Characterization of multiaxial mechanical properties of cardiovascular soft tissue is essential in order to better understand their growth and remodeling in homeostatic conditions and in response to injury or pathological conditions. Though numerous phenomenological models have been proposed to characterize such multiaxial mechanical behavior, the approach has certain drawbacks regarding experimental determination of the model coefficients. We propose a method that aims to overcome these drawbacks. The approach makes use of orthogonal polynomials to fit the biaxial test data and suggests a way to derive the strain energy function from these analytical fits by way of minimizing the deviation of the behavior from hyperelastic ideal. Using the proposed method, a strain energy function for a lymphatic vessel is derived and the method is compared with traditional ones that used non-orthogonal polynomials as independent variables in the functional form for strain energy. The unique coefficient values obtained using the proposed method, for the first time gives us an opportunity to attribute a physical characteristic of the material to the coefficient values. The method also provides a way to assess two different material behaviors by way of comparing their deviation from the hyperelastic behavior when a similar test protocol is used to collect the data, over a similar deformation range and the order of polynomial function is chosen so as to give a similar error of fit. The behavior of mesenteric lymph vessels from normal cows, cows subjected to sham surgery and those subjected to 3 days of edematous conditions by venous occlusion are compared using this method. To be able to better understand the changes in mechanical behavior, morphological analysis of the vessels was carried out and the geometric and structural changes in these vessels were studied. We found that the behavior of bovine mesenteric lymph vessels subjected to a high flow condition shows a small difference in their mechanical behavior as compared to the vessels from normal a cow and a cow subjected to sham surgery. The geometry and structure of these vessels also showed marked differences from the other two. The thickness to radius ratio increased and a rise in percentage of area occupied by smooth muscle cells and medial collagen was observed. Though not all the differences were statistically significant, we conclude that the behavior and the morphology are suggestive of the remodeling of the vessel in response to altered hemodynamic conditions and require further investigation.

In addition to leukocytes, secondary lymphoid organs are populated by non-hematopoietic stromal cells. This diverse group of cells supports lymphocyte migration and homing, facilitates antigen delivery, and promotes T cell survival. However, there is relatively little known about the specific molecules governing the roles that these cells play in regulating dendritic cell (DC) motility and lymph node architecture. Here, we examine the interaction between two molecules, CLEC-2 and podoplanin (PDPN), that are critical for DC migration and maintaining structural integrity of lymph nodes. Together, these studies identify novel functions of lymph node stromal cells and a unique function for PDPN in the immune system. In response detecting an potentially harmful antigen, DCs in peripheral tissues mature and travel to downstream lymph nodes by following chemokine gradients secreted by lymphatic endothelial cells (LECs) and fibroblastic reticular cells (FRCs) present in the lymph node paracortex. We discovered that, in addition to chemokines, DC migration requires CLEC-2 on DCs, as engagement of CLEC-2 with PDPN, which is expressed by LECs and FRCs, incites DC motility and is required for DC entry into the lymphatics, efficient arrival in the lymph node, and migration along the FRC network within the lymph node. Next, we examined the effect of this interaction with respect to the stromal cell. Through a combination approaches, we discovered that PDPN is a master regulator of contractility in FRCs. The fact that FRCs are contractile cells was previously reported, but our study is the first to identify a function for this contractility: upon blockade of PDPN-mediated contractility, lymph nodes became enlarged, the FRC network became more sparse, and there were increased numbers of lymphocytes in the lymph node. Importantly, during an immune response, these changes resulted in more proliferation of antigen-specific T cells and impaired contraction of the lymph node upon resolution of inflammation. Finally, we found that CLEC-2 binding PDPN recapitulated the effect of PDPN deletion. Thus, during an immune response, CLEC-2+ DCs would use PDPN to efficiently migrate to the lymph node and simultaneously cause FRCs to relax and prepare the lymph node for expansion.

Lymph nodes (LNs) are dynamic organs responsible for providing a supportive and centralized environment for the generation of immune response. Utilizing a highly organized network of non-hematopoietic stromal cells, the LN serves as the context in which the immune system collects and presents antigen, promotes innate and adaptive immune interaction, and generates protective cell-mediated and humoral immunity. In this way, proper organization and function of the LN environment is a critical component of effective immunity, and understanding its complexity has direct impact on the ability to generate and modulate primary immune response to specific antigens. To this end, the LN architecture, underlying stromal networks, and environmental and cellular responses to influenza vaccination were investigated. Using novel approaches to conduit imaging, details of the collagen network that comprises the LN scaffolding have been integrated into current understandings of LN architecture. The cellular compartment responsible for the maintenance of that scaffolding, fibroblastic reticular cells (FRCs), have been studied using an induced diptheria toxin receptor model. By specifically ablating the FRC population in mice, their role in the maintenance of T cell homeostasis has been confirmed in vivo. More surprisingly, a disruption of the FRC network resulted in a loss of B cell follicle structure within LNs, and a reduction in humoral immunity to influenza vaccination. These findings led to the identification of a new subset of FRCs which reside in B cell follicles, and serve as a critical source of the B cell survival factor BAFF. Turning towards the hematopoietic response to influenza vaccination, a highly unexpected lymph node resident dendritic cell (LNDC) response has been identified following vaccine antigen deposition within specialized sites in the LN medulla. Rapid migration of LNDCs into these sites optimizes exposure of the population to viral antigen, and de novo synthesis of a CXCL10 chemokine gradient by activated LNDCs ensures efficient antigen specific \(CD4^+\) T cell response, and protective humoral immunity - independent of migratory dendritic cell status. Altogether, these studies highlight a highly dynamic, responsive LN environment with direct influence on primary immune response - the understanding of which has broad implications in vaccine biology.

No description available.

Diss. (sammanfattning) Göteborg : Univ. , 2009. / Härtill 4 uppsatser.

Thesis (Ph.D. in Reproductive Sciences) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 125-140). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xvi, 218 p.; also includes graphics (some col.). Includes bibliographical references (p. 200-218). Available online via OhioLINK's ETD Center

Thesis (Ph. D.)--University of Virginia, 2007. / Spine title: Mechanism of tolerance to tyrosinase. Includes bibliographical references. Also available online through Digital Dissertations.

Breast cancer is the second leading cause of cancer-related death in women in the United States. Complications that lead to mortality of cancer patients are associated with tumor metastasis. Specifically, lymphatic metastasis in breast cancer patients strongly correlates with poor patient survival and this process is facilitated by the formation of new tumor lymphatic vessels termed lymphangiogenesis. Previously, our lab reported that lymphangiogenesis was promoted by a distinct subset of bone marrow (BM)-derived myeloid cells that co-express lymphatic-specific markers designated as myeloid-derived endothelial cell progenitors (M-LECPs). Furthermore, our lab has generated M-LECP in vitro from a mouse macrophage cell line (RAW264.7) by LPS stimulation. Taken together, these data suggest that chronically inflamed sites drive M-LECP differentiation and that these cells can contribute to the formation of new lymphatic vessels and promote lymph node metastasis. Evidence supporting this hypothesis was indicated by high levels of circulating M-LECP in peripheral blood of breast cancer patients but undetectable levels in healthy donors, cancer-free donors. Additionally, the generation of M-LECP was prompted through TLR4-signaling pathway, and de novo expression of VEGFR-3 and VEGF-C. This co-expression produces an autocrine loop essential for pro-lymphatic reprogramming in both primary human monocytes and the immature monocytic cell line, THP-1. Taken together, these data indicate the major regulatory role of TLR4 in inflammation-driven lymphangiogenesis involves the recruitment and differentiation of M-LECP, a process that may promote lymphatic metastasis.

Thesis (MTech (Nursing))--Cape Peninsula University of Technology, 2011. / To determine the incidence, risk factors and the treatment of lymphedema after breast cancer treatment at the oncology unit of KATH, Kumasi, Ghana from 01 January 2005 to 31 December 2008. Descriptive retrospective survey was used. Using a data capture sheet, data was collected from the medical records of the breast cancer patients. Breast cancer and lymphedema-related variables were collected. Data was analyzed as descriptive statistics. Chi-square test was applied to determine whether or not two variables are independent variables. Among 313 patients treated for breast cancer between 2005 and 2008, 31 (9.9%) developed lymphedema after treatment. A chi-square test showed that axillary lymph node dissection was statistically a significant risk factor of lymphedema (Chi-square test value=7.055, P value=0.008). Radiation and late stage of breast cancer diagnosis may have contributed in development of lymphedema despite having P value> 0.05. Age, body mass index (BMI) and hypertension were also not associated with lymphedema.