneous hypersensitivity reactions in obese mice. We found that obese mice have impaired lymphatic function, characterized by leaky capillary lymphatics and decreased collecting vessel pumping capacity. In addition, obese mice displayed heightened dermatitis responses to inflammatory skin stimuli, resulting in both higher peak inflammation and a delayed clearance of inflammatory responses. Injection of recombinant vascular endothelial growth factor-C remarkably increased lymphangiogenesis, lymphatic function, and lymphatic endothelial cell expression of chemokine (C-C motif) ligand 21, while decreasing inflammation and expression of inducible nitrous oxide synthase. These changes resulted in considerably decreased dermatitis responses in both lean and obese mice. Taken together, our findings suggest that obesity-induced changes in the lymphatic system result in an amplified and a prolonged inflammatory response. PMID:26176761

  13. Satellite link protocols design for the CODE system

    NASA Astrophysics Data System (ADS)

    Fernandez, A.; Vidaller, L.; Miguel, C.; Briones, D.

    1989-05-01

    The design of satellite link protocols for Very Small Aperture Terminals (VSAT) systems is outlined. The CODE system (Cooperative Olympus Data Experiment) is a VSAT system with two main characteristics: very low bit error rate, and multiple access over FDM channels in the inbound link. The design of the link protocols for this system covers two main aspects: error control procedures and medium access control procedures. In order to analyze both aspects, a profile of the average user of the CODE system is defined in terms of types of traffic and of messages arrival and service rates for every type of traffic. An analysis of the mean time between failures is made, and the average delay and through-put for different access methods are computed, including stability analysis for Aloha-based systems.

  14. 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

  15. 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

  16. 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

  17. Contributions of the lymphatic and microvascular systems to fluid absorption from the synovial cavity of the rabbit knee.

    PubMed

    Levick, J R

    1980-09-01

    1. The trans-synovial flow (Qs) of Ringer solution from the cavity of immobile knee (stifle) joints was determined in anaesthetized rabbits when intra-articular hydrostatic pressure (PJ) was elevated in steps from 2 to 25 cm H2O. 2. It has been demonstrated previously (Levick, 1978) that slope DQs/dPJ shows an abrupt sixfold increase at a 'breaking point' (PB) around 9 . 5 cm H2O, rising from a mean of 0 . 49 microliter.min-1 cm H2O-1 (PJ less than PB) to 2 . 81 microliter.min-1 cm H2O-1 (PJ greater than PB). 3. Perforation of the synovial intima by an intra-articular cannula increased dQs/dPJ below breaking pressure and thus largely abolished the breaking point phenomenon, indicating that the phenomenon might be simulated by a break-down in synovial resistance to flow. 4. Ligation of the femoral lymph trunks draining the joint did not significantly alter the relationship between Qs and PJ. The slope dQs/dPJ was 0 . 60 +/- 0 . 17 microliter.min-1 cm H2O-1 (mean +/- S.E.) below a breaking pressure of 8 . 8--10.5 cm H2O, and 2 . 90 +/- 0 . 64 microliter.min-1 cm H2O-1 above breaking pressure. Thus changes in synovial lymph flow did not explain the breaking point phenomenon. 5. Interruption of synovial blood flow by vascular clamps or by killing the animal reduced, but did not abolish fluid absorption; nor was the breaking point phenomenon abolished. Slope dQs/dPJ increased from 0 . 37 +/- 0 . 06 microliter.min-1 cm H2O-1 below breaking point (10 . 5 +/- 1 . 0 cm H2O) to between 1 . 82 and 0 . 96 +/- 0 . 15 microliter.min-1 cm H2O-1 above breaking pressure. Fluid accumulated in extra-synovial interstitial spaces. 6. When the synovial intima was divested of its surrounding tissues, lymphatic and vascular supplies by extensive dissection, the denuded synovium still showed a marked increase in hydraulic conductivity at normal breaking pressures. The breaking point phenomenon was therefore not caused by changes in extra-synovial interstitial pressure or compliance. 7. It

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Primary and Secondary Lymphatic Valve Development: Molecular, Functional and Mechanical Insights

    PubMed Central

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

    2015-01-01

    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. PMID:25086182

  5. 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. PMID:25086182

  6. 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. PMID:26453331

  7. Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development

    PubMed Central

    Wu, June K.; Kitajewski, Christopher; Reiley, Maia; Keung, Connie H.; Monteagudo, Julie; Andrews, John P.; Liou, Peter; Thirumoorthi, Arul; Wong, Alvin

    2015-01-01

    Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133− cells isolated from LM fluids. CD133− LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133− LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs. PMID:25719418

  8. 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

  9. Measurement and protocol for evaluating video and still stabilization systems

    NASA Astrophysics Data System (ADS)

    Cormier, Etienne; Cao, Frédéric; Guichard, Frédéric; Viard, Clément

    2013-01-01

    This article presents a system and a protocol to characterize image stabilization systems both for still images and videos. It uses a six axes platform, three being used for camera rotation and three for camera positioning. The platform is programmable and can reproduce complex motions that have been typically recorded by a gyroscope mounted on different types of cameras in different use cases. The measurement uses a single chart for still image and videos, the texture dead leaves chart. Although the proposed implementation of the protocol uses a motion platform, the measurement itself does not rely on any specific hardware. For still images, a modulation transfer function is measured in different directions and is weighted by a contrast sensitivity function (simulating the human visual system accuracy) to obtain an acutance. The sharpness improvement due to the image stabilization system is a good measurement of performance as recommended by a CIPA standard draft. For video, four markers on the chart are detected with sub-pixel accuracy to determine a homographic deformation between the current frame and a reference position. This model describes well the apparent global motion as translations, but also rotations along the optical axis and distortion due to the electronic rolling shutter equipping most CMOS sensors. The protocol is applied to all types of cameras such as DSC, DSLR and smartphones.

  10. A Model for Interstitial Drainage Through a Sliding Lymphatic Valve.

    PubMed

    Heppell, Charles; Roose, Tiina; Richardson, Giles

    2015-06-01

    This study investigates fluid flow and elastic deformation in tissues that are drained by the primary lymphatic system. A model is formulated based on the Rossi hypothesis that states that the primary lymphatic valves, which are formed by overlapping endothelial cells around the circumferential lining of lymphatic capillaries, open in response to swelling of the surrounding tissue. Tissue deformation and interstitial fluid flow through the tissue are treated using the Biot equations of poroelasticity and, the fluid flux (into the interstitium) across the walls of the blood capillaries, is assumed to be linearly related to the pressure difference across the walls via a constant of proportionality (the vascular permeability). The resulting model is solved in a periodic domain containing one blood capillary and one lymphatic capillary starting from a configuration in which the tissue is undeformed. On imposition of a constant pressure difference between blood and lymphatic capillaries, the solutions are found to settle to a steady state. Given that the magnitude of pressure fluctuations in the lymphatic system is much smaller than this pressure difference between blood and lymph, it is postulated that the resulting steady-state solution gives a good representation of the state of the tissue under physiological conditions. The effects of changes to the Young's modulus of the tissue, the blood-lymphatic pressure difference, vascular permeability and valve dimensions on the steady state are investigated and discussed in terms of their effects on oedema in the context of age- and pregnancy-related changes to the body. PMID:25911590

  11. A protocol for secure communication in large distributed systems

    NASA Astrophysics Data System (ADS)

    Anderson, D. P.; Ferrari, D.; Rangan, P. V.; Sartirana, B.

    1987-01-01

    A mechanism for secure communication in large distributed systems is proposed. The mechanism, called Authenticated Datagram Protocol (ADP), provides message authentication and, optionally, privacy of data. ADP is a host-to-host datagram protocol, positioned below the transport layer; it uses public-key encryption to establish secure channels between hosts and to authenticate owners, and single-key encryption for communication over a channel and to ensure privacy of the messages. ADP is shown to satisfy the main security requirements of large distributed systems, to provide end-to-end security in spite of its relatively low level, and to exhibit several advantages over schemes in which security mechanisms are at a higher level. The results of a trace-driven measurement study of ADP performance show that its throughput and latency are acceptable even within the limitations of today's technology, provided single-key encryption/decryption can be done in hardware.

  12. Control systems and coordination protocols of the secretory pathway.

    PubMed

    Luini, Alberto; Mavelli, Gabriella; Jung, Juan; Cancino, Jorge

    2014-01-01

    Like other cellular modules, the secretory pathway and the Golgi complex are likely to be supervised by control systems that support homeostasis and optimal functionality under all conditions, including external and internal perturbations. Moreover, the secretory apparatus must be functionally connected with other cellular modules, such as energy metabolism and protein degradation, via specific rules of interaction, or "coordination protocols". These regulatory devices are of fundamental importance for optimal function; however, they are generally "hidden" at steady state. The molecular components and the architecture of the control systems and coordination protocols of the secretory pathway are beginning to emerge through studies based on the use of controlled transport-specific perturbations aimed specifically at the detection and analysis of these internal regulatory devices. PMID:25374666

  13. The Linked Systems Protocol and the Future of Bibliographic Networks and Systems.

    ERIC Educational Resources Information Center

    Buckland, Michael K.; Lynch, Clifford A.

    1987-01-01

    Describes the Linked Systems Protocol, a draft national standard for bibliographic information retrieval aimed at developing an extended protocol for the movement of bibliographic information from one system to another, and its implications for library automation, the individual librarian, and the library user. (CLB)

  14. 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.

  15. Prognostic Value of a Simplified Anatomically Based Nomenclature for Fetal Nuchal Lymphatic Anomalies

    PubMed Central

    Longstreet, Beck; Balakrishnan, Karthik; Saltzman, Babette; Perkins, Jonathan A.; Dighe, Manjiri

    2015-01-01

    Objective To propose an anatomic classification for fetal nuchal lymphatic anomalies that will be clinically useful and to evaluate the classification’s value in predicting chromosomal abnormalities, pregnancy outcomes, other associated fetal anomalies, and spontaneous resolution of these lesions. Study Design Retrospective cohort study. Setting Tertiary academic hospital and affiliated tertiary children’s hospital. Subjects and Methods Mother-baby pairs diagnosed with fetal nuchal lymphatic anomalies in a prenatal ultrasound database. Anomalies were classified as nuchal thickening, dorsal lymphatic malformation, or ventral lymphatic malformation. Pregnancy outcomes, prevalence of chromosomal and anatomic abnormalities, and rates of spontaneous lesion resolution were determined for each group. Results The study included 189 patients: 58 with nuchal thickening, 120 with dorsal lymphatic malformation, and 11 with ventral lymphatic malformation. In fetuses for whom chromosomal analysis was available, chromosomal abnormalities were strongly associated with dorsal lymphatic malformations (83%), less associated with nuchal thickening (29%), and not associated with ventral lymphatic malformations. Dorsal lymphatic malformation predicted high rates of elective (43%) and spontaneous (20%) termination of pregnancy and showed the strongest association with cardiac, renal, and skeletal anomalies. Nuchal thickening was more likely to resolve in utero than dorsal lymphatic malformations, while no ventral lymphatic malformation resolved spontaneously. Conclusions Fetal nuchal anomalies demonstrate significant and clinically important prognostic differences depending on their anatomic location. The simple classification system proposed here therefore provides useful information to clinicians involved in the pre- and postnatal management of children with these anomalies. PMID:25411310

  16. Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis

    PubMed Central

    Altiok, Eda; Ecoiffier, Tatiana; Sessa, Roberto; Yuen, Don; Grimaldo, Sammy; Tran, Colin; Li, David; Rosner, Michael; Lee, Narae; Uede, Toshimitsu; Chen, Lu

    2015-01-01

    Purpose We recently reported that corneal lymphatic vessels develop integrin alpha-9 (Itga-9)-positive valves during inflammatory lymphangiogenesis. The purpose of this study was to further investigate the role of Itga-9 in corneal lymphatic valve formation in vivo and lymphatic endothelial cell (LEC) functions in vitro. Methods Standard murine suture placement model was used to study the effect of Itga-9 blockade on lymphatic valve formation in vivo using Itga-9 neutralizing antibody. Whole-mount corneas were harvested for immunofluorescent microscopic analysis. Additionally, human LEC culture system was used to examine the effect of Itga-9 gene knockdown on cell functions using small interfering RNAs (siRNAs). Results Itga-9 blockade in vivo significantly reduced the number of lymphatic valves formed in the inflamed cornea. Moreover, Itga-9 gene knockdown in human LECs suppresses cell functions of proliferation, adhesion, migration, and tube formation. Conclusions Itga-9 is critically involved in corneal lymphatic valve formation. Further investigation of the Itga-9 pathway may provide novel strategies to treat lymphatic-related diseases occurring both inside and outside the eye. PMID:26431485

  17. 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. PMID:26214518

  18. 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

  19. 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

  20. 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

  1. ASSESSMENT PROTOCOLS: DURABILITY OF PERFORMANCE OF A HOME RADON REDUCTION SYSTEM

    EPA Science Inventory

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

  2. 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

  3. 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

  4. Current and future lymphatic imaging modalities for tumor staging.

    PubMed

    Murtaza, Ghulam; Gao, Kuo; Liu, Tiegang; Tariq, Imran; Sajjad, Ashif; Akram, Muhammad Rouf; 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

  5. 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

  6. 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

  7. 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

  8. 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…

  9. Work-related road traffic injury: a multilevel systems protocol

    PubMed Central

    Newnam, Sharon; Sheppard, Dianne M; Griffin, Mark A; McClure, Roderick J; Heller, Gillian; Sim, Malcolm R; Stevenson, Mark R

    2014-01-01

    Background Although road traffic injury is reported as the leading cause of work-related death in Australia, it is not clear, due to limitations in previous methods used, just how large a burden it is. Many organisations are unaware of the extent of work-related road traffic injury and, importantly, what can be done to reduce the burden. The proposed research will (i) estimate the prevalence of work-related road traffic injury and (ii) identify the organisational determinants associated with work-related road traffic injury. Methods and design The current study is designed to enumerate the problem and identify the individual driver-level, the supervisor-level and organisational-level factors associated with work-related road traffic injury. The multilevel systems protocol will involve a series of cross-sectional surveys administered to drivers of fleet vehicles (n=1200), supervisors of the drivers (n=1200) and senior managers (n=300) within the same organisation. Discussion The novel use of the multilevel systems protocol is critical to be able to accurately assess the specific determinants of driving safety within each context of an organisation. Results The results are expected to highlight that reducing injury in the workplace requires more than just individual compliance with safety procedures. It will also establish, for the first time, an occupational translation taskforce to ensure that the research findings are adopted into work-place practice and thereby directly contribute to reductions in work-related road traffic injury. PMID:24478230

  10. 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

  11. 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.

  12. 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...

  13. 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.

  14. Return of lymphatic function after flap transfer for acute lymphedema.

    PubMed Central

    Slavin, S A; Van den Abbeele, A D; Losken, A; Swartz, M A; Jain, R K

    1999-01-01

    OBJECTIVE: The goals of this work were to develop animal models of lymphedema and tissue flap transfer, and to observe physiologic changes in lymphatic function that occur in these models over time, both systemically with lymphoscintigraphy (LS) and locally using fluorescence microlymphangiography (FM). SUMMARY BACKGROUND DATA: Although lymphedema has been managed by a combination of medical and surgical approaches, no effective long-term cure exists. Surgical attempts aimed at reconnecting impaired lymphatic channels or bypassing obstructed areas have failed. METHODS: The tails of rats (A groups) and mice (B groups) were used because of their different features. Lymphedema was created by ligation of the lymphatics at the tail base and quantified by diameter measurements there. In the experimental group, rectus abdominis myocutaneous flap was transferred across the ligation. In addition to the ligation (A1 and B1) and ligation + flap (A2 and B2) groups, three control groups were included: sham flap with ligation (B4), sham flap alone (B5), and normal (A3 and B3) animals. Observations were made at weekly time points for lymphatic function and continuity. RESULTS: Lymphedema was successfully created in the mouse ligation groups (B1 and B4) and sustained for the entire length of observation (up to 14 weeks). Lymphatic continuity was restored in those animals with transferred flaps across the ligation site (A2 and B2), as seen both by LS and FM. Sham flaps did not visibly affect lymphatic function nor did they cause any visible swelling in the tail. CONCLUSIONS: Acute lymphedema developing after ligation of tail lymphatics in mice can be prevented by myocutaneous flap transfer. Restored lymphatic continuity and function were demonstrable using lymphoscintigraphy and fluorescence microlymphangiography. Images Figure 2. Figure 4. Figure 5. PMID:10077056

  15. 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

  16. 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.

  17. Cardiac lymphatics are heterogeneous in origin and respond to injury

    PubMed Central

    Klotz, Linda; Norman, Sophie; Vieira, Joaquim Miguel; Masters, Megan; Rohling, Mala; Dubé, Karina N.; Bollini, Sveva; Matsuzaki, Fumio; Carr, Carolyn A.; Riley, Paul R.

    2015-01-01

    The lymphatic vasculature is a blind-ended network crucial for tissue fluid homeostasis, immune surveillance and lipid absorption from the gut. Recent evidence has proposed an entirely venous-derived mammalian lymphatic system. In contrast, we reveal here that cardiac lymphatic vessels have a heterogeneous cellular origin, whereby formation of at least part of the cardiac lymphatic network is independent of sprouting from veins. Multiple cre-lox based lineage tracing revealed a potential contribution from the hemogenic endothelium during development and discrete lymphatic endothelial progenitor populations were confirmed by conditional knockout of Prox1 in Tie2+ and Vav1+ compartments. In the adult heart, myocardial infarction (MI) promoted a significant lymphangiogenic response, which was augmented by treatment with VEGF-C resulting in improved cardiac function. These data prompt the re-evaluation of a century-long debate on the origin of lymphatic vessels and suggest that lymphangiogenesis may represent a therapeutic target to promote cardiac repair following injury. PMID:25992544

  18. 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

  19. The Glymphatic-Lymphatic Continuum: Opportunities for Osteopathic Manipulative Medicine.

    PubMed

    Hitscherich, Kyle; Smith, Kyle; Cuoco, Joshua A; Ruvolo, Kathryn E; Mancini, Jayme D; Leheste, Joerg R; Torres, German

    2016-03-01

    The brain has long been thought to lack a lymphatic drainage system. Recent studies, however, show the presence of a brain-wide paravascular system appropriately named the glymphatic system based on its similarity to the lymphatic system in function and its dependence on astroglial water flux. Besides the clearance of cerebrospinal fluid and interstitial fluid, the glymphatic system also facilitates the clearance of interstitial solutes such as amyloid-β and tau from the brain. As cerebrospinal fluid and interstitial fluid are cleared through the glymphatic system, eventually draining into the lymphatic vessels of the neck, this continuous fluid circuit offers a paradigm shift in osteopathic manipulative medicine. For instance, manipulation of the glymphatic-lymphatic continuum could be used to promote experimental initiatives for nonpharmacologic, noninvasive management of neurologic disorders. In the present review, the authors describe what is known about the glymphatic system and identify several osteopathic experimental strategies rooted in a mechanistic understanding of the glymphatic-lymphatic continuum. PMID:26927910

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  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. Lymphatic Targeting of Nanosystems for Anticancer Drug Therapy.

    PubMed

    Abellan-Pose, Raquel; Csaba, Noemi; Alonso, Maria Jose

    2016-01-01

    The lymphatic system represents a major route of dissemination in metastatic cancer. Given the lack of selectivity of conventional chemotherapy to prevent lymphatic metastasis, in the last years there has been a growing interest in the development of nanocarriers showing lymphotropic characteristics. The goal of this lymphotargeting strategy is to facilitate the delivery of anticancer drugs to the lymph node-resident cancer cells, thereby enhancing the effectiveness of the anti-cancer therapies. This article focuses on the nanosystems described so far for the active or passive targeting of oncological drugs to the lymphatic circulation. To understand the design and performance of these nanosystems, we will discuss first the physiology of the lymphatic system and how physiopathological changes associated to tumor growth influence the biodistribution of nanocarriers. Second, we provide evidence on how the tailoring of the physicochemical characteristics of nanosystems, i.e. particle size, surface charge and hydrophilicity, allows the modulation of their access to the lymphatic circulation. Finally, we provide an overview of the relationship between the biodistribution and antimetastatic activity of the nanocarriers loaded with oncological drugs, and illustrate the most promising active targeting approaches investigated so far. PMID:26675222

  7. 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

  8. Finite-Time Consensus of Multiagent Systems With a Switching Protocol.

    PubMed

    Liu, Xiaoyang; Lam, James; Yu, Wenwu; Chen, Guanrong

    2016-04-01

    In this paper, we study the problem of finite-time consensus of multiagent systems on a fixed directed interaction graph with a new protocol. Existing finite-time consensus protocols can be divided into two types: 1) continuous and 2) discontinuous, which were studied separately in the past. In this paper, we deal with both continuous and discontinuous protocols simultaneously, and design a centralized switching consensus protocol such that the finite-time consensus can be realized in a fast speed. The switching protocol depends on the range of the initial disagreement of the agents, for which we derive an exact bound to indicate at what time a continuous or a discontinuous protocol should be selected to use. Finally, we provide two numerical examples to illustrate the superiority of the proposed protocol and design method. PMID:25974952

  9. 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.

  10. Distribution and Alteration of Lymphatic Vessels in Knee Joints of Normal and Osteoarthritic Mice

    PubMed Central

    Shi, Jixiang; Liang, Qianqian; Zuscik, Michael; Shen, Jie; Chen, Di; Xu, Hao; Wang, Yong-Jun; Chen, Yan; Wood, Ronald W.; Li, Jia; Boyce, Brendan F.; Xing, Lianping

    2014-01-01

    Objective To investigate the distribution and alteration of lymphatic vessels and draining function in knee joints of normal and osteoarthritic mice. Methods For the mouse models of osteoarthritis (OA), we used mice with meniscal-ligamentous injury or mice with conditional knockout of the gene for cartilage transforming growth factor β (TGF β) type II receptor. The severity of cartilage loss and joint destruction was assessed histologically. Capillary and mature lymphatic vessels were identified and analyzed using double immunofluorescence staining and a whole-slide digital imaging system. Lymphatic drainage of knee joints was examined using near-infrared lymphatic imaging. Patient joint specimens obtained during total knee or hip arthroplasty were evaluated to verify the content validity of the mouse findings. Results Lymphatic vessels were distributed in soft tissues (mainly around the joint capsule, ligaments, fat pads, and muscles of normal knees). The number of lymphatic vessels, particularly the number of capillaries, was significantly increased in joints of mice with mild OA, while the number of mature lymphatic vessels was markedly decreased in joints of mice with severe OA. OA knees exhibited significantly decreased lymph clearance. The number of both capillary and mature lymphatic vessels was significantly decreased in the joints of patients with OA. Conclusion The whole-slide digital imaging system is a powerful tool, enabling the identification and assessment of lymphatic microvasculature in the entire mouse knee. Lymphatic capillaries and mature vessels are present in various soft tissues around articular spaces. Abnormalities of lymphatic vessels and draining function, including significantly reduced numbers of mature vessels and impaired clearance, are present in OA joints. PMID:24574226

  11. New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype

    PubMed Central

    Ran, Sophia

    2012-01-01

    Background Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs) contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency in vivo and lack of model systems allowing in-depth molecular analyses in vitro. Our goal was to establish a cell culture model to characterize inflammation-induced macrophage-to-LECP differentiation under controlled conditions. Methodology/Principal Findings Time-course analysis of diaphragms from lipopolysaccharide (LPS)-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50%) incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS in vitro. Activated RAW264.7 cells co-expressed VEGF-C that induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a 68% overlap with endogenous CD11b+/VEGFR-3+ LECPs in the expression of lymphatic-specific genes. Moreover, when injected into LPS- but not saline-treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed diaphragm followed by integration into 18% of lymphatic vessels. Conclusions/Significance We present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the “RAW model” mimics fundamental features of

  12. Plasticity of Blood- and Lymphatic Endothelial Cells and Marker Identification

    PubMed Central

    Keuschnigg, Johannes; Karinen, Sirkku; Auvinen, Kaisa; Irjala, Heikki; Mpindi, John-Patrick; Kallioniemi, Olli; Hautaniemi, Sampsa; Jalkanen, Sirpa; Salmi, Marko

    2013-01-01

    The distinction between lymphatic and blood vessels is biologically fundamental. Here we wanted to rigorously analyze the universal applicability of vascular markers and characteristics of the two widely used vascular model systems human microvascular endothelial cell line-1 (HMEC-1) and telomerase-immortalized microvascular endothelial cell line (TIME). Therefore we studied the protein expression and functional properties of the endothelial cell lines HMEC-1 and TIME by flow cytometry and in vitro flow assays. We then performed microarray analyses of the gene expression in these two cell lines and compared them to primary endothelial cells. Using bioinformatics we then defined 39 new, more universal, endothelial-type specific markers from 47 primary endothelial microarray datasets and validated them using immunohistochemistry with normal and pathological tissues. We surprisingly found that both HMEC-1 and TIME are hybrid blood- and lymphatic cells. In addition, we discovered great discrepancies in the previous identifications of blood- and lymphatic endothelium-specific genes. Hence we identified and validated new, universally applicable vascular markers. Summarizing, the hybrid blood-lymphatic endothelial phenotype of HMEC-1 and TIME is indicative of plasticity in the gene expression of immortalized endothelial cell lines. Moreover, we identified new, stable, vessel-type specific markers for blood- and lymphatic endothelium, useful for basic research and clinical diagnostics. PMID:24058540

  13. New Horizons for Imaging Lymphatic Function

    PubMed Central

    Sharma, Ruchi; Wendt, Juliet A.; Rasmussen, John C.; Adams, Kristen E.; Marshall, Milton V.; Sevick-Muraca, Eva M.

    2011-01-01

    In this review, we provide a comprehensive summary of noninvasive imaging modalities used clinically for the diagnosis of lymphatic diseases, new imaging agents for assessing lymphatic architecture and cancer status of lymph nodes, and emerging near-infrared (NIR) fluorescent optical imaging technologies and agents for functional lymphatic imaging. Given the promise of NIR optical imaging, we provide example results of functional lymphatic imaging in mice, swine, and humans, showing the ability of this technology to quantify lymph velocity and frequencies of propulsion resulting from the contractility of lymphatic structures. PMID:18519956

  14. 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

  15. 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.

  16. An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

    PubMed

    Korsgren, Erik; Korsgren, Olle

    2016-04-01

    The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. PMID:26822093

  17. Picture archiving and communications systems protocol based on ISO-OSI standard

    NASA Astrophysics Data System (ADS)

    Martinez, Ralph; Nam, Jiseung; Dallas, William J.; Osada, Masakazu; McNeill, Kevin M.; Ozeki, Takeshi; Komatsu, Ken-Ichi

    1991-07-01

    During the last decade, the concept of picture archiving and communication systems (PACS) has evolved and matured to integrate digital image information in a hospital. PACS integrates various imaging devices, database archive systems, and image viewing workstations. One of the most difficult problems for integration is the standardization of communication protocols required to connect devices from different vendors. When the ACR-NEMA standard was announced for communications in digital radiology in 1985, it solved some of the problems for PACS with a hardware interface, a set of software commands, and a consistent set of data formats. However, it has been found to be inadequate for networked PACS environments, not only because of its point-to-point nature and lack of a network layer, but also because of its inflexibility to allow other services and protocols to be added in the future. Based on previous experience, the case is made for a new standard for PACS networks and a suggested approach for new protocol is presented. This paper addresses the development of a new standard for PACS protocol layers and attempts to define the protocols from a layered-systems approach. The basis for the new protocol definition is primarily the International Organization for Standardization/Open Systems Interconnection (ISO/OSI) protocols and the data format portion of ACR-NEMA standard. The scope and rationale of the proposed protocol, background, and relationship to PACS technology are discussed. The proposed PACS protocol covers the protocol service definition and specification for the application, presentation, session, transport, and network layers. The proposed PACS protocol is intended to facilitate the development of PACSs by several vendors capable of interfacing with each other. The new PACS protocols will also support a global PACS environment.

  18. 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

  19. Lymphatic drainage from the eye: A new target for therapy.

    PubMed

    Yucel, Yeni; Gupta, Neeru

    2015-01-01

    Lowering intraocular pressure (IOP) has been central to glaucoma care for over a century. In order to prevent sight loss from disease, there has been considerable focus on medical and surgical methods to improve fluid drainage from the eye. In spite of this, our understanding of exactly how aqueous humor leaves the eye is not complete. Recently, lymphatic vessels have been discovered in the human uvea, with studies showing lymphatic fluid outflow in several models, in addition to evidence for their pharmacological enhancement. The presence of a lymphatic outflow system points to an exciting, expanded understanding of how fluid and particulate materials such as proteins move out of the eye, and how IOP may be regulated. We coin the term "uveolymphatic pathway"-to reflect a comprehensive and compelling new target for glaucoma and an exciting opportunity for future investigations to better understand the eye in health and disease. PMID:26497791

  20. 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

  1. Fault-Tolerant Consensus of Multi-Agent System With Distributed Adaptive Protocol.

    PubMed

    Chen, Shun; Ho, Daniel W C; Li, Lulu; Liu, Ming

    2015-10-01

    In this paper, fault-tolerant consensus in multi-agent system using distributed adaptive protocol is investigated. Firstly, distributed adaptive online updating strategies for some parameters are proposed based on local information of the network structure. Then, under the online updating parameters, a distributed adaptive protocol is developed to compensate the fault effects and the uncertainty effects in the leaderless multi-agent system. Based on the local state information of neighboring agents, a distributed updating protocol gain is developed which leads to a fully distributed continuous adaptive fault-tolerant consensus protocol design for the leaderless multi-agent system. Furthermore, a distributed fault-tolerant leader-follower consensus protocol for multi-agent system is constructed by the proposed adaptive method. Finally, a simulation example is given to illustrate the effectiveness of the theoretical analysis. PMID:25415998

  2. Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice

    PubMed Central

    Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

    2015-01-01

    AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels

  3. Observer Use of Standardized Observation Protocols in Consequential Observation Systems

    ERIC Educational Resources Information Center

    Bell, Courtney A.; Yi, Qi; Jones, Nathan D.; Lewis, Jennifer M.; McLeod, Monica; Liu, Shuangshuang

    2014-01-01

    Evidence from a handful of large-scale studies suggests that although observers can be trained to score reliably using observation protocols, there are concerns related to initial training and calibration activities designed to keep observers scoring accurately over time (e.g., Bell, et al, 2012; BMGF, 2012). Studies offer little insight into how…

  4. 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.

  5. 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.

  6. 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…

  7. 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

  8. 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...

  9. 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.

  10. 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

  11. 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. ...

  12. 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 » ...

  13. Lymphatic complications after vascular interventions

    PubMed Central

    Obara, Andrzej; Maruszynski, Marek; Witkowski, Adam; Dąbrowski, Maciej; Chmielak, Zbigniew

    2014-01-01

    Introduction Lymphorrhea due to classical and mini-invasive surgical interventions on femoral and popliteal arteries is a serious hindrance to patient treatment. Depending on the experience of a particular center, the incidence and frequency of this type of complication may constitute a serious clinical problem. While the level of lymphorrhea intensity and its duration result in certain foreseeable consequences, their treatment can be a time-consuming and multistep procedure. Aim To compare different types of vascular interventions with lymphorrhea occurrence. Material and methods The authors conducted a retrospective analysis of lymphatic complications based on the material collected between 2005 and 2012 at the Department of Vascular and Endovascular Surgery of the Military Institute of Medicine in Warsaw and in the Department of Interventional Cardiology and Angiology of the Institute of Cardiology in Anin, Warsaw, in 2009–2012. Results Maintaining due thoroughness when dissecting tissues and treating the cutting line in this area with ligatures and tissue puncture are the most reliable methods of minimizing the risk of lymphatic leakage after surgical procedures performed in a classical way. The lymphatic complication under analysis is far less likely to occur when procedures are performed as planned and an endovascular technique is used – statistical significance p < 0.05. Minimally invasive and fully percutaneous procedures performed via needle puncture, including the use of the fascial closure technique to close the femoral artery, eliminate the likelihood of the occurrence of this vascular complication – statistical significance was found with p value less than 0.05. Conclusions We concluded that in every case by minimizing the vascular approach we protected the patient against lymphatic complications. PMID:25337168

  14. Effect of postural changes on human lymphatic capillary pressure of the skin.

    PubMed Central

    Franzeck, U K; Fischer, M; Costanzo, U; Herrig, I; Bollinger, A

    1996-01-01

    1. The influence of postural changes on cutaneous lymphatic capillary pressure and venous pressure was measured at the dorsum of the foot in twelve healthy volunteers. Measurements were performed in the supine and sitting positions. 2. Lymphatic skin capillaries were visualized by fluorescence microlymphography with fluorescein isothiocyanate (FITC)-Dextran 150000. Subsequently a lymphatic capillary was punctured with a glass micropipette and pressure was measured using the servo-nulling technique. Lymphatic capillary pressure, venous pressure, heart and respiration rates were recorded simultaneously. 3. Mean lymphatic capillary pressure was significantly higher (P = 0.0096) in the sitting (9.9 +/- 3.0 mmHg) than in the supine (3.9 +/- 4.2 mmHg) position. There was no significant difference (P = 0.09) between lymphatic capillary pressure and venous pressure (6.8 +/- 3.4 mmHg) in the supine position. During sitting mean lymphatic capillary pressure was significantly lower (P = 0.0022) than mean venous pressure (53.3 +/- 4.1 mmHg). The smaller increase in lymphatic capillary pressure may be caused by the discontinuous fluid column in the lymphatic system and enhanced orthostatic contractile activity of lymphatic collectors and precollectors. Spontaneous low frequency pressure fluctuations occurred in 89% of recordings during sitting, which was significantly (P = 0.02) higher than in the supine position (54%). 4. The present results support the suggestion of enhanced intrinsic contractile activity of lymph precollectors and collectors in the dependent position. This mechanism is primarily responsible for the propulsion of lymph from the periphery to the thoracic duct during quiet sitting, when extrinsic pumping by the calf muscles is not active. PMID:8842016

  15. Photothermolysis of lymphatic endothelial cells by gold nanoshell-mediated hyperthermia.

    PubMed

    Chen, Kui; Soto, Israel; Monroe, W Todd; Alexander, J Steven

    2014-07-01

    Tumor-associated lymphatics and lymphangiogenesis have been shown to play important roles in promoting tumor growth and metastasis. However, the lymphatic system has received much less attention as a target of intervention in cancer treatment compared to the blood vascular system. In this study, we explored the feasibility of photothermal therapy targeting the lymphatic system as a strategy for inhibiting lymphatics-mediated tumor metastasis. Specifically, photothermolysis of lymphatic endothelial cells (LECs) via gold nanoshell-mediated hyperthermia was investigated. Near-Infrared-absorbing Au nanoshells (AuNSs) were synthesized and used as the photothermal coupling agent. After 24-hr incubation, significant amount of the AuNSs were taken up by murine simian virus lymphatic endothelial cells with minimal cytotoxicity. Thermally-induced injury to LECs was found to occur above a threshold temperature of 46 degrees C. Preliminary data also suggested apoptosis as the mechanism of thermally-induced cell death in this temperature range. In a proof-of-concept experiment, AuNS-mediated photothermal heating was found to induce cell death in statistically higher percent of LECs incubated with AuNSs after 15-min laser irradiation compared to the controls. We believed that the findings in this study represent the first step in developing AuNS-mediated photothermal therapy as a potential strategy to disrupt tumor-associated lymphatics. PMID:24758030

  16. [Multi-bed & multi-parameter central monitoring system based on TCP/IP protocol].

    PubMed

    Lian, S J; Hu, D K; Zhao, M H; Tang, L H

    2000-02-01

    Communication is one of the key problems to a central monitoring system. In this paper we put forward a central monitoring system using TCP/IP as the network protocol, Windows NT4.0 as the platform, forming a Intranet in a hospital. We also discussed the communication problem between the bed-side monitoring station and the central monitoring station in detail and then put forward a new protocol--Hospital Central Monitor Protocol (HCMP) based on TCP/IP to transfer monitoring data. It is easy to achieve tele-monitoring through the current communication subsystem. PMID:12583091

  17. 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

  18. Field validation of protocols developed to evaluate in-line mastitis detection systems.

    PubMed

    Kamphuis, C; Dela Rue, B T; Eastwood, C R

    2016-02-01

    This paper reports on a field validation of previously developed protocols for evaluating the performance of in-line mastitis-detection systems. The protocols outlined 2 requirements of these systems: (1) to detect cows with clinical mastitis (CM) promptly and accurately to enable timely and appropriate treatment and (2) to identify cows with high somatic cell count (SCC) to manage bulk milk SCC levels. Gold standard measures, evaluation tests, performance measures, and performance targets were proposed. The current study validated the protocols on commercial dairy farms with automated in-line mastitis-detection systems using both electrical conductivity (EC) and SCC sensor systems that both monitor at whole-udder level. The protocol for requirement 1 was applied on 3 commercial farms. For requirement 2, the protocol was applied on 6 farms; 3 of them had low bulk milk SCC (128×10(3) cells/mL) and were the same farms as used for field evaluation of requirement 1. Three farms with high bulk milk SCC (270×10(3) cells/mL) were additionally enrolled. The field evaluation methodology and results were presented at a workshop including representation from 7 international suppliers of in-line mastitis-detection systems. Feedback was sought on the acceptance of standardized performance evaluation protocols and recommended refinements to the protocols. Although the methodology for requirement 1 was relatively labor intensive and required organizational skills over an extended period, no major issues were encountered during the field validation of both protocols. The validation, thus, proved the protocols to be practical. Also, no changes to the data collection process were recommended by the technology supplier representatives. However, 4 recommendations were made to refine the protocols: inclusion of an additional analysis that ignores small (low-density) clot observations in the definition of CM, extension of the time window from 4 to 5 milkings for timely alerts for CM

  19. 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.

  20. 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

  1. Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life.

    PubMed

    Hess, Paul R; Rawnsley, David R; Jakus, Zoltán; Yang, Yiqing; Sweet, Daniel T; Fu, Jianxin; Herzog, Brett; Lu, MinMin; Nieswandt, Bernhard; Oliver, Guillermo; Makinen, Taija; Xia, Lijun; Kahn, Mark L

    2014-01-01

    Mammals transport blood through a high-pressure, closed vascular network and lymph through a low-pressure, open vascular network. These vascular networks connect at the lymphovenous (LV) junction, where lymph drains into blood and an LV valve (LVV) prevents backflow of blood into lymphatic vessels. Here we describe an essential role for platelets in preventing blood from entering the lymphatic system at the LV junction. Loss of CLEC2, a receptor that activates platelets in response to lymphatic endothelial cells, resulted in backfilling of the lymphatic network with blood from the thoracic duct (TD) in both neonatal and mature mice. Fibrin-containing platelet thrombi were observed at the LVV and in the terminal TD in wild-type mice, but not Clec2-deficient mice. Analysis of mice lacking LVVs or lymphatic valves revealed that platelet-mediated thrombus formation limits LV backflow under conditions of impaired valve function. Examination of mice lacking integrin-mediated platelet aggregation indicated that platelet aggregation stabilizes thrombi that form in the lymphatic vascular environment to prevent retrograde blood flow. Collectively, these studies unveil a newly recognized form of hemostasis that functions with the LVV to safeguard the lymphatic vascular network throughout life. PMID:24292710

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

    PubMed

    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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  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. 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).

  10. 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

  11. Evaluation of immunohistochemical markers of lymphatic and blood vessels in canine mammary tumours.

    PubMed

    Sleeckx, N; Van Brantegem, L; Fransen, E; Van den Eynden, G; Casteleyn, C; Veldhuis Kroeze, E; Van Ginneken, C

    2013-05-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Bitches with spontaneously arising CMTs represent a promising animal model for human breast cancer research. The aim of the present study was to develop an immunohistochemical protocol for the identification of blood and lymphatic vessels in CMTs. Antibodies specific for human lymphatic vessels (prox-1, lyve-1, podoplanin and D2-40) and blood vessels (von Willebrand factor [vWf], CD31 and CD34) were utilized. Serial sections of 18 samples (eight samples of normal canine mammary tissue, five benign and five malignant CMTs) were examined. Antibodies specific for podoplanin, D2-40 and CD34 showed no immunoreactivity with canine tissue. Prox-1 and CD31 were determined to be the most suitable markers for lymphatic and blood vessels, respectively. PMID:23123127

  12. 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

  13. An efficient two-tier causal protocol for mobile distributed systems.

    PubMed

    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

  14. Molecular mechanisms of lymphatic metastasis in solid tumors of the gastrointestinal tract

    PubMed Central

    Langheinrich, Melanie C; Schellerer, Vera; Perrakis, Aristotelis; Lohmüller, Clemens; Schildberg, Claus; Naschberger, Elisabeth; Stürzl, Michael; Hohenberger, Werner; Croner, Roland S

    2012-01-01

    Tumor cell dissemination from the primary tumor site to distant organs is one of the characteristic properties of malignant tumors and represents a crucial step in the progression of disease. Although the pattern of spread may vary in different types of carcinomas, dissemination via the lymphatic system represents a common event in metastasis. The extent of lymph node metastasis is one of the major determinants for the prognosis of patients with gastrointestinal carcinomas and guides the therapeutically management. During the last decades, significant attention has been given to the molecular mechanisms that control lymphatic metastasis. The process of lymphangiogenesis has come into the focus. Lymphangiogenesis, the formation of newly lymphatics, comprises a series of complex cellular events and is controlled by a balance between pro- and anti-lymphangiogenic signals. This article will briefly describe the lymphatic system and then provide an overview of the molecular players involved in tumor lymphangiogenesis. PMID:22977656

  15. GENERAL: Consensus protocol for multi-agent continuous systems

    NASA Astrophysics Data System (ADS)

    Tan, Fu-Xiao; Guan, Xin-Ping; Liu, De-Rong

    2008-10-01

    Based on the algebraic graph theory, the networked multi-agent continuous systems are investigated. Firstly, the digraph (directed graph) represents the topology of a networked system, and then a consensus convergence criterion of system is proposed. Secondly, the issue of stability of multi-agent systems and the consensus convergence problem of information states are all analysed. Furthermore, the consensus equilibrium point of system is proved to be global and asymptotically reach the convex combination of initial states. Finally, two examples are taken to show the effectiveness of the results obtained in this paper.

  16. Consensus of multi-agent linear dynamic systems via impulsive control protocols

    NASA Astrophysics Data System (ADS)

    Jiang, Haibo; Yu, Jianjiang; Zhou, Caigen

    2011-06-01

    In this article, we introduce impulsive control protocols for multi-agent linear dynamic systems. First, an impulsive control protocol is designed for network with fixed topology based on the local information of agents. Then sufficient conditions are given to guarantee the consensus of the multi-agent linear dynamic systems by the theory of impulsive systems. Furthermore, how to select the discrete instants and impulsive matrices is discussed. The case that the topologies of networks are switching is also considered. Numerical simulations show the effectiveness of our theoretical results.

  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. Distribution of prosaposin in rat lymphatic tissues.

    PubMed

    Shimokawa, Tetsuya; Nabeka, Hiroaki; Yamamiya, Kimiko; Wakisaka, Hiroyuki; Takeuchi, Takashi; Kobayashi, Naoto; Matsuda, Seiji

    2013-06-01

    Prosaposin (PSAP) is as a trophic factor and an activator protein for sphingolipid hydrolase in lysosomes. We generated a specific antibody to PSAP and examined the spatiotemporal distribution of PSAP-immunoreactive (PSAP-IR) cells in the lymphatic tissues of Wistar rats. Immunoblots of tissue homogenates separated electrophoretically showed a single band for PSAP in brain but two bands in spleen. PSAP-IR cells were distributed in both the red and white pulp of the spleen, in both the cortex and medulla of the thymus and in mesenteric lymph nodes. Many PSAP-IR cells were found in the dome portion of Peyer's patches and the number of PSAP-IR cells increased with the age of the rat. To identify the PSAP-IR cells, double- and triple-immunostainings were performed with antibodies against PSAP, CD68 and CD1d. The large number of double- and triple-positive cells suggested that antigen-presenting cells contained much PSAP in these lymphatic tissues. Intense expression of PSAP mRNA, examined by in situ hybridisation, was observed in the red pulp and corona of the spleen. In rats, the PSAP gene generates two alternative splicing forms of mRNA: Pro+9 containing a 9-base insertion and Pro+0 without the insertion. We examined the expression patterns of the alternative splicing forms of PSAP mRNA in the spleen. The presence of both types of mRNA (Pro+9 and Pro+0) indicated that the spleen contains various types of prosaposin-producing and/or secreting cells. These findings suggest diverse functions for PSAP in the immune system. PMID:23420452

  1. Scenario-based Participatory Design of A Collaborative Clinical Trial Protocol Authoring System

    PubMed Central

    Weng, Chunhua; Gennari, John H.; McDonald, David W.

    2003-01-01

    We present our experience of using prototype scenarios to actively involve users in the design of a collaborative clinical trial protocol authoring system. This method enables us to do usability testing and elicit prompt user feedback at the early phase of design. We conclude that it is an effective approach to the design of complex medical information systems. PMID:14728554

  2. An Efficient and Secure Certificateless Authentication Protocol for Healthcare System on Wireless Medical Sensor Networks

    PubMed Central

    Guo, Rui; Wen, Qiaoyan; Jin, Zhengping; Zhang, Hua

    2013-01-01

    Sensor networks have opened up new opportunities in healthcare systems, which can transmit patient's condition to health professional's hand-held devices in time. The patient's physiological signals are very sensitive and the networks are extremely vulnerable to many attacks. It must be ensured that patient's privacy is not exposed to unauthorized entities. Therefore, the control of access to healthcare systems has become a crucial challenge. An efficient and secure authentication protocol will thus be needed in wireless medical sensor networks. In this paper, we propose a certificateless authentication scheme without bilinear pairing while providing patient anonymity. Compared with other related protocols, the proposed scheme needs less computation and communication cost and preserves stronger security. Our performance evaluations show that this protocol is more practical for healthcare system in wireless medical sensor networks. PMID:23710147

  3. An efficient and secure certificateless authentication protocol for healthcare system on wireless medical sensor networks.

    PubMed

    Guo, Rui; Wen, Qiaoyan; Jin, Zhengping; Zhang, Hua

    2013-01-01

    Sensor networks have opened up new opportunities in healthcare systems, which can transmit patient's condition to health professional's hand-held devices in time. The patient's physiological signals are very sensitive and the networks are extremely vulnerable to many attacks. It must be ensured that patient's privacy is not exposed to unauthorized entities. Therefore, the control of access to healthcare systems has become a crucial challenge. An efficient and secure authentication protocol will thus be needed in wireless medical sensor networks. In this paper, we propose a certificateless authentication scheme without bilinear pairing while providing patient anonymity. Compared with other related protocols, the proposed scheme needs less computation and communication cost and preserves stronger security. Our performance evaluations show that this protocol is more practical for healthcare system in wireless medical sensor networks. PMID:23710147

  4. 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.

  5. 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

  6. Critical Casimir forces in a magnetic system: An experimental protocol

    NASA Astrophysics Data System (ADS)

    Lopes Cardozo, David; Jacquin, Hugo; Holdsworth, Peter C. W.

    2014-11-01

    We numerically test an experimentally realizable method for the extraction of the critical Casimir force based on its thermodynamic definition as the derivative of the excess free energy with respect to system size. Free energy differences are estimated for different system sizes by integrating the order parameter along an isotherm. The method could be developed for experiments on magnetic systems and could give access to the critical Casimir force for any universality class. By choosing an applied field that opposes magnetic ordering at the boundaries, the Casimir force is found to increase by an order of magnitude over zero-field results.

  7. Extensive Fetal Congenital Subcutaneous Mixed Venous Lymphatic Lesion: Prenatal Diagnosis and Postnatal Management

    PubMed Central

    Odibo, I. N.; Linam, L. E.; Richter, G. E.; Jackson, R. J.; Dajani, N. K.

    2015-01-01

    Vascular lesions may be categorized as proliferative tumors, such as hemangiomas, or nonproliferative malformations that include capillary, lymphatic, venous, arterial, or mixed lesions. Lymphatic malformations are benign localized congenital malformations of the lymphatic system. They may be microcystic or macrocystic lesions or a combination of both. The lesions may also be uniseptate or multiseptate, and are more commonly located in the head and neck or axillary region. Prenatal diagnosis is based on ultrasound and magnetic resonance imaging. Postnatal management largely depends on the size and location of the lesion. This is the first case report of prenatally diagnosed extensive subcutaneous macrocystic venous lymphatic malformation involving the fetal thorax, back, pelvis, and lower extremities. Prenatal course and postnatal management are described. This report will aid other specialists in the field of prenatal diagnosis and postnatal surgery in the evaluation and management of these patients. PMID:26199796

  8. A new communication protocol family for a distributed spacecraft control system

    NASA Technical Reports Server (NTRS)

    Baldi, Andrea; Pace, Marco

    1994-01-01

    In this paper we describe the concepts behind and architecture of a communication protocol family, which was designed to fulfill the communication requirements of ESOC's new distributed spacecraft control system SCOS 2. A distributed spacecraft control system needs a data delivery subsystem to be used for telemetry (TLM) distribution, telecommand (TLC) dispatch and inter-application communication, characterized by the following properties: reliability, so that any operational workstation is guaranteed to receive the data it needs to accomplish its role; efficiency, so that the telemetry distribution, even for missions with high telemetry rates, does not cause a degradation of the overall control system performance; scalability, so that the network is not the bottleneck both in terms of bandwidth and reconfiguration; flexibility, so that it can be efficiently used in many different situations. The new protocol family which satisfies the above requirements is built on top of widely used communication protocols (UDP and TCP), provides reliable point-to-point and broadcast communication (UDP+) and is implemented in C++. Reliability is achieved using a retransmission mechanism based on a sequence numbering scheme. Such a scheme allows to have cost-effective performances compared to the traditional protocols, because retransmission is only triggered by applications which explicitly need reliability. This flexibility enables applications with different profiles to take advantage of the available protocols, so that the best rate between sped and reliability can be achieved case by case.

  9. 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.

  10. 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

  11. Protocol feasibility workflow using an automated multi-country patient cohort system.

    PubMed

    Soto-Rey, Iñaki; Trinczek, Benjamin; Karakoyun, Töresin; Dugas, Martin; Fritz, Fleur

    2014-01-01

    The Electronic Health Record for Clinical Research (EHR4CR) project aims to improve the current process of clinical trials, providing a technological platform that supports the design and execution of trials. For the protocol feasibility scenario, the system currently allows the user to create a set of in-/exclusion criteria to find patients matching these criteria across sites located in several countries. The automated multi-country patient cohort system developed in EHR4CR implies substantial changes on the current protocol feasibility process, which will be reflected in this study. PMID:25160335

  12. [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

  13. 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.

  14. 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. PMID:21472692

  15. 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.

  16. 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

  17. Patterns of lymphatic drainage from the skin in patients with melanoma.

    PubMed

    Uren, Roger F; Howman-Giles, Robert; Thompson, John F

    2003-04-01

    An essential prerequisite for a successful sentinel lymph node biopsy (SLNB) procedure is an accurate map of the pattern of lymphatic drainage from the primary tumor site in each patient. In melanoma patients, mapping requires high-quality lymphoscintigraphy, which can identify the actual lymphatic collecting vessels as they drain into the sentinel lymph nodes. Small-particle radiocolloids are needed to achieve this goal, and imaging protocols must be adapted to ensure that all true sentinel nodes, including those in unexpected locations, are found in every patient. Clinical prediction of lymphatic drainage from the skin is not possible. The old clinical guidelines based on Sappey's lines therefore should be abandoned. Patterns of lymphatic drainage from the skin are highly variable from patient to patient, even from the same area of the skin. Unexpected lymphatic drainage from the skin of the back to sentinel nodes in the triangular intermuscular space and, in some patients, through the posterior body wall to sentinel nodes in the para-aortic, paravertebral, and retroperitoneal areas has been found. Lymphatic drainage from the head and neck frequently involves sentinel nodes in multiple node fields and can occur from the base of the neck up to nodes in the occipital or upper cervical areas or from the scalp down to nodes at the neck base, bypassing many node groups. The sentinel node is not always found in the nearest node field and is best defined as "any lymph node receiving direct lymphatic drainage from a primary tumor site." Lymphatic drainage can occur from the upper limb to sentinel nodes above the axilla. Drainage to the epitrochlear region from the hand and arm as well as to the popliteal region from the foot and leg is more common than was previously thought. Interval nodes, which lie along the course of a lymphatic vessel between a lesion site and a recognized node field, are not uncommon, especially in the trunk. Drainage across the midline of the body

  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. 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…

  20. 78 FR 54945 - Privacy Act; System of Records: Protocol Records, State-33

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-06

    ...Notice is hereby given that the Department of State proposes to amend an existing system of records, Protocol Records, State-33, pursuant to the provisions of the Privacy Act of 1974, as amended (5 U.S.C. 552a) and Office of Management and Budget Circular No. A-130, Appendix...

  1. Wavelength attack on practical continuous-variable quantum-key-distribution system with a heterodyne protocol

    NASA Astrophysics Data System (ADS)

    Ma, Xiang-Chun; Sun, Shi-Hai; Jiang, Mu-Sheng; Liang, Lin-Mei

    2013-05-01

    We present the wavelength attack on a practical continuous-variable quantum-key-distribution system with a heterodyne protocol, in which the transmittance of beam splitters at Bob's station is wavelength dependent. Our strategy is proposed independent of but analogous to that of Huang [arXiv:1206.6550v1 [quant-ph

  2. 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…

  3. 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

  4. Lymphangiogenesis and Lymphatic Remodeling Induced by Filarial Parasites: Implications for Pathogenesis

    PubMed Central

    Bennuru, Sasisekhar; Nutman, Thomas B.

    2009-01-01

    Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures in vitro. Moreover, serum from patently infected (microfilaria positive) patients and those with longstanding chronic lymphatic obstruction induced significantly increased LEC proliferation compared to sera from uninfected individuals. Differentiation of LEC into tube-like networks was found to be associated with significantly increased levels of matrix metalloproteases and inhibition of their TIMP inhibitors (Tissue inhibitors of matrix metalloproteases). Comparison of global gene expression induced by live parasites in LEC to parasite-unexposed LEC demonstrated that filarial parasites altered the expression of those genes involved in cellular organization and development as well as those associated with junction adherence pathways that in turn decreased trans-endothelial transport as assessed by FITC-Dextran. The data suggest that filarial parasites directly induce lymphangiogenesis and lymphatic differentiation and provide insight into the mechanisms underlying the pathology seen in lymphatic filariasis. PMID:20011114

  5. [ A comparative lympho-scintigraphic evaluation of manual lymphatic drainage and pressotherapy in edema of the arm following treatment of a breast tumor].

    PubMed

    Janbon, C; Ferrandez, J C; Vinot, J M; Serin, D

    1990-01-01

    Manual lymphatic drainage (MLD) and pressure-therapy are part of the therapeutical gears used in physiotherapy for reducing edema. The solution to the problem of the reduction fo lymphedema of the extremities rests with the evacuation of the liquid phase and the resorption of the stagnant proteins in the interstitial compartment not being collected by the lymphatic system. The injection of a 99 Technetium-labelled colloid substance provides a functional approach to the problem of lymphatic stasis. PMID:2212876

  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. Integrated obesity care management system -implementation and research protocol

    PubMed Central

    Baillargeon, Jean-Patrice; Carpentier, André; Donovan, Denise; Fortin, Martin; Grant, Andrew; Simoneau-Roy, Judith; St-Cyr-Tribble, Denise; Xhignesse, Mariane; Langlois, Marie-France

    2007-01-01

    Background Nearly 50% of Canadians are overweight and their number is increasing rapidly. The majority of obese subjects are treated by primary care physicians (PCPs) who often feel uncomfortable with the management of obesity. The current research proposal is aimed at the development and implementation of an innovative, integrated, interdisciplinary obesity care management system involving both primary and secondary care professionals. Methods We will use both action and evaluative research in order to achieve the following specific objectives. The first one is to develop and implement a preceptorship-based continuing medical education (CME) program complemented by a web site for physicians and nurses working in Family Medicine Groups (FMGs). This CME will be based on needs assessment and will be validated by one FMG using questionnaires and semi structured interviews. Also, references and teaching tools will be available for participants on the web site. Our second objective is to establish a collaborative intra and inter-regional interdisciplinary network to enable on-going expertise update and networking for FMG teams. This tool consists of a discussion forum and monthly virtual meetings of all participants. Our third objective is to evaluate the implementation of our program for its ability to train 8 FMGs per year, the access and utilization of electronic tools and the participants' satisfaction. This will be measured with questionnaires, web logging tools and group interviews. Our fourth objective is to determine the impact for the participants regarding knowledge and expertise, attitudes and perceptions, self-efficacy for the management of obesity, and changes in FMG organization for obesity management. Questionnaires and interviews will be used for this purpose. Our fifth objective is to deliver transferable knowledge for health professionals and decision-makers. Strategies and pitfalls of setting up this program will also be identified. Conclusion This

  8. 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.

  9. Anti-collision protocols for RFID systems exploiting multi-antenna readers

    NASA Astrophysics Data System (ADS)

    Li, Xin; Zhang, Yimin; Amin, Moeness G.

    2009-05-01

    In conventional RFID systems, only one tag can be identified at a time. Tag collisions occur if more than one tag simultaneously occupies the shared RF channel, resulting in low identification efficiency and long delay, particularly when the population of tags is large. In this paper, we propose two RFID anti-collision protocols, both are based on framed slotted ALOHA (FSA), to concurrently identify multiple tags by using a multi-antenna reader. The first one is Blind Identification Protocol, which relies on blind estimation of the channel between the activated tags and the reader and, as such, does not require redesign of the existing RFID tags. The second one is Orthogonal ID-aided Identification Protocol which estimates the channels with the use of temporary orthogonal IDs, which are randomly selected by the tags and are inserted at the head of each tag's reply signal. The use of orthogonal IDs facilitates both the detection of activated tags and the channel estimation. Unlike code division multiple access (CDMA) techniques which rely on the use of excessive bandwidth and require redesign of tags, the proposed protocols use multiple antennas at the reader to support concurrent identification of multiple tags without the requirement of additional bandwidth and no or minimal modifications to the existing tags. As a result, the proposed techniques yield significant improvement of the identification efficiency and reduction of the identification delay. We analyze, in an analytical framework, the identification efficiency of the proposed protocols, and the optimum frame size is derived.

  10. Lymphatic endothelial differentiation in pulmonary lymphangioleiomyomatosis cells.

    PubMed

    Davis, Jennifer M; Hyjek, Elizabeth; Husain, Aliya N; Shen, Le; Jones, Jennifer; Schuger, Lucia A

    2013-08-01

    Pulmonary lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm affecting almost exclusively women of childbearing age. LAM belongs to the family of perivascular epithelioid cell tumors, characterized by spindle and epithelioid cells with smooth muscle and melanocytic differentiation. LAM cells infiltrate the lungs, producing multiple, bilateral lesions rich in lymphatic channels and forming cysts, leading to respiratory insufficiency. Here we used antibodies against four lymphatic endothelial markers-podoplanin (detected by D2-40), prospero homeobox 1 (PROX1), vascular endothelial growth factor receptor 3 (VEGFR-3), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1)-to determine whether LAM cells show lymphatic differentiation. Twelve of 12 diagnostic biopsy specimens (early-stage LAM) and 19 of 19 explants (late-stage LAM) showed immunopositivity for D2-40 in most neoplastic cells. PROX1, VEGFR-3, and LYVE1 immunoreactivity varied from scarce in the early stage to abundant in the late stage. Lymphatic endothelial, smooth muscle, and melanocytic markers were partially co-localized. These findings indicate that lymphatic endothelial differentiation is a feature of LAM and provide evidence of a previously unidentified third lineage of differentiation in this neoplasm. This study has implications for the histological diagnosis of LAM, the origin of the neoplastic cells, and potential future treatment with drugs targeting lymphangiogenesis. PMID:23609227