Browsing by Subject "Bone Marrow"
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Item AB1-42 Antibody Producing Plasma Cells in DNA AB42 Trimer Immunized Mice Reside Predominantly in the Bone Marrow(2013-01-22) Zacharias, Tresa; Langworthy, Suzanna; Fu, Min; Anderson, Larry; Stuve, Olaf; Rosenburg, Roger; Lambracht-Washington, DorisAlzheimer's disease (AD) is the most common form of age-related dementia and affects nearly 40 million people worldwide. Immunotherapy provides a possible avenue for prophylaxis of AD, but a clinical trial (AN1792) in which patients with early AD were immunized with Aβ1-42 peptide was halted after the occurrence of meningoencephalitis in 6% of the immunized people which was attributed to a T cell autoimmune response. DNA vaccination has been shown to have a polarized Th2 immune response that lacks many of the features responsible for inflammation seen in peptide immunizations. In this study, we show a new feature of the DNA Aβ42 trimer elicited B cell immune response and present data for the presence of a long lived plasma cell pool residing within the bone marrow in DNA immunized mice but not in peptide immunized mice. Two groups of mice were analyzed: one group of B6C3F1 mice (n=20) were studied 4 months after the last DNA vaccination, and a second group of BALB/c mice (n=14), which received DNA or peptide immunizations, were analyzed 10 days following the last immunization. The comparison of antibody producing cells in bone marrow and spleen for the DNA and peptide immunized mice with an Antibody Forming Cell (AFC) ELISPOT assay and subsequent ELISAs showed that bone marrow plasma cells from DNA immunized mice produced more anti-Aβ42 IgG producing cells and higher levels of secreted IgG antibodies. In peptide immunized mice, more IgG antibody producing cells were found to reside in the spleen. These data indicate that the bone marrow may be an important reservoir for B cells following DNA Aβ42 immunization and is in line with studies showing that the bone marrow represents an excellent niche for the survival of long lived plasma cells and a lifetime source for antibody producing B cells which are independent of continuous antigen specific stimulation. Further studies are needed to show whether it is possible to define additional phenotypic characteristics for the antigen specific B cell immune response in DNA Aβ42 trimer immunized mice or differences in the TH subsets directly involved in initial signaling events to B cells in the germinal center reactions.Item Advanced MR Imaging of Bone Marrow: Quantification of Signal Alterations on T1-Weighted Dixon and T2-Weighted Dixon Sequences in Red Marrow, Yellow Marrow and Pathologic Marrow Lesions(2019-03-27) Sasiponganan, Chayanit; Chhabra, Avneesh; Pezeshk, Parham; Ashikyan, OganesBACKGROUND: Characterization of bone marrow through qualitative changes in signal intensity (SI) have not been evaluated on T2-weighted (W) Dixon imaging. OBJECTIVE: We hypothesized that T2W Dixon imaging SI changes are similar to those on T1W Dixon imaging and can be used to effectively characterize bone marrow. METHODS: 144 patients (77 controls with yellow and red marrow regions, 64 lesions--33 benign and 31 malignant) between January 2016 - December 2017 were retrospectively identified. For the control group, fixed 2 cm2 region of interests (ROI) were drawn at L5, bilateral ilium and femurs on in-phase and opposed-phase T1W and T2W Dixon images. For the lesion group, ROI of best fit were drawn around each lesion on in-phase and opposed-phase T2W Dixon images. SI changes for each group were compared. Inter-reader analysis was performed. RESULTS: Yellow marrow exhibited smaller SI changes as compared to red marrow on both T1W and T2W Dixon at all locations (p < 0.0001) except at L5 on T2W Dixon (p = 0.206). Both benign and malignant lesions showed significantly smaller SI changes as compared to both yellow (p = 0.0087, p <0.0001) and red marrow (p = 0.0004, p < 0.0001) on T2W Dixon. Malignant lesions exhibited smaller SI change as compared to benign lesions on T2W Dixon (p = 0.0005). Signal intensity loss on both red and yellow marrow were smaller on T1W Dixon as compared to T2W Dixon (0.49-0.64, 0.27-0.31 vs 0.70-0.74, 0.48-0.71). Inter-reader agreements were excellent (0.91-0.97). CONCLUSION: SI change calculated from T2W Dixon imaging can adequately differentiate between yellow marrow, red marrow and osseous lesions--both benign and malignant.Item [News](1982-02-05) Willding, LizItem Pancytopenia and the hypocellular bone marrow(1985-04-25) Fleischman, Roger A.Item Predicting Severe Hematologic Toxicity from Extended-Field Chemoradiation of Para-Aortic Nodal Metastases from Cervical Cancer(2017-01-17) Yan, Kevin; Ramirez, Ezequiel; Gu, Xuejun; Albuquerque, KevinBACKGROUND AND PURPOSE: To determine significant factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node (PALN) metastasis treated with concurrent chemoradiation with a specific focus on radiation dose to total bone marrow (BMTOT) and active bone marrow (BMACT). To create a nomogram using significant factors to predict HT in these patients. MATERIAL AND METHODS: 38 Patients with cervical cancer and PALN metastasis who underwent 18F-FDG-PET / CT before treatment with extended field radiation therapy (EFRT) and concurrent cisplatin were analyzed. BMACT was defined as the region within BMTOT with a standardized uptake value (SUV) greater than or equal to the mean for the individual. Blood counts were collected weekly from the beginning of radiation treatment to the end of radiation treatment. HT was graded based on the guidelines set by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. RESULTS: 19 patients (50%) had Grade 3 or higher hematologic toxicity (HT3+), not including lymphocyte toxicity. Patients who were obese (n=12) were less likely to get HT3+ compared to patients who were not obese (p=0.03) despite getting the same weight related dose of chemotherapy. Volume of BMTOT receiving 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 78.56% (p=0.01), 47.14% (p=0.00), and 20.36% (p=0.01) respectively. Volume of BMACT receiving 10 Gy, 20 Gy, 30 Gy, and 45 Gy were significant predictors for HT3+ at 95.50% (p=0.03), 80.52% (p=0.05), 59.64% (p=0.03), and 31.74% (p=0.01) respectively. Through logistic regression, the probability of developing HT3+ is given by the equation: Prob(HT3+) = 1 / (1 + exp(7.34 + 0.22*BMI - 0.44*Mean Dose to BMTOT)). Patients who had HT3+ received an average of 4 cycles of chemotherapy and 62 days of treatment time, significantly different than the 4.74 chemotherapy cycles and 53 days of treatment in patients without HT3+ (p=0.05, 0.00 respectively). CONCLUSIONS: Both higher patient BMI and bone marrow irradiation were associated with HT3+. A simplified nomogram has been created to predict HT3+ in these patients. Radiation parameters have been identified for cervical cancer patients with PALN involvement receiving EFRT concurrently with chemotherapy. Bone marrow sparing approaches for EFRT need to be addressed to improve patient care.Item The Roles of Major Histocompatibility Complex Class I and Foxk1 in Natural Killer Cell Development(2007-12-18) Moody, Leslie Ann; Bennett, MichaelPathways leading to the development of functionally mature Natural Killer cells from bone marrow progenitors are incompletely characterized. Several reports have indicated the necessity of class I Major Histocompatibility Complex-Ly49 interactions to generate functionally mature Natural Killer cells. Natural Killer cells from mice deficient in Major Histocompatibility Complex class I exhibit impaired lytic ability against class I+and class I- targets. It has been proposed that class I interactions with inhibitory Ly49s are required for generation of lytic Natural Killer cells; cells that do not receive these signals fail to become activated. To investigate further the role of class I-Natural Killer cell interactions during development, we produced chimeric mice using class I- mice, in which the hematopoietic system was derived from class I-expressing mice. We discovered that class I+ Natural Killer cells that are developed in a class I- environment are not functional, despite the presence of class I on hematopoietic cells. This indicates that the environment in which Natural Killer cells are developed determines their function and further supports the role of the bone marrow microenvironment in Natural Killer cell development. A complete understanding of Natural Killer cell development would involve determining which transcription factors drive development of Natural Killer cells from stem cells to mature, functional Natural Killer cells. Several transcription factors have been described to be necessary for Natural Killer cell development. Mice lacking these transcription factors often have a deficit in Natural Killer cells in vivo. Here we illustrate a role for the forkhead transcription factor, Foxk1, in Natural Killer cell development. Foxk1-/- mice have significantly fewer Natural Killer cells than do wild-type mice and their remaining Natural Killer cells have decreased cytotoxicity. An increase in the percentage of cells in a developmentally important expansion stage indicates that Foxk1 acts there. However, Foxk1 seems to play no role in the thymic development of Natural Killer cells; cells with phenotypic characteristics of thymus-derived Natural Killer cells are present in Foxk1-/- mice. Our studies show a clear role for Major Histocompatibility Complex class I and Foxk1 in the development of functionally mature Natural Killer cells in mice.Item [Southwestern News](1996-08-12) McNeill, Bridgette RoseItem [UT Southwestern Medical Center News](2010-09-03) Morales, KatherineItem [UT Southwestern Medical Center News](2013-02-24) Carlton, Jeffrey