- Browse by Author
Browsing by Author "Rosen, Elliot D."
Now showing 1 - 5 of 5
Results Per Page
Sort Options
Item The Effect of Dimethyl Sulfoxide on Macromolecular Structures(Office of the Vice Chancellor for Research, 2013-04-05) Slaton, Jennifer A.; Johnson, Merrell A.; Rosen, Elliot D.; Petrache, Horia I.Hemorrhagic and thrombotic disorders are a consequence of the body’s inability to form effective blood clots. A major component of the hemostatic clot is a polymerized fibrin network. The network is formed by polymerization of fibrin which is generated by the enzymatic processing of the precursor fibrinogen in blood by the coagulation enzyme thrombin. In our study we investigated how dimethyl sulfoxide (DMSO) effects the formation of the fibrin mesh. These networks were grown over micron-sized pores in polymer membranes with varying concentrations of DMSO. The samples were characterized optically using confocal and differential interference contrast microscopies. Image analysis was performed to determine the structural changes in the fibrin organization.Item The Effect of Free Amino Acids on Fibrin Formation(Office of the Vice Chancellor for Research, 2014-04-11) Dow, Anna M.; Johnson, Merrell A.; Rosen, Elliot D.; Ray, Bruce D.; Petrache, Horia I.Fibrinogen, a plasma protein, is a main component of blood clot formation. In the event of an injury, blood loss is hindered through a process that forms a thrombus by conversion of fibrinogen to fibrin induced by activation of the enzyme thrombin. The fibrin network structure depends on the concentration of thrombin, as expected, but is also highly influenced by its environment during formation. In particular, we find that fibrin formation is altered in the presence of zwitterions. Zwitterions are dipolar molecules, typically highly polarizable, exhibiting both a positive and a negative charge depending on the pH of the solution. Amino acids are highly abundant zwitterions in biological materials. In this study we measured by visible/UV-spectroscopy the effects of various types of amino acids on the rate of fibrin network formation. We show that the electrical charge and type of amino acid, such as lysine, glycine and arginine, inhibits or promotes formation of fibrin networks. Such an ability to decrease or increase the rate of coagulation can be valuable in the treatment of patients suffering from hemostatic and thrombotic disorders.Item Prevention of human PC-346C prostate cancer growth in mice by a xenogeneic tissue vaccine(Springer, 2007) Suckow, Mark A.; Rosen, Elliot D.; Wolter, William R.; Sailes, Valerie; Jeffrey, Randy; Tenniswood, Martin; Medical and Molecular Genetics, School of MedicineVaccination, as an approach to prostate cancer, has largely focused on immunotherapy utilizing specific molecules or allogeneic cells. Such methods are limited by the focused antigenic menu presented to the immune system and by immunotolerance to antigens recognized as “self”. To examine if a xenogeneic tissue vaccine could stimulate protective immunity in a human prostate cancer cell line, a vaccine was produced by glutaraldehyde fixation of harvested PAIII prostate cancer cells tumors (GFT cell vaccine) from Lobund-Wistar rats. Immunocompetent Ncr-Foxn1 mice were vaccinated with the GFT cell vaccine four times, 7 days apart. The control animals were either not vaccinated or vaccinated with media or glutaraldehyde-fixed PC346C human prostate cancer cells and adjuvant. About 8 days after the final boost, serum and spleens were harvested. The splenocytes were co-incubated with PC346C cells and then transplanted orthotopically into sygneneic immunodeficient nude mice. About 10 weeks later, the prostates were weighed and sampled for histolologic examination. The spleens were harvested from additional mice, and the splenocytes were cultured, either with or without pulsing by GFT cells, and the supernatants harvested 72 h later for cytokine analysis. Results showed that vaccination with GFT cells resulted in increased serum antibody to a PAIII cell lysate; reduced weight of the prostate/seminal vesicle complex and reduced incidence of prostate cancer in nude mice; increased splenocyte supernatant levels of TNF-α, IL-2, IFN-γ and IL-12, cytokines associated with Th1 immunity; and increased splenocyte supernatant levels of IL-4 and IL-10, cytokines associated with Th2 immunity. In summary, the results suggest that use of a xenogeneic tissue vaccine can stimulate protective immunity against human prostate cancer cells.Item Segmentation, Reconstruction, and Analysis of Blood Thrombus Formation in 3D 2-Photon Microscopy Images(SpringerOpen, 2009-09-06) Mu, Jian; Liu, Xiaomin; Kamocka, Malgorzata M.; Xu, Zhiliang; Alber, Mark S.; Rosen, Elliot D.; Chen, Danny Z.; Medical and Molecular Genetics, School of MedicineWe study the problem of segmenting, reconstructing, and analyzing the structure growth of thrombi (clots) in blood vessels in vivo based on 2-photon microscopic image data. First, we develop an algorithm for segmenting clots in 3D microscopic images based on density-based clustering and methods for dealing with imaging artifacts. Next, we apply the union-of-balls (or alpha-shape) algorithm to reconstruct the boundary of clots in 3D. Finally, we perform experimental studies and analysis on the reconstructed clots and obtain quantitative data of thrombus growth and structures. We conduct experiments on laser-induced injuries in vessels of two types of mice (the wild type and the type with low levels of coagulation factor VII) and analyze and compare the developing clot structures based on their reconstructed clots from image data. The results we obtain are of biomedical significance. Our quantitative analysis of the clot composition leads to better understanding of the thrombus development, and is valuable to the modeling and verification of computational simulation of thrombogenesis.Item Vaccination against prostate cancer using a live tissue factor deficient cell line in Lobund–Wistar rats(Springer, 2007) Heinrich, Julie E.; Pollard, Morris; Wolter, William A.; Liang, Zhong; Song, Hui; Rosen, Elliot D.; Suckow, Mark A.; Medical and Molecular Genetics, School of MedicineReducing expression of the tissue factor gene in prostate adenocarcinoma cells (PAIII) results in a cell line that, in vivo, mimics the growth of wildtype (wt) PAIII. However, instead of continuing to grow and metastasize as wt PAIII tumors do, tissue factor deficient PAIII (TFD PAIII) masses spontaneously regress after several weeks. Although whole cell vaccines are typically inactivated prior to administration to prevent proliferation within the host, numerous studies have suggested that exposure to live, attenuated, whole tumor cells, and the extracellular microenvironment they recruit, increases immunotherapeutic potential. Here, we provide support for this notion, and a strategy through which to implement it, by demonstrating that subcutaneous vaccinations with the TFD PAIII protect the Lobund-Wistar rat against subsequent wt PAIII cell challenge. TFD PAIII immunized rats suffered significantly less metastasis of wt PAIII challenge tumors compared to unvaccinated naïve controls rats. These results offer the intriguing possibility that the TFD PAIII vaccine is an effective system for the prevention and, possibly, the treatment of prostate cancer.